Linkage analyses of four regions previously implicated in dyslexia: Confirmation of a locus on chromosome 15q
Linkage analyses of four regions previously implicated in dyslexia: Confirmation of a locus on chromosome 15q
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DOI：
10.1002/ajmg.b.30018
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发表时间：
2004-11-15
影响因子：
2.8
通讯作者：
Raskind, WH
中科院分区：
文献类型：
--
作者：
Chapman, NH;Igo, RP;Raskind, WH
阅读障碍是一种常见的复杂疾病，被认为与遗传有关。已经有许多报道表明，阅读障碍和连续阅读障碍相关表型与基因组的几个区域有联系。我们试图确认(1)语音解码的准确性和效率的连续措施的联系；(2)利用111个家族共898个成员，对2p、6p、15q和18p染色体上的单字读取（WID）准确性进行了研究。我们使用单标记和多点方差成分连锁分析和马尔可夫链蒙特卡罗（MCMC）联合分离和连锁分析对这些区域进行初步检查。使用MCMC分离分析估计的模型进行传统的参数负荷评分分析，结果是肯定的。在染色体2p、6p和18p上未发现正连锁信号。两种分析方法都发现了WID与15q染色体连锁的证据。在距离D15S143 3 cM处，单标记参数lod得分最高，为2.34。多点分析将假定的易感基因定位于标记GATA50CO3和D15S143之间的间隔，该区域位于最近的一个涉及注意缺陷/多动障碍的基因组筛选区域和DYX1C1之间，DYX1C1是阅读障碍的候选基因。发育障碍区域连锁信号的明显多样性可能是图谱和/或模型规范错误的结果，模糊了单个基因对不同表型的多效性作用，或者它可能反映了多个基因的存在。这篇文章包含补充材料，可以在美国医学遗传学杂志网站http://www.interscience.wiley.com/jpages/0148-7299:1/suppmat/index.html上查看。(C) 2004 Wiley-Liss, Inc。
Dyslexia is a common, complex disorder, which is thought to have a genetic component. There have been numerous reports of linkage to several regions of the genome for dyslexia and continuous dyslexia-related phenotypes. We attempted to confirm linkage of continuous measures of (1) accuracy and efficiency of phonological decoding; and (2) accuracy of single word reading (WID) to regions on chromosomes 2p, 6p, 15q, and 18p, using 111 families with a total of 898 members. We used both single-marker and multipoint variance components linkage analysis and Markov Chain Monte Carlo (MCMC) joint segregation and linkage analysis for initial inspection of these regions. Positive results were followed with traditional parametric lod score analysis using a model estimated by MCMC segregation analysis. No positive linkage signals were found on chromosomes 2p, 6p, or 18p. Evidence of linkage of WID to chromosome 15q was found with both methods of analysis. The maximum single-marker parametric lod score of 2.34 was obtained at a distance of 3 cM from D15S143. Multipoint analyses localized the putative susceptibility gene to the interval between markers GATA50CO3 and D15S143, which falls between a region implicated in a recent genome screen for attention-deficit/hyperactivity disorder, and DYX1C1, a candidate gene for dyslexia. This apparent multiplicity of linkage signals in the region for developmental disorders may be the result of errors in map and/or model specification obscuring the pleiotropic effect of a single gene on different phenotypes, or it may reflect the presence of multiple genes. This article contains supplementary material, which maybe viewed at the American Journal of Medical Genetics website at http://www.interscience.wiley.com/jpages/0148-7299:1/suppmat/index.html. (C) 2004 Wiley-Liss, Inc.