MOLECULAR ANALYSIS OF COLLAGENS IN THE CHONDRODYSPLASIAS

该项目建议调查缺陷在以下方面的作用 软骨发育不良中的软骨胶原。 软骨发育不良是临床上的结缔组织疾病。 由不成比例的矮小身材和骨骼异常定义。 严重程度从轻微到致命不等，骨关节炎是一种常见的 许多这类疾病的特征。第II类缺陷 胶原基因(COL2Al)在少数病例中被鉴定为 脊柱骨骺发育不良(SED)，软骨生成II，和 软骨生成减少，遗传连锁分析已牵连 Stickler综合征部分家系COL2A1基因缺陷 遗传性骨关节病与常染色体显性遗传 骨性关节炎。我们假设其他方面的缺陷 软骨特异的胶原基因构成了额外的 软骨发育不良。 这项提议的目标是：1)进一步确定突变的特征 在对上述疾病负责的COL2Al中，2)至 突变的位置和性质与临床的关系 表型，以及3)开发和实施分子工具来 确定缺陷在其他软骨中的作用 胶原蛋白。为了实现这些目标，将从 患有SED、软骨生成和软骨生成减少的患者，使用 目前的分子技术。研究对方的角色 软骨特异性胶原蛋白(IX、X和XI型)、DNA 这些基因的多态性将被开发出来，以便于 在Stickler家系中测试这些基因座作为“候选基因” 综合征，多发性骨盆发育不良，以及类似的疾病。 了解导致这些疾病的分子缺陷 应该澄清这些疾病的染色体位置和 确定额外胶原蛋白突变的作用 结缔组织遗传性疾病的基因。

This project proposes to investigate the role of defects in cartilage collagens in the chondrodysplasias. The chondrodysplasias are disorders of connective tissue clinically defined by disproportionate short stature and skeletal anomalies. Severity ranges from mild to lethal, and osteoarthritis is a common feature of many of these disorders. Defects in the type II collagen gene (COL2Al) have been characterized in a few cases of spondyloepiphyseal dysplasia (SED), achondrogenesis II, and hypochondrogenesis, and genetic linkage analysis has implicated defects in COL2A1 in some kindreds with Stickler syndrome (hereditary osteoarthropathy) and autosomal dominant osteoarthritis. We hypothesize that defects in other cartilage-specific collagen genes underlie additional chondrodysplasias. The goals of this proposal are 1) to further characterize mutations in COL2Al responsible for the disorders listed above, 2) to correlate the location and nature of the mutations with clinical phenotypes, and 3) to develop and implement molecular tools to determine the role of defects in other cartilage-specific collagens. To achieve these goals, cDNA will be analyzed from patients with SED, achondrogenesis, and hypochondrogenesis, using current molecular techniques. To study the roles of the other cartilage-specific collagens (types IX, X, and XI), DNA polymorphisms for these genes will be developed to facilitate testing these loci as "candidate genes" in families with Stickler syndrome, multiple epiphyseal dysplasia, and similar disorders. Understanding the molecular defects that produce these diseases should clarify the chromosomal locations of the disorders and determine the contribution of mutations in additional collagen genes to heritable disorders of connective tissue.