Genome sequencing for rightward hemispheric language dominance
Genome sequencing for rightward hemispheric language dominance
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DOI：
10.1111/gbb.12572
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发表时间：
2019-06-01
影响因子：
2.5
通讯作者：
Francks, Clyde
中科院分区：
文献类型：
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作者：
Carrion-Castillo, Amaia;Van der Haegen, Lise;Francks, Clyde
大多数人在语言处理的各个方面都具有左半球优势，但只有大约 1% 的成年人具有非典型逆转的右半球语言优势 (RHLD)。语言左偏性背后的遗传发育程序尚不清楚，非典型变异的原因也是如此。我们进行了一项探索性全基因组测序研究，假设强渗透性、罕见的基因突变有时可能与 RHLD 有关。这类似于内脏器官的位置反转（心脏、肺等的左右镜像反转），这有时是由于单基因突变造成的。参考大型群体遗传数据集，对 33 名 RHLD 受试者以及 34 名具有典型语言偏侧性的受试者（14 名左撇子）的基因组进行了测序和分析。如果 33 例 RHLD 病例中至少有 10 例存在罕见、高渗透性、单基因效应，并且没有对照，则该样本能够检测到罕见的、高渗透性的单基因效应，但在超过 5 例 RHLD 病例中，没有单个基因发生突变，而在对照中未突变。源自无脊椎动物左右轴形成机制的假设导致在 RHLD 受试者中检测到与肌动蛋白细胞骨架有关的基因内的突变负荷增加。后一项发现为分子遗传对半球语言优势的影响提供了初步的初步见解。
Most people have left-hemisphere dominance for various aspects of language processing, but only roughly 1% of the adult population has atypically reversed, rightward hemispheric language dominance (RHLD). The genetic-developmental program that underlies leftward language laterality is unknown, as are the causes of atypical variation. We performed an exploratory whole-genome-sequencing study, with the hypothesis that strongly penetrant, rare genetic mutations might sometimes be involved in RHLD. This was by analogy with situs inversus of the visceral organs (left-right mirror reversal of the heart, lungs and so on), which is sometimes due to monogenic mutations. The genomes of 33 subjects with RHLD were sequenced and analyzed with reference to large population-genetic data sets, as well as 34 subjects (14 left-handed) with typical language laterality. The sample was powered to detect rare, highly penetrant, monogenic effects if they would be present in at least 10 of the 33 RHLD cases and no controls, but no individual genes had mutations in more than five RHLD cases while being un-mutated in controls. A hypothesis derived from invertebrate mechanisms of left-right axis formation led to the detection of an increased mutation load, in RHLD subjects, within genes involved with the actin cytoskeleton. The latter finding offers a first, tentative insight into molecular genetic influences on hemispheric language dominance.