Model-Based Linkage Analysis of a Quantitative Trait
Linkage Analysis is a family-based method of analysis to examine whether any typed genetic markers cosegregate with a given trait, in this case a quantitative trait. If linkage exists, this is taken as evidence in support of a genetic basis for the trait. Historically, linkage analysis was performed using a binary disease trait, but has been extended to include quantitative disease measures. Quantitative traits are desirable as they provide more information than binary traits. Linkage analysis can be performed using single-marker methods (one marker at a time) or multipoint (using multiple markers simultaneously). In model-based linkage analysis the genetic model for the trait of interest is specified. There are many software options for performing linkage analysis. Here, we use the program package Statistical Analysis for Genetic Epidemiology (S.A.G.E.). S.A.G.E. was chosen because it also includes programs to perform data cleaning procedures and to generate and test genetic models for a quantitative trait, in addition to performing linkage analysis. We demonstrate in detail the process of running the program LODLINK to perform single-marker analysis, and MLOD to perform multipoint analysis using output from SEGREG, where SEGREG was used to determine the best fitting statistical model for the trait.
Key wordsLinkage analysis Quantitative trait LOD score Recombination fraction Statistical analysis for genetic epidemiology (S.A.G.E.) Model-based Segregation analysis Pedigree likelihood
- 1.Ott J (1999) Analysis of human genetic linkage. University Press, Baltimore MDGoogle Scholar
- 4.Bailey-Wilson JE (2005) Parametric versus nonparametric and two-point versus multipoint: controversies in gene mapping. In: Dunn M et al (eds) Encyclopedia of genetics, genomics, proteomics and bioinformatics. John Wiley & Sons, Ltd, Hoboken, N.JGoogle Scholar
- 12.S.A.G.E. 6.4 (2016). Statistical analysis for genetic epidemiology http://darwin.cwru.edu/sage/.
- 15.Lange K et al (2001) Mendel version 4.0: a complete package for the exact genetic analysis of discrete traits in pedigree and population data sets. Am J Hum Genet S69:504Google Scholar