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甲基化不仅可以指示干细胞状态,还能预测同性恋

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发表于 2016-8-5 06:28 |显示全部帖子
利用DNA甲基化标记物预测同性恋成为可能
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2016-07-28 表观遗传学快讯
1 t4 ~. X0 a7 o3 [5 dPgmNr 95: A novel predictive model of sexual orientation using epigenetic markers.# P- C" {# M: _  p6 J' k" S8 D
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T. C. Ngun 1 ; W. Guo 2 ; N. M. Ghahramani 3 ; K. Purkayastha 1 ; D. Conn 4 ; F. J. Sanchez 5 ; S. Bocklandt 1 ; M. Zhang 2,6 ; C. M. Ramirez 4 ; M. Pellegrini 7 ; E. Vilain 1
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View Session DetailAdd to Schedule
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Institutes
2 Y" H* l& p- k$ F0 F7 }2 P4 |2 I1) Department of Human Genetics, David Geffen School of Medicine at University of California Los Angeles (UCLA), Los Angeles, CA, USA; 2) Bioinformatics Division and Center for Synthetic & Systems Biology, TNLIST, Tsinghua University, Beijing 100084, China; 3) Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; 4) Fielding School of Public Health, UCLA, Los Angeles, CA, USA; 5) Department of Counseling Psychology, The University of Wisconsin-Madison, WI, USA; 6) Department of Molecular and Cell Biology, Center for Systems Biology, The University of Texas at Dallas, Richardson, TX 75080, USA; 7) Department of Molecular, Cellular, and Developmental Biology, UCLA, Los Angeles, CA, USA.
& a" \0 l4 H, r; Z' UAbstract:8 N2 O- F  U  \) y3 E
Sexual orientation is one of the most pronounced sex differences in the animal kingdom. Although upwards of 95% of the general population is heterosexual, a small but significant proportion of individuals (3-5%) is homosexual. Male sexual orientation has been linked to several genomic loci, with Xq28 and 8p12 being the most replicated. As with other complex traits, environmental factors may also play an important role. Firstly, monozygotic twins show substantial levels of discordance for this trait. Secondly, each male pregnancy a woman has increases the chance that her next son will be homosexual by 33% (the fraternal birth order effect). Thirdly, early life androgen exposure in women is associated with increased rates of non-heterosexual identity. Taken together, the evidence suggests a role for non-genetic and, possibly, epigenetic influences on sexual orientation. Our aim in this study was to create a predictive model for sexual orientation using epigenetic markers. We created our model based on genome-wide DNA methylation patterns in 37 monozygotic male twin pairs that were discordant for sexual orientation. 10 monozygotic twin pairs concordant for homosexuality were included as a control population. Genomic sites where methylation occurred were consolidated into short regions based on proximity and correlation of their methylation patterns to increase the signal to noise ratio. We then applied the FuzzyForest algorithm to our dataset. Briefly, regions were clustered into modules using Weighted Gene Coexpression Network Analysis and recursive feature elimination was performed with the random forest algorithm (RF) to identify regions most relevant to sexual orientation. The highest prediction accuracy was achieved using information from just 9 regions. Some of these regions were associated with the regulatory domains of two genes, CIITA and KIF1A. The former is a transcriptional regulator that is sometimes referred to as the master control factor of class II major histocompatibility complex genes. The latter is a neuron-specific transport protein that is important for movement of synaptic vesicle precursors along axons. Our results demonstrate that studies of the epigenome can yield new insights into the biological underpinnings of sexual orientation and provide strong support to the hypothesis that epigenetics is involved in sexual orientation. To our knowledge, this is the first example of a biomarker-based predictive model for sexual orientation.
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原文链接:http://mp.weixin.qq.com/s?__biz= ... jaU2Q%3D%3D&#rd$ p3 N7 \$ W" L

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