Knowledge Resource Center for Ecological Environment in Arid Area
DOI | 10.1371/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
![]() |
ISSN | 1553-7404 |
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). |
条目包含的文件 | 条目无相关文件。 |
除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。