Field L L, Kaplan B J
Department of Medical Genetics, Faculty of Medicine, Alberta Children's Hospital, University of Calgary, Calgry, Alberta, Canada.
Am J Hum Genet. 1998 Nov;63(5):1448-56. doi: 10.1086/302107.
Previous studies have suggested that a locus predisposing to specific reading disability (dyslexia) resides on chromosome 6p23-p21.3. We investigated 79 families having at least two siblings affected with phonological coding dyslexia, the most common form of reading disability (617 people genotyped, 294 affected), and we tested for linkage with the genetic markers reported to be linked to dyslexia in those studies. No evidence for linkage was found by LOD score analysis or affected-sib-pair methods. However, using the affected-pedigree-member (APM) method, we detected significant evidence for linkage and/or association with some markers when we used published allele frequencies with weighting of rarer alleles. APM results were not significant when we used marker allele frequencies estimated from parents. Furthermore, results were not significant with the more robust SIMIBD method using either published or parental marker frequencies. Finally, family-based association analysis using the AFBAC program showed no evidence for association with any marker. We conclude that the APM method should be used only with extreme caution, because it appears to have generated false-positive results. In summary, using a large data set with high power to detect linkage, we were unable to find evidence for linkage or association between phonological coding dyslexia and chromosome 6p markers.
先前的研究表明，导致特定阅读障碍（诵读困难）的一个基因座位于6号染色体的6p23 - p21.3区域。我们调查了79个家庭，这些家庭中至少有两个兄弟姐妹患有语音编码诵读困难，这是阅读障碍最常见的形式（对617人进行了基因分型，其中294人患病），并且我们对那些研究中报道的与诵读困难相关的遗传标记进行了连锁测试。通过对数优势计分分析或患病同胞对方法均未发现连锁证据。然而，使用患病家系成员（APM）方法，当我们使用已公布的等位基因频率并对稀有等位基因进行加权时，我们检测到了一些标记与连锁和/或关联的显著证据。当我们使用从父母那里估计的标记等位基因频率时，APM结果并不显著。此外，使用更稳健的SIMIBD方法，无论是使用已公布的还是父母的标记频率，结果都不显著。最后，使用AFBAC程序进行的基于家系的关联分析未显示与任何标记存在关联的证据。我们得出结论，APM方法的使用应极其谨慎，因为它似乎产生了假阳性结果。总之，通过使用一个具有高检测连锁能力的大数据集，我们未能找到语音编码诵读困难与6号染色体p标记之间存在连锁或关联的证据。
