GENETIC CONTRIBUTIONS TO LEARNING DISABILITIES SUBTYPES

阅读障碍和书写障碍是常见和复杂的障碍是常见和复杂的障碍，具有长期的教育，经济和社会影响。了解生物学基础可能会导致更早和更具体的干预。本项目将通过评估具有学习障碍（LD）特征的种类来研究涉及阅读障碍和书写障碍特定亚型的遗传因素。有5个具体目标。1. 扩充有阅读困难和/或书写困难谱系的DNA和细胞系库。先证者的确定（未来五年500名）将扩展到9年级，以继续招募有阅读障碍和书写障碍合并的先证者，并增加招募只有书写障碍表型的先证者。2. 继续确定LD亚型的传播模式。语言表现型将加以扩大，包括形态学过程、家族聚集模式和前一个赠款周期发现的相互依赖性，还将调查作为数量特征的注意力不集中的共病和计算能力丧失的共病。最可能具有遗传病因的LD亚表型将在分离分析中进行评估，以开发用于连锁分析的模型。3. 检测学习障碍亚型的联系。1、2、6、7和15号染色体上的候选区域，已经进行基因分型，将评估其与LD表型的联系，并进行全基因组扫描以确定其他候选区域。4. 对连锁分析中发现的最有希望的区域进行精细比例的定位，以实现基因鉴定。5. 优化UWLDC数据库，并对数据进行质量控制分析。该项目与临床核心密切合作，进行仔细的表型分析，并与统计核心进行所有统计遗传分析。这些目标将通过应用新兴的强大的分析方法来加速实现。项目III也与项目I和项目II联系在一起，将语言表型扩展到包括形态学过程。通过对使用fMRS测量作为数量性状的可行性的探索性研究，将项目III与项目IV联系起来。

Dyslexia and dysgraphia are common and complex disorders are common and complex disorders that have long-term educational, economic, and social repercussions. Understanding the biologic basis may lead to earlier and more specific intervention. This project will investigate genetic factors involved in specific subtypes of dyslexia and dysgraphia by evaluating kindreds well-characterized from learning disabilities (LD). There are 5 specific aims. 1. To expand a bank of DNA and cell lines from pedigrees with dyslexia and/or dysgraphia. Ascertainment of probands (500 over the next five years) will be extended to grade 9, for continued recruitment of probands with combined dyslexia and dysgraphia and for increased recruitment of probands with the dysgraphia-only phenotype. 2. To continue to determine transmission patterns of LD subtypes. The language phenotype will be broadened to include morphological processes and the familial aggregation patterns and interdependence of the findings of the previous grant cycle, comorbidity of inattention as a quantitative trait and comorbidity of calculation disability will also be investigated. The LD subphenotypes most likely to have a genetic etiology will be evaluated in segregation analyses to develop models for use in linkage analyses. 3. To detect linkage of learning disabilities subtypes. Candidate regions on chromosomes 1, 2, 6, 7, and 15, already genotyped, will be evaluated for linkage to LD phenotypes and a genome-wide scan will be performed to identify other candidate regions. 4. To perform fine scale mapping of the most promising regions identified in the linkage analyses to enable gene identification. 5. To optimize the UWLDC database and to perform quality control analyses of the data. This Project is carried out in close collaboration with the Clinical Core for the careful phenotyping and with the Statistical Core for all statistical genetic analyses. The goals will be expedited by applying emerging powerful analysis methods. Project III is also linked to Projects I and II in extending the language phenotype to include morphologic processes. Project III is linked to Project IV via an exploratory study of the feasibility of using fMRS measurements as the quantitative trait.