Molecular genetics of familial laryngeal paralysis

家族性喉麻痹的分子遗传学

• 批准号: 6835712
• 负责人: JOSE M MANALIGOD
• 金额: $ 19.47万
• 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/6835712
• 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（由申请人提供）：喉麻痹是一种常见的原因， 婴儿喘鸣和气道阻塞，通常需要气管造口术或其他 外科手术以提供充足的气道。遗传性喉炎 已经描述了瘫痪，表明遗传因素可能是主要的 因为某些案件。本研究的长期目标是确定 遗传机制在喉麻痹中的作用。待测试的假设 基因突变导致家族性喉外展肌麻痹（FLAP）。 该项目的具体目标是：1）确定与 FLAP-遗传连锁分析的家庭，其中FLAP分离是 通过基于PCR的短串联重复序列多态性筛选完成 （STRP）面板，覆盖整个人类基因组。证实了这一点 使用LOD评分法和计算机程序进行统计分析， SLINK、LINKAGE 5.1和HOMOG。2)为了在染色体上识别候选基因， 与FLAP相关的区域-在FLAP中识别已知和预测的基因 通过对来自人类基因组计划的数据进行序列分析来确定基因区域。 位置候选基因优先用于突变筛选，根据 与FLAP表型一致的基因表达和功能， 可能的疾病机制。3)识别FLAP致病基因-单个 链构象多态性（SSCP）凝胶分析和直接测序， 用于筛选基因组DNA中的FLAP突变。检测到的突变是 通过群体筛选进一步分析，计算机分析突变的 序列和组织原位杂交研究，以确定 一种特定的基因突变导致了FLAP