Petryshen T L, Kaplan B J, Fu Liu M, de French N S, Tobias R, Hughes M L, Field L L
Department of Medical Genetics, University of Calgary, Calgary, Alberta, Canada.
Am J Med Genet. 2001 Aug 8;105(6):507-17. doi: 10.1002/ajmg.1475.
A linkage study of 96 dyslexia families containing at least two affected siblings (totaling 877 individuals) has found evidence for a dyslexia susceptibility gene on chromosome 6q11.2-q12 (assigned the name DYX4). Using a qualitative phonological coding dyslexia (PCD) phenotype (affected, unaffected, or uncertain diagnoses), two-point parametric analyses found highly suggestive evidence for linkage between PCD and markers D6S254, D6S965, D6S280, and D6S251 (LOD(max) scores = 2.4 to 2.8) across an 11 cM region. Multipoint parametric analysis supported linkage of PCD to this region (peak HLOD = 1.6), as did multipoint nonparametric linkage analysis (P = 0.012). Quantitative trait linkage analyses of four reading measures (phonological awareness, phonological coding, spelling, and rapid automatized naming speed) also provided evidence for a dyslexia susceptibility locus on chromosome 6q. Using a variance-component approach, analysis of phonological coding and spelling measures resulted in peak LOD scores at D6S965 of 2.1 and 3.3, respectively, under 2 degrees of freedom. Furthermore, multipoint nonparametric quantitative trait sibpair analyses suggested linkage between the 6q region and phonological awareness, phonological coding, and spelling (P = 0.018, 0.017, 0.0005, respectively, for unweighted sibpairs < 18 years of age). Although conventional significance thresholds were not reached in the linkage analyses, the chromosome 6q11.2-q12 region clearly warrants investigation in other dyslexia family samples to attempt replication and confirmation of a dyslexia susceptibility gene in this region.
一项对96个诵读困难家庭（至少有两个患病兄弟姐妹，共877人）的连锁研究发现，6号染色体q11.2-q12区域存在一个诵读困难易感基因（命名为DYX4）。使用定性语音编码诵读困难（PCD）表型（患病、未患病或诊断不确定），两点参数分析发现，在一个11厘摩的区域内，PCD与标记D6S254、D6S965、D6S280和D6S251之间存在高度提示性的连锁证据（最大LOD分数 = 2.4至2.8）。多点参数分析支持PCD与该区域的连锁（峰值HLOD = 1.6），多点非参数连锁分析也是如此（P = 0.012）。对四项阅读指标（语音意识、语音编码、拼写和快速自动命名速度）的数量性状连锁分析也为6号染色体q上的诵读困难易感基因座提供了证据。使用方差成分法，对语音编码和拼写指标的分析在D6S965处分别得到了2.1和3.3的峰值LOD分数，自由度为2。此外，多点非参数数量性状同胞对分析表明，6q区域与语音意识、语音编码和拼写之间存在连锁（对于年龄小于18岁的未加权同胞对，P分别为0.018、0.017、0.0005）。尽管连锁分析未达到传统的显著阈值，但6号染色体q11.2-q12区域显然值得在其他诵读困难家庭样本中进行研究，以尝试复制和确认该区域的诵读困难易感基因。
