title: A high-resolution survey of deletion polymorphism in the human genome.
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.
authors.affiliation: Department of Human Genetics, The University of Chicago, 920 East 58th Street, Chicago, Illinois 60637, USA.
authors.forename: Donald F
authors.initials: DF
authors.lastname: Conrad
authors.forename: T Daniel
authors.initials: TD
authors.lastname: Andrews
authors.forename: Nigel P
authors.initials: NP
authors.lastname: Carter
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Hurles
authors.forename: Jonathan K
authors.initials: JK
authors.lastname: Pritchard
mesh_terms: D030541:Databases, Genetic; D015894:Genome, Human; D006801:Humans; D017403:In Situ Hybridization / Q000379:methods; D007391:International Cooperation; D046228:Microarray Analysis / Q000379:methods; D008957:Models, Genetic; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D015203:Reproducibility of Results; D017384:Sequence Deletion