UTILITY AND EFFICIENCY OF LINKED MARKER GENES FOR GENETIC-COUNSELING .2. IDENTIFICATION OF LINKAGE PHASE BY OFFSPRING PHENOTYPES

  • 1 January 1982
    • journal article
    • research article
    • Vol. 34  (4) , 531-551
Abstract
For a linked marker locus to be useful for genetic counseling, the counselee must be heterozygous for both disease and marker loci and his or her linkage phase must be known. When the phenotypes of the counselee''s previous children for the disease and marker loci are known, the linkage phase can often be inferred with a high probability, and thus it is possible to conduct genetic counseling. To evaluate the utility of linked marker genes for genetic counseling, the accuracy of prediction of the risk for a prospective child with a given marker gene to develop the genetic disease and the proportion of families in which a particular marker locus can be used for genetic counseling are studied for X-linked recessive, autosomal dominant and autosomal recessive diseases. In the case of X-linked genetic diseases, information from children is very useful for determining the linkage phase of the counselee and predicting the genetic disease. In the case of autosomal dominant diseases, not all children are informative, but if the number of children is large, the phenotypes of children are often more informative than the information from grandparents. In the case of autosomal recessive diseases, information from grandparents is usually useless, since they show a normal phenotype for the disease locus. If information on the phenotypes of children is used, however, the linkage phase of the counselee and the risk of a prospective child can be inferred with a high probability. The proportion of informative families depends on the dominance relationship and frequencies of marker alleles, and the number of children. In general, codominant markers are more useful than are dominant markers, and a locus with high heterozygosity is more useful than is a locus with low heterozygosity.