Genetic linkage analysis in the age of whole-genome sequencing

Nat Rev Genet. 2015 May;16(5):275-84. doi: 10.1038/nrg3908. Epub 2015 Mar 31.

Abstract

For many years, linkage analysis was the primary tool used for the genetic mapping of Mendelian and complex traits with familial aggregation. Linkage analysis was largely supplanted by the wide adoption of genome-wide association studies (GWASs). However, with the recent increased use of whole-genome sequencing (WGS), linkage analysis is again emerging as an important and powerful analysis method for the identification of genes involved in disease aetiology, often in conjunction with WGS filtering approaches. Here, we review the principles of linkage analysis and provide practical guidelines for carrying out linkage studies using WGS data.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Algorithms
  • Female
  • Genetic Linkage*
  • Genome, Human
  • Genome-Wide Association Study / methods
  • Genome-Wide Association Study / statistics & numerical data
  • Genotyping Techniques
  • Humans
  • Lod Score
  • Male
  • Pedigree
  • Penetrance
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Sequence Analysis, DNA
  • Software