Genetic Analysis of Keloid Formation

描述（由申请方提供）：瘢痕疙瘩形成是一种伤口愈合疾病，主要影响美国皮肤较深的少数人群。瘢痕疙瘩发生零星或可作为常染色体显性或隐性性状遗传。导致瘢痕疙瘩瘢痕形成的基因突变和下游级联反应尚未确定。鉴定这些基因对于理解瘢痕疙瘩病因学是至关重要的，因为生物化学和细胞生物学方法尚未导致瘢痕疙瘩形成原因的鉴定。瘢痕疙瘩提供了一个理想的模型来研究一般瘢痕形成的关键机制。本申请的一个目的是招募具有遗传性瘢痕疙瘩形成的家族。我们建立了一个独特的家庭招聘合作伙伴网络。第二个目标是确定家族性瘢痕疙瘩形成患者的基因和基因突变。将采集DNA样本，并检测与已确定的几个易感基因位点的共分离。共分离家系将用于基因座的精细定位。来自未映射到这些基因座的家族的基因组DNA将用于全基因组筛选和连锁分析，以鉴定额外的瘢痕疙瘩基因座。我们将使用参数和非参数方法进行连锁分析。

DESCRIPTION (provided by applicant): Keloid formation is a wound healing disorder which affects primarily darker-skinned minority populations in the US. Keloids occur sporadically or can be inherited as an autosomal dominant or recessive trait. Gene mutations and downstream cascades that are causative for keloid scarring have not been identified. Identifying such genes is fundamental to the understanding of keloid pathoetiology since biochemical and cell biological approaches have not lead to the identification of the cause for keloid formation. Keloids present an ideal model to study key mechanisms for scar formation in general. One objective of this application is to recruit families with inheritable keloid formation. We have established a unique network of collaborators for family recruitment. The second objective is to identify genes and gene mutations in patients with familial keloid formation. DNA samples will be collected and tested for cosegregation to several susceptibility gene loci that were already identified. Cosegregating families will be used for fine mapping of loci. Genomic DNA from families that do not map to these loci will be used for genome-wide screening and linkage analysis in order to identify additional keloid gene loci. We will carry out linkage analysis using parametric and non-parametric approaches.