National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD, USA.
Hum Genet. 2013 Apr;132(4):385-96. doi: 10.1007/s00439-012-1252-5. Epub 2012 Dec 13.
We describe a pedigree of 71 individuals from the Republic of Cameroon in which at least 33 individuals have a clinical diagnosis of persistent stuttering. The high concentration of stuttering individuals suggests that the pedigree either contains a single highly penetrant gene variant or that assortative mating led to multiple stuttering-associated variants being transmitted in different parts of the pedigree. No single locus displayed significant linkage to stuttering in initial genome-wide scans with microsatellite and SNP markers. By dividing the pedigree into five subpedigrees, we found evidence for linkage to previously reported loci on 3q and 15q, and to novel loci on 2p, 3p, 14q, and a different region of 15q. Using the two-locus mode of Superlink, we showed that combining the recessive locus on 2p and a single-locus additive representation of the 15q loci is sufficient to achieve a two-locus score over 6 on the entire pedigree. For this 2p + 15q analysis, we show LOD scores ranging from 4.69 to 6.57, and the scores are sensitive to which marker is chosen for 15q. Our findings provide strong evidence for linkage at several loci.
我们描述了来自喀麦隆共和国的一个 71 人的家系，其中至少有 33 人被临床诊断为持续性口吃。口吃个体的高度集中表明，该家系要么包含一个单一的高外显率基因变异，要么是由于选择性交配导致与口吃相关的多个变异在不同的家系部分中传递。在使用微卫星和 SNP 标记进行的初始全基因组扫描中，没有单个基因座与口吃显示出显著的连锁。通过将家系分为五个亚系，我们发现了与先前报道的 3q 和 15q 上的基因座以及 2p、3p、14q 和 15q 上的新基因座的连锁证据。使用 Superlink 的两基因座模式，我们表明，将 2p 上的隐性基因座和 15q 上的单基因座加性表现相结合，足以在整个家系中获得超过 6 的两基因座得分。对于这个 2p+15q 分析，我们显示 LOD 得分范围从 4.69 到 6.57，并且分数对 15q 中选择哪个标记敏感。我们的研究结果为几个基因座的连锁提供了强有力的证据。
