PHENOTYPE DELINEATION AND GENETIC MODELING OF AUTISM

自闭症的表型描述和基因建模

• 批准号: 2889860
• 负责人: Susan L SANTANGELO
• 金额: $ 11.6万
• 依托单位: TUFTS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-08-01 至 2001-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2889860
• 关键词: autism; biomarker; family genetics; genetic markers; genetic models; human subject; interview; linkage mapping; phenotype; psychometrics; statistics /biometry

Investigating the genetics of autism presents particular challenges (due to features such as limited vertical transmission, and small family size), over and above the usual difficulties of modeling complex and heterogeneous disorders. Therefore, clarification of the phenotypic expression of the genetic liability underlying autism is a critical first step. A method for exploring the phenotypic boundaries of autism and identifying relatives of autistic probands affected with a broad or multidimensional phenotype will be developed using data from the Baltimore Family Study of Autism. The method will then be replicated, in a quasi- validation step, with data from two additional sets of autism families (one simplex and one multiplex) collected in Iowa with the use of instruments and measures similar or identical to those used in the Baltimore study. The method for identifying the affected will be tested for its utility in improving the power of genetic modeling, including segregation and linkage analyses. The segregation analyses will be carried out on the two data sets described above. The linkage studies will be carried out with simulated data; both trait and marker genotypes will be simulated for pedigrees with the phenotypic characteristics of the families we have actually observed. Then both likelihood-based and non-parametric linkage analysis will be carried out to determine statistical power under various models and misclassification schemes. More generally, I hope this work will contribute to the development of methods for correctly classifying affected relatives in families expressing other complex disorders with ambiguous phenotypic expression, and to the search for genes for other neuropsychiatric disorders.

研究自闭症的遗传学提出了特殊的挑战（由于 有限的垂直传播和小家庭规模等特点）， 超越复杂建模的通常困难 异质性疾病。 因此，表型的澄清 表达自闭症背后的遗传倾向是至关重要的首要任务 步。 探索自闭症表型边界的方法 识别受广泛或影响的自闭症先证者的亲属 将使用来自巴尔的摩的数据开发多维表型 自闭症家庭研究。 然后该方法将被复制，以准 验证步骤，使用来自另外两组自闭症家庭的数据 （一个单工和一个多工）在爱荷华州收集，使用 与《公约》中使用的类似或相同的工具和措施 巴尔的摩研究。 将测试识别受影响者的方法 因其在提高遗传建模能力方面的实用性，包括 分离和连锁分析。 将对两个数据集进行分离分析 如上所述。 关联研究将通过模拟进行 数据;性状和标记基因型都将针对具有以下特征的谱系进行模拟 我们实际观察到的家族的表型特征。 然后基于似然性和非参数的连锁分析都将是 确定各种模型下的统计功效 错误分类方案。 更一般地说，我希望这项工作能够 有助于开发正确分类的方法 患有其他复杂疾病的家庭中受影响的亲属 模糊的表型表达，以及寻找其他基因 神经精神疾病。

项目成果

Incorporating language phenotypes strengthens evidence of linkage to autism

• DOI: 10.1002/ajmg.1497
• 发表时间: 2001-08-08
• 期刊: AMERICAN JOURNAL OF MEDICAL GENETICS
• 作者: Bradford, Y;Haines, J;Piven, J
• 通讯作者: Piven, J

An autosomal genomic screen for autism.

自闭症常染色体基因组筛查。

• 发表时间: 2001
• 期刊: American journal of medical genetics
• 作者: CollaborativeLinkageStudyofAutism

The importance of watching our weights: how the choice of weights for non-independent sib pairs can dramatically alter results.

观察权重的重要性：非独立同胞对权重的选择如何显着改变结果。

• DOI: 10.1002/gepi.1370170763
• 发表时间: 1999
• 期刊: Genetic epidemiology.
• 作者: VanEerdewegh,P;Dupuis,J;Santangelo,SL;Hayward,LB;Blacker,D
• 通讯作者: Blacker,D

Evidence supporting WNT2 as an autism susceptibility gene.

• DOI: 10.1002/ajmg.1401
• 发表时间: 2001-07
• 期刊: American journal of medical genetics
• 作者: T. Wassink;J. Piven;V. Vieland;Jian Huang;R. Swiderski;Jennifer Pietila;T. Braun;G. Beck;S. Folstein;Jonathon L. Haines;V. Sheffield

Predictors of cognitive test patterns in autism families

• DOI: 10.1017/s0021963099004461
• 发表时间: 1999-10-01
• 期刊: JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY
• 影响因子: 7.6
• 作者: Folstein, SE;Santangelo, SL;Wzorek, M
• 通讯作者: Wzorek, M