The genetic bases of reading and related processes in Russian

描述（由申请人提供）：本项目旨在提高我们对阅读的遗传基础和相关过程的认识和理解。长期以来，人们都知道，阅读，无论是作为能力还是残疾，以及与阅读相关的过程，都是可遗传的，但该领域一直很难集中在这种（疾病）能力的特定候选基因上。该领域已经确定了分子遗传学发现之间缺乏趋同的一些原因。这些原因包括缺乏权力，表型评估的不一致，也许还有对英语的关注，这在世界语言中是一个特殊的异常值。在这个应用程序中，我们试图通过使用讲俄语的兄弟姐妹（n = 400对）和不一致的单身子女（n = 1,500）的大样本来克服以前研究的一些局限性，他们在阅读和阅读相关评估方面的表现通过嵌入在特定理论框架中的评估电池仔细取样。我们将利用通过俄罗斯同胞对的全基因组短串联重复多态性（STRP）连锁研究（WGLS）获得的初步发现，并建议对WGLS中确定的感兴趣区域进行基于单核苷酸多态性（SNP）的调查，使用来自这2300个个体（同胞对和单胞胎）的DNA上的约4,500个靶向SNP进行基因分型，以及多变量阅读相关表型。所提出的样本、技能和技术的结合提供了一个相当吸引人的机会，无论是在科学上还是在方法上。该R21将产生试点数据，以：(1)确定构建基于流行病学的俄罗斯特殊阅读障碍（SRD）儿童大型样本的可行性；(2)研究同一样本上STRP和SNP数据结合的可用性；(3)估计遗传效应的大小，如果得到证实，并利用更明确和需要资金的技术（如测序）设计后续研究。

DESCRIPTION (provided by applicant): This project is aimed at enhancing our knowledge and understanding of the genetic bases of reading and related processes. It has long been known that reading, whether qualified as ability or disabilities, along with reading-related processes, are heritable, but it has been rather difficult for the field to converge on specific gene candidates for this (dis)ability. The field has identified a number of reasons for such a lack of convergence among the molecular-genetic findings. These reasons include lack of power, inconsistencies in phenotypic evaluations, and, perhaps, the focus on English, which is a particular outlier among world languages. In this application, we attempt to overcome some of the limitations of previous studies by working with large samples of Russian-speaking siblings (n = 400 pairs) and discrepant singletons (n = 1,500), whose performance on reading and reading-related assessments is carefully sampled through an assessment battery embedded in a particular theoretical framework. We will capitalize on preliminary findings obtained through a whole-genome short-tandem-repeat-polymorphism (STRP) linkage study (WGLS) of Russian sib pairs and propose to complete a single-nucleotide-polymorphism (SNP)-based investigation of the regions of interest identified in the WGLS using ~4,500 targeted SNPs genotyped on the DNA from these 2300 individuals (sib pairs and singletons) and multivariate reading-related phenotypes. The proposed combination of samples, skills, and technologies provides a rather appealing opportunity, both scientifically and methodologically. This R21 will generate pilot data to (1) establish the feasibility of constructing a large epidemiologically-based sample of Russian children with specific reading disability (SRD); (2) investigate the usability of combining STRP and SNP data obtained on the same sample; and (3) estimate the sizes of genetic effects, if confirmed, and design subsequent studies utilizing more definitive and funding-demanding technologies (e.g., sequencing).