Chakravarti A, Nei M
Am J Hum Genet. 1982 Jul;34(4):531-51.
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. It is shown that 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 we use information on the phenotypes of children, 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.
对于一个用于遗传咨询的连锁标记位点而言，咨询者在疾病位点和标记位点上都必须是杂合的，并且其连锁相必须是已知的。研究表明，当咨询者之前孩子在疾病位点和标记位点的表型已知时，通常能够以较高概率推断出连锁相，从而可以进行遗传咨询。为了评估连锁标记基因在遗传咨询中的效用，针对X连锁隐性、常染色体显性和常染色体隐性疾病，研究了根据给定标记基因预测未来孩子患遗传病风险的准确性以及特定标记位点可用于遗传咨询的家庭比例。对于X连锁遗传病，来自孩子的信息对于确定咨询者的连锁相和预测遗传病非常有用。对于常染色体显性疾病，并非所有孩子都能提供有用信息，但如果孩子数量较多，孩子的表型通常比来自祖父母的信息更具参考价值。对于常染色体隐性疾病，来自祖父母的信息通常没有用处，因为他们在疾病位点表现为正常表型。然而，如果我们利用孩子表型的信息，咨询者的连锁相和未来孩子的患病风险通常能够以较高概率推断出来。提供有用信息的家庭比例取决于标记等位基因的显性关系和频率以及孩子的数量。一般来说，共显性标记比显性标记更有用，杂合度高的位点比杂合度低的位点更有用。
