Use of Linkage Analysis, Genome-Wide Association Studies, and Next-Generation Sequencing in the Identification of Disease-Causing Mutations

Methods Mol Biol. 2013;1015:127-46. doi: 10.1007/978-1-62703-435-7_8.


For the past two decades, linkage analysis and genome-wide analysis have greatly advanced our knowledge of the human genome. But despite these successes the genetic architecture of diseases remains unknown. More recently, the availability of next-generation sequencing has dramatically increased our capability for determining DNA sequences that range from large portions of one individual's genome to targeted regions of many genomes in a cohort of interest. In this review, we highlight the successes and shortcomings that have been achieved using genome-wide association studies (GWAS) to identify the variants contributing to disease. We further review the methods and use of new technologies, based on next-generation sequencing, that are becoming increasingly used to expand our knowledge of the causes of genetic disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Genetic Linkage*
  • Genetic Predisposition to Disease*
  • Genome, Human
  • Genome-Wide Association Study / methods*
  • High-Throughput Nucleotide Sequencing / methods*
  • Humans
  • Mutation / genetics