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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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Journal ArticleDOI
TL;DR: An epigenetic approach based on analysis of several histone post-translational modifications to find the first epigenetic hints of the X:Y sex chromosome system regulation in S. latifolia found a possible differential regulation of each female X allele and results agree with the mammal-like dosage compensation regulation.

6 citations

Book ChapterDOI
01 Jan 1999
TL;DR: For example, this article showed that the difference in chromosome number does not result in sex-specific differences in the total amount of X-encoded RNAs or proteins, and that female cells with two copies of every X-linked gene synthesized the same amount of protein products as males cells with half the number of genes.
Abstract: We have known for the greater part of the 20th century that mammalian females and males differ in both number and kind of sex chromosomes. While females have two X-chromosomes (XX), males have one X- and one Y-chromosome (XY). Both the X and Y carry genes that enhance female and male reproductive function, respectively. Because the Y-chromosome is relatively small and carries only a few genes, this sex chromosome difference means that females essentially have double the number of sex-chromosome genes compared to males. Yet, biochemical evidence indicates that this difference in chromosome number does not result in sex-specific differences in the total amount of X-encoded RNAs or proteins. In other words, female cells with two copies of every X-linked gene synthesized the same amount of protein products as males cells with half the number of genes. For years, this equation puzzled biologists. Clearly, some form of dosage compensation akin to those found in other sexual organisms must exist in mammals.

6 citations

Journal ArticleDOI
TL;DR: It is hypothesised that the process of NRXI may provide a mechanism for some hereditary breast or ovarian cancers independent of BRCA1 / BRCa2 associated disease because of its strong association with invasive ovarian cancers.
Abstract: Editor—The process of X chromosome inactivation was identified as early as 1960 when Ohno and Hauschka1described the presence of a pyknotic X chromosome in both benign and malignant cell lines. Mary Lyon formalised the role of X inactivation and its relationship to dosage compensation of X chromosome genetic material in a letter to Nature in 1961.2 This phenomenon, now known as the Lyon hypothesis, states that only one X chromosome is transcriptionally active in a given female cell. While the Lyon hypothesis dictates that the X inactivation process is random, skewing of this process to the point of non-random X chromosome inactivation is a known mechanism associated with the development of X linked genetic diseases in females.3 Our laboratory has been interested in the association of non-random X chromosome inactivation (NRXI) with ovarian cancer.4 Not only does this process violate a basic biological principle, the Lyon hypothesis, but it also provides a mechanism to bypass one of two steps generally accepted as necessary for the development of a cancer phenotype, dictated by the Knudson two hit model.5 The process of X inactivation silences one of two alleles for a particular gene and hence creates a state of functional loss of heterozygosity. Thus, X linked tumour suppressor genes can require only a single mutational event (or “hit”) to contribute to the process of carcinogenesis. Furthermore, with NRXI, hypothetical germline mutation of tumour suppressor genes could contribute to early onset disease. We have hypothesised that the process of NRXI may provide a mechanism for some hereditary breast or ovarian cancers independent of BRCA1 / BRCA2 associated disease because of its strong association with invasive ovarian cancers.4 More recently, data from our group suggest that this association extends to breast and endometrial, but not …

6 citations

Journal ArticleDOI
TL;DR: X chromosome inactivation ensures the dosage compensation of X-linked genes in XX females compared to their XY male counterpart as discussed by the authors, which is characterised by the specific recruitment of an inhibitory ribonu.
Abstract: X chromosome inactivation ensures the dosage compensation of X-linked genes in XX females compared to their XY male counterpart. It is characterised by the specific recruitment of an inhibitory ribonu

6 citations

Journal ArticleDOI
TL;DR: This work examined the association of over 14,000 X chromosome single nucleotide polymorphisms (SNPs) with sex-associated BD traits using two statistical approaches that account for whether a SNP may be undergoing or escaping XCI.
Abstract: Bipolar disorder (BD) affects both sexes, but important sex differences exist with respect to its symptoms and comorbidities. For example, rapid cycling (RC) is more prevalent in females, and alcohol use disorder (AUD) is more prevalent in males. We hypothesize that X chromosome variants may be associated with sex-specific characteristics of BD. Few studies have explored the role of the X chromosome in BD, which is complicated by X chromosome inactivation (XCI). This process achieves “dosage compensation” for many X chromosome genes by silencing one of the two copies in females, and most statistical methods either ignore that XCI occurs or falsely assume that one copy is inactivated at all loci. We introduce new statistical methods that do not make these assumptions. We investigated this hypothesis in 1001 BD patients from the Genetic Association Information Network (GAIN) and 957 BD patients from the Mayo Clinic Bipolar Disorder Biobank. We examined the association of over 14,000 X chromosome single nucleotide polymorphisms (SNPs) with sex-associated BD traits using two statistical approaches that account for whether a SNP may be undergoing or escaping XCI. In the “XCI-informed approach,” we fit a sex-adjusted logistic regression model assuming additive genetic effects where we coded the SNP either assuming one copy is expressed or two copies are expressed based on prior knowledge about which regions are inactivated. In the “XCI-robust approach,” we fit a logistic regression model with sex, SNP, and SNP-sex interaction effects that is flexible to whether the region is inactivated or escaping XCI. Using the “XCI-informed approach,” which considers only the main effect of SNP and does not allow the SNP effect to differ by sex, no significant associations were identified for any of the phenotypes. Using the “XCI-robust approach,” intergenic SNP rs5932307 was associated with BD (P = 8.3 × 10−8), with a stronger effect in females (odds ratio in males (ORM) = 1.13, odds ratio in females for a change of two allele copies (ORW2) = 3.86). X chromosome association studies should employ methods which account for its unique biology. Future work is needed to validate the identified associations with BD, to formally assess the performance of both approaches under different true genetic architectures, and to apply these approaches to study sex differences in other conditions.

6 citations


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