Feingold E, Siegmund D O
Department of Biostatistics, Emory University, Atlanta, GA 30322, USA.
Am J Hum Genet. 1997 Apr;60(4):965-78.
We investigate strategies for detecting linkage of recessive and partially recessive traits, using sibling pairs and inbred individuals. We assume that a genomewide search is being conducted and that locus heterogeneity of the trait is likely. For sibling pairs, we evaluate the efficiency of different statistics under the assumption that one does not know the true degree of recessiveness of the trait. We recommend a sibling-pair statistic that is a linear compromise between two previously suggested statistics. We also compare the power of sibling pairs to that of more distant relatives, such as cousins. For inbred individuals, we evaluate the power of offspring of different types of matings and compare them to sibling pairs. Over a broad range of trait etiologies, sibling pairs are more powerful than inbred individuals, but for traits caused by very rare alleles, particularly in the case of heterogeneity, inbred individuals can be much more powerful. The models we develop can also be used to examine specific situations other than those we look at. We present this analysis in the idealized context of a dense set of highly polymorphic markers. In general, incorporation of real-world complexities makes inbred individuals, particularly offspring of distant relatives, look slightly less useful than our results imply.
我们研究了利用同胞对和近亲个体来检测隐性和部分隐性性状连锁的策略。我们假设正在进行全基因组搜索，并且该性状存在基因座异质性。对于同胞对，在不知道性状真实隐性程度的假设下，我们评估了不同统计量的效率。我们推荐一种同胞对统计量，它是之前提出的两种统计量之间的线性折衷。我们还比较了同胞对与更远亲属（如表亲）的检验效能。对于近亲个体，我们评估了不同类型交配后代的检验效能，并将其与同胞对进行比较。在广泛的性状病因范围内，同胞对比近亲个体更具检验效能，但对于由非常罕见的等位基因引起的性状，特别是在存在异质性的情况下，近亲个体可能更具检验效能。我们开发的模型还可用于研究我们所关注情况之外的特定情形。我们在一组密集的高度多态性标记的理想化背景下进行了此分析。一般来说，纳入现实世界的复杂性使得近亲个体，特别是远亲的后代，看起来比我们的结果所暗示的用处稍小。
