Derivation of consensus inactivation status for X-linked genes from genome-wide studies

Biology of Sex Differences

Bradley P. Balaton²  Allison M. Cotton¹  Carolyn J. Brown² 

[1] Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada

[2] Department of Medical Genetics, Molecular Epigenetics Group, Life Sciences Institute, University of British Columbia, Vancouver, Canada

关键词: DNA methylation;    Allelic imbalance;    Somatic cell hybrids;    Escape from X-chromosome inactivation;    Dosage compensation;    X-chromosome inactivation;   

Others  :  1235125
DOI  :  10.1186/s13293-015-0053-7

 received in 2015-10-27, accepted in 2015-12-14,  发布年份 2015

【 摘 要 】

Background

X chromosome inactivation is the epigenetic silencing of the majority of the genes on one of the X chromosomes in XX therian mammals. In humans, approximately 15 % of genes consistently escape from this inactivation and another 15 % of genes vary between individuals or tissues in whether they are subject to, or escape from, inactivation. Multiple studies have provided inactivation status calls for a large subset of the genes on the X chromosome; however, these studies vary in which genes they were able to make calls for and in some cases which call they give a specific gene.

Methods

This analysis aggregated three published studies that have examined X chromosome inactivation status of genes across the X chromosome, generating consensus calls and identifying discordancies. The impact of expression level and chromosomal location on X chromosome inactivation status was also assessed.

Results

Overall, we assigned a consensus XCI status 639 genes, including 78 % of protein-coding genes expressed outside of the testes, with a lower frequency for non-coding RNA and testis-specific genes. Study-specific discordancies suggest that there may be instability of XCI during cell culture and also highlight study-specific variations in call type. We observe an enrichment of discordant genes at boundaries between genes subject to and escaping from inactivation.

Conclusions

This study has compiled a comprehensive list of X-chromosome inactivation statuses for genes and also discovered some biases which will help guide future studies examining X-chromosome inactivation.

【 授权许可】

   
2015 Balaton et al.

【 图 表 】

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