Identification of Dosage Sensitive Genes on 18q

18q 剂量敏感基因的鉴定

• 批准号: 7152856
• 负责人: JANNINE De Mars CODY
• 金额: $ 37.43万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-01-14 至 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7152856
• 关键词: 18q; Autistic Disorder; Candidate Disease Gene; Child; Childhood; Chromosome Deletion; Chromosome abnormality; Chromosomes; Chromosomes, Human, Pair 18; Classification; Cleft Palate; Clinical; Clinical Research; Clinical assessments; Data; Development; Developmental Delay Disorders; Disease; External auditory canal; G-Banding; Gene Deletion; Genes; Genomics; Genotype; Goals; Healthcare; Human; Human Genome Project; Individual; Infant; Karyotype; Life; Live Birth; Modeling; Molecular Analysis; Molecular Models; Morbidity - disease rate; Mutation; Neurons; Numbers; Persons; Phenotype; Point Mutation; Polymerase Chain Reaction; Population; Process; Purpose; Recruitment Activity; Research; Research Personnel; Resolution; Screening procedure; Secondary to; Single-Gene Defect; Social Work; Somatotropin; Syndrome; Testing; Therapeutic; Time; base; clinically significant; cohort; disability; dosage; dysmyelination; experience; genome database; genome sequencing; growth hormone deficiency; interest; microdeletion; mortality; multidisciplinary; novel; novel strategies; novel therapeutics; programs; size; tool

DESCRIPTION (provided by applicant): One of every 180 live-born infants has a chromosome abnormality making it a leading cause of disability. Human genome sequence data now permits the identification of specific genes associated with each aneusomy, the correlation of these genes with specific phenotypes, and ultimately therapeutic options. Toward this end, we have established and sustained a large multidisciplinary team: The Chromosome 18 Clinical Research Center. Herein, we propose a model for identifying the specific gene(s) associated with each phenotypic feature of 18q deletions (dosage sensitive genes). The model may be widely applicable to other chromosome abnormalities. Deletions of 18q are among the most common of the chromosome abnormalities, yet no dosage sensitive genes have been identified whose hemizygosity results in haploinsufficiency and therefore a phenotype. Our goal is to identify dosage sensitive genes on 18q and to characterize the clinical consequences of this hemizygosity. Building on our extensive experience with the chromosome 18 syndromes, we propose to correlate specific key phenotypic features (dysmyelination, growth hormone deficiency, atretic/stenotic ear canals, autism, cleft palate, and severe developmental delay) with the deletion of particular regions of chromosome 18q (critical region). To further narrow this critical region to a candidate gene (or genes), we will study karyotypically normal children with a specific phenotype (e.g., dysmyelination) and search for microdeletions in the previously identified critical region on chromosome 18. This strategy has already been used to identity a candidate gene responsible for the dysmyelination phenotype. Sequencing of the candidate gene in the phenotype specific population will identify additional individuals with chromosome 18q based disease. Then, the karyotypically normal child with chromosome 18q based disease will be clinically assessed to determine the spectrum of expressivity. This last step will initiate the process of comprehensively defining the phenotype resulting from deletion or mutation of an individual dosage sensitive gene. Furthermore, it will begin to piece together the genotypic components that combine to generate the full phenotype of a child with an 18q deletion.

描述（由申请人提供）：每180个活产婴儿中就有一个染色体异常，这是导致残疾的主要原因。人类基因组序列数据现在允许鉴定与每个动脉瘤相关的特定基因，这些基因与特定表型的相关性，以及最终的治疗选择。