Mapping of complex traits by single-nucleotide polymorphisms

Am J Hum Genet. 1998 Jul;63(1):225-40. doi: 10.1086/301909.

Abstract

Molecular geneticists are developing the third-generation human genome map with single-nucleotide polymorphisms (SNPs), which can be assayed via chip-based microarrays. One use of these SNP markers is the ability to locate loci that may be responsible for complex traits, via linkage/linkage-disequilibrium analysis. In this communication, we describe a semiparametric method for combined linkage/linkage-disequilibrium analysis using SNP markers. Asymptotic results are obtained for the estimated parameters, and the finite-sample properties are evaluated via a simulation study. We also applied this technique to a simulated genome-scan experiment for mapping a complex trait with two major genes. This experiment shows that separate linkage and linkage-disequilibrium analyses correctly detected the signals of both major genes; but the rates of false-positive signals seem high. When linkage and linkage-disequilibrium signals were combined, the analysis yielded much stronger and clearer signals for the presence of two major genes than did two separate analyses.

Publication types

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

MeSH terms

  • Biosensing Techniques
  • Chromosome Mapping / methods*
  • Chromosome Mapping / statistics & numerical data
  • Genetic Diseases, Inborn / genetics
  • Genetic Linkage / genetics*
  • Genetic Markers / genetics
  • Genome, Human
  • Genotype
  • Humans
  • Linkage Disequilibrium / genetics*
  • Models, Genetic
  • Nucleotides / genetics*
  • Pedigree
  • Polymorphism, Genetic / genetics*

Substances

  • Genetic Markers
  • Nucleotides