Genetic dissection of complex traits

Medical genetics was revolutionized during the 1980s by the application of genetic mapping to locate the genes responsible for simple Mendelian diseases. Most diseases and traits, however, do not follow simple inheritance patterns. Genetics have thus begun taking up the even greater challenge of the genetic dissection of complex traits. Four major approaches have been developed: linkage analysis, allele-sharing methods, association studies, and polygenic analysis of experimental crosses. This article synthesizes the current state of the genetic dissection of complex traits--describing the methods, limitations, and recent applications to biological problems.

[1]  H. Jeffreys,et al.  Theory of probability , 1896 .

[2]  N. Morton Sequential tests for the detection of linkage. , 1955, American journal of human genetics.

[3]  J. Ott Analysis of Human Genetic Linkage , 1985 .

[4]  W. Browner,et al.  Are all significant P values created equal? The analogy between diagnostic tests and clinical research. , 1987, JAMA.

[5]  E. Lander,et al.  Mapping mendelian factors underlying quantitative traits using RFLP linkage maps. , 1989, Genetics.

[6]  N. Risch,et al.  A note on multiple testing procedures in linkage analysis. , 1991, American journal of human genetics.

[7]  D. Weeks,et al.  Efficient strategies for genomic searching using the affected-pedigree-member method of linkage analysis. , 1994, American journal of human genetics.

[8]  Elliot S. Gershon,et al.  Genetic approaches to mental disorders , 1994 .

[9]  S. Lohr Statistics (2nd Ed.) , 1994 .

[10]  R. Doerge,et al.  Empirical threshold values for quantitative trait mapping. , 1994, Genetics.

[11]  R. Straub,et al.  A potential vulnerability locus for schizophrenia on chromosome 6p24–22: evidence for genetic heterogeneity , 1995, Nature Genetics.

[12]  E. Lander,et al.  Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results , 1995, Nature Genetics.

[13]  J. Ziegle,et al.  Evidence for a susceptibility locus for schizophrenia on chromosome 6pter–p22 , 1995, Nature Genetics.

[14]  J. Witte,et al.  Genetic dissection of complex traits. , 1994, Nature genetics.

[15]  P. Sham Statistics in human genetics , 1997 .

[16]  N J Cox,et al.  Allele-sharing models: LOD scores and accurate linkage tests. , 1997, American journal of human genetics.