Gene Discovery in Muscular Dystrophy

肌营养不良症的基因发现

• 批准号: 8830482
• 负责人: PETER B. KANG
• 金额: $ 34.86万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-05-01 至 2018-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8830482
• 关键词: Affect; Amino Acids; Animal Model; Attention; Biological Models; Biopsy; Candidate Disease Gene; Clinical; Clinical Data; DNA Sequence; Data; Data Set; Databases; Diagnostic; Dideoxy Chain Termination DNA Sequencing; Disease; Enrollment; Ethnic Origin; Family; Family Process; Frequencies; Future; Generations; Genes; Genetic; Genetic Counseling; Genetic Techniques; Genetic screening method; Genotype; Health; Hereditary Disease; Immunohistochemistry; In Vitro; Individual; Investigation; Knowledge; Laboratories; Lead; Limb-Girdle Muscular Dystrophies; Medical Genetics; Modeling; Molecular; Molecular Diagnosis; Mouse Cell Line; Muscle; Muscle Weakness; Muscular Dystrophies; Mutation; Myopathy; Natural regeneration; Nature; Neurology; Outcome; Participant; Pathogenicity; Pathway interactions; Patients; Pattern; Phenotype; Physicians; Principal Investigator; Process; Publishing; Quality of life; Recruitment Activity; Reproducibility; Research; Research Personnel; Scanning; Scientific Advances and Accomplishments; Scientist; Sequence Analysis; Severities; Skeletal Muscle; Technology; Test Result; Therapeutic; Work; Zebrafish; accurate diagnosis; case-by-case basis; clinical Diagnosis; exome; exome sequencing; experience; fly; gene discovery; genetic disorder diagnosis; genetic linkage analysis; genome sequencing; grasp; human disease; human tissue; improved; kindred; new technology; next generation sequencing; novel; novel strategies; outcome forecast; regenerative; repaired; research study; satellite cell; screening

DESCRIPTION (provided by applicant): Limb-girdle muscular dystrophy (LGMD) is a class of muscular dystrophies characterized by progressive proximal skeletal muscle weakness and a distinct pattern of abnormalities on muscle biopsy. However, the LGMDs have a number of genetic causes and an array of different clinical outcomes. The quality of life has improved significantly for affected individuals, due primarily to supportive treatment, but currently no cur is available. A significant proportion of individuals affected by LGMD do not have mutations in the known genes, indicating that several causative genes for LGMD have yet to be discovered. The search for these genes has until recently been difficult, as many affected individuals represent sporadic cases, and thus potential LOD scores would be low and linkage scans would yield many candidates genes. The rapid advances in next generation sequencing technology is lowering these barriers, and will change many assumptions about genetic diagnosis in the research and clinical realms. Next generation sequencing will enable researchers and clinicians to identify causative mutations in sporadic cases as well as larger families that yield broad, low, or multiple linkage peaks with an abundance of candidate genes. The investigator along with his laboratory and his collaborators, have enrolled many kindreds affected by LGMD. Several of these families have a high likelihood of yielding novel causative genes. This combined approach, using both linkage analysis and next generation sequencing, is a powerful one that will broaden our knowledge of the muscular dystrophies. Next generation sequencing is already being applied in clinical settings, and a better understanding of the strengths and limitations of this technology will be important to grasp to make the greatest use of its potential.

描述（由申请人提供）：肢带型肌营养不良症（LGMD）是一类肌营养不良症，其特征为进行性近端骨骼肌无力和肌肉活检异常的独特模式。然而，LGMD有许多遗传原因和一系列不同的临床结果。主要由于支持性治疗，受影响个体的生活质量已显著改善，但目前尚无cur可用。很大一部分受LGMD影响的个体在已知基因中没有突变，这表明LGMD的几个致病基因尚未被发现。直到最近，对这些基因的搜索一直很困难，因为许多受影响的个体代表散发病例，因此潜在的LOD分数将很低，连锁扫描将产生许多候选基因。下一代测序技术的快速发展正在降低这些障碍，并将改变研究和临床领域中有关基因诊断的许多假设。下一代测序将使研究人员和临床医生能够识别散发病例以及较大家族中的致病突变，这些突变产生广泛，低， 或具有大量候选基因的多个连锁峰。研究者沿着他的实验室和他的合作者，已经招募了许多受LGMD影响的患者。这些家族中有几个很有可能产生新的致病基因。这种结合的方法，使用连锁分析和下一代测序，是一个强大的，将扩大我们的肌肉萎缩症的知识。下一代测序已经应用于临床环境，更好地了解这项技术的优势和局限性对于充分利用其潜力至关重要。