Lod Score

Abstract

Lod scores are test statistics used to detect genetic linkage, which is the dependence in descent of deoxyribonucleic acid (DNA) at locations that are nearby in the genome. Lod scores are based on likelihood ratios and hence require parametric models for both trait and genetic marker phenotypes. The classical two‐locus lod score is introduced, and its use in linkage detection is described. Given a genetic marker map, a multilocus map‐specific lod score may be used to map causal trait loci against that framework map. Issues of ascertainment and trait‐model uncertainty are briefly described. A basic assumption of lod score analysis is that dependence between trait and marker data is only through the dependence in DNA descent. Modern genetic marker data allow accurate estimates of shared genome descending to currently observed individuals. This descent may then be used in trait data analyses, providing new approaches to lod score analyses.

Key Concepts

  • DNA that is at locations on the same chromosome is genetically linked.
  • DNA at linked locations tends to cosegregate from parents to offspring.
  • Linkage analysis is the determination of locations of DNA‐affecting traits of interest from evidence of this cosegregation in defined pedigrees.
  • Genetic markers at known positions in the genome provide a framework against which DNA‐affecting traits of interest may be mapped.
  • The lod score is a statistic that measures the strength of dependence in segregation between DNA affecting a trait and DNA at locations of specified markers.
  • The lod score is based on likelihood, and so requires a parametric model for trait data and genetic marker data.
  • The classical lod score is robust to ascertainment through trait phenotypes.
  • Modern genetic marker data permit inference of shared descent of genome, even in the absence of a specified pedigree structure.
  • The lod score may be based on this inferred shared genome among individuals with observed trait phenotypes.

Keywords: linkage detection; sequential test; significance levels; multilocus analysis; recombination frequencies; trait models; ascertainment effects; DNA descent

References

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Further Reading

A paper detailing many of the early statistical ideas concerning the detection of human genetic linkage is that of Smith . A recommended modern text is Ott . A paper which reviews a more modern view of lod score computation and analysis is that of Thompson .

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How to Cite close
Thompson, Elizabeth A(Nov 2016) Lod Score. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0005400.pub2]