A sensitive method for detecting variation in copy numbers of duplicated genes

Genome Res. 2003 Sep;13(9):2171-7. doi: 10.1101/gr.1188203.

Abstract

Gene duplications are common in the vertebrate genome, and duplicated loci often show a variation in copy number that may have important phenotypic effects. Here we describe a powerful method for quantification of duplicated copies based on pyrosequencing. A reliable quantification was obtained by amplification of the duplication break-point and a corresponding nonduplicated sequence in a competitive PCR assay. A comparison with an independent method for quantification based on the Invader technology revealed an excellent correlation between the two methods. The pyrosequencing-based method was evaluated by analyzing variation in copy number at the duplicated KIT/Dominant white locus in pigs. We were able to distinguish haplotypes at this locus by combining the duplication breakpoint test with a diagnostic test for a functionally important splice mutation in the duplicated gene. An extensive allelic variation, including the presence of a new allele carrying a single KIT copy expected to encode a truncated KIT receptor, was revealed when analyzing white pigs from commercial lines.

Publication types

  • Comparative Study
  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms*
  • Alleles
  • Animals
  • Female
  • Gene Dosage*
  • Genes, Dominant / genetics
  • Genes, Duplicate / genetics*
  • Genetic Variation / genetics*
  • Genetics, Population / methods
  • Genotype
  • Hair Color / genetics
  • Male
  • Pedigree
  • Proto-Oncogene Proteins c-kit / genetics
  • Sensitivity and Specificity
  • Sequence Analysis, DNA / methods
  • Sequence Analysis, DNA / statistics & numerical data
  • Swine

Substances

  • Proto-Oncogene Proteins c-kit