Genetic studies of specific language impairment (SLI) using consanguineousfamilies

使用近亲家庭进行特定语言障碍 (SLI) 的遗传学研究

• 批准号: 10378769
• 负责人: Muhammad Hashim Raza
• 金额: $ 14.63万
• 依托单位: UNIVERSITY OF KANSAS LAWRENCE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-10 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10378769
• 关键词: Acute; Affect; Age; Alleles; Attention; Candidate Disease Gene; Child; Chromosome Mapping; Clinical; Communication; Complex; Development; Developmental Delay Disorders; Diagnosis; Digit structure; Disease; Enrollment; Extended Family; Family; Family Study; Family member; Frequencies; Gene Expression; Genes; Genetic; Genetic Diseases; Genetic Status; Genetic study; Goals; Hearing problem; Heritability; Homo; Individual; Intellectual functioning disability; Investigation; Language; Learning; Life; Maps; Measures; Mental Retardation; Methods; Molecular; National Institute on Deafness and Other Communication Disorders; Nature; Neurodevelopmental Disorder; Nuclear Family; Other Genetics; Outcome; Pakistan; Pathway interactions; Performance; Phenotype; Pilot Projects; Population; Population Control; Prevalence; Questionnaires; Recording of previous events; Reporting; Research; Salvelinus; Sampling; Schools; Short-Term Memory; Speech; Speech Disorders; Stuttering; Suggestion; Translating; Twin Studies; United States; Vocabulary Test; affection; autism spectrum disorder; base; case control; cohort; consanguineous family; developmental disease; disease classification; exome sequencing; genetic analysis; genetic pedigree; genetic variant; genome wide association study; genome-wide; genomic locus; hearing impairment; hereditary hearing loss; improved; mutant; novel; peer; rare variant; recruit; risk variant; screening; skills; social; specific language impairment; success; transmission process

Project Summary/Abstract Specific language impairment (SLI) affects up to 7% of individuals in the United States. SLI affects communica- tion, learning, and social abilities, and requires additional attention in school. The causes of SLI are not known. However, twin studies and family studies clearly demonstrate that there are genetic components involved in the transmission of this disorder. There have been several linkage studies of small, outbred SLI families, but to date these studies have had limited success identifying causative genes for this disorder. Very few attempts were made to report SLI loci in extended families with independent replication. There is a need for further focus on a family-based approach, specifically using consanguineous families, to detect SLI loci that can allow us to identify causative genes. The long-term objectives of the proposed study are to identify genes responsible for SLI by studying consanguineous families ascertained from Pakistan. Recently, a similar approach was used, which identified the first gene responsible for stuttering, another phenotypically and genetically complex disor- der. We initially performed genetic analysis in 14 consanguineous SLI families in Pakistan. Our preliminary linkage mapping in SLI families suggested SLI loci, which is a proof of principle, but it also demonstrated the need to extend gene-mapping and phenotyping in additional SLI families from Pakistan. We propose three specific aims to achieve. Age appropriate means and standard deviations will be calculated in Pakistani sam- ples for multiple language assessments (Aim#1). Genome-wide gene mapping will be performed in well char- acterized multigenerational consanguineous SLI families (Aim#2). The frequency of common homozygosity regions will be estimated in Pakistani samples (Aim#3).

项目摘要/摘要 在美国，高达7%的人患有特殊语言障碍(SLI)。SLI影响社区- 能力、学习和社交能力，在学校需要额外的关注。SLI的原因尚不清楚。 然而，双胞胎研究和家庭研究清楚地表明， 这种混乱的传播。已经有几个关于SLI小家庭的连锁研究，但 日期这些研究在确定这种疾病的致病基因方面取得了有限的成功。很少有尝试 在具有独立复制的家系中报告SLI基因座。有必要进一步关注 以家庭为基础的方法，特别是使用近亲家庭来检测SLI基因座，这可以让我们 找出致病基因。这项拟议研究的长期目标是确定与 SLI通过研究从巴基斯坦确定的血亲家庭。最近，一种类似的方法也被使用， 它确定了第一个导致口吃的基因，另一种表型和遗传复杂的疾病- 德尔。我们最初对巴基斯坦14个有血缘关系的SLI家系进行了基因分析。我们的预赛 SLI家系中的连锁图谱提示SLI基因座，这是原理的证明，但它也证明了 需要在来自巴基斯坦的其他SLI家庭中扩大基因图谱和表型。我们提出三个建议 要实现的具体目标。适当年龄的平均数和标准差将以巴基斯坦萨姆计算- 用于多种语言评估的PLES(目标1)。全基因组的基因图谱将被很好地进行- 具有多代血缘关系的SLI家族的特征(目标2)。常见纯合子的频率 将在巴基斯坦样本中估计区域(目标3)。