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.
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