Common deletion polymorphisms in the human genome.
The locations and properties of common deletion variants in the human genome are largely unknown. We describe a systematic method for using dense SNP genotype data to discover deletions and its application to data from the International HapMap Consortium to characterize and catalogue segregating deletion variants across the human genome. We identified 541 deletion variants (94% novel) ranging from 1 kb to 745 kb in size; 278 of these variants were observed in multiple, unrelated individuals, 120 in the homozygous state. The coding exons of ten expressed genes were found to be commonly deleted, including multiple genes with roles in sex steroid metabolism, olfaction and drug response. These common deletion polymorphisms typically represent ancestral mutations that are in linkage disequilibrium with nearby SNPs, meaning that their association to disease can often be evaluated in the course of SNP-based whole-genome association studies.
McCarroll
Steven A
SA
Department of Molecular Biology, Massachusetts General Hospital, 55 Fruit Street, Boston, Massachusetts 02114, USA.
Hadnott
Tracy N
TN
Perry
George H
GH
Sabeti
Pardis C
PC
Zody
Michael C
MC
Barrett
Jeffrey C
JC
Dallaire
Stephanie
S
Gabriel
Stacey B
SB
Lee
Charles
C
Daly
Mark J
MJ
Altshuler
David M
DM
D030541:Databases, Genetic; D005091:Exons; D005821:Genetic Techniques; D015894:Genome, Human; D006720:Homozygote; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015810:Linkage Disequilibrium; D008957:Models, Genetic; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D044469:Racial Groups / Q000235:genetics; D017384:Sequence Deletion