Genetic Mapping of Familial Idiopathic Scoliosis

家族性特发性脊柱侧凸的基因图谱

• 批准号: 7143612
• 负责人: JOSE ANTONIO MORCUENDE
• 金额: $ 12.05万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7143612
• 关键词: bioinformatics; children; chromosomes; clinical research; conditioning; diagnosis; family; family genetics; gene mutation; genes; genetic mapping; genetics; genotype; molecular genetics; motivation; spine; training

DESCRIPTION (provided by applicant): As evidenced by this application for a CDA (K08), the candidate desires to obtain expertise in molecular genetics, and to apply this expertise to the investigation of scoliosis. As a pediatric orthopaedist with a strong interest in the molecular genetics of pediatric musculoskeletal disorders, the candidate has begun genetic investigations of idiopathic scoliosis and clubfoot. He joined the faculty as a clinician-scientist and is in a position, with the support of this award, to move toward independent investigations into the molecular genetic basis of these disorders. Adolescent idiopathic scoliosis (AIS) is a highly prevalent condition affecting 2-3% of the adolescent population. Although the specific cause has not been established, there is strong evidence that genetic factors play a role. Isolating the gene(s) responsible for AIS will start a chain of scientific events with significant implications for both public health and healthcare spending. Annually, screening for this condition costs the national healthcare system over $56 million dollars, and over $180 million for AIS surgery, of which $48 million was charged to Medicaid. Recent work provides evidence for linkage of AIS to chromosome 16 (as reported by Miller et al.); the same area of linkage was found in a large pedigree evaluated in our laboratory (Lod score 3.17). The goal of this proposal is to better define this chromosomal region and to evaluate candidate genes in an effort to identify an AlS-disease gene. In order to maximize the likelihood of success and to provide for a variety of training experiences, two complementary approaches are proposed: 1) detailed characterization of the region of interest by high-density marker genotyping, and the use of gene annotation information for candidate gene mutation analysis. This work will be supported by our high-throughput sequencing and screening capabilities, state-of-the-art Center for Bioinformatics and Computational Biology, and the Center for Statistical Genetics Research. The candidate will be mentored by a Howard Hughes geneticist at the University of Iowa, and secondarily by recognized experts in statistical genetics, genetic computational bioinformatics, through a rigorous, well-organized series of didactic coursework. Together, the training plan and research proposal provide for a breadth of training, the potential for meaningful discovery, and support for the establishment of an independent research career.

描述（由申请人提供）： 正如该申请CDA（K08）所证明的那样，候选人希望获得分子遗传学方面的专业知识，并将这种专业知识应用于脊柱侧弯的研究。作为一名小儿骨科医生，对小儿肌肉骨骼疾病的分子遗传学有浓厚的兴趣，该候选人已经开始对特发性脊柱侧弯和俱乐部杆的遗传研究。他以临床医生的身份加入该学院，并在该奖项的支持下，朝着对这些疾病的分子遗传基础进行独立研究。青少年特发性脊柱侧弯（AIS）是一种高度普遍的疾病，影响了青少年人群的2-3％。尽管尚未确定具体原因，但有充分的证据表明遗传因素起着作用。隔离负责AIS的基因将启动一系列科学事件，对公共卫生和医疗保健支出产生重大影响。每年，对这种情况进行筛查，国家医疗保健系统的费用超过了5600万美元，AIS手术的损失超过1.8亿美元，其中4,800万美元被收取给医疗补助。最近的工作提供了AI与16号染色体连接的证据（如Miller等人的报道）；在我们的实验室评估的大型血统中发现了相同的连锁区域（LOD得分3.17）。该提案的目的是更好地定义该染色体区域并评估候选基因，以识别ALS-蛋白酶基因。为了最大程度地提高成功的可能性并提供各种培训经验，提出了两种互补方法：1）通过高密度标记基因分型来详细表征感兴趣的区域，以及将基因注释信息用于候选基因突变分析。这项工作将得到我们的高通量测序和筛查能力，最先进的生物信息学和计算生物学中心以及统计遗传学研究中心的支持。候选人将由爱荷华大学的霍华德·休斯（Howard Hughes）遗传学家指导，其次，由公认的统计遗传学，遗传计算生物信息学专家通过一系列严格，组织良好的教学课程进行指导。培训计划和研究建议共同提供了广度的培训，有意义的发现的潜力以及对建立独立研究职业的支持。