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Dosage compensation

About: Dosage compensation is a research topic. Over the lifetime, 1920 publications have been published within this topic receiving 124589 citations.


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TL;DR: The analysis presented here supports and suggests a biological explanation for peculiarities of fragile-X inheritance described by others as "clustering" and the "Sherman paradox" as consequences of a very small number of oogonial progenitor cells.
Abstract: Laird has proposed that the human fragile-X syndrome is caused by abnormal chromosome imprinting. The analysis presented here supports and extends this proposal. Using published pedigrees that include DNA polymorphism (RFLP) data, we establish that the states of the fragile-X mutation termed "imprinted" and "nonimprinted" usually can be distinguished by the level of cytogenetic expression of the fragile-X chromosome. This information is then used to assess the state of the fragile-X allele in carrier progeny of individual women who inherited a nonimprinted fragile-X chromosome. From this assessment, an estimate is made of the frequency, in individual women, of primary oocytes with an imprinted fragile-X chromosome. The results of this analysis provide additional support for the specific model in which chromosome imprinting occurs in a female in, on average, half of her primary oocytes. This is the expected frequency if X-chromosome inactivation is the initial step in the imprinting of the mutant fragile-X allele. Moreover, this analysis suggests a biological explanation for peculiarities of fragile-X inheritance described by others as "clustering" and the "Sherman paradox." We interpret these peculiarities as consequences of a very small number of oogonial progenitor cells. Two progenitor cells for oogonia is the best integer estimate of the number of such cells at the time of the initial event that leads to chromosome imprinting.

29 citations

Journal ArticleDOI
Eva Jablonka1
TL;DR: In the early stages of chromosome evolution, a role was played by epigenetic modifications of the chromatin structure that did not depend directly on genetic changes as discussed by the authors, which could have resulted from spontaneous epimutations at a sex-determining locus or, in mammals, from selection in females for the epigenetic silencing of imprinted regions of the paternally derived sex chromosome.
Abstract: Summary In most discussions of the evolution of sex chromosomes, it is presumed that the morphological differences between the X and Y were initiated by genetic changes. An alternative possibility is that, in the early stages,akeyrolewasplayedbyepigeneticmodifications of chromatin structure that did not depend directly on geneticchanges.Suchmodificationscouldhaveresulted from spontaneous epimutations at a sex-determining locus or, in mammals, from selection in females for the epigenetic silencing of imprinted regions of the paternally derived sex chromosome. Other features of mammalian sex chromosomes that are easier to explain if the epigenetic dimension of chromosome evolution is considered include the relatively large number of X-linked genesassociatedwithhumanbraindevelopment,andthe overrepresentation of spermatogenesis genes on the X. Both may be evolutionary consequences of dosage compensation through X-inactivation. BioEssays 26:1327– 1332, 2004. 2004 Wiley Periodicals, Inc.

29 citations

Journal ArticleDOI
TL;DR: The past years have been marked by the discovery of several molecular events that accompany chromosome-wide silencing, and one of the most surprising aspects of this phenomenon is that the two X homologs are treated differently even though they are present within the same nucleus.
Abstract: Early development of female mammals is accompanied by transcriptional inactivation of one of their two X chromosomes. This leads to monoallelic expression of most of the X chromosome and ensures dosage compensation with respect to males (XY). One of the most surprising aspects of this phenomenon is that the two X homologs are treated differently even though they are present within the same nucleus. In eutherian mammals, such as humans and mice, either the maternal or the paternal X is inactivated during early embryogenesis. Once set up, the silent state is epigenetically transmitted as cells divide, so that adult females are mosaics of clonal cell populations, which express either of their two X chromosomes. The past years have been marked by the discovery of several molecular events that accompany chromosome-wide silencing.

29 citations

Journal ArticleDOI
01 Mar 2017-Genetics
TL;DR: The results indicate that both Myc dosage and tra expression play crucial roles in determining sex-specific size in Drosophila larvae and adult tissue.
Abstract: Drosophila females are larger than males. In this article, we describe how X-chromosome dosage drives sexual dimorphism of body size through two means: first, through unbalanced expression of a key X-linked growth-regulating gene, and second, through female-specific activation of the sex-determination pathway. X-chromosome dosage determines phenotypic sex by regulating the genes of the sex-determining pathway. In the presence of two sets of X-chromosome signal elements (XSEs), Sex-lethal (Sxl) is activated in female (XX) but not male (XY) animals. Sxl activates transformer (tra), a gene that encodes a splicing factor essential for female-specific development. It has previously been shown that null mutations in the tra gene result in only a partial reduction of body size of XX animals, which shows that other factors must contribute to size determination. We tested whether X dosage directly affects animal size by analyzing males with duplications of X-chromosomal segments. Upon tiling across the X chromosome, we found four duplications that increase male size by >9%. Within these, we identified several genes that promote growth as a result of duplication. Only one of these, Myc, was found not to be dosage compensated. Together, our results indicate that both Myc dosage and tra expression play crucial roles in determining sex-specific size in Drosophila larvae and adult tissue. Since Myc also acts as an XSE that contributes to tra activation in early development, a double dose of Myc in females serves at least twice in development to promote sexual size dimorphism.

29 citations

Journal ArticleDOI
TL;DR: Recent evidence supporting a model for mutually exclusive choice that involves homologous chromosome pairing and the placement of asymmetric chromatin marks on the two Xs is highlighted.
Abstract: Loci associated with noncoding RNAs have important roles in X-chromosome inactivation (XCI), the dosage compensation mechanism by which one of two X chromosomes in female cells becomes transcriptionally silenced. The Xs start out as epigenetically equivalent chromosomes, but XCI requires a cell to treat two identical X chromosomes in completely different ways: One X chromosome must remain transcriptionally active while the other becomes repressed. In the embryo of eutherian mammals, the choice to inactivate the maternal or paternal X chromosome is random. The fact that the Xs always adopt opposite fates hints at the existence of a trans-sensing mechanism to ensure the mutually exclusive silencing of one of the two Xs. This paper highlights recent evidence supporting a model for mutually exclusive choice that involves homologous chromosome pairing and the placement of asymmetric chromatin marks on the two Xs.

29 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
202330
202272
202183
202051
201980
201870