KELOID FORMATION

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。本研究的长期目标是了解纤维化疾病中真皮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，是由异常伤口修复过程中成纤维细胞过度活跃引起的。相对大量的瘢痕疙瘩形成的家族病例使得有可能提出一种遗传方法来鉴定负责增加细胞增殖和细胞外基质表达的基因。我们执行基因组宽筛选和连锁分析，适当的大家庭折磨常染色体显性形式的遗传性瘢痕疙瘩形成。随后我们鉴定和分析染色体位点。我们已经确定了可能的疾病基因位点，目前正在建立瘢痕疙瘩位点的高分辨率地图。需要确定和招募更多的家庭，以验证和进一步表征这些位点。将对这些家庭进行共本地化测试。没有共定位到现有位点的合适家族将用于全基因组筛选。

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.