Large-scale copy number polymorphism in the human genome

Science. 2004 Jul 23;305(5683):525-8. 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Bacterial Proteins / metabolism
  • Cell Line, Transformed
  • Chromosome Aberrations
  • Chromosome Mapping
  • Chromosomes, Human / genetics
  • Deoxyribonuclease HindIII / metabolism
  • Deoxyribonucleases, Type II Site-Specific / metabolism
  • Female
  • Gene Deletion
  • Gene Dosage*
  • Gene Duplication
  • Gene Frequency
  • Genetic Variation*
  • Genome, Human*
  • Humans
  • Male
  • Markov Chains
  • Oligonucleotide Array Sequence Analysis
  • Polymorphism, Genetic*


  • Bacterial Proteins
  • Deoxyribonuclease HindIII
  • BglII endonuclease
  • Deoxyribonucleases, Type II Site-Specific