Genetic analysis of keloids

描述(申请人提供)：瘢痕疙瘩是一种良性的胶原性肿瘤，在皮肤过度的伤口愈合反应中发展。瘢痕疙瘩通常是家族性的，但确切的传播方式尚不清楚。这项拟议工作的长期目标是确定使个人容易患上瘢痕疙瘩的基因(S)。这将使用位置克隆策略来实现。第一个目标是使用扩展的多重家族来定位基因(S)，然后通过筛选与疾病共分离的多态区域来识别突变(S)。 这项建议的直接目标是在几个非裔美国人大家庭中使用连锁作图协议来确定瘢痕疙瘩基因(S)的染色体位置。之所以选择非裔美国人，是因为黑人的瘢痕疙瘩患病率是白人的20倍。初步数据表明，瘢痕疙瘩可能在遗传上是不同的，因此重要的是只关注一个种族群体，在那里，与这种疾病的病因有关的基因可能会较少。测绘将通过从有多个瘢痕疙瘩形成的家庭中招募受试者和筛选与疾病表型相关联的微卫星标记来完成。最初的研究将集中在14Q染色体上，在初步研究中已经确定了一个可能的瘢痕疙瘩基因。

DESCRIPTION (provided by applicant): Keloids are benign collagenous tumors that develop during an exaggerated wound healing response of the skin. Keloids are often familial, but the exact mode of transmission is unclear. The long-term goal of the proposed work is to identify the gene(s) that predipose individuals to keloids. This will be accomplished using a positional cloning strategy. The first aim is to map the gene(s) using extended multiplex families, and then to identify the mutation(s) by screening the mapped region for polymorphisms that co-segregate with the disease. The immediate goal of this proposal is to identify the chromosomal location of the keloid gene(s), using linkage-mapping protocols in several large African-American families. African-Americans have been chosen because the prevalence of keloids is -20 fold higher in Blacks than in Whites. Preliminary data suggest that keloids may be genetically heterogeneous, making it important to focus on only one ethnic group where it is likely that fewer genes will be involved in the etiology of this disease. Mapping will be accomplished by recruiting subjects from families with multiple keloid formers and screening microsatellite markers for linkage to the disease phenotype. Studies will initially focus on chromosome 14q, where a putative keloid locus has been identified in preliminary studies.