Genetic analysis of keloids

描述（由申请人提供）：瘢痕疙瘩是良性胶原性肿瘤，在皮肤过度伤口愈合反应期间发生。瘢痕疙瘩通常是家族性的，但确切的传播方式尚不清楚。这项工作的长期目标是确定使个体易患瘢痕疙瘩的基因。这将使用定位克隆策略来完成。第一个目的是使用扩展的多重家族来绘制基因图，然后通过筛选与疾病共分离的多态性的绘制区域来鉴定突变。 这项建议的直接目标是确定瘢痕疙瘩基因的染色体位置，在几个大的非洲裔美国人家庭中使用连锁图谱协议。选择非洲裔美国人是因为黑人的瘢痕疙瘩患病率比白人高20倍。初步数据表明，瘢痕疙瘩可能是遗传异质性的，因此重要的是要集中在一个种族群体，它可能是较少的基因将参与这种疾病的病因。将通过从多发性瘢痕疙瘩形成者家族中招募受试者并筛选与疾病表型连锁的微卫星标记来完成定位。研究最初将集中在染色体14 q上，在初步研究中已经确定了假定的瘢痕疙瘩基因座。

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.