Grigorenko E L, Wood F B, Meyer M S, Hart L A, Speed W C, Shuster A, Pauls D L
Department of Psychology, Yale University, New Haven, CT, USA.
Am J Hum Genet. 1997 Jan;60(1):27-39.
Six extended dyslexic families with at least four affected individuals were genotyped with markers in three chromosomal regions: 6p23-p21.3, 15pter-qter, and 16pter-qter. Five theoretically derived phenotypes were used in the linkage analyses: (1) phonological awareness; (2) phonological decoding; (3) rapid automatized naming; (4) single-word reading; and (5) discrepancy between intelligence and reading performance, an empirically derived, commonly used phenotype. Two-point and multipoint allele-sharing analyses of chromosome 6 markers revealed significant evidence (P < 10(-6)) for linkage of the phonological awareness phenotype to five adjacent markers (D6S109, D6S461, D6S299, D6S464, and D6S306). The least compelling results were obtained with single-word reading. In contrast, with chromosome 15 markers, a LOD score of 3.15 was obtained for marker D15S143 at theta = 0.0 with single-word reading. Multipoint analyses with markers adjacent to D15S143 (D15S126, D15S132, D15S214, and D15S128) were positive, but none reached acceptable significance levels. Chromosome 15 analyses with the phonological awareness phenotype were negative. Parametric and nonparametric linkage analyses with chromosome 16 markers were negative. The most intriguing aspect of the current findings is that two very distinct reading-related phenotypes, reflecting different levels in the hierarchy of reading-related skills, each contributing to different processes, appear to be linked to two different chromosomal regions.
对六个至少有四名患者的诵读困难扩展家族进行了基因分型，所用标记位于三个染色体区域：6p23 - p21.3、15pter - qter和16pter - qter。连锁分析中使用了五种理论上推导的表型：(1)语音意识；(2)语音解码；(3)快速自动命名；(4)单字阅读；(5)智力与阅读表现之间的差异，这是一种根据经验推导且常用的表型。对6号染色体标记的两点和多点等位基因共享分析显示，有显著证据（P < 10(-6)）表明语音意识表型与五个相邻标记（D6S109、D6S461、D6S299、D6S464和D6S306）连锁。单字阅读得到的结果最不显著。相比之下，对于15号染色体标记，在θ = 0.0时，单字阅读标记D15S143的LOD得分为3.15。与D15S143相邻的标记（D15S126、D15S132、D15S214和D15S128）的多点分析呈阳性，但均未达到可接受的显著水平。15号染色体语音意识表型分析为阴性。16号染色体标记的参数和非参数连锁分析均为阴性。当前研究结果最引人关注的方面是，两个非常不同的与阅读相关的表型，反映了阅读相关技能层次结构中的不同水平，各自对不同过程有贡献，似乎与两个不同的染色体区域连锁。
