KELOID FORMATION

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这项研究的长期目标是了解纤维化疾病中皮肤组织新生的分子机制。为了实现这一目标，我们研究了遗传性瘢痕疙瘩的形成。瘢痕疙瘩是皮肤或角膜的良性肿瘤，由成纤维细胞在不正常的伤口修复过程中过度活跃引起。瘢痕疙瘩形成的家族性病例数量相对较多，这使得提出一种遗传学方法来鉴定导致细胞增殖和细胞外基质表达增加的基因成为可能。我们对患有常染色体显性遗传性瘢痕疙瘩形成的适当大家族进行全基因组筛选和连锁分析。随后，我们对这些染色体座位进行了鉴定和分析。我们已经确定了可能的疾病基因座，目前正在建立瘢痕疙瘩基因座的高分辨率图谱。需要确定和招募更多的家庭，以核实和进一步确定这些基因座的特征。这些家庭将接受共同本地化测试。不与现有基因座共定位的合适的家系将用于全基因组筛查。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The long-term goal of this study is to understand the molecular mechanisms of neoformation of dermal tissue in fibrotic diseases. To achieve this goal we study hereditary keloid formation. Keloids are benign tumors of the skin or cornea caused by overactivity of fibroblasts during abnormal wound repair. The relatively large number of familial cases of keloid formation makes it possible to propose a genetic approach for the identification of a gene responsible for increased cell proliferation and extracellular matrix expression. We perform genome wide screening and linkage analysis of suitably large families afflicted with the autosomal dominant form of hereditary keloid formation. Subsequently we identify and analyze the chromosomal loci. We have identified possible disease gene loci and are now in the process of establishing high resolution maps of the keloid loci. Additional families need to be identified and recruited to verify and further characterize the loci. These families will be tested for co-localization. Suitable families that do not co-localize to an existing locus will be used for genome wide screening.