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人类基因组中大规模拷贝数变异的全球模式揭示了染色体组织的复杂性。

Global patterns of large copy number variations in the human genome reveal complexity in chromosome organization.

作者信息

Veerappa Avinash M, Suresh Raviraj V, Vishweswaraiah Sangeetha, Lingaiah Kusuma, Murthy Megha, Manjegowda Dinesh S, Padakannaya Prakash, Ramachandra Nallur B

机构信息

Genetics and Genomics Lab,Department of Studies in Genetics & Genomics,University of Mysore,Manasagangotri,Mysore-06,Karnataka,India.

Nitte University Centre for Science Education & Research,K. S. Hegde Medical Academy,Nitte,University,Deralakatte,Mangalore-18,Karnataka,India.

出版信息

Genet Res (Camb). 2015 Sep 22;97:e18. doi: 10.1017/S0016672315000191.

Abstract

Global patterns of copy number variations (CNVs) in chromosomes are required to understand the dynamics of genome organization and complexity. For this study, analysis was performed using the Affymetrix Genome-Wide Human SNP Array 6.0 chip and CytoScan High-Density arrays. We identified a total of 44 109 CNVs from 1715 genomes with a mean of 25 CNVs in an individual, which established the first drafts of population-specific CNV maps providing a rationale for prioritizing chromosomal regions. About 19 905 ancient CNVs were identified across all chromosomes and populations at varying frequencies. CNV count, and sometimes CNV size, contributed to the bulk CNV size of the chromosome. Population specific lengthening and shortening of chromosomal length was observed. Sex bias for CNV presence was largely dependent on ethnicity. Lower CNV inheritance rate was observed for India, compared to YRI and CEU. A total of 33 candidate CNV hotspots from 5382 copy number (CN) variable region (CNVR) clusters were identified. Population specific CNV distribution patterns in p and q arms disturbed the assumption that CNV counts in the p arm are less common compared to long arms, and the CNV occurrence and distribution in chromosomes is length independent. This study unraveled the force of independent evolutionary dynamics on genome organization and complexity across chromosomes and populations.

摘要

为了解基因组组织和复杂性的动态变化,需要研究染色体上拷贝数变异(CNV)的全球模式。在本研究中,使用Affymetrix全基因组人类SNP Array 6.0芯片和CytoScan高密度阵列进行分析。我们从1715个基因组中总共鉴定出44109个CNV,个体平均有25个CNV,这建立了群体特异性CNV图谱的初稿,为确定染色体区域的优先级提供了依据。在所有染色体和群体中,以不同频率鉴定出约19905个古老的CNV。CNV数量,有时还有CNV大小,构成了染色体的大部分CNV大小。观察到染色体长度存在群体特异性的延长和缩短。CNV存在的性别偏差在很大程度上取决于种族。与YRI和CEU相比,印度的CNV遗传率较低。从5382个拷贝数(CN)可变区(CNVR)簇中总共鉴定出33个候选CNV热点。p臂和q臂中群体特异性的CNV分布模式打破了p臂中CNV计数比长臂中少见的假设,并且染色体中CNV的出现和分布与长度无关。这项研究揭示了独立进化动力学对跨染色体和群体的基因组组织和复杂性的影响。

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