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What is meant by genomic imprinting being reversible?

What is meant by genomic imprinting being reversible?



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I'm not trying to understand the underlying molecular processes, rather understand it conceptually. This is what it says in my coursebook:

"The imprint, obtained during gametogenesis, is reversible: an allele with paternal imprint will, after transmission through the female germline, be changed into an allele with maternal imprint.

In other words:
Paternal imprinting means that some gene obtained from your father is 'silenced'. These 'silenced tags' remain during your whole life, but are reset during the formation of egg-cells or sperm-cells.
Some genes are always silenced in egg-cells, others in sperm-cells.

There is a continuous activation and deactivation in function of the parent who transmits the gene"

I don't understand how the first paragraph and the last paragraph can both be correct.

If the paternal imprint changes into a maternal imprint after passing through the germline, this implies that the gene is just deactivated in the chromosome that is passed on and we call is paternal or maternal depending on who passes it on.

On the other hand, the last paragraph (and the middle one) imply that, if you receive a gene with maternal imprint from your mother as a man, your body resets the 'silencing' during gametogenesis, realizes a sperm cell is being made and decides not to silence it since it will now be passed on from a father. Only this can explain why it would lead to continuous activation/deactivation or reversibility.

Which of the two is correct?


Only during the formation of egg-cells or sperm-cells one can leave the maternal or paternal imprint, respectively. So for example a man, will leave its paternal imprint on an allele (during spermatogenesis) that was given by his mother (while the allele was maternally imprinted in the rest of his body).


Genetics, Epidemiology, and Counseling

Parental Imprinting

Parental imprinting is another mechanism that could account for skewed maternal transmission of certain congenital heart defects. 154–156 , 166 The hallmark of inheritance of an “imprinted” allele is whether the abnormal gene derives from the maternal or paternal genetic complement. Maternal and paternal genomes do not function equivalently during development. Studies of mouse embryogenesis have shown that embryos with a diploid set of only maternal chromosomes (gynogenomes) or with a diploid set of only paternal chromosomes (androgenomes) die in utero. 167 Paternally derived zygotes develop predominantly extra embryonic tissues, whereas maternally derived zygotes undergo embryogenesis but experience extremely limited development of trophoblast and other extra embryonic tissues. Mice with Robertsonian translocations have been used to produce offspring with partial disomy of one chromosome. Offspring with identical genotypes have characteristically different phenotypes, depending on whether the disomic chromosomes derive from a maternal or paternal line. 168 Offspring that are paternally nullisomic and maternally disomic for portions of chromosome 11 are smaller than normal littermates. Conversely, offspring that are maternally nullisomic and paternally disomic for chromosome 11 are larger than normal littermates. For other chromosome segments, duplication and deficiency combinations are lethal. These observations strongly imply that there are uniquely male and female genetic contributions that occur during development.

A major mechanism by which imprinting is established is believed to be the degree of DNA methylation. 169 , 170 The pattern of methylation is consistent with the requirements of imprinting: (1) the pattern persists stably throughout DNA replication and cell division in somatic tissues and (2) the pattern is erased in the germ line and then differentially established once more in sperm and egg genomes.

An example of parental imprinting in human disease is the Beckwith-Wiedeman syndrome, which is characterized by macroglossia, gigantism, umbilical anomalies, and occasionally cardiomyopathy. Microdeletions in a differentially methylated region on chromosome 11 cause the loss of imprinting of the gene coding for the growth factor IGF2, resulting in the mutant phenotype.


Abstract

Parent-specific gene expression (genomic imprinting) is an evolutionary puzzle because it forgoes an important advantage of diploidy — protection against the effects of deleterious recessive mutations. Three hypotheses claim to have found a countervailing selective advantage of parent-specific expression. Imprinting is proposed to have evolved because it enhances evolvability in a changing environment, protects females against the ravages of invasive trophoblast, or because natural selection acts differently on genes of maternal and paternal origin in interactions among kin. The last hypothesis has received the most extensive theoretical development and seems the best supported by the properties of known imprinted genes. However, the hypothesis is yet to provide a compelling explanation for many examples of imprinting.


INTRODUCTION

Genomic imprinting is a genetic phenomenon in which the same genes express differently, depending on their parental origin [ 1]. On the molecular level, genomic imprinting may result from DNA methylation, histone modification, non-coding RNAs (ncRNA) and even long distance interchromosomal interactions [ 2]. As a ubiquitous phenomenon in nature, genomic imprinting has been broadly identified in plants [ 3], animals [ 4, 5] and humans [ 6, 7].

The role of genomic imprinting in shaping an organism's development has been unanimously recognized [ 8–10]. The imprinting effect on traits of interest can be characterized by different types. When the paternal allele at a gene is expressed and the maternal allele is inactivated, this feature of imprinting is referred to as paternal imprinting. Maternal imprinting is defined similarly. Genomic imprinting has been traditionally viewed as a mono-allelic expression with complete maternal or paternal silence. The definition has been revised by the inclusion of partial imprinting which signifies the different levels of expression for alleles inherited from different parents [ 11, 12]. Note that these classifications are all based on the additive effect of an imprinting locus. Often imprinting can cause change of interactions among alleles. Cheverud et al. [ 13] recently illustrated a scheme for characterizing the potential diversity of imprinting patterns, in which imprinting patterns are classified as either parental expression (paternal or maternal) or dominance (bipolar and polar). To date this is the most complete classification list for genomic imprinting.

Recent studies have shown the power of genetic mapping in the identification of epigenetic modification of imprinted genes or imprinted quantitative trait loci (iQTLs) on complex traits such as the variance component methods for family based pedigree data in human linkage analysis [ 14–16] the variance component methods for experimental crosses [ 17, 18] the regression-based approaches for controlled crosses between outbreed parents [ 19, 20] and between inbreed lines [ 21–23]. In a regular iQTL mapping study, two sex-specific reciprocal heterozygotes (e.g. AMaF and aMAF) are not fully informative or distinguishable. However, as shown by Cui et al. [ 21], the information about sex-specific differences in recombination fraction can be used to infer the imprinting effect of an iQTL.

Most imprinted genes play important roles in controlling embryonic and post-natal growth and development in mammals [ 8–10]. As a highly complex process, genomic imprinting is involved in a number of growth axes operating coordinately at different development stages [ 24], and shows time-dependent effect during development [ 25]. The unbalanced expression of an imprinted gene that occurs during a development stage challenges the traditional paradigm of inheritance and mapping methods. We argue that traditional methods, by treating a trait measured at a certain developmental stage as mapping subject, without considering the correlation information at different developmental stages, are less powerful in dissecting dynamic iQTL effects. Cui et al. [ 26] recently proposed a functional iQTL mapping framework underlying developmental characteristics which incorporates a mathematical function that best describes a developmental feature into an iQTL mapping framework. Such an approach can estimate and test time-specific imprinting effect at specific developmental stages, and displays several merits over traditional iQTL mapping methods.

Current mapping procedures for iQTL inference are all based on single iQTL models, estimating and testing one locus at a time without considering the effects of other iQTLs. When multiple iQTLs are presented in the genome, such approaches are less efficient under the likelihood-based framework [ 27]. For a dynamic trait, the number of parameters being estimated is several folds larger than those for a univariate trait. In our previous QTL mapping model, we demonstrated that a Bayesian mapping method can handle this issue well with high computational efficiency [ 28]. In this study, we unify the two endeavors, Bayesian mapping of developmental traits and iQTL inference, into a unified framework called Bayesian functional multiple iQTL mapping (Bafmim). We propose an efficient Bayesian model selection strategy for multiple iQTL inference for developmental traits. The inference for the number, position and effect of multiple iQTLs as well as for different imprinting patterns is provided. The statistical behavior of the proposed method is illustrated by simulation studies. The utility of the method is shown by applying to a real data set. A total of six iQTLs are identified with Bafmim, among which two were missed by the likelihood-based method. The proposed approach has great implications in understanding the function of imprinted genes governing developmental characteristics.


Lessons from bird brains

Eckhard Hess’s research on imprinting helped to popularize an emerging field of research—one that that explored genetic and learned aspects of early behavior.

December 2011, Vol 42, No. 11

In 2003, as winter began to creep across the Russian tundra, a man in a hang glider led a small flock of Siberian cranes on a 3,000-mile migration from the Arctic Circle to the Caspian Sea. The birds needed the help. Traditional migratory routes led the endangered birds over the dangerous and war-torn skies of Pakistan and Afghanistan, exposing them to gunfire. And the captive-bred birds simply didn't know how to get to their winter feeding grounds. Italian aviator Angelo d'Arrigo showed them the way — and the cranes followed, thanks to principles of imprinting cleverly harnessed by scientists at the Crane Breeding Centre at the Oka Nature Reserve, near Moscow.

Famously described by zoologist Konrad Lorenz in the 1930s, imprinting occurs when an animal forms an attachment to the first thing it sees upon hatching. Lorenz discovered that newly hatched goslings would follow the first moving object they saw — often Lorenz himself. As a result, he was often trailed by a half-dozen waddling geese as he tended the grounds of his Austrian estate.

Though Lorenz's work spurred interest in the early social attachment of animals, scientists found it difficult to study. Because young animals would often imprint on the first object they saw, imprinting research required complete control of the environment.

In the 1950s, a young psychologist named Eckhard Hess (1916–86) devised an apparatus for just this purpose.

As a young boy in Germany, Hess took an early interest in animals raised in his family's barnyard in East Prussia. Later, when they moved to the suburbs, he began observing animals in nearby forests and fields, often bringing them home with him. When Hess was 11, he and his family immigrated to the United States. He earned a PhD in psychology in 1948 from Johns Hopkins University, then took a position at the University of Chicago, where he remained for the rest of his career.

In the 1950s, Hess and A.O. Ramsay, a high school biology teacher from Maryland, began studying imprinting in the laboratory with papier-mâché mallard ducks fitted with off-center wheels that mimicked waddling. The researchers created a great variety of model ducks to experiment with, including ducks with moving heads and ducks with built-in heaters.

By means of pulleys and cords operated from a distance, Hess and his colleagues released newly hatched ducklings from a small cardboard box. The model duck would emit a sound — either a tape-recorded duck call or a human mimicking one — and move around a runway via a motorized arm. Levers on the runway floor kept track of the ducklings' steps to measure their following behavior. At the end of the experiment, a trap door in the runway's floor returned the ducklings to their box.

With this imprinting apparatus, Hess and his colleagues tested several scenarios. For example, they found that the ducklings could also be imprinted on objects other than papier-mâché decoys. Ducklings would also follow a colored sphere, but imprinting was stronger for blue spheres than for white ones. Hess and Ramsay also tried unsuccessfully to imprint ducklings with auditory cues before they hatched by placing speakers in the incubator or nest. Over the course of many experiments, the researchers found that prime time for imprinting was 13 to 16 hours after hatching.

Like previous imprinting researchers, Hess took his work home with him, raising chickens, geese, starlings, ducks, hamsters, lambs and other animals at his country home in Maryland. He and his wife fed and cared for the animals, and sometimes enlisted the help of household appliances unintended for such purposes. Their first gosling, for example, was hatched in a makeshift incubator that was ordinarily used as a place for the rising of yeast dough. By 1985, he and his wife had raised a population of nearly 100 Canada geese.

Through the work of Lorenz, Hess and others, imprinting research drew wide attention. It shed light on many important and controversial topics of 1950s psychology, most notably the problem of heredity and learning. Imprinting, it seemed, was different from most forms of learning. It appeared irreversible and confined to a critical period, and seemed not to require reinforcement. Later research suggested that imprinting may in fact be reversible and may extend beyond the critical period identified by Lorenz and Hess. Regardless, their findings helped to usher in a new era of research on behaviors that appeared to be genetically determined and learned.

Researchers continue to examine imprinting as an example of tightly constrained learning that involves genetic predispositions. And, as the Italian aviator Angelo d'Arrigo showed, imprinting research has practical applications for conserving endangered species. Sadly, d'Arrigo died in 2006 while performing at an airshow in Sicily. However, the practical applications of imprinting continue to be used for similar projects, including Operation Migration, which is teaching captive-born whooping cranes to follow small aircrafts south for the winter.


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Plant Viruses and Technology

3 VIGS Vectors

VIGS vectors differ from protein expression vectors in that they are directed at silencing the target gene. As described in Chapter 9, Section IV , most viruses encode genes that suppress RNA silencing which could also affect the silencing of the target genes. This presents a conundrum in that the viral vector requires silencing suppression for efficient replication but the silencing suppression could compromise the effect of the insert on the target. Obviously a balance between the two has to be achieved. TRV appears to be an effective VIGS vector (reviewed by MacFarlane, 2010 ) due, in part, to its very wide host range and induction of strong and fairly uniform silencing in tissues throughout the plant. Its VIGS efficiency is dependent on the plant species being used with N. benthamiana being the most responsive. The method of introducing the vector into the host can also influence the effects of the silencing suppressor. Hao et al. (2011) found that using the Agrobacterium-mediated coinfiltration system ( Brigneti et al., 1998 Roth et al., 2004 ) CNV p20 failed to act as a silencing suppressor although other experiments showed that it is a suppressor.

See Section III, C for the use of VIGS vectors.


What is meant by genomic imprinting being reversible? - Biology

The genotype of an embryo controls phenotype via the developmental process. Genes regulate development BUT, genes do not exist in isolation, they exist in the environment of the cell. An important question in developmental biology is the relative contribution of the egg cytoplasm (regulated by the maternal genome) versus the zygotic genome. Another related question of importance is how cells differentiate during development to stably express a specialized subset of genes relevant to their specialized functions, e.g., neurons, muscle cells, liver cells, etc. Is DNA irreversibly lost or altered during differentiation in response to cytoplasmic signals?

MAJOR Question of Development: Do all cells have the same DNA? This is termed the theory of Genome Equivalence.

Ideal experimental proof of Genomic Equivalence would be to transplant the nucleus from an adult differentiated cell into an enucleated egg. Will nuclei from all differentiated somatic cells support normal development? If true, then the DNA in all fully differentiated somatic cells is equivalent and the process of differentiation proceeds by fully reversible changes to the DNA.

Amphibian Cloning (John Gurdon, 1975)
The techniques for nuclear transplantation were developed by John Gurdon. He chose an amphibian, the leopard frog ((Rana pipiens ) as a model system because of the large size of the egg (the frog had long been a model system to study early development because of size, availability and ease of rearing animals in the lab). Using small glass micropipettes he hand fabricated with a microforge he developed techniques for:

1. Enucleating eggs

2. Transferring in a new nucleus.

3. Activating the developmental program in the egg.


As you can see from the figure the early blastula nuclei are the best at supporting normal development to the tadpole stage (80% of the time).

Late embryonic and larval nuclei support development to the tadpole stage in less than 1% of the transplantations. These nuclear transplantation experiments supported the hypothesis of Genome Equivalent, but also suggested that the changes occurring in the genome during development and differentiation were difficult to undo. No fertile adults were obtained.

The question still remained: Can fully differentiated somatic cells support normal development when transplanted into an enucleated egg? Further nuclear transplantations studies were done with another more primitive frog (Xenopus laevis) that develops at a much faster rate than the leopard frog. In addition, the idea that the egg cytoplasm reprograms the nuclei was further tested by serially transplanting nuclei from somatic cells to eggs, allowing them to divide to the blastula stage, and then transplanting them back to an enucleated egg. This significantly improved the success rate and led to the development of adult frogs from transplanted intestinal nuclei. Frogs were still sterile. Neuronal nuclei still would not support normal development.

Nuclei from intestinal epithelial cells transplanted into enucleated Xenopus eggs gave rise to feeding tadpoles in about 1% of the transplantations. BUT, when serial nuclear transplantations were performed the success rate increased to about 10%.

Conclusion – Stronger support for theory of Genomic equivalence. Cellular differentiation occurs through reversible changes to DNA. Exposure to egg Cytoplasm is able to cause nuclear reprogramming of nucleus from differentiated somatic cell.

The partial success of cloning frogs led to many attempts at cloning mammals, all unsuccessful until Dolly. In 1997 the scientific world was pleasantly surprised by the first mammalian clone produced by nuclear transfer of an adult somatic cell nucleus.

Ian Wilmot and his colleagues produced Dolly (see http://www.synapses.co.uk/science/clone.html for humorous account)

Sheep were cloned from somatic cell nuclei of adult female sheep. Cells from mammary glands were dissociated and grown in culture. The tissue culture media was adjusted to starve cells and maintain them in the G zero stage of the cell cycle. This was probably the key difference that led to success for this group. Most scientists that had tried cloning mammalian cells assumed that using a nucleus from a rapidly dividing cell would work best since nuclei in early embryos normally undergo rapid divisions. Fusion of enucleated oocyte with mammary cell was produced with an electrical pulse that also activated development in the oocyte.

434 attempts for 1 success! So it is still a very inefficient process. Since the successful cloning (nuclear transfer) that produced Dolly many other mammals have been successfully produced by cloning (cows, pigs, cats, mice, humans NOT YET). However, the success rate is still very low

Because of the low success rate there are still questions concerning the nature of the somatic cells. It may be that endogenous stem cells are the source of nuclei for successful clones. Still no success with neurons.

Transgenic animal: animal that expresses a transgene a foreign gene inserted into the genome by using recombinant DNA and in vitro cloning techniques.

Reproductive Cloning: Using nuclear transfer and cloning techniques to generate a genetically identical animals.

Therapeutic Cloning: Using recombinant DNA and cloning techniques to generate genetically engineered or defined totipotent or pluripotent stems cells for treatment of diseases, or production of tissues for transplantation.

Why Clone Mammals?
It can be hard to produce large amounts of human proteins for therapeutic purposes. One possibility is to insert a transgene (human) for the desired protein into cow or sheep under the regulatory control of an engineered regulatory domain so it will be secreted in milk (eg. Lactalbumin). In this way large quantities of the desired human protein will be secreted into the milk and easily purified.

However, transgenic mammals made via DNA injection into pronucleus can be difficult to make and the transgene is often unstable. Expression levels are variable and often change in subsequent generations.

Cloning allows more precise genetic engineering of cells – and rapid expansion of "perfect" animals. In agriculture that means clones of the "best" milk producing cow or the derby winning horse.


In Humans it means true cures of genetic diseases, eg. Cystic Fibrosis. However there is also the potential for human engineering of any genetically characterized human trait

Therapeutic Cloning could be used to cure some human diseases. STEM Cells are potential therapies for many diseases such as diabetes, Parkinson&rsquos disease, heart disease and many more. There is the potential to use genetic material from a patient&rsquos own cells to generate perfect replacements for damaged tissue.

Why is cloning so difficult? Remember that the "sucess" rate is very low (less than 1%).
Most common phenotypes observed in Nuclear Transfer cloned animals are fetal growth abnormalities, including increased placental and birth weight. Remember that DNA is changed during differentiation and furthermore we know that during gametogenesis specialized changes occur in the male and female gametes. Genetic studies and naturally occurring human genetic diseases have shown that in some cases the disease phenotype varies dramatically depending on whether the mutated gene is from the male or female gamete. One example described in the book is a deletion on chromosome 15. If a child receives the defective chromosome from the father it gets Prader-Willi syndrome (mild retardation, obesity, small gonads, and small stature), while if the child receives the defective chromosome from the mother it gets Angelman syndrome (severe retardation, seizures, lack of speech).

It has been known for many years that the sperm and egg nucleus are not equivalent in their ability to support development.


If a sperm fertilizes an egg missing the female pronucleus the result is called an hydatiform mole and consists of placental but no embryonic tissue. An egg will sometimes spontaneously activate without being fertilized by a sperm. The parthenogenic activation leads to the development of a small disorganized embryo and a small placental. Both of course are early embryonic lethal.

It turns out that during differentiation of the gametes the DNA is specifically altered in a sex (sperm and egg) specific way that leads to differential gene expression in the genes of the two gametes. The term for this is imprinting and is the result of differential methylation of the regulator regions of genes. Thus the patterns of methylation during gametogenesis are distinct in the in the sperm and egg nucleus.

Why are the male and female pronuclei non-equivalent? Answer may lie in the genetic conflict between the male and female.


What is meant by genomic imprinting being reversible? - Biology

Campbell Biology Chapter 15 (powell_h)

1) When Thomas Hunt Morgan crossed his red-eyed F₁ generation flies to each other, the F₂ generation included both red- and white-eyed flies. Remarkably, all the white-eyed flies were male. What was the explanation for this result?

A) The gene involved is on the Y chromosome.
B) The gene involved is on the X chromosome.
C) The gene involved is on an autosome, but only in males.
D) Other male-specific factors influence eye color in flies.
E) Other female-specific factors influence eye color in flies.

2) Sturtevant provided genetic evidence for the existence of four pairs of chromosomes in Drosophila in which of these ways?

A) There are four major functional classes of genes in Drosophila.
B) Drosophila genes cluster into four distinct groups of linked genes.
C) The overall number of genes in Drosophila is a multiple of four.
D) The entire Drosophila genome has approximately 400 map units.
E) Drosophila genes have, on average, four different alleles.

3) Which of the following is the meaning of the chromosome theory of inheritance as expressed in the early 20th century?

A) Individuals inherit particular chromosomes attached to genes.
B) Mendelian genes are at specific loci on the chromosome and in turn segregate during meiosis.
C) Homologous chromosomes give rise to some genes and crossover chromosomes to other genes.
D) No more than a single pair of chromosomes can be found in a healthy normal cell.
E) Natural selection acts on certain chromosome arrays rather than on genes.

4) Thomas Hunt Morgan's choice of Drosophila melanogaster has been proven to be useful even today. Which of the following has/have continued to make it a most useful species?

I. its four pairs of chromosomes
II. a very large number of visible as well as biochemically mutant phenotypes
III. easy and inexpensive maintenance
IV. short generation time and large number of offspring

A) I and IV only
B) II and III only
C) I, II, and III only
D) II, III, and IV only
E) I, II, III, IV, and V

5) A woman is found to have 47 chromosomes, including three X chromosomes. Which of the following describes her expected phenotype?

A) masculine characteristics such as facial hair
B) enlarged genital structures
C) excessive emotional instability
D) normal female
E) sterile female

6) Males are more often affected by sex-linked traits than females because

A) male hormones such as testosterone often alter the effects of mutations on the X chromosome.
B) female hormones such as estrogen often compensate for the effects of mutations on the X chromosome.
C) X chromosomes in males generally have more mutations than X chromosomes in females.
D) males are hemizygous for the X chromosome.
E) mutations on the Y chromosome often worsen the effects of X-linked mutations.

7) SRY is best described in which of the following ways?

A) a gene present on the X chromosome that triggers female development
B) an autosomal gene that is required for the expression of genes on the Y chromosome
C) a gene region present on the Y chromosome that triggers male development
D) an autosomal gene that is required for the expression of genes on the X chromosome
E) a gene required for development, and males or females lacking the gene do not survive past early childhood

8) In cats, black fur color is caused by an X-linked allele the other allele at this locus causes orange color. The heterozygote is tortoiseshell. What kinds of offspring would you expect from the cross of a black female and an orange male?
A) tortoiseshell females tortoiseshell males
B) black females orange males
C) orange females orange males
D) tortoiseshell females black males
E) orange females black males

9) Red-green color blindness is a sex-linked recessive trait in humans. Two people with normal color vision have a color-blind son. What are the genotypes of the parents?
A) XcXc and XcY
B) XcXc and XCY
C) XCXC and XcY
D) XCXC and XCY
E) XCXc and XCY

10) Cinnabar eyes is a sex-linked recessive characteristic in fruit flies. If a female having cinnabar eyes is crossed with a wild-type male, what percentage of the F₁ males will have cinnabar eyes?
A) 0%
B) 25%
C) 50%
D) 75%
E) 100%

11) Calico cats are female because
A) the males die during embryonic development.
B) a male inherits only one of the two X-linked genes controlling hair color.
C) the Y chromosome has a gene blocking orange coloration.
D) only females can have Barr bodies.
E) multiple crossovers on the Y chromosome prevent orange pigment production.

12) In birds, sex is determined by a ZW chromosome scheme. Males are ZZ and females are ZW. A recessive lethal allele that causes death of the embryo is sometimes present on the Z chromosome in pigeons. What would be the sex ratio in the offspring of a cross between a male that is heterozygous for the lethal allele and a normal female?
A) 2:1 male to female
B) 1:2 male to female
C) 1:1 male to female
D) 4:3 male to female
E) 3:1 male to female

13) Sex determination in mammals is due to the SRY region of the Y chromosome. An abnormality of this region could allow which of the following to have a male phenotype?
A) Turner syndrome, 45, X
B) translocation of SRY to an autosome of a 46, XX individual
C) a person with an extra X chromosome
D) a person with one normal and one shortened (deleted) X
E) Down syndrome, 46, XX

14) In humans, clear gender differentiation occurs, not at fertilization, but after the second month of gestation. What is the first event of this differentiation?
A) formation of testosterone in male embryos
B) formation of estrogens in female embryos
C) anatomical differentiation of a penis in male embryos
D) activation of SRY in male embryos and masculinization of the gonads
E) activation of SRY in females and feminization of the gonads

15) Duchenne muscular dystrophy (DMD) is caused by a gene on the human X chromosome. The patients have muscles that weaken over time because they have absent or decreased dystrophin, a muscle protein. They rarely live past their 20s. How likely is it for a woman to have this condition?

A) Women can never have this condition.
B) One-half of the daughters of an affected man could have this condition.
C) One-fourth of the children of an affected father and a carrier mother could have this condition.
D) Very rarely would a woman have this condition the condition would be due to a chromosome error.
E) Only if a woman is XXX could she have this condition.

16) Women (and all female mammals) have one active X chromosome per cell instead of two. What causes this?

A) modification of the XIST gene so that it is active only on one X chromosome, which then becomes inactive
B) activation of the Barr gene on one of the two X chromosomes that then inactivates
C) crossover between the XIST gene on one X chromosome and a related gene on an autosome
D) inactivation of the XIST gene on the X chromosome derived from the male parent
E) the removal of methyl (CH3) groups from the X chromosome that will remain active

17) Which of the following statements is true of linkage?
A) The closer two genes are on a chromosome, the lower the probability that a crossover will occur between them.
B) The observed frequency of recombination of two genes that are far apart from each other has a maximum value of 100%.
C) All of the traits that Mendel studied–seed color, pod shape, flower color, and others–are due to genes linked on the same chromosome.
D) Linked genes are found on different chromosomes.
E) Crossing over occurs during prophase II of meiosis.

18) How would one explain a testcross involving F₁ dihybrid flies in which more parental-type offspring than recombinant-type offspring are produced?

A) The two genes are closely linked on the same chromosome.
B) The two genes are linked but on different chromosomes.
C) Recombination did not occur in the cell during meiosis.
D) The testcross was improperly performed.
E) Both of the characters are controlled by more than one gene.

19) What does a frequency of recombination of 50% indicate?
A) The two genes are likely to be located on different chromosomes.
B) All of the offspring have combinations of traits that match one of the two parents.
C) The genes are located on sex chromosomes.
D) Abnormal meiosis has occurred.
E) Independent assortment is hindered.

20) What is the reason that linked genes are inherited together?
A) They are located close together on the same chromosome.
B) The number of genes in a cell is greater than the number of chromosomes.
C) Chromosomes are unbreakable.
D) Alleles are paired together during meiosis.
E) Genes align that way during metaphase I of meiosis.

21) Three genes at three loci are being mapped in a particular species. Each has two phenotypes, one of which is markedly different from the wild type. The unusual allele of the first gene is inherited with either of the others about 50% of the time. However, the unusual alleles of the other two genes are inherited together 14.4% of the time. Which of the following describes what is happening?
A) The genes are showing independent assortment.
B) The three genes are linked.
C) The first gene is linked but the other two are not.
D) The first gene is assorting independently from the other two that are linked.
E) The first gene is located 14.4 units apart from the other two.

22) The centimorgan (cM) is a unit named in honor of Thomas Hunt Morgan. To what is it equal?
A) the physical distance between two linked genes
B) 1% frequency of recombination between two genes
C) 1 nanometer of distance between two genes
D) the distance between a pair of homologous chromosomes
E) the recombination frequency between two genes assorting independently

23) Recombination between linked genes comes about for what reason?
A) Mutation on one homolog is different from that on the other homolog.
B) Independent assortment sometimes fails because Mendel had not calculated appropriately.
C) When genes are linked they always "travel" together at anaphase.
D) Crossovers between these genes result in chromosomal exchange.
E) Nonrecombinant chromosomes break and then re-join with one another.

24) Why does recombination between linked genes continue to occur?
A) Recombination is a requirement for independent assortment.
B) Recombination must occur or genes will not assort independently.
C) New allele combinations are acted upon by natural selection.
D) The forces on the cell during meiosis II always result in recombination.
E) Without recombination there would be an insufficient number of gametes.

25) Map units on a linkage map cannot be relied upon to calculate physical distances on a chromosome for which of the following reasons?
A) The frequency of crossing over varies along the length of the chromosome.
B) The relationship between recombination frequency and map units is different in every individual.
C) Physical distances between genes change during the course of the cell cycle.
D) The gene order on the chromosomes is slightly different in every individual.
E) Linkage map distances are identical between males and females.

26) Which of the following two genes are closest on a genetic map of Drosophila?
A) b and vg
B) vg and cn
C) rb and cn
D) cn and b
E) b and rb

27) If nondisjunction occurs in meiosis II during gametogenesis, what will be the result at the completion of meiosis?
A) All the gametes will be diploid.
B) Half of the gametes will be n + 1, and half will be n - 1.
C) 1/4 of the gametes will be n + 1, 1/4 will be n - 1, and 1/2 will be n.
D) There will be three extra gametes.
E) Two of the four gametes will be haploid, and two will be diploid.

28) One possible result of chromosomal breakage is for a fragment to join a nonhomologous chromosome. What is this alteration called?
A) deletion
B) transversion
C) inversion
D) translocation
E) duplication

29) A nonreciprocal crossover causes which of the following products?
A) deletion only
B) duplication only
C) nondisjunction
D) deletion and duplication
E) duplication and nondisjunction

30) In humans, male-pattern baldness is controlled by an autosomal gene that occurs in two allelic forms. Allele Hn determines nonbaldness, and allele Hb determines pattern baldness. In males, because of the presence of testosterone, allele Hb is dominant over Hn. If a man and woman both with genotype HnHb have a son, what is the chance that he will eventually be bald?
A) 0%
B) 25%
C) 33%
D) 50%
E) 75%

31) Of the following human aneuploidies, which is the one that generally has the most severe impact on the health of the individual?
A) 47, +21
B) 47, XXY
C) 47, XXX
D) 47, XYY
E) 45, X

32) A phenotypically normal prospective couple seeks genetic counseling because the man knows that he has a translocation of a portion of his chromosome 4 that has been exchanged with a portion of his chromosome 12. Although he is normal because his translocation is balanced, he and his wife want to know the probability that his sperm will be abnormal. What is your prognosis regarding his sperm?

A) 1/4 will be normal, 1/4 will have the translocation, and 1/2 will have duplications and deletions.
B) All will carry the same translocation as the father.
C) None will carry the translocation since abnormal sperm will die.
D) His sperm will be sterile and the couple might consider adoption.
E) 1/2 will be normal and the rest will have the father's translocation.

33) Abnormal chromosomes are frequently found in malignant tumors. Errors such as translocations may place a gene in close proximity to different control regions. Which of the following might then occur to make the cancer worse?

A) an increase in nondisjunction
B) expression of inappropriate gene products
C) a decrease in mitotic frequency
D) death of the cancer cells in the tumor
E) sensitivity of the immune system

34) An inversion in a human chromosome often results in no demonstrable phenotypic effect in the individual. What else may occur?
A) There may be deletions later in life.
B) Some abnormal gametes may be formed.
C) There is an increased frequency of mutation.
D) All inverted chromosomes are deleted.
E) The individual is more likely to get cancer.

35) What is the source of the extra chromosome 21 in an individual with Down syndrome?
A) nondisjunction in the mother only
B) nondisjunction in the father only
C) duplication of the chromosome
D) nondisjunction or translocation in either parent
E) It is impossible to detect with current technology.

36) Down syndrome has a frequency in the U.S. population of

1/700 live births. In which of the following groups would you expect this frequency to be significantly higher?
A) people in Latin or South America
B) the Inuit and other peoples in very cold habitats
C) people living in equatorial areas of the world
D) very small population groups
E) No groups have such higher frequency.

37) A couple has a child with Down syndrome. The mother is 39 years old at the time of delivery. Which of the following is the most probable cause of the child's condition?
A) The woman inherited this tendency from her parents.
B) One member of the couple carried a translocation.
C) One member of the couple underwent nondisjunction in somatic cell production.
D) One member of the couple underwent nondisjunction in gamete production.
E) The mother had a chromosomal duplication.

38) In 1956 Tijo and Levan first successfully counted human chromosomes. What is the reason it took so many years to do so?
A) Watson and Crick's structure of DNA was not done until 1953.
B) Chromosomes were piled up on top of one another in the nucleus.
C) Chromosomes were not distinguishable during interphase.
D) A method had not yet been devised to halt mitosis at metaphase.
E) Chromosomes were piled up on top of one another in the nucleus, chromosomes were not distinguishable during interphase, and a method had not yet been devised to halt mitosis at metaphase.

39) At which phase(s) is it preferable to obtain chromosomes to prepare a karyotype?
A) early prophase
B) late telophase
C) anaphase
D) late anaphase or early telophase
E) late prophase or metaphase

40) What is a syndrome?
A) a characteristic facial appearance
B) a group of traits, all of which must be present if an aneuploidy is to be diagnosed
C) a group of traits typically found in conjunction with a particular chromosomal aberration or gene mutation
D) a characteristic trait usually given the discoverer's name
E) a characteristic that only appears in conjunction with one specific aneuploidy

41) Which of the following is known as a Philadelphia chromosome?

A) a human chromosome 22 that has had a specific translocation
B) a human chromosome 9 that is found only in one type of cancer
C) an animal chromosome found primarily in the mid-Atlantic area of the United States
D) an imprinted chromosome that always comes from the mother
E) a chromosome found not in the nucleus but in mitochondria

42) At what point in cell division is a chromosome lost so that, after fertilization with a normal gamete, the result is an embryo with 45, X?

I. an error in anaphase I
II. an error in anaphase II
III. an error of the first postfertilization mitosis
IV. an error in pairing

A) I or II only
B) II or IV only
C) III or IV only
D) I, II, or III only
E) I, II, III, or IV

43) Which of the following is true of aneuploidies in general?
A) A monosomy is more frequent than a trisomy.
B) 45 X is the only known human live-born monosomy.
C) Some human aneuploidies have selective advantage in some environments.
D) Of all human aneuploidies, only Down syndrome is associated with mental retardation.
E) An aneuploidy resulting in the deletion of a chromosome segment is less serious than a duplication.

44) A gene is considered to be non-Mendelian in its inheritance pattern if it seems to "violate" Mendel's laws. Which of the following would be considered Mendelian?
A) a gene whose expression varies depending on the gender of the transmitting parent
B) a gene derived solely from maternal inheritance
C) a gene transmitted via the cytoplasm or cytoplasmic structures
D) a gene transmitted to males from the maternal line and from fathers to daughters
E) a gene transmitted by a virus to egg-producing cells

45) Genomic imprinting is generally due to the addition of methyl (–CH3) groups to C nucleotides in order to silence a given gene. If this depends on the sex of the parent who transmits the gene, which of the following must be true?
A) Methylation of C is permanent in a gene.
B) Genes required for early development stages must not be imprinted.
C) Methylation of this kind must occur more in males than in females.
D) Methylation must be reversible in ovarian and testicular cells.
E) The imprints are transmitted only to gamete-producing cells.

46) Correns described that the inheritance of variegated color on the leaves of certain plants was determined by the maternal parent only. What phenomenon does this describe?
A) mitochondrial inheritance
B) chloroplast inheritance
C) genomic imprinting
D) infectious inheritance
E) sex-linkage

47) Mitochondrial DNA is primarily involved in coding for proteins needed for electron transport. Therefore, in which body systems would you expect most mitochondrial gene mutations to be exhibited?
A) the immune system and the blood
B) the excretory and respiratory systems
C) the skin and senses
D) the nervous and muscular systems
E) the circulation system

48) A certain kind of snail can have a right-handed direction of shell coiling (D) or left-handed coiling (d). If direction of coiling is due to a protein deposited by the mother in the egg cytoplasm, then a Dd egg-producing snail and a dd sperm-producing snail will have offspring of which genotype(s) and phenotype(s)?

A) 1/2 Dd:1/2 dd all right coiling
B) all Dd all right coiling
C) 1/2 Dd:1/2 dd half right and half left coiling
D) all Dd all left coiling
E) all Dd half right and half left coiling

49) Which of the following produces a Mendelian pattern of inheritance?
A) genomic imprinting
B) a mitochondrial gene mutation
C) a chloroplast gene mutation
D) viral genomes that inhabit egg cytoplasm
E) a trait acted upon by many genes

50) Suppose that a gene on human chromosome 18 can be imprinted in a given pattern in a female parent but not in a male parent. A couple in whom each maternal meiosis is followed by imprinting of this gene have children. What can we expect as a likely outcome?
A) All sons but no daughters will bear their mother's imprinting pattern.
B) All daughters but no sons will bear their mother's imprinting pattern.
C) All sons and daughters will have a 50% chance of receiving the mother's imprinting pattern.
D) All the children will bear their mother's imprinting pattern but only daughters will then pass it down.
E) Each of the children will imprint a different chromosome.

This a map of four genes on a chromosome (See Image)

51) Between which two genes would you expect the highest frequency of recombination?
A) A and W
B) W and E
C) E and G
D) A and E
E) A and G

52) In a series of mapping experiments, the recombination frequencies for four different linked genes of Drosophila were determined as shown in Figure 15.2. What is the order of these genes on a chromosome map?
A) rb-cn-vg-b
B) vg-b-rb-cn
C) cn-rb-b-vg
D) b-rb-cn-vg
E) vg-cn-b-rb

53) The pedigree in Figure 15.3 shows the transmission of a trait in a particular family. Based on this pattern of transmission, the trait is most likely
A) mitochondrial.
B) autosomal recessive.
C) sex-linked dominant.
D) sex-linked recessive.
E) autosomal dominant.

A man who is an achondroplastic dwarf with normal vision marries a color-blind woman of normal height. The man's father was 6 feet tall, and both the woman's parents were of average height. Achondroplastic dwarfism is autosomal dominant, and red-green color blindness is X-linked recessive.

54) How many of their daughters might be expected to be color-blind dwarfs?
A) all
B) none
C) half
D) one out of four
E) three out of four

A man who is an achondroplastic dwarf with normal vision marries a color-blind woman of normal height. The man's father was 6 feet tall, and both the woman's parents were of average height. Achondroplastic dwarfism is autosomal dominant, and red-green color blindness is X-linked recessive.

55) What proportion of their sons would be color-blind and of normal height?
A) none
B) half
C) one out of four
D) three out of four
E) all

A man who is an achondroplastic dwarf with normal vision marries a color-blind woman of normal height. The man's father was 6 feet tall, and both the woman's parents were of average height. Achondroplastic dwarfism is autosomal dominant, and red-green color blindness is X-linked recessive.

56) They have a daughter who is a dwarf with normal color vision. What is the probability that she is heterozygous for both genes?
A) 0%
B) 25%
C) 50%
D) 75%
E) 100%

A plantlike organism on the planet Pandora can have three recessive genetic traits: bluish leaves, due to an allele (a) of gene A a feathered stem, due to an allele (b) of gene B and hollow roots due to an allele (c) of gene C. The three genes are linked and recombine as follows:

A geneticist did a testcross with an organism that had been found to be heterozygous for the three recessive traits and she was able to identify progeny of the following phenotypic distribution (+ = wild type): (See Image)

57) Which of the following are the phenotypes of the parents in this cross?
A) 2 and 5
B) 1 and 6
C) 4 and 8
D) 3 and 7
E) 1 and 2

A plantlike organism on the planet Pandora can have three recessive genetic traits: bluish leaves, due to an allele (a) of gene A a feathered stem, due to an allele (b) of gene B and hollow roots due to an allele (c) of gene C. The three genes are linked and recombine as follows:

A geneticist did a testcross with an organism that had been found to be heterozygous for the three recessive traits and she was able to identify progeny of the following phenotypic distribution (+ = wild type): (See Image)

58) In which progeny phenotypes has there been recombination between genes A and B?
A) 1, 2, 5, and 6
B) 1, 3, 6, and 7
C) 2, 4, 5, and 8
D) 2, 3, 5, and 7
E) in all 8 of them

A plantlike organism on the planet Pandora can have three recessive genetic traits: bluish leaves, due to an allele (a) of gene A a feathered stem, due to an allele (b) of gene B and hollow roots due to an allele (c) of gene C. The three genes are linked and recombine as follows:

A geneticist did a testcross with an organism that had been found to be heterozygous for the three recessive traits and she was able to identify progeny of the following phenotypic distribution (+ = wild type): (See Image)

59) If recombination is equal to distance in centimorgans (cM), what is the approximate distance between genes A and B?
A) 1.5 cM
B) 3 cM
C) 6 cM
D) 15 cM
E) 30 cM

A plantlike organism on the planet Pandora can have three recessive genetic traits: bluish leaves, due to an allele (a) of gene A a feathered stem, due to an allele (b) of gene B and hollow roots due to an allele (c) of gene C. The three genes are linked and recombine as follows:

A geneticist did a testcross with an organism that had been found to be heterozygous for the three recessive traits and she was able to identify progeny of the following phenotypic distribution (+ = wild type): (See Image)

60) What is the greatest benefit of having used a testcross for this experiment?
A) The homozygous recessive parents are obvious to the naked eye.
B) The homozygous parents are the only ones whose crossovers make a difference.
C) Progeny can be scored by their phenotypes alone.
D) All of the progeny will be heterozygous.
E) The homozygous recessive parents will be unable to cross over.

A geneticist did a testcross with an organism that had been found to be heterozygous for the three recessive traits and she was able to identify progeny of the following phenotypic distribution (+ = wild type): (See Image)

61) The greatest distance among the three genes is between a and c. What does this mean?
A) Gene a is closest to b.
B) Genes are in the order: a–b–c.
C) Gene a is not recombining with c.
D) Gene a is between b and c.
E) Distance a–b is equal to distance a–c.


Basics: Imprinting

I've been busy — I'm teaching genetics this term, and usually the first two thirds of the course is trivial to prepare for — we're covering Mendelian genetics, and the early stuff is material the students have seen before and are at least generally familiar with the concepts, and all I have to do is cover them a little deeper and with a stronger quantitative component. That's relatively easy.

The last part of the course, though, is where we start moving into uncharted waters for them, and every year I have to rethink how I'm going to cover the non-Mendelian concepts, and sometimes my ideas work well, and sometimes they don't. If I teach it for another 20 years, I'll eventually reach the point where every lecture has been honed into a comprehensible ideal. At least that's my dream.

Anyway, one of the subjects we're covering in the next lecture or two is imprinting, and I know from past experience that this can cause mental meltdowns in my students. This makes no sense if you're used to thinking in Punnett squares! So I've been reworking this little corner of the class, and as long as I'm putting together a ground-up tutorial on the subject, I thought I might as well put it on the web. So here you are, a basic introduction to imprinting.

Here's a somewhat hypothetical situation. You have two genes, A and B, which have different roles in the two sexes. In females, A is inactivated by modification of the DNA — methyl groups are added to the DNA strand to prevent transcription. I've drawn it below with a little pink box to indicate the female pattern of methylation. The female still has two active copies of the B gene.

The male has the complementary pattern. He uses the A gene, but turns off the B gene with methyl groups. In my cartoon, I've drawn a little blue box to show the male pattern of methylation.

Now the happy couple produces gametes, eggs and sperm. The female produces egg cells that still have the female pattern of methylation—gene A is turned off. The male produces sperm that have gene B turned off. And then they get together at fertilization to produce a zygote or embryo which has a mixed pattern of methylation: on one chromosome, A is inactivated, and on the other chromosome, B is inactivated. This means that the zygote still has one functioning A and B gene…it has both working.

What's described above is the normal state of affairs. Now it may be that the zygote needs both A and B genes functional — there could be functions at the sexually indifferent stage of early development that demand that both genes be operational. Later, when the sexes differentiate, then the embryo may change the pattern of methylation to that seen in one sex or the other. So, for instance, if the zygote happened to be male, it would remove the little pink methylation block to turn on both A genes, and put a blue methylation block on the B gene.

So far, so good, I hope. Now let's look at an unusual situation.

This diagram is just like the one above, with one change. The male has a deletion on one chromosome, marked in red, that destroys both the A and B genes on that chromosome. He's fine, though: he still has a working copy of the A gene on the other chromosome, and because he's male, he had the B gene shut off anyway. It's all good, until he starts producing sperm…and half of his sperm will carry the deletion, and therefore will not contribute either an A or B gene to his progeny.

With some genes, this is OK, because he can count on his female partner to provide good copies of the A and B genes, making up for his shortcoming. In this case, though, there's a problem: yes, the mother provides an A and B gene, but the A gene is methylated or imprinted, and doesn't do anything in the embryo! This can be big trouble if the A gene provides something essential for early development.

There's another way this problem can come up that doesn't involve a deletion—it's called uniparental disomy.

In this case, the mother has a nondisjunction, an error in meiosis that produces an egg with two instead of one copy of the chromosome. This is bad news, because when fertilized by a normal sperm, the zygote will be trisomic for that chromosome. Trisomies are deleterious the only viable autosomal trisomy in humans is trisomy 21, also known as Down syndrome, so this accident is most likely to result in a spontaneous abortion and loss of the embryo. However, sometimes in the cases of trisomies, cells will 'kick out' the extra chromosome and develop normally. That's a useful mechanism for rescuing the embryo from a meiotic error, but in this case it has an additional problem.

What if the extra chromosome that is booted out is the one from the male?

Now the zygote is left with the right number of chromosomes (it is disomic), but they both come from one parent (uniparental), and have the pattern of imprinting of that parent. In this example, both A genes are maternally imprinted and blocked from expression, so the embryo is effectively lacking A.

Does this ever happen in the real world? Yes. In humans we've got one clear example, called Prader-Willi syndrome. There is a series of genes on chromosome 15 that have different patterns of methylation in males and females, and as diagrammed above, in normal cases the zygote receives both the male and female pattern of methylation, and all is well. If a zygote receives only the female pattern, either because of a deletion on the father's chromosome or because of uniparental disomy, it will develop abnormally, exhibiting a range of common effects that include early hyperphagia (they can't stop eating), obesity, and learning disabilities.

There is also a complementary syndrome. What if the deletion is on the maternal chromosome, so only the paternal pattern of gene expression is found in the zygote? It's exactly the same genetics, but the sole difference is in whether the trait is passed on from the mother, or from the father. In this case, the child would have Angelman syndrome, cause by an absence of necessary maternal gene products. Angelman syndrome is much more severe, causing large developmental delays, seizures, and ataxia, or jerky movements (also, curiously, Angelman kids are often also cheerful, happy people).

The important point here is that you don't just inherit genes: you also inherit a history of modification of those genes. Your chromosomes are modified by passage through your mother and your father, and normally, that pattern isn't visible because the modifications complement each other to produce progeny with a functional mixture of active and inactive genes. In some cases, though, heritable or developmental changes to the chromosomes allow us to peek through and see the effect of imprinting.

More like this

Came for the atheism, stayed for the science.
Thanks PZ

Came for the science then rejected atheism.

More limitations coming from evolution the Designer.

My, it's inscrutable, in a curiously deluded and sinister manner.

I think that that sounds like a good explanation. The real-world examples really help. Thank you for the informative post!

My neice has Angelmans, and I had wondered the root of it. This is the clearest explanation I have ever heard. Thanks!

This is a really nice explanation, especially the explanation of why it might be important to have both genes active up to a certain point. I found it easy enough to follow, and liked the use of human genetic problems for an example.

Nice. Genetics over lunch and General Relativity before work. Good day.

Came for the science then rejected atheism.

That's good. First the admission that your thinking processes are either blocked by prejudice, or incapable of coming to an intelligent conclusion. Then should come a good education, and the practice of thinking. And someday, you might be able to think rationally.

Then again, if you're Facilis and/or Eric, improvement seems a dim, dim hope.

"the only viable trisomy in humans is trisomy 21, also known as Down syndrome"

Sorry PZ, I'm going to have to disagree with you. Even given a strict definition of "viable" such as "can produce offspring" which rules out most of them, Triple X is certainly viable.

I can understand why you'd want to simplify things for class, but I think you still need to be accurate.

Now you've made me go an insert the word "autosomal".

This isn't the simple version for class. This is the simple version for the world that hasn't taken my class.

Null_Hypothesis: "Came for the science then rejected atheism."

You "rejected" atheism because of this blog? That's amazing! Somehow I tend to think you had always accepted God and while you may have questioned your belief there was always belief. Or else you wouldn't use the phrase "rejected atheism" becuase you would understand how silly that sounds.

Thanks for the breakdown PZ, but makes me a little paranoid of all the things that could happen if I ever have children. I'll have to take a look at how common these syndromes are.

PZ, I honestly don't like your explanation!
I think you may have simplified to the point it is no longer correct.

I find figure one especially troublesome. It makes it seem as though imprinting is epigenetically homozygous in adult cells, and is maintained through gametogenesis. While the details are still fuzzy, it seems that the consensus in the field is that the imprinting is wiped clean and reset somehow during gametogenesis.

My understanding was that the male/female imprints can be maintained into adulthood. What is the basis of saying the imprinting patterns goes homozygous in adults after development? Rather than being maintained as epigenetically heterozygous?

Also, I would rather see the IGF2 pathway story used as an example than disease. Imprinting allows males to upregulate the IGF2 pathway while females downregulate it (the probable result of an evolutionary arms race over fitness). Removing the female imprints involved results in too-large embryos, removing the male imprints results in runts. Maintaining imprinting results in balance due to the heterozygosity at the epigenetic level.

Did you make the figures yourself?

Not only online HTML validation, but online proof-reading too :o)

This is simplified. Imagine revising the cartoons so that the imprinting is cleared (as it is) and reset at different stages in development -- it would be unwieldy.

Oh the anger. it must bother you so. This is a topic about imprinting, so I won't further taint it with philosophy and religious crap.

Wouldn’t you expect the adult female and adult male to also have a maternally and paternally inherited imprinting pattern, just like the zygote?

Okay, I figure it was simplified, but there is still the problem of the adults being epistatically homozygous for the imprinting!

At least for some genes, imprinting is maintained as heterozygous through adulthood. It even seems like loss of heterozygosity for imprinting may be related to cancer and other diseases.

I would rather see a revised form of your figure one, showing heterozygously imprinted adults, and setting of the imprint one way or the other at the arrows indicating gametogenesis.

I don't think it makes the story more complex to teach that the imprint is set during gametogenesis. As it stands I think it is misleading, maybe even wrong.

pink sasquatch : Oh please consider poor little people like me who never took biology even as an elective in undergrad. I'd like to understand what you've described, but at the moment it's a bit beyond me. That's the trouble with simplification I think. but you have to start some where to have something to add further and more accurate explanations to.

Sorry, I wasn't gearing my comments to the non-geneticist - I was using specific lingo to get across to PZ what I see as a problem in his explanation.

Basically, in figure one I think the adult chromosome diagrams should both look like the zygote chromosome diagram. As it stands now I think it is incorrect.

Hopefully that clears up some of my lingo-infested criticism.

Simplification is fine, unless it is wrong!

Makes sense to me and gets across the core concept in a manner that would continue to make sense were I to print out the pictures and come back to them later, without your words explaining.

Apparently it's simplified a lot according to the other posters but I felt that it gets across that point you concluded with quite clearly.

I don't know about you, pals, but from now on I'm going to ignore Null_Hypothesis for my own mental health.
PZ, thanks for the lesson! I just took my bio final yesterday, though. I can't impress my professor with my new imprinting knowledge now.

Well, I felt like I learned something right up until Pink Sasquatch crushed my sense of minimal accomplishment. Are you telling me it takes more than surfing teh Internets to understand biology? What a disappointment.

That was very well written, very well explained. In fact, I'm going to have to bag some of the approach for a tutorial next term. Credit where it's due -)

It is clear when explaining science, even to an undergrad class, that it often helps to strip it of the minutiae of detail such that the general premise can be conveyed. For those interested in the topic, it is then a matter of building upon this foundation, supplementing the initial model with the evidence of the greater detail that one would invariably expect in any biological system.

Genetic imprinting is an absolutely fascinating subject, and the data on other epigenetic processes in everything from bacteria to humans are hugely exciting.

. from now on I'm going to ignore Null_Hypothesis for my own mental health.

Man, I don't remember imprinting being anything like that. I'm really going to have to reread Heretics of Dune.

wow, censorship . I guess freedom of speech is under attack from all parties. If you don't mind, I'd like to use this topic as an opportunity to learn about epigenesis and imprinting to further my understanding of the fascinating world we are a part of. All hail Wikipedia.

hehe, that was a typo. Should have read epigenetics, not epigenesis. Kind of funny.

So far all I understand is this:
XX and XY hook up, get jiggy, and most often, what is predicted to happen, happens. However, at random intervals, there is an epic fail and then shit happens. Some failures are understood to cause specific, and possibly negative results, but is this also one part of the mutation process related to evolution?

methyl groups are added to the DNA strand to prevent transcription.

PZ, maybe you need to expand on this more, since I was lead to understand that this is a very important concept for embryonic development as well as for mature living which I learned about when reading "Microcosm: E. coli And The New Science of Life" By Carl Zimmer.

Way to not understand the difference between being ignored and being censored. I too will reject the Null Hypothesis.

#11, there are people who discover PZ while going through an atheistic phase, and don't find all the answers here either.
Being mildly theistic can be much for comforting in daily life than PZ's fundamentalist atheist brand. And if only because Xmas is so much easier to explain to kids as "birth of Jesus" than "shopping mania".

How does one be a fundamentalist atheist?

Hey, Null. Maybe you should use Wikipedia to look up the definition of the word "censorship." If someone decides not to read your crappy post, that ain't "censorship." That's "smart."

Maybe it would help if instead of seeing the "Adult" cells as belonging to a somatic line, we're actually looking at cells in the adult in the midst of oogenesis or spermatogenesis.

"I too will reject the Null Hypothesis."

Haha, so you accept H1? What would that be?

Wow what a compliment. You so cannot stand to have your assumptions challenged by observations, that you too would prefer to bury it out of sight. I think I'm on to something!

killfile totally doesn't work for me. All it does is put the gumbies in the background of the comment, but it doesn't remove the comment. If it actually removed dumb comments like it said it was supposed to, then I'd recommend it to others, but.

I am jealous of you people with firefox.

Mu: Eh, I guess. Why on earth would they be looking for all the answers here though!? Seriously. Then again, I came here for hot beard action and squid porn.

Null: "I think I'm on to something!"

No, really you're not. You just aren't clever enough that people find you worth arguing with so they'd just as soon ignore you. I do this with my grandmother often, but then again she has alzheimers. What's your excuse?

I am jealous of you people with firefox.

It is free. Or are you at work and locked into IE?

I thought I understood the explanation, but is there a one sentence definition of imprinting? Something like, "Imprinting is the process whereby genes are expressed only from either the maternal or paternal line." Or am I misunderstanding? The whole rest of the post seems an attempt to explain how this can mess up occasionally.

Someone complains about coming for science, then argues about everything but -- and subsequently hijacks the comments of a layperson who would just like to understand a basic concept. please see comment #30.

Maybe it would help if instead of seeing the "Adult" cells as belonging to a somatic line, we're actually looking at cells in the adult in the midst of oogenesis or spermatogenesis.

Maybe make explicit in the diagrams that these are adult germ line cells?

revBDC: yep. I can't download it at work. They get really angry when we do that and won't fix any other problems that occur on our computers so long as the offending sofware is there. I don't want another rebuild! I shouldn't complain. Company X lets us post on blogs at least!

I think that I'd be a bigger fan of this explanation if it was a degree or three more sophisticated/complex. Even for the general public, there is such a thing as oversimplifying a bit too much. We're not here because we're the general general public - we're here because we're the general nerdy public, after all.

I had a mean daddy. Scientists are discovering that it changes the development of the brain. I guess I'm a freak.

They get really angry when we do that and won't fix any other problems that occur on our computers so long as the offending sofware is there. I don't want another rebuild! I shouldn't complain. Company X lets us post on blogs at least!

Yeah I understand. I am a member of "they" or rather I am the king of "they" at my company.

"Maybe make explicit in the diagrams that these are adult germ line cells?"

That would make enough sense for me. At first I might not understand why that was significant, but later I would have absorbed passively the idea that it might be. Good teaching method there.

So let me see if I understand this correctly. Are you saying that, through imprinting, mutations which developed in parents during their own embryo phase, but which are not represented in their complete gene line, can be passed on to their offspring? Is this something like Lamarck's inheritance of acquired characteristics at the genetic level, or is it more mundane and procedural than that?

well I've enjoyed this friendly banter, but I am now seriously going to get down to the serious business of learning about imprinting.

To Alice, according to Wikipedia, "In mammals, genomic imprinting describes the processes involved in introducing functional inequality between two parental alleles of a gene."

pink [email protected]: Simplification is fine, unless it is wrong!

All simplification is wrong. In fact, all models are wrong. It's just the degree to which they are wrong that matters. :-)

Sorry. The statistician has to get his jabs in when he can :-) Remember Monty Python? "It's only a model!"

Excellent! So simple even a physicist can understand it!

A suggestion, unless I'm misunderstanding -

If the graphic showed a piece actually separate from the chromosome to demonstrate the deletion, it might be clearer what's going on. It is that kind of deletion, rather than a deactivating point deletion, right-?

rBDC: LOL! I work for a different part of the larger body that "they" also work within. So we're allies.

blueelm, you can get a lot of interesting points on the intellectual side of atheism in this blog if you filter out the polemic bashing of creotards. I consider that part the entertainment.

Yeah I understand. I am a member of "they" or rather I am the king of "they" at my company.

"they" are often too busy stopping stupid people from doing stupid things to be able to allow not-so-stupid people to do un-stupid things like install firefox.

Also, if they allowed the not-so-stupid people to do moderately unstupid things, the stupids would cry afoul and demand to download SpamGenerator XXXThousand and the Spyware-o-Rama Toolbar

killfile totally doesn't work for me. All it does is put the gumbies in the background of the comment, but it doesn't remove the comment.

Interesting! I've never seen that behaviour or noticed it reported before. What browser version are you running, and have you poked into the killfile script code itself?

Oh — and how does it behave on other blogs? I'm pretty sure that the gumbies are defined via some CSS which is specific to Pharyngula.

So let me see if I understand this correctly. Are you saying that, through imprinting, mutations which developed in parents during their own embryo phase, but which are not represented in their complete gene line, can be passed on to their offspring? Is this something like Lamarck's inheritance of acquired characteristics at the genetic level, or is it more mundane and procedural than that?

Actually, these aren't mutations. Think of them as padlocks. They don't change the DNA base pairs, they prevent the genes from being used. (Yes there's a chemical change, but it is fully reversible - take off the methyl group and you have the original DNA) So yeah, it's just something that's mundane and procedural.

I am colourblind, a protonope. This means I don't process red light at all. This creates all sort of colour confusions, for example, I can't tell the blue and the pink apart. (That's weird, I know. ) My suggestion is to not necessarily rely on the colours to identify what you intend to discriminate. The labels are good, a highly visible key is good, a background-other-than-white is good. Just please don't assume because they are different colours to most people that there isn't someone like me in your class who can't see the difference.

I know from my own experience, that I'm especially prone to not distinguishing colours especially on high contrast backgrounds like projected slides.

You may have students with colour deficient vision like mine or a related deficiency.

That is my one and only technical criticism, and it's one I wish I could have shared with all my professors down the years. I put it here for your consideration and I hope it helps.

Will there be actual mating involved in the lab component to the lecture?

"Oh the anger. it must bother you so. "

I've often wondered if trolls actually think they're making people angry by posting something stupid, or if they hope to make people angry by calling them angry when they've shown absolutely no signs of being angry.

Either way, it's a huge waste of effort and time.

well, that was understandable, even with the in-comment corrections :-)

however, just like another poster said, this stuff makes me paranoid about breeding. bu the time i might be ready to do so, I'd probably be too scared of all the shit that can go wrong to actually go through with it :-p

It would help. It might also be worth (depending on how much development they've received so far) explaining that there's a LOT of new DNA methylation which occurs in the blastocyst. DNA methylation itself is reversible, with the exception of those in the Imprinted genes. which behave (largely) as you describe them.
My Post-doc is looking at where those methyl groups come from in blastocysts.

at convo regarding firefox
i cannot download at work either. so i have firefox, photoshop, and some random programs installed onto a jump drive that i just leave plugged in. photoshop runs a little slow but firefox runs perfect(bonus is that i can go to the sites they have blocked on IE)

And if only because Xmas is so much easier to explain to kids as "birth of Jesus" than "shopping mania".

Really? How is "we give each other presents to make each other happy" harder to explain than — deep breath — "The Creator of the Universe, who apparently decided to hide all evidence of his existence, decided to forgive humans for violating rules which he made up, so he sacrificed his son, who was really himself, to himself, in a way which left at most the tiniest bits of historical evidence, and which people always describe as 'dying for our sins', even though at other times those same people hate the idea of punishing the innocent, and even though it wasn't really 'dying' anyway, so much as it was a really bad weekend, because the son whom the father sacrificed to himself is now up in Heaven deciding who is good and bad, and today we celebrate the birth of that son-who-is-really-also-the-father (on a day which some guys picked because they wanted to take advantage of the celebrations which were already happening this time of year) by telling each other stories which are really amalgams of the weird and contradictory tales handed down in various books which were written decades after the events they claim to describe (the oldest surviving copies of which date to decades later still), stories which feature stars leading people around like GPS systems and a whole lot of murdered babies."

Actually, these aren't mutations. Think of them as padlocks. They don't change the DNA base pairs, they prevent the genes from being used. (Yes there's a chemical change, but it is fully reversible - take off the methyl group and you have the original DNA) So yeah, it's just something that's mundane and procedural.

Wait, I could be confused myself, but I was under the impression the original comment was about deletion (fig 2), and this is describing Methylation (fig 1). But I could have misunderstood the .

Thanks for posting this. My education in the sciences is not very extensive, so every little bit helps.

Ah, ok thanks W. Kevin Vicklund.

(God sends the "wise men" a dream to warn them to get their asses out of town, but he doesn't do anything to stay Herod's soldiers or safeguard the innocent children? All those babies and toddlers had to die just to demonstrate the seriousness of the situation? Dude! Bethlehem was like totally a town of redshirts!)

all models are wrong. It's just the degree to which they are wrong that matters.

Huh! And all this time I thought imprinting had something to do with geese getting obsessed with Konrad Lorenz!

"John, when people thought the earth was flat, they were wrong. When people thought the earth was spherical, they were wrong. But if you think that thinking the earth is spherical is just as wrong as thinking the earth is flat, then your view is wronger than both of them put together."

Thanks, PZ. This article is the best explanation of my nephew's trisomy 21. The little guy wasn't viable for long, but he was amazing.

The science articles don't often get as many comments as the rest do, and I haven't expressed my appreciation for them as much as I should have. I will now, as commenting on all articles is actually easier once logged in on the new system. Thanks, PZ.

Null_Hypothesis, you are an idiot. You popped a provocative comment in on #2, completely unprovoked, accused a person who commented on it of having anger issues, sprayed around some poor-quality snark, then said you were wanting to focus on the science. Way to hypocrite, you null-brained religieuse.

PZ, let me ask you a specific question or two that may clear up some of my SIWOTI feelings towards your post:

You have an example of good-for-male and good-for-female genes being selectively and homozygously turned off or on in opposite patterns in males or females as a result of imprinting. What are you basing this on? Is there a single real example of this?

My understanding is that imprinting accomplishes the selective expression of EITHER the male OR the female allele in BOTH sexes - both during development and in some adult tissues. This is hypothesized to be the evolutionary outcome of different fitness interests for males and females expressed through their progeny. Imprinted genes are biallelically expressed in some tissue/developmental timepoints, but I hadn't heard that they were biallelically turned off in one sex and turned on in the other via a parental imprinting mechanism.

Can you give one example of a gene that is homozygously turned off in one sex, and on in the other, by imprinting?

In other words, one example where imprinting produces sexually-dimorphic expression of a gene?

Richard Healy -> Have you ever tried the Protanope tools here? The RG2BY (probably the one that would work for you) and RG2MG links on that page you can right-click and bookmark when you run into an image, viewing the image on its own web page and clicking the bookmark will throw it through the tool's processor.

I didn't know that pink and blue would be confusable colours in protanope vision. Vischeck was such a neat site for trying to check out how web sites look to colour-blind people, but I felt so bad for taxing their server by looking at ICanHazCheeseburger that I haven't been back :)

Blake:
I use IE6 (I know, right!?) at work, and Firefox 3.x at home. Pharyngula is the only place where I have killfile on my home computer.

So imprinting does give us males an enduring and essential part in reproduction. The sci-fi scenario of the women getting rid of us guys and reproducing parthenogenetically won't work. Thanks, imprinting.

Whew!
But just tell it to the whiptail lizards.

You're over-analyzing. The chromosomes also don't do it with little pink boxes for the girls, and little blue ones for the boys. The key thing here is to get across the basic concept, of genes that are differentially activated/inactivated in sperm and egg. This has been the hard idea to get across to students.

Otherwise, yes, these processes are much more dynamic than I can illustrate in a couple of quick cartoons.

Sorry, PZ, I'm not over-analyzing, and after a quick brush-up on the subject, I'll say your description is flat-out wrong.

"You have two genes, A and B, which have different roles in the two sexes."

WRONG. This is not a characteristic of imprinted genes.

"In females, A is inactivated by modification of the DNA — methyl groups are added to the DNA strand to prevent transcription. I've drawn it below with a little pink box to indicate the female pattern of methylation. The female still has two active copies of the B gene.

The male has the complementary pattern. He uses the A gene, but turns off the B gene with methyl groups."

WRONG. Imprinting does not act in a biallelic, sexually dimorphic manner as you describe.

"Later, when the sexes differentiate, then the embryo may change the pattern of methylation to that seen in one sex or the other. So, for instance, if the zygote happened to be male, it would remove the little pink methylation block to turn on both A genes, and put a blue methylation block on the B gene."

WRONG. This does not happen. Imprinting does not act in a biallelic, sexually dimorphic manner as you describe.

My criticisms have nothing to do with how "dynamic" the processes are, or your cartoon representations: they have to do with the very basic facts you are presenting being completely untrue.

Imprinting accomplishes the selective expression of EITHER the male OR the female allele of a given gene in BOTH sexes, NOT sexually dimorphic expression of a gene.

Honestly, I am unsure that you understand imprinting yourself given your description of it. PLEASE do not teach these falsehoods to your students, or leave them unchanged here - others have mentioned that they will use them for educational material elsewhere.

I suggest the following as a decent (though possibly dated) review:
Nature Reviews Genetics 2, 21-32 (January 2001)
Genomic imprinting: parental influence on the genome
Wolf Reik & Jörn Walter

Hmmm. When did you install the killfile script? The latest version is applicable to many more blogs it'd be interesting to see how it behaves on your computer.

Ritchie> I'm not familiar with that site in particular, but I am registered with Colbindor (referenced at the bottom of the page) which has some *very* useful tools and articles on colour vision deficiencies and I've used to filters on Vischeck (for the first time EVER I saw the numbers on the Ishihara plates - it was a thrill, I don't mind admitting!)

The in-browser or image up-loader correctional aids work by boosting the spectral channels, which alters the hues of each colour but makes distinguishing colours of different hues possible. It's a kind of messy fix to the problem because it generates a kind of false-colour image that helps to distinguish different colours easier by altering the contrast (which is the problem) but the colours are themselves changed, so it's kind of useless to refer to them as blue and pink anymore - even if the distinction didn't mean much before. That's because filters absorb some spectral frequencies, those that pass through appear brighter and it is the distinction in contrast between the brighter and darker colours which then distinguishes them though still not by hue.

What I mean is my actual colour space, my spectrum is reduced. A protanomolous person is less sensitive, in my case it's shorter. I can and will confuse hues of all colours within a range because more of my colours are similar. And I will tend to distinguish colours using other cues like context and especially brightness and luminosity. Isolated colours (on, for instance, slides) where there is no context, the luminosity is the same, and my reduced spectrum just plays havoc with how sensitive I am to the colour differences and how visible they are.

On PZ's 1st slide, I can follow the example *because* they are labelled but the colours aren't distinct. Although I appreciate for everyone else this must sound mad.
because . er red-green-colourblindness - doesn't that mean you only confuse red with green? and the answer is no. I can confuse pink and blue - and here's why:

For a dichromat like me, every possible colour I can match is a result of matching just two of the primary colours of light rather than the normal three. If you plot a graph for the colour space of visible light (like the CIE 1931 Chromaticity diagram) it's possible to draw on that graph straight lines which represent all the points along which the colours will look the same, that is will have the same hue and saturation.(These are the pseudoisochromatic colours that form the basis of the colour vision tests)

Light is of course subtractive when it comes to colour, and there are only three primary colours, so all hues are made of a mixture and combination of these . A pink object - a case in point - is reflecting both red and blue light. (try googling an RGB slide and making pink mixing amounts of red and blue) then remember that I do not have any long wavelength (red) cones so am not sensitive to red light, and suddenly it makes sense why I can (very) easily confuse pink and blue.

Colblinor has some especially good explanations of colourblindness and it's effects. I recommend it highly.

You left out the rather crucial sentence before my description.

I am not describing any real genes. There is no A and B gene. There are no pink and blue blocks. There is no comparably simple situation in human genetics. I know the real situation is much more complex than what I've described here.However, you can't simply throw something on the level of the Reik and Walter paper at undergraduates cold -- you have to get them to understand the general concept first, then you build to real world complexity.This isn't so hard. It's how genetics has always worked — we also know that relatively few genes operate with the clear simplicity of Mendel's rules, but we still teach them those simple cases first.

PZ, that's a ridiculous sidestep and you know it. How would you react if I said it was fine to teach Intelligent Design in public schools in great detail as long as preface it with "here's a somewhat hypothetical situation"? "Here's a somewhat hypothetical situation", DNA is single-stranded everyone, since you are incapable of understanding the complexity of double-stranded DNA. Just plain ridiculous.

(And I'm not asking you to throw the Reik and Walter paper at undergrads, but I do think that figure 3 of their paper is easier to understand than your figure 1.)

My point has nothing to with complexity, it has to do with you teaching imprinting falsely.

- Imprinting DOES NOT result in sexually-dimorphic expression of genes.

- Imprinting DOES result in the selective expression of either the male or the female allele of a given gene in both sexes.

I'm not sure why you think the latter is necessarily more complex than former, but that shouldn't matter in any case when one of them is FALSE, and the other is TRUE.

If something is too complex for students to grasp at a given level, we shouldn't teach it wrong just for the sake of teaching it.

I honestly don't understand what your issue is on this point, other than perhaps you don't feel like revising your tutorial. You should not teach students things you know are false. Your description of imprinting is wrong. Not oversimplified, but WRONG. It would be better for you to not teach it at all!

In any case, it is very frustrating. Why not revise it?

Pink Sasquatch, what is your experience in teaching introductory courses?

Imprinting and color blindness, two interesting topics for the price of one.

Okay PZ, let me ask another question:

Why mention the (incorrect) sexually dimorphic expression phase at all?

By doing so, you are ADDING complexity to your description, not simplifying it. You are also making your explanation untrue.

Look again at figure 3 of Reik & Walter and compare it to your explanation. You've added an unnecessary, incorrect step in your description.

Why? It only complicates things.

Blake, I don't bother with most of the stuff, which is why I will never be asked to give a theological discourse at church. I'm one of those cherry-picking-the positive-skip-the-nonsense(especially everything BC) guys. Luckily, my specific brand of superstition is pretty easy, as long as I go for my crackers and don't kill anyone.

Count me as another interested, nerdy, but non-science-trained type who appreciates getting the simple explanation as a baseline.

Until a child has the ABCs figured out, reading (in English) is impossible. Don't ask us simpletons to read a chapter book when we're still working out that C sometimes sounds like CAT and other times like CELL.

I do have experience teaching undgrads, but it shouldn't take any experience teaching to come to the conclusion that knowingly teaching something wrong is acceptable. It is better to not teach it all, or reserve it for higher-level classes.

PZ's version of imprinting here is wrong by definition. Check NCBI bookshelf for any number of definitions of imprinting from standard textbooks. None of them will include the weird (incorrect) extra step that PZ has added to the process in order to make it more 'simple'.

PZ isn't teaching the ABCs in this post. He's adding a few extra letters to the alphabet that no one else uses. It's only complicating the issue.

That's why I find it so frustrating.

Pink Sasquatch, as an ex college teacher I strongly disagree with you. Some concepts are best learned in increments. The students need to have the proper background, sometimes in other disciplines, in order to understand the subtleties of the concepts. If I introduced NMR spectra in introductory organic, I didn't expect the students to learn third order coupling as sophomores. That can wait.

So, you're saying that PZ either is knowingly teaching something wrong or isn't doing his job properly. This based on a blog post to a general audience.

I think that's an extraordinary claim.

No, I've stripped away a great many complications to present this as if the male/female differences in imprinting were constant -- we all know this is not the case. However, I'm not really willing to get into erasure and resetting of methylation states and epigenotype spreading at this level of discussion. The point here is to introduce a very general idea, how deletions can expose different patterns of gene expression on maternal and paternal chromosomes. I am not talking about developmental patterns at all. That's it. It's a cartoon of the actual genetics, OK?

It's nice that you mentioned the Reik and Walter article. In class, right after I introduce the concept by way of the admittedly greatly simplified version shown here, I bring up figure 1 from that paper and we talk about the actual genes involved, and I try to explain that there are many more complexities involved. That's about where it has to be left, because there are only 3 more weeks in the term, and I still have to cover chromosome structure, a little bit of genomics, and some developmental genetics in that time. and the obvious reality here is that everything has to be abridged.

Pink Sasquatch:
Fortunately (for everyone) I deleted my first post to you. RIght or not, the imperious hand-wringing tone is. off-putting. (There - no hair curling, spittle flecked invectives this time) & Unless you're being facetious, lose the exclamation marks or your posts might be as well be typed in Comic Sans font with a screened Monty Python character in the background. Have a good day!

there are only 3 more weeks in the term, and I still have to cover chromosome structure, a little bit of genomics, and some developmental genetics in that time

No wonder why my high school history classes never got past World War II.

Well, keep in mind that Pink Sasquatch is right — I'm really compressing the whole process a lot to try and get straight to the core principles. If you're closer to the subject, it hurts to see important bits whittled away.

There's not much I can do to satisfy everyone. Pedagogy is often about compromise.

There's not much I can do to satisfy everyone. Pedagogy is often about compromise.

Sounds like a good lesson to me. I'm a senior in hs now (not off to UMM, sorry, PZ), took AP Bio last year, and with that background it pretty much makes sense to me this way.

Sounds like this is for a decently basic level course, right?

Blake, I don't bother with most of the stuff, which is why I will never be asked to give a theological discourse at church. I'm one of those cherry-picking-the positive-skip-the-nonsense(especially everything BC) guys

Theologians do that too. In some sense, the tradition is as old as Christianity itself: the first guy we know of who tried to establish what the Christian canon should be was Marcion of Sinope (c. 85–160 CE), whose Bible consisted only of a few Pauline epistles and an edited version of Luke.

Pedagogy is often about compromise.

No. Not even in the face of Armageddon. Never compromise. Hehn.

PZ, maybe I'm not getting across my key point to you. I'm really not trying to come off as an unsatisfiable asshole.

You say, "It's a cartoon of the actual genetics, OK?"

And I say, "Okay, but the cartoon is wrong, OK?"

Imprinting never goes to biallelic sexually dimorphic expression like you state.

This is an EXTRA step that you've added. PLEASE let me know that you understand this. You've added an EXTRA step to the process/cartoon.

I don't care about the developmental details, erasure or resetting. I wouldn't teach that either. I care about the genetics. And the genetics, as you've presented them, are wrong.

Here is the extra step you've added:

"Later, when the sexes differentiate, then the embryo may change the pattern of methylation to that seen in one sex or the other. So, for instance, if the zygote happened to be male, it would remove the little pink methylation block to turn on both A genes, and put a blue methylation block on the B gene."

This is not part of imprinting, and seems to me to complicate things. You are not "stripping away the complications", you are adding some. And they are wrong.

I hope you understand this.

I'm with Pink Sasquatch on this one. It's a disservice to couple one correct concept, "maternal and paternal chromosomes can have different patterns of gene expression, which we discover through deletions" with one more obvious, broader-ranging, simpler, and incorrect concept, "these genes act differently in males and females." How are you going to explain deleterious effects from uniparental disomy while your diagram clearly shows that two pink boxes are BAD for the embryo, but FINE in the mother of said embryo?

Any of these students that go on in genetics, or encounter a disease affected by imprinting, are going to remember "different in males in females" when they ought to be remembering "different when FROM males than when FROM females". IMHO, that is not so hard to explain. I suggest:

An imprinted gene is a gene whose alleles have different levels of activity depending on whether the allele came from the sperm or the egg that produced the animal.

Here's another non-science explanation from keepkidshealthy:

"In children with Prader Willi Syndrome, this chromosomal deletion is derived from the father. If the same microdeletion were derived from the mother, then it would cause Angelman syndrome instead. The process where a chromosomal abnormality can cause different syndromes depending on if it is inherited from the mother or father is called genetic imprinting."

No I'm not a professor I'm just a genetics M.S. who has TA'd introductory genetics and adores imprinting.

I agree with your post entirely. We don't disagree at all.

I have a problem with an incorrect part of PZ's description, and not his oversimplification of it. He is, in fact, adding an extra, incorrect step that complicates the process. His description is wrong because of this.

This doesn't happen it is wrong:

"Later, when the sexes differentiate, then the embryo may change the pattern of methylation to that seen in one sex or the other. So, for instance, if the zygote happened to be male, it would remove the little pink methylation block to turn on both A genes, and put a blue methylation block on the B gene."

Apparently I'm not communicating well here.

I'm happy you showed up. I was beginning to feel like a lone kook.

Pink Sasquatch, you remind of one of my old colleagues who was terrible at teaching P-chem to the juniors. He expected them to grasp concepts that were easy for him to see, but difficult for the students. He tended to grade harshly since the students did not pick up on the subtleties. And he was not thought well of by the students.
Sometimes one should just introduce a concept without going heavily into details that might confuse the students, even if it may be scientifically inaccurate due to subtleties.
I'm certain PZ has a better idea of what his students are capable of learning than you.

Try http://portableapps.com/ for all your Firefox-on-a-(USB)-stick needs.

Pink Sasquatch:
I admit I am not a teacher and I don't know that much college level biology, but I think I am following you pretty well. To me what PZ is doing sound almost exactly like how some concepts in Comp. Sci. are taught (for very good reason).

Stuff is sometimes vastly simplified, or sometimes even taught in an actually incorrect form in order to get the concepts across. For example, we are first taught ascii and straight binary counting, with no mention of ISO 8859, unicode/UTF-8 or binary coded decimal, two's complement, or IEEE floating point. The freshmen learning binary counting and ascii would freak out and abandon the program if you started with FP, two's compliment and Unicode.

This is true, your point isn't coming across at all well. What I'm trying to get across in those few lines is the idea that the pattern of methylation is not fixed, but will change in the early weeks of embryogenesis—that the pattern inherited from the parents will be erased and reset to something different. The only reason I'm reusing my little pink and blue boxes is that they don't add an unnecessary new pattern to the picture I could have drawn them with a green box in a different location, and explained that this will be changed yet again when this embryo matures and begins gametogenesis and starts slapping the blue/pink boxes on DNA in the germ line, but trust me. tossing in a whole bunch of novel methylation patterns and multiple steps to the long, long process is going to add nothing but confusion. That has to be saved for later, not on the first day students get exposed to the idea.But otherwise, this is simply a cartoon version of erasure and alteration of methylation patterns as the embryo differentiates, as Reik and Walter explain it.

The only thing I've done in my description is limited myself to only using two possible methylation patterns. I also tell the students this is a gross simplification. I am not about to get into a discussion of every nuance and detail in this kind of class, or with this particular internet audience. You're free to do so yourself, and that's actually one of the purposes of these comments — so that more informed readers can expand on the stuff I only skim over. Where you're going awry is in not simply trying to explain more cool stuff about this topic, but instead seem to be freaking out over a pedagogical necessity.Build on the rough framework I've thrown up in this post, don't throw a tantrum and try to throw it all out. That doesn't help with understanding at all.

I'm happy you showed up. I was beginning to feel like a lone kook.

Another kook here. I think this post does not really avoid talking about erasure and resetting methylation states, rather it implies that they occur during embryonic development (when the embryo is already multicellular - how would that work exactly?) I don't think it would make the explanation more complicated to put the erasure step in the right place.

This is true, your point isn't coming across at all well. What I'm trying to get across in those few lines is the idea that the pattern of methylation is not fixed, but will change in the early weeks of embryogenesis—that the pattern inherited from the parents will be erased and reset to something different.

But it's not because the embryo needs both genes during development and then switches both chromosomes to the "female" or "male" position during sex differentation. That wouldn't be imprinting, it would be something else. The pattern of methylation in the somatic cells of the embryo is fixed. The change occurs only in the germ line of the embryo.

I used to teach celestial navigation. Just about the first thing I'd tell my students is "Forget Copernicus, for our purposes the Earth is fixed in the center of the universe and the sky rotates around the Earth." This completely false concept makes celestial navigation easier to understand and makes the math a whole lot simpler.

PZ I see another glaring mistake.

There is absolutely no bacon in that post.

As one who is severely unhabituated to the fiendish complexity of developmental biology or genetics and just about all science dealing with them thar animicules and their innards, I certainly couldn't say whether whatever I'm reading is "wrong".

But what I read in PZ's "ground-up tutorial" here made pretty good and consistent sense to me. I read through it again. I still groked it.

An introductory tome to ease the transition from Mandelian to non-Mandelian concepts. (PZ says so).

From the "relatively easy" to something potentially confusing enough for "mental meltdown". I girded my mental loins. I got through it. I didn't see any inconsistencies.

Despite a few treacherous spots it made good sense every step of the way. Then again, I'm a dunce, and I always manage to find it treacherous. I have to concentrate hard and go over and over and reread repeatedly whenever I'm reading about things that boast a metabolism and the ability to reproduce. Just the phrase "organic chemistry" makes me wince. I had to look up "Punnett squares". Had no idea what the hell that was. Had to find out. But I have an unusually stubborn nature (or is it masochism?) and I refuse to accept defeat. If I start it, I must finish it. I just want to understand.

I'm slow, but that also gives me a good idea of why technical material is difficult for people who aren't nearly as stubborn as I am. But just because I'm slow doesn't mean I can't detect a false argument or an inconsistent one. I didn't see any in PZ's piece. It made sense to me, from top to bottom. I could TELL he was employing a hypothetical exercise. HE SAYS SO.

A means of using a hypothetical in order to introduce a transition to another concept, in this case, non-Mendelian genetics in terms of an exercise.

Many mathematicians and maths instructors are familiar with the tactic. They do it all the time. It may not be pretty, but it's practically useful. It really works. The exercise doesn't have to be right. All it has to do is introduce the tools in a consistent way, step by step, so one can see how it might work, stepwise. (Even musicians know the value of exercise).

With mangy screwy formalisms, you don't throw students into the deep-end of the quicksand without arming them first by building a few new neural connections (dendrites, right?) with which to cope. You give them a chance to grasp a foothold, a purchase, a ladder of some kind by which, rung by rung, step by step they can confidently reach the next restful ausicht and be able to gasp, with a comprehension that apparently comes from nowhere, "AHA. "

It clicks because of the scaffolding that was erected. Never mind that the final building doesn't look like the scaffold. The scaffold isn't "wrong" just because it doesn't exactly match the looks of the building. The scaffold has nothing to do with the building other than to have fostered the building's construction. Without the scaffolding, the building would never exist. Once the scaffold is removed, the building stands. That's what counts.

PZ concludes in his last paragraph what his "EXERCISE" was all about. There's nothing "wrong" here. It's a valid introduction that sets things up for the final assault towards the "AHA. " - WHEN, it comes to actually understanding this business about "imprinting". I'm sure PZ has those next chapters too.

Even though I've adored it since I was a child - I LOVE biology - he's once again made me think AND comprehend what was formerly an impeneterably complicated concept that is (to me, anyway) a frontier of a field which has often been as difficult for me to digest as tar.

pink sasquatch. PZ isn't teaching undergrads here. He's just giving some ropes of exercise to dopes like me. I certainly don't dispute your contentions, but I'm pretty sure you don't have much of a handle on PZ's actual intentions here either. You insist PZ must be accurate with the business of imprinting, but as much of a dunce as I am, even I can plainly see that's NOT the whole point of his post. He mentions it as a point of departure, saying, in effect, "in order to see how this works, try thinking about this exercise". It will help. It's not always a question of immediate accuracy. It's just a question of whether people ever get a chance to understand a relatively complicated thing in the first place.

The difference between a good teacher and a lousy one is that the good one knows how to ease me into it by exercise like this, that shows me I actually CAN float. The lousy one throws me directly into the deep end of the quicksand. There's actually no real TEACHING in that. No transition whatsoever. All of a sudden one finds oneself sinking in cold quicksand, and nothing is learned. except maybe something idiotic like, "difficult science can't be taught to slow-witted people" or, "I'll never understand this stuff because teacher thinks I'm a dimwit".

Try and relax. Practicing the chops, even if they're a bit off the mark is a Good Thing. It CAN lead to undertsanding the accurate parts, just by suggesting the differences.

Or are you suggesting that scientific instruction - even in an informal setting such as this - is an inherently dogmatic enterprise, where an audience (or students) cannot be trusted to have the wit to find out more for themselves after having their curiosity piqued? If you think so, than you would probably consider people like me even dumber than we already know we are. Such an attitude would make you a false teacher: there'd be no point to teaching OR making sure that everything was absolutely accurate, then, would there?

Again, I don't disagree with what you are saying, and I'm not worried about subtleties/details/simplification in the way that people seem to think.

I don't think you get why I'm frustrated, but since you have a chemistry background I'll put it to you this way:

This isn't comparable to teaching NMR without teaching third order coupling. This is comparable to teaching NMR by describing how time of flight mass spectrometry works.

"Build on the rough framework I've thrown up in this post, don't throw a tantrum and try to throw it all out. "

But even the rough framework is off. I also didn't try to throw it all out - I suggested you remove all the incorrect stuff you added about sexually dimorphic expression, which is extraneous and has nothing to do with imprinting. It simply does not belong there, and adds complication and confusion. I'm not sure why that is so hard to understand. The rest of your post would be fine. I'm also not sure why you are so defensive of your blue and pink boxes. I have no problems with those, either.

Honestly, you've made a number of false statements in the post that make me wonder if your understanding of imprinting is correct.

"What I'm trying to get across in those few lines is the idea that the pattern of methylation is not fixed, but will change in the early weeks of embryogenesis—that the pattern inherited from the parents will be erased and reset to something different."

If this is what you are trying to get across, then you are indeed misunderstanding imprinting.

I am not saying that facts in your post are wrong because it is oversimplified.
I am saying that facts in your post are wrong because they are wrong (at least in the context of imprinting).

You write: "Later, when the sexes differentiate, then the embryo may change the pattern of methylation to that seen in one sex or the other. So, for instance, if the zygote happened to be male, it would remove the little pink methylation block to turn on both A genes, and put a blue methylation block on the B gene."

This has nothing to do with imprinting and will not be found in any textbook under imprinting.

"Where you're going awry is in not simply trying to explain more cool stuff about this topic, but instead seem to be freaking out over a pedagogical necessity."

Sorry I'm not adding "cool stuff" or that I seem to be a pedagogue. Really I'm "freaking out" because it sounds as if you plan to teach some weird hypothetical situation about sexually dimorphic expression and call it "imprinting". That's just not right.

What textbook are you using, out of curiosity?

PZ, your description of imprinting is wrong. Period. It is not wrong because of simplication, it is wrong because you added extra complications that have nothing to do with imprinting. It is not hard to correct, and I'm not sure why you are so stubbornly resistant to the idea.

Sorry, this was wrong:
The pattern of methylation in the somatic cells of the embryo is fixed.
Should have said that the imprinting pattern in the somatic cells of the embryo is fixed. The methylation itself is not fixed. As the Reik and Walter paper says, one of the outstanding questions is:

How are imprints maintained when there is genome-wide active and passive demethylation in the early embryo?

But it is maintained, somehow, otherwise we wouldn't have things like the Prader-Willi syndrome. Right?

Well, I, for one, both enjoyed the original post and the ensuing conversation. Both have taught me quite a bit. Thanks moth to PZ and pink sasquatch.

I have to admit that without PZ's refresher, I wouldn't have remembered enough to get the sasquatch's point.

Pink Sasquatch, you are being unnecessarily pedantic. As one who has taught remedial chemistry to a graduate level course, if your audience can't understand what you are trying to teach, you shouldn't be teaching that way. My third order argument is correct. This needs to be simplified so PZ's students can understand the basic concept. You are so wrapped up in the correct science that the total concept will blow over the student's heads. Been there, done that, revised notes.

Im not a specialist in this,but this abstract from an article in Nature does seem to suggest that PZ's simplified explanation is at least not incorrect.

Pink Sasquatch - Just noting the original objection*:

I find figure one especially troublesome. It makes it seem as though imprinting is epigenetically homozygous in adult cells, and is maintained through gametogenesis.

PZ, your description of imprinting is wrong. Period. It is not wrong because of simplication, it is wrong because you added extra complications that have nothing to do with imprinting. It is not hard to correct, and I'm not sure why you are so stubbornly resistant to the idea.

Perhaps you'd care to correct it, since it's not hard to do - what edits should be made to the post to get it not wrong?

--
* and, what proportion of the general public would follow that? )

I could have taught third order NMR coupling in introduction to Organic Chemistry, but if it took me two weeks to get there, and the organic group decided at most 2 days on NMR, it would throw the whole years syllabus off. You can't always go into gory details and get where you must to hand students off to the next course if you fail to cover the expected material. Sometimes you sacrifice depth to get breadth.

Good point. You don't like that paragraph? Rewrite it. I'm willing to patch in a revision, as long as you don't turn it into a complicated mish-mash.

To Nerd of Redhead and John Morales:

Sorry if I'm speaking over your heads, but in this thread I'm not speaking to you, I'm not speaking to undergrads, and I'm not speaking to the general public. I'm speaking to PZ Myers, who should be able to grasp the terminology since he is qualified to teach the material.

I have no problem with simplifying material or leaving out extensive details.

Your repeated hounding on these points is off-base, since I don't disagree with you.

Perhaps you'd care to correct it, since it's not hard to do - what edits should be made to the post to get it not wrong?

for starters (sorry for butting in pink sasquatch), the normal "Adults" all should look like the "Zygote" in Figure 1. This was pointed out early on by pink sasquatch and Matt in #18.

To PZ @#123 who says, "Good point. You don't like that paragraph? Rewrite it. I'm willing to patch in a revision, as long as you don't turn it into a complicated mish-mash."

You know, earlier I actually considered sitting down and spending some time rewriting your post and rearranging your figures to try to get my point across. And then I thought:

"Fuck that. Let PZ write his own damned lecture."

It should be enough for you to realize that your description of imprinting is wrong, or at least misleading, to change it yourself. You are the one responsible for it.

To Rorschach #120: I think that paper is describing a special case in which imprinting is not reset. but I only skimmed it. I was working on this:

"Perhaps you'd care to correct it, since it's not hard to do - what edits should be made to the post to get it not wrong?"

Please see below for my suggested edits to PZ's original material.

Here's a somewhat hypothetical situation. You have two genes, A and B, which have different roles in the embryo. As the ovary produces eggs, A is inactivated by modification of the DNA — methyl groups are added to the DNA strand to prevent transcription. I've drawn it below with a little pink box to indicate the maternal pattern of methylation. The prospective germ cell still has two active copies of the B gene.

The male germ cells have the complementary pattern. His sperm use the A gene, but turn off the B gene with methyl groups. In my cartoon, I've drawn a little blue box to show the paternal pattern of methylation.

Now the happy couple mixes their gametes, eggs and sperm. The female produces egg cells that have the maternal pattern of methylation—gene A is turned off. The male produces sperm that have gene B turned off. And then they get together at fertilization to produce a zygote or embryo which has a mixed pattern of methylation: on one chromosome, A is inactivated, and on the other chromosome, B is inactivated. This means that the zygote still has one functioning A and B gene…it has both working, just like the parents.

So far, so good, I hope. Now let's look at an unusual situation.

This diagram is just like the one above, with one change. Some of the male's sperm have a deletion on one chromosome, marked in red, that destroys both the A and B genes on that chromosome. If a sperm carrying the deletion fertilizes an egg, it will not contribute either an A or B gene to his progeny.

With some genes, this is OK, because he can count on his female partner to provide good copies of the A and B genes, making up for his shortcoming. In this case, though, there's a problem: yes, the mother provides an A and B gene, but the A gene is methylated or imprinted, and doesn't do anything in the embryo! This can be big trouble if the A gene provides something essential for early development.

There's another way this problem can come up that doesn't involve a deletion—it's called uniparental disomy.

In this case, the mother has had a nondisjunction, an error in meiosis that produces an egg with two instead of one copy of the chromosome. This is bad news, because when fertilized by a normal sperm, the zygote will be trisomic for that chromosome. Trisomies are deleterious the only viable autosomal trisomy in humans is trisomy 21, also known as Down syndrome, so this accident is most likely to result in a spontaneous abortion and loss of the embryo. However, sometimes in the cases of trisomies, cells will 'kick out' the extra chromosome and develop normally. That's a useful mechanism for rescuing the embryo from a meiotic error, but in this case it has an additional problem.

What if the extra chromosome that is booted out is the one from the male?

Now the zygote is left with the right number of chromosomes (it is disomic), but they both come from one parent (uniparental), and have the pattern of imprinting of that parent. In this example, both A genes are maternally imprinted and blocked from expression, so the embryo is effectively lacking A.

Does this ever happen in the real world? Yes. In humans we've got one clear example, called Prader-Willi syndrome. There is a series of genes on chromosome 15 that have different patterns of methylation in sperm and eggs, and as diagrammed above, in normal cases the zygote receives both the maternal and paternal pattern of methylation, and all is well. If a zygote receives only the maternal pattern, either because of a deletion on the father's chromosome or because of uniparental disomy, it will develop abnormally, exhibiting a range of common effects that include early hyperphagia (they can't stop eating), obesity, and learning disabilities.

There is also a complementary syndrome. What if the deletion is on the maternal chromosome, so only the paternal pattern of gene expression is found in the zygote? It's exactly the same genetics, but the sole difference is in whether the trait is passed on from the mother, or from the father. In this case, the child would have Angelman syndrome, cause by an absence of necessary maternal gene products. Angelman syndrome is much more severe, causing large developmental delays, seizures, and ataxia, or jerky movements (also, curiously, Angelman kids are often also cheerful, happy people).

The important point here is that you don't just inherit genes: you also inherit a history of modification of those genes. Your chromosomes are modified by passage through your mother and your father, and normally, that pattern isn't visible because the modifications complement each other to produce progeny with a functional mixture of active and inactive genes. In some cases, though, heritable or developmental changes to the chromosomes allow us to peek through and see the effect of imprinting.

Pteryxx speaking again. I made minor edits, with the exception of one paragraph:

"What's described above is the normal state of affairs. Now it may be that the zygote needs both A and B genes (to have both copies) functional — there could be functions at the sexually indifferent stage of early development that demand that both genes (alleles) be operational. Later, when the sexes differentiate, then the embryo may change the pattern of methylation to that seen in one sex or the other. So, for instance, if the zygote happened to be male, it would remove the little pink methylation block to turn on both A genes, and put a blue methylation block on the B gene."

Ptx says: As far as I know, embryos don't activate both copies of imprinted genes in their somatic tissues, and imprinting patterns don't change during sex differentiation, again in somatic tissues. At least in general this doesn't happen there may be special cases in depth. Therefore I suggest striking this paragraph entirely. Otherwise, I put my suggested edits in parentheses.


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