A CLASS OF TESTS FOR LINKAGE USING AFFECTED PEDIGREE MEMBERS
A CLASS OF TESTS FOR LINKAGE USING AFFECTED PEDIGREE MEMBERS
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DOI：
10.2307/2533202
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发表时间：
1994-03-01
期刊：
影响因子：
1.9
通讯作者：
HALPERN, J
中科院分区：
文献类型：
--
作者：
WHITTEMORE, AS;HALPERN, J
我们描述了一类非参数测试的链接之间的标记和基因假定存在和控制易感性的疾病。这些测试是通过为受影响的谱系成员之间的每一种可能的标记等位基因共享模式（血统识别）分配一个分数来形成的，然后将与观察到的标记基因型和受影响成员的家谱关系相容的所有模式的分数平均下来。不同的分数函数给出不同的测试。其中一个功能检查了受影响谱系成员对之间的标记等位基因相似性，给出了类似于Fimmers等人（1989年）的测试，《基于受影响谱系成员的多点定位和连锁：遗传分析研讨会》，R. C. Elston， M. a . Spence， S. E. Hodge和J. W. MacCluer（主编），123-128；城市：艾伦·r·利斯)。第二个功能是检查受影响成员的任意子集之间的等位基因相似性，而不仅仅是对。由此产生的测试可能比仅基于受影响成员对的测试更有效。这种方法有几个优点：它不需要了解疾病遗传模式；它不需要在标记处明确地确定血统身份；它不会因无亲缘关系的受影响成员（如配偶）之间偶然的等位基因相似性而遭受变异；它允许未受影响成员的标记基因型提供受影响成员之间等位基因共享的信息；它允许精确的p值计算。计算需求将测试限制在具有很少（< 16）个受影响成员的许多系谱。
We describe a class of nonparametric tests for linkage between a marker and a gene assumed to exist and to govern susceptibility to a disease. The tests are formed by assigning a score to each possible pattern of marker allele sharing (identity-by-descent) among affected pedigree members, and then averaging the scores over all patterns compatible with the observed marker genotype and genealogical relationship of the affected members. Different score functions give different tests. One function, which examines marker allele similarity across pairs of affected pedigree members, gives a test similar to that of Fimmers et al. (1989, in Multipoint Mapping and Linkage Based on Affected Pedigree Members: Genetic Analysis Worshop, R. C. Elston, M. A. Spence, S. E. Hodge,and J. W. MacCluer (eds), 123-128; City: Alan R. Liss). A second function examines allele similarity across arbitrary subsets, not just pairs, of affected members. The resulting test can be more powerful than the one based solely on pairs of affected members. The approach has several advantages: it does not require knowledge of the mode of disease inheritance; it does not require unambiguous determination of identity-by-descent at the marker; it does not suffer from variability due to chance allele similarity among affected members who are unrelated, such as spouses; it allows marker genotypes of unaffected members to contribute information on allele sharing among the affected; it permits calculation of exact P-values. Computational requirements limit the tests to many pedigrees with few (< 16) affected members.