A high-resolution survey of deletion polymorphism in the human genome

Don Conrad, T. Daniel Andrews, Nigel P. Carter, Matthew E. Hurles, Jonathan K. Pritchard

Research output: Contribution to journalArticle

506 Citations (Scopus)

Abstract

Recent work has shown that copy number polymorphism is an important class of genetic variation in human genomes1-4. Here we report a new method that uses SNP genotype data from parent-offspring trios to identify polymorphic deletions. We applied this method to data from the International HapMap Project5 to produce the first high-resolution population surveys of deletion polymorphism. Approximately 100 of these deletions have been experimentally validated using comparative genome hybridization on tiling-resolution oligonucleotide microarrays. Our analysis identifies a total of 586 distinct regions that harbor deletion polymorphisms in one or more of the families. Notably, we estimate that typical individuals are hemizygous for roughly 30-50 deletions larger than 5 kb, totaling around 550-750 kb of euchromatic sequence across their genomes. The detected deletions span a total of 267 known and predicted genes. Overall, however, the deleted regions are relatively gene-poor, consistent with the action of purifying selection against deletions. Deletion polymorphisms may well have an important role in the genetics of complex traits; however, they are not directly observed in most current gene mapping studies. Our new method will permit the identification of deletion polymorphisms in high-density SNP surveys of trio or other family data.

Original languageEnglish (US)
Pages (from-to)75-81
Number of pages7
JournalNature Genetics
Volume38
Issue number1
DOIs
StatePublished - Jan 1 2006
Externally publishedYes

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Human Genome
Single Nucleotide Polymorphism
DNA Copy Number Variations
HapMap Project
Comparative Genomic Hybridization
Chromosome Mapping
Oligonucleotide Array Sequence Analysis
Genes
Genotype
Genome
Population
Surveys and Questionnaires

ASJC Scopus subject areas

  • Genetics

Cite this

Conrad, D., Andrews, T. D., Carter, N. P., Hurles, M. E., & Pritchard, J. K. (2006). A high-resolution survey of deletion polymorphism in the human genome. Nature Genetics, 38(1), 75-81. https://doi.org/10.1038/ng1697

A high-resolution survey of deletion polymorphism in the human genome. / Conrad, Don; Andrews, T. Daniel; Carter, Nigel P.; Hurles, Matthew E.; Pritchard, Jonathan K.

In: Nature Genetics, Vol. 38, No. 1, 01.01.2006, p. 75-81.

Research output: Contribution to journalArticle

Conrad, D, Andrews, TD, Carter, NP, Hurles, ME & Pritchard, JK 2006, 'A high-resolution survey of deletion polymorphism in the human genome', Nature Genetics, vol. 38, no. 1, pp. 75-81. https://doi.org/10.1038/ng1697
Conrad, Don ; Andrews, T. Daniel ; Carter, Nigel P. ; Hurles, Matthew E. ; Pritchard, Jonathan K. / A high-resolution survey of deletion polymorphism in the human genome. In: Nature Genetics. 2006 ; Vol. 38, No. 1. pp. 75-81.
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