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Population-genetic nature of copy number variations in the human genome
Copy number variations (CNVs) are universal genetic variations, and their association with disease has been increasingly recognized. We designed high-density microarrays for CNVs, and detected 3000–4000 CNVs (4–6% of the genomic sequence) per population that included CNVs previously missed because o...
Autores principales: | , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Oxford University Press
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2816609/ https://www.ncbi.nlm.nih.gov/pubmed/19966329 http://dx.doi.org/10.1093/hmg/ddp541 |
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author | Kato, Mamoru Kawaguchi, Takahisa Ishikawa, Shumpei Umeda, Takayoshi Nakamichi, Reiichiro Shapero, Michael H. Jones, Keith W. Nakamura, Yusuke Aburatani, Hiroyuki Tsunoda, Tatsuhiko |
author_facet | Kato, Mamoru Kawaguchi, Takahisa Ishikawa, Shumpei Umeda, Takayoshi Nakamichi, Reiichiro Shapero, Michael H. Jones, Keith W. Nakamura, Yusuke Aburatani, Hiroyuki Tsunoda, Tatsuhiko |
author_sort | Kato, Mamoru |
collection | PubMed |
description | Copy number variations (CNVs) are universal genetic variations, and their association with disease has been increasingly recognized. We designed high-density microarrays for CNVs, and detected 3000–4000 CNVs (4–6% of the genomic sequence) per population that included CNVs previously missed because of smaller sizes and residing in segmental duplications. The patterns of CNVs across individuals were surprisingly simple at the kilo-base scale, suggesting the applicability of a simple genetic analysis for these genetic loci. We utilized the probabilistic theory to determine integer copy numbers of CNVs and employed a recently developed phasing tool to estimate the population frequencies of integer copy number alleles and CNV–SNP haplotypes. The results showed a tendency toward a lower frequency of CNV alleles and that most of our CNVs were explained only by zero-, one- and two-copy alleles. Using the estimated population frequencies, we found several CNV regions with exceptionally high population differentiation. Investigation of CNV–SNP linkage disequilibrium (LD) for 500–900 bi- and multi-allelic CNVs per population revealed that previous conflicting reports on bi-allelic LD were unexpectedly consistent and explained by an LD increase correlated with deletion-allele frequencies. Typically, the bi-allelic LD was lower than SNP–SNP LD, whereas the multi-allelic LD was somewhat stronger than the bi-allelic LD. After further investigation of tag SNPs for CNVs, we conclude that the customary tagging strategy for disease association studies can be applicable for common deletion CNVs, but direct interrogation is needed for other types of CNVs. |
format | Text |
id | pubmed-2816609 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-28166092010-02-05 Population-genetic nature of copy number variations in the human genome Kato, Mamoru Kawaguchi, Takahisa Ishikawa, Shumpei Umeda, Takayoshi Nakamichi, Reiichiro Shapero, Michael H. Jones, Keith W. Nakamura, Yusuke Aburatani, Hiroyuki Tsunoda, Tatsuhiko Hum Mol Genet Articles Copy number variations (CNVs) are universal genetic variations, and their association with disease has been increasingly recognized. We designed high-density microarrays for CNVs, and detected 3000–4000 CNVs (4–6% of the genomic sequence) per population that included CNVs previously missed because of smaller sizes and residing in segmental duplications. The patterns of CNVs across individuals were surprisingly simple at the kilo-base scale, suggesting the applicability of a simple genetic analysis for these genetic loci. We utilized the probabilistic theory to determine integer copy numbers of CNVs and employed a recently developed phasing tool to estimate the population frequencies of integer copy number alleles and CNV–SNP haplotypes. The results showed a tendency toward a lower frequency of CNV alleles and that most of our CNVs were explained only by zero-, one- and two-copy alleles. Using the estimated population frequencies, we found several CNV regions with exceptionally high population differentiation. Investigation of CNV–SNP linkage disequilibrium (LD) for 500–900 bi- and multi-allelic CNVs per population revealed that previous conflicting reports on bi-allelic LD were unexpectedly consistent and explained by an LD increase correlated with deletion-allele frequencies. Typically, the bi-allelic LD was lower than SNP–SNP LD, whereas the multi-allelic LD was somewhat stronger than the bi-allelic LD. After further investigation of tag SNPs for CNVs, we conclude that the customary tagging strategy for disease association studies can be applicable for common deletion CNVs, but direct interrogation is needed for other types of CNVs. Oxford University Press 2010-03-01 2009-12-05 /pmc/articles/PMC2816609/ /pubmed/19966329 http://dx.doi.org/10.1093/hmg/ddp541 Text en © The Author 2009. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/2.0/uk/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Articles Kato, Mamoru Kawaguchi, Takahisa Ishikawa, Shumpei Umeda, Takayoshi Nakamichi, Reiichiro Shapero, Michael H. Jones, Keith W. Nakamura, Yusuke Aburatani, Hiroyuki Tsunoda, Tatsuhiko Population-genetic nature of copy number variations in the human genome |
title | Population-genetic nature of copy number variations in the human genome |
title_full | Population-genetic nature of copy number variations in the human genome |
title_fullStr | Population-genetic nature of copy number variations in the human genome |
title_full_unstemmed | Population-genetic nature of copy number variations in the human genome |
title_short | Population-genetic nature of copy number variations in the human genome |
title_sort | population-genetic nature of copy number variations in the human genome |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2816609/ https://www.ncbi.nlm.nih.gov/pubmed/19966329 http://dx.doi.org/10.1093/hmg/ddp541 |
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