Genetic linkage: sampling issues and multipoint mapping.
Genetic linkage is an important tool in determining the genetic contribution to the etiology of behavior disorders and psychiatric disease. Successful linkage studies employ large sample sizes. It is of particular relevance in psychiatric diseases, where the clinical workup is so extensive, to evaluate sample requirements critically. Recent studies indicate that extensive sampling, out to second-degree relatives, will not assist in identifying linkages although it may inflate the sample size considerably. The impact of the assumption about the mode of inheritance of the psychiatric trait and the effect of reduced penetrance are discussed. Multipoint mapping has the added advantage of using information from many markers simultaneously. This is helpful both in identifying individuals at risk to develop disease and in locating a gene with sufficient precision to determine the gene product. There are complications in applying multipoint mapping but these are generally of a technical nature and soluble. Recent suggestions for handling complications for multipoint mapping are evaluated. The correct design of the sampling procedure for selecting families and for selecting marker loci to use will greatly reduce the volume of work required for linkage studies and enhance the chances for success.
Spence
M A
MA
Department of Psychiatry, UCLA School of Medicine 90024.
D002869:Chromosome Aberrations / Q000235:genetics*; D025063:Chromosome Disorders; D002874:Chromosome Mapping; D008040:Genetic Linkage; D005819:Genetic Markers; D006801:Humans; D001523:Mental Disorders / Q000235:genetics*
D005819:Genetic Markers