The Genetics of Specific Language Impairment

特定语言障碍的遗传学

• 批准号: 7479755
• 负责人: James Bruce Tomblin
• 金额: $ 59.86万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7479755
• 关键词: Adult; Autistic Disorder; Biological; Candidate Disease Gene; Characteristics; Child; Chromosomal translocation; Chromosomes; Chromosomes, Human, Pair 7; Cognitive; Condition; Coupled; DNA; Data; Data Set; Databases; Daughter; Development; Equilibrium; Family; Family member; Genes; Genetic; Genome; Genomics; Genotype; Heritability; Human; Impairment; Individual; Individual Differences; Intelligence; Laboratories; Language; Language Development; Language Development Disorders; Language Disorders; Learning; Linguistics; Location; Longitudinal Studies; Maps; Measures; Methods; Molecular Genetics; Mothers; Mutation; Neurologic; Parents; Pathway interactions; Phenotype; Psychological Theory; Publishing; Range; Reading; Regulator Genes; Research; Sampling; Sensory; Siblings; Speech; System; Testing; Tissue Sample; Tissues; Vocabulary; Work; base; density; endophenotype; experience; follow-up; genetic linkage analysis; high school; insight; interest; microdeletion; neurophysiology; neuropsychological; proband; programs; skills; specific language impairment; trait; transmission process; young adult

DESCRIPTION (provided by applicant): Linguistic and psychological theory coupled with empirical studies on the heritability of individual differences in language development and language disorders support the hypothesis that the capacity for language development in humans is genetically influenced. The proposed research will provide for further understanding of this genetic influence on language by studying individuals with specific language impairment (SLI) who have poor language development despite normal linguistic experience, sensory abilities, and nonverbal intelligence. Individuals with SLI provide an excellent means of identifying quantitative trait genetic loci that are likely to contribute to the full range of individual differences in language development and use. The proposed research will use two complementary strategies. First, it will take advantage of two individuals (TB) with severe developmental speech and language impairment, who also have a chromosomal translocation that appears to involve the FOXP2 gene. The FOXP2 gene is known to be a regulatory gene implicated in developmental speech and language disorder. This strategy will contrast the neuroanatomical, neurophysiological, and neuropsychological characteristics of these two individuals with their unaffected family members. This work will emphasize the procedural and declarative learning systems and vocabulary and sentence use. Thus, this strategy moves from gene to language phenotype to understand the neurologic and cognitive pathways between gene and phenotype. The second strategy will use a large epidemiologic sample of young adults with SLI along with their siblings who have participated in a 10-year longitudinal study. The language status, as well as associated conditions of these individuals, has been studied extensively. Furthermore, DNA samples have already been obtained from the SLI probands, siblings, and their parents. Thus, a valuable data bank of Doth tissue and phenotypes is available to identify genes by means of high density genome-wide screens using sib-pair linkage methods and follow-up fine mapping methods using transmission disequilibrium tests (TDT). Additionally, ongoing fine mapping of candidate genes and regions of interest informed by findings from our laboratories and other laboratories will be carried out along with microdeletion studies. Additional phenotyping of the SLI probands and siblings will be conducted to obtain procedural and declarative learning measures and additional language measures that parallel the data to be obtained from the TB family. The learning measures are to serve as endophyenotypes that may be more sensitive and specific to genetic influence. The phenotypes and endophenotypes from these individuals will then be used in conjunction with the existing genotyping for additional genome-wide screens and further follow-up fine mapping studies.

描述（由申请人提供）：语言和心理理论，再加上关于语言发展和语言疾病中个体差异的遗传力的经验研究支持以下假设：人类语言发展的能力受到基因影响。拟议的研究将通过研究具有正常语言经验，感官能力和非语言智能的人语言发展的个体（SLI）来进一步了解对语言的这种遗传影响。具有SLI的个体提供了一种识别定量性状遗传基因座的出色手段，这些方法可能会导致语言发展和使用方面的各个个体差异。拟议的研究将使用两种互补策略。首先，它将利用两个具有严重发育性言语和语言障碍的人（TB），他们的染色体易位似乎涉及FOXP2基因。众所周知，FOXP2基因是涉及发展语音和语言障碍的调节基因。该策略将与未受影响的家庭成员的神经解剖学，神经生理和神经心理学特征进行对比。这项工作将强调程序和声明性学习系统以及词汇和句子使用。因此，该策略从基因转移到语言表型，以了解基因和表型之间的神经系统和认知途径。第二种策略将使用大量的患有SLI的年轻人的流行病学样本以及参加了为期10年纵向研究的兄弟姐妹。已经对这些人的语言状态以及相关条件进行了广泛的研究。此外，已经从SLI概率，兄弟姐妹及其父母那里获得了DNA样品。因此，使用SIB-PAIR链接方法和使用传输不平衡测试（TDT）的随访精细映射方法（TDT），可以使用高密度的全基因组筛选来鉴定基因的宝贵数据库。此外，将与微骨骼研究一起进行候选基因和感兴趣的区域的持续精细映射。将进行SLI检验和兄弟姐妹的其他表型，以获取程序和声明性学习措施以及其他语言措施，这些措施与从结核病家族获得的数据平行。学习措施是用作内生态性型，可能对遗传影响更敏感和特异性。然后，这些个体的表型和内型型将与现有基因分型结合使用，以进行其他全基因组筛选，并进一步随访精细的映射研究。