Molecular genetics of familial laryngeal paralysis

家族性喉麻痹的分子遗传学

• 批准号: 6433905
• 负责人: JOSE M MANALIGOD
• 金额: $ 18.96万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-03-01 至 2006-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6433905
• 关键词: blood tests; computer data analysis; family genetics; functional /structural genomics; gene expression; genetic disorder; genetic markers; genetic polymorphism; genetic screening; genetic susceptibility; human genetic material tag; human subject; in situ hybridization; larynx disorder; linkage mapping; molecular biology information system; molecular genetics; nucleic acid sequence; paralysis; patient oriented research; polymerase chain reaction; protein structure function; vocal cords

DESCRIPTION (provided by applicant): Laryngeal paralysis is a frequent cause of stridor and airway obstruction in infants, often requiring tracheostomy or other surgical procedures to provide an adequate airway. Hereditary forms of laryngeal paralysis have been described, indicating that genetic factors may be a primary cause of certain cases. The long term objective of this study is to identify the role of genetic mechanisms in laryngeal paralysis. The hypothesis to be tested is that genetic mutations cause familial laryngeal abductor paralysis (FLAP). The specific aims of this project are: 1) To identify genetic loci linked to FLAP- Genetic linkage analysis of families in which FLAP segregates is accomplished by PCR-based screening with a short tandem repeat polymorphism (STRP) panel that covers the entire human genome. This is confirmed by statistical analysis using the LOD score method and the computer programs, SLINK, LINKAGE 5.1 and HOMOG. 2) To identify candidate genes in the chromosomal region(s) linked to FLAP- known and predicted genes are identified within FLAP genetic region(s) by sequence analysis of data from the Human Genome Project. Positional candidate genes are prioritized for mutation screening according to gene expression and function that appear consistent with the FLAP phenotype and its possible disease mechanisms. 3) To identify FLAP-causing genes- Single strand conformation polymorphism (SSCP) gel analysis and direct sequencing are used to screen genomic DNA for FLAP-causing mutations. Detected mutations are further analyzed by population screening, computer analysis of the mutated sequence, and tissue in situ hybridization studies to determine the likelihood that a specific genetic mutation causes FLAP.

描述(申请人提供)：喉部麻痹是一种常见的病因 婴儿的喘鸣和呼吸道阻塞，通常需要气管切开或其他 提供足够的呼吸道的外科手术。遗传性喉型 已经描述了瘫痪，这表明遗传因素可能是主要的 某些案件的原因。这项研究的长期目标是确定 遗传机制在喉麻痹中的作用。需要检验的假设 是基因突变导致家族性喉展肌麻痹(皮瓣)。 该项目的具体目标是：1)识别与 带瓣分离的家系的带瓣遗传连锁分析 通过短串联重复序列多态进行基于PCR的筛查 覆盖整个人类基因组的(STRP)面板。这一点得到了以下证实 使用LOD计分方法和计算机程序进行统计分析， Slink、Link5.1和Homog。2)确定染色体上的候选基因 与翻盖相关的区域(S)--已知和预测的基因在翻盖内被识别 通过对来自人类基因组计划的数据进行序列分析，获得了S的基因区域。 对位置候选基因进行优先排序以进行突变筛选 基因的表达和功能似乎与皮片的表型和 其可能的疾病机制。3)识别引起襟翼的基因--单一 链构象多态(SSCP)凝胶分析和直接测序 用于筛选基因组DNA中导致翻瓣的突变。检测到的突变是 进一步通过群体筛查、计算机分析突变株 序列和组织原位杂交研究以确定可能性 一种特定的基因突变会导致耳垂。