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

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

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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

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ASJC Scopus subject areas

  • Genetics

Cite this

Conrad, D. F., 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