Large-Scale Copy Number Polymorphism in the Human Genome

• Published in: Science (American Association for the Advancement of Science) Vol. 305; no. 5683; pp. 525 - 528
• Main Authors: Sebat, Jonathan, Lakshmi, B., Troge, Jennifer, Alexander, Joan, Young, Janet, Lundin, Pär, Månér, Susanne, Massa, Hillary, Walker, Megan, Chi, Maoyen, Navin, Nicholas, Lucito, Robert, Healy, John, Hicks, James, Ye, Kenny, Reiner, Andrew, Gilliam, T. Conrad, Trask, Barbara, Patterson, Nick, Zetterberg, Anders, Wigler, Michael
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 23-07-2004; The American Association for the Advancement of Science
• Subjects: Alleles; Angelman syndrome; Bacterial Proteins - metabolism; Biochemistry; Biological and medical sciences; Cancer; Cell Line, Transformed; Chromosome Aberrations; Chromosome Mapping; Chromosomes, Human - genetics; Deoxyribonuclease HindIII - metabolism; Deoxyribonucleases, Type II Site-Specific - metabolism; Diploidy; DNA probes; Duplication; Female; Fundamental and applied biological sciences. Psychology; Gene Deletion; Gene Dosage; Gene Duplication; Gene Frequency; Genes; Genes. Genome; Genetic aspects; Genetic diversity; Genetic polymorphism; Genetic Variation; Genetics; Genome, Human; Genomes; Genomics; Human genetics; Human genome; Human Genome Project; Humans; Male; Markov Chains; Medicin och hälsovetenskap; Molecular and cellular biology; Molecular genetics; Nervous system diseases; Oligonucleotide Array Sequence Analysis; Polymorphism; Polymorphism, Genetic; Human; Genetic variability; Genome; Copy number; Polymorphism
• ISSN: 0036-8075; 1095-9203; 1095-9203
• DOI: 10.1126/science.1098918

The extent to which large duplications and deletions contribute to human genetic variation and diversity is unknown. Here, we show that large-scale copy number polymorphisms (CNPs) (about 100 kilobases and greater) contribute substantially to genomic variation between normal humans. Representational oligonucleotide microarray analysis of 20 individuals revealed a total of 221 copy number differences representing 76 unique CNPs. On average, individuals differed by 11 CNPs, and the average length of a CNP interval was 465 kilobases. We observed copy number variation of 70 different genes within CNP intervals, including genes involved in neurological function, regulation of cell growth, regulation of metabolism, and several genes known to be associated with disease.