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Related Experiment Videos

Linkage analysis using single nucleotide polymorphisms.

Brian L Browning1, Donna L Brashear, Andy A Butler

  • 1GlaxoSmithKline, Research Triangle Park, NC 27709, USA. brian.l.browning@gsk.com

Human Heredity
|December 8, 2004
PubMed
Summary

Single nucleotide polymorphism (SNP) linkage analysis effectively identifies type 2 diabetes (T2D) regions. SNP markers provide similar genetic linkage information as microsatellite markers, improving T2D gene discovery.

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Area of Science:

  • Human Genetics
  • Statistical Genetics
  • Genomics

Background:

  • Multipoint linkage analysis is crucial for identifying genes associated with complex diseases like type 2 diabetes (T2D).
  • Previous studies utilized microsatellite markers for T2D linkage analysis.
  • The SNP Consortium (TSC) developed a SNP linkage map for broader genomic coverage.

Purpose of the Study:

  • To evaluate the utility of TSC SNP markers for multipoint linkage analysis in T2D.
  • To compare the performance of SNP markers against established microsatellite markers in T2D linkage studies.
  • To develop an algorithm for multipoint linkage analysis of tightly linked marker clusters.

Main Methods:

  • Performed multipoint linkage analysis using 83 TSC SNP markers across three T2D-linked regions (190 cM total).

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  • Assumed a small, non-zero intracluster genetic distance (0.03 cM) due to low linkage disequilibrium.
  • Utilized GENEHUNTER PLUS and ASM software for linkage analysis, comparing results with microsatellite data.

    • Main Results:

    • SNP markers yielded average information content and LOD score curves comparable to microsatellite maps (10 cM spacing).
    • The performance of SNP markers was robust across different pedigree structures and missing data patterns.
    • An extended Lander-Green algorithm was developed for multipoint analysis of tightly linked marker clusters.

    Conclusions:

    • TSC SNP markers are effective for multipoint linkage analysis in T2D genetics.
    • SNP marker analysis provides similar power to microsatellite analysis for T2D linkage.
    • The developed algorithm enhances multipoint linkage analysis for complex marker data.