Dyslexia is a common heterogeneous disorder with a significant genetic component. Multiple studies have replicated the evidence for linkage between variously defined phenotypes of dyslexia and chromosomal regions on 15q21 (DYX1) and 6p22.2 (DYX2). Based on association studies and the possibility for functional significance of several polymorphisms, candidate genes responsible for the observed linkage signal have been proposed-DYX1C1 for 15q21, and KIAA0319 and DCDC2 for 6p22.2. We investigated the evidence for contribution of these candidate genes to dyslexia in our sample of multigenerational families. Our previous quantitative linkage analyses in this dataset provided supportive evidence for linkage of dyslexia to the locus on chromosome 15, but not to the locus on chromosome 6. In the current study, we used probands from 191 families for a case control analysis, and proband-parent trios for family-based TDT analyses. The observation of weak evidence for transmission disequilibrium for one of the two studied polymorphisms in DYX1C1 suggests involvement of this gene in dyslexia in our dataset. We did not find evidence for the association of KIAA0319 or DCDC2 alleles to dyslexia in our sample. We observed a slight tendency for an intronic deletion in DCDC2 to be associated with worse performance on some quantitative measures of dyslexia in the probands in our sample, but not in their parents.

译文

诵读困难症是一种常见的异质性疾病,具有重要的遗传成分。多项研究已经复制了阅读障碍的各种表型与15q21(DYX1)和6p22.2(DYX2)上的染色体区域之间联系的证据。基于关联研究和几种多态性可能具有功能重要性的可能性,提出了负责观察到的连锁信号的候选基因-DYX1C1用于15q21,KIAA0319和DCDC2用于6p22.2。我们调查了多代家庭样本中这些候选基因对阅读障碍的贡献的证据。我们先前在该数据集中进行的定量连锁分析为阅读障碍与15号染色体上的基因座连锁提供了支持证据,但与6号染色体上的基因座没有关联。在本研究中,我们使用了191个家庭的先证者进行病例对照分析,并且先证者-parent三重奏,用于基于家庭的TDT分析。对DYX1C1中两个研究的多态性之一的传递不平衡证据不足的观察表明,该基因参与了我们数据集中的阅读障碍。在我们的样本中,我们没有发现有关KIAA0319或DCDC2等位基因与阅读障碍的关联的证据。我们观察到在样本中先证者(而非其父母)的阅读障碍的一些定量测量中,DCDC2内含子缺失的轻微趋势与较差的表现有关。

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