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

Nat Genet. 2006 Jan;38(1):75-81. doi: 10.1038/ng1697. Epub 2005 Dec 4.

Abstract

Recent work has shown that copy number polymorphism is an important class of genetic variation in human genomes. 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 Project 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Databases, Genetic
  • Genome, Human*
  • Humans
  • In Situ Hybridization / methods
  • International Cooperation
  • Microarray Analysis / methods
  • Models, Genetic
  • Polymorphism, Genetic*
  • Polymorphism, Single Nucleotide
  • Reproducibility of Results
  • Sequence Deletion*