Gene Discovery in Muscular Dystrophy

肌营养不良症的基因发现

基本信息

批准号：
8578930
负责人：
PETER B. KANG
金额：
$ 17.71万
依托单位：
BOSTON CHILDREN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-05-01 至 2013-10-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8578930
关键词：
Affect Amino Acids Animal Model Attention Biological Models Biopsy Candidate Disease Gene Clinical Clinical Data DNA Sequence Data Data Set Databases Diagnosis 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 Hereditary Disease Immunohistochemistry In Vitro Individual Investigation Knowledge Laboratories Lead Limb-Girdle Muscular Dystrophies 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 case-by-case basis clinical Diagnosis exome exome sequencing experience fly gene discovery genetic linkage analysis genome sequencing grasp human disease human tissue improved kindred new technology next generation sequencing novel novel strategies outcome forecast public health relevance regenerative repaired research study satellite cell screening

项目摘要

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）：肢体肌肉营养不良症（LGMD）是一类肌肉营养不良的，其特征是进行性近端骨骼肌无力和肌肉活检异常的独特模式。但是，LGMD具有许多遗传原因和一系列不同的临床结果。由于支持性治疗，目前尚无CUR可用，因此受影响的个体的生活质量显着改善。受LGMD影响的个体中很大一部分在已知基因中没有突变，表明LGMD的几种病因基因尚未发现。由于许多受影响的个体代表零星的病例，因此对这些基因的搜索一直很困难，因此潜在的LOD得分将很低，而连锁扫描将产生许多候选基因。下一代测序技术的快速进步正在降低这些障碍，并将改变有关研究和临床领域遗传诊断的许多假设。下一代测序将使研究人员和临床医生能够确定零星病例的病因突变以及较大的家庭，这些家庭产生了广泛，低，低，低的家庭或具有丰富候选基因的多个连锁峰。调查人员与他的实验室和合作者一起招募了许多受LGMD影响的亲戚。这些家庭中有几个很有可能产生新的致病基因。这种合并的方法是使用链接分析和下一代测序，是一种有力的方法，它将扩大我们对肌肉营养不良的知识。下一代测序已经应用于临床环境中，对该技术的优势和局限性有更好的了解对于掌握最大利用其潜力将很重要。