Combined linkage and linkage disequilibrium mapping for genome screens

Genet Epidemiol. 2000 Oct;19(3):211-34. doi: 10.1002/1098-2272(200010)19:3<211::AID-GEPI3>3.0.CO;2-L.


Linkage analysis and association studies, two major approaches for genetic studies of human diseases, are useful for mapping genes that are highly penetrant, but both use only part of the information that is available for mapping disease genes. Therefore, they provide limited utility when used alone. In this report, we present combined linkage and linkage disequilibrium mapping that simultaneously utilizes linkage and linkage disequilibrium information for mapping human disease genes. Compared with the existing linkage analysis and association study methods, this method has several advantages: 1) it has high statistical power by a joint analysis of linkage and linkage disequilibrium for localizing disease susceptibility loci: 2) it unifies the theory of linkage analysis and linkage disequilibrium mapping, 3) it retains the general framework for linkage analysis and, hence, can be easily incorporated into the existing software for the linkage analysis. The proposed LLDM is applied to familial hemophagocytic lymphohistiocytosis (FHL) disease.

Publication types

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

MeSH terms

  • Chromosome Mapping / methods*
  • Gene Frequency / genetics
  • Genes, Recessive
  • Genetic Predisposition to Disease / genetics*
  • Genetic Testing / methods*
  • Genome, Human*
  • Genotype
  • Histiocytosis, Non-Langerhans-Cell / genetics
  • Humans
  • Likelihood Functions
  • Linkage Disequilibrium / genetics*
  • Lod Score
  • Pedigree
  • Penetrance