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DOI10.1371/journal.pgen.1002692
Genomic Hypomethylation in the Human Germline Associates with Selective Structural Mutability in the Human Genome
Li, Jian1,2,3; Harris, R. Alan1,2; Cheung, Sau Wai2; Coarfa, Cristian1,2; Jeong, Mira2; Goodell, Margaret A.2; White, Lisa D.2; Patel, Ankita2; Kang, Sung-Hae2; Shaw, Chad2; Chinault, A. Craig2; Gambin, Tomasz4,5; Gambin, Anna; Lupski, James R.2,6,7; Milosavljevic, Aleksandar1,2,3
通讯作者Li, Jian
来源期刊PLOS GENETICS
ISSN1553-7404
出版年2012
卷号8期号:5
英文摘要

The hotspots of structural polymorphisms and structural mutability in the human genome remain to be explained mechanistically. We examine associations of structural mutability with germline DNA methylation and with non-allelic homologous recombination (NAHR) mediated by low-copy repeats (LCRs). Combined evidence from four human sperm methylome maps, human genome evolution, structural polymorphisms in the human population, and previous genomic and disease studies consistently points to a strong association of germline hypomethylation and genomic instability. Specifically, methylation deserts, the,1% fraction of the human genome with the lowest methylation in the germline, show a tenfold enrichment for structural rearrangements that occurred in the human genome since the branching of chimpanzee and are highly enriched for fast-evolving loci that regulate tissue-specific gene expression. Analysis of copy number variants (CNVs) from 400 human samples identified using a custom-designed array comparative genomic hybridization (aCGH) chip, combined with publicly available structural variation data, indicates that association of structural mutability with germline hypomethylation is comparable in magnitude to the association of structural mutability with LCR-mediated NAHR. Moreover, rare CNVs occurring in the genomes of individuals diagnosed with schizophrenia, bipolar disorder, and developmental delay and de novo CNVs occurring in those diagnosed with autism are significantly more concentrated within hypomethylated regions. These findings suggest a new connection between the epigenome, selective mutability, evolution, and human disease.


类型Article
语种英语
国家USA ; Poland
收录类别SCI-E
WOS记录号WOS:000304864000022
WOS关键词COPY NUMBER VARIATION ; SEGMENTAL DUPLICATIONS ; MEIOTIC RECOMBINATION ; DNA METHYLATION ; INCREASE RISK ; REARRANGEMENTS ; DISORDERS ; EVOLUTION ; GENE ; ARCHITECTURE
WOS类目Genetics & Heredity
WOS研究方向Genetics & Heredity
资源类型期刊论文
条目标识符http://119.78.100.177/qdio/handle/2XILL650/174493
作者单位1.Baylor Coll Med, Bioinformat Res Lab, Epigenome Ctr, Houston, TX 77030 USA;
2.Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA;
3.Baylor Coll Med, Program Struct & Computat Biol & Mol Biophys, Houston, TX 77030 USA;
4.Warsaw Univ Technol, Inst Comp Sci, Warsaw, Poland;
5.Warsaw Univ, Inst Informat, Warsaw, Poland;
6.Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA;
7.Texas Childrens Hosp, Houston, TX 77030 USA
推荐引用方式
GB/T 7714
Li, Jian,Harris, R. Alan,Cheung, Sau Wai,et al. Genomic Hypomethylation in the Human Germline Associates with Selective Structural Mutability in the Human Genome[J],2012,8(5).
APA Li, Jian.,Harris, R. Alan.,Cheung, Sau Wai.,Coarfa, Cristian.,Jeong, Mira.,...&Milosavljevic, Aleksandar.(2012).Genomic Hypomethylation in the Human Germline Associates with Selective Structural Mutability in the Human Genome.PLOS GENETICS,8(5).
MLA Li, Jian,et al."Genomic Hypomethylation in the Human Germline Associates with Selective Structural Mutability in the Human Genome".PLOS GENETICS 8.5(2012).
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