SNP discovery in associating genetic variation with human disease phenotypes

Mutat Res. 2005 Jun 3;573(1-2):41-53. doi: 10.1016/j.mrfmmm.2005.01.005.


With the completion of the human genome project, attention is now rapidly shifting towards the study of individual genetic variation. The most abundant source of genetic variation in the human genome is represented by single nucleotide polymorphisms (SNPs), which can account for heritable inter-individual differences in complex phenotypes. Identification of SNPs that contribute to susceptibility to common diseases will provide highly accurate diagnostic information that will facilitate early diagnosis, prevention, and treatment of human diseases. Over the past several years, the advancement of increasingly high-throughput and cost-effective methods to discover and measure SNPs has begun to open the door towards this endeavor. Genetic association studies are considered to be an effective approach towards the detection of SNPs with moderate effects, as in most common diseases with complex phenotypes. This requires careful study design, analysis and interpretation. In this review, we discuss genetic association studies and address the prospect for candidate gene association studies, comparing the strengths and weaknesses of indirect and direct study designs. Our focus is on the continuous need for SNP discovery methods and the use of currently available prescreening methods for large-scale genetic epidemiological research until more advanced sequencing methods currently under development will become available.

Publication types

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

MeSH terms

  • Base Sequence
  • Chromatography, High Pressure Liquid
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • Genetic Variation*
  • Humans
  • Linkage Disequilibrium
  • Phenotype
  • Polymorphism, Single Nucleotide*