Diversity of human copy number variation and multicopy genes.

Bibliographic Collection: 
MOCA Reference, APE
Publication Type: Journal Article
Authors: Sudmant, Peter H; Kitzman, Jacob O; Antonacci, Francesca; Alkan, Can; Malig, Maika; Tsalenko, Anya; Sampas, Nick; Bruhn, Laurakay; Shendure, Jay; Eichler, Evan E
Corporate Author: 1000 Genomes Project
Year of Publication: 2010
Journal: Science
Volume: 330
Issue: 6004
Pagination: 641-6
Date Published: 10/2010
Publication Language: eng
ISSN: 1095-9203
Keywords: Chromosome Mapping, Continental Population Groups, Databases, Nucleic Acid, DNA Copy Number Variations, Evolution, Molecular, Female, Gene Conversion, Gene Dosage, Gene Duplication, Gene Frequency, Genes, Duplicate, Genetic Variation, Genome, Human, Genomics, Genotype, Haplotypes, Humans, Male, Polymorphism, Single Nucleotide, Sequence Analysis, DNA

Copy number variants affect both disease and normal phenotypic variation, but those lying within heavily duplicated, highly identical sequence have been difficult to assay. By analyzing short-read mapping depth for 159 human genomes, we demonstrated accurate estimation of absolute copy number for duplications as small as 1.9 kilobase pairs, ranging from 0 to 48 copies. We identified 4.1 million "singly unique nucleotide" positions informative in distinguishing specific copies and used them to genotype the copy and content of specific paralogs within highly duplicated gene families. These data identify human-specific expansions in genes associated with brain development, reveal extensive population genetic diversity, and detect signatures consistent with gene conversion in the human species. Our approach makes ~1000 genes accessible to genetic studies of disease association.

DOI: 10.1126/science.1197005
Alternate Journal: Science