DESCRIPTION (provided by applicant): Keloids result from an exaggerated response to wound healing of the skin. They grow beyond the original boundaries of the injury to the skin, causing cosmetic deformities, and there is no known treatment that consistently prevents their occurrence or recurrence. The existence of families in which multiple members are affected with keloids over several generations and that certain ethnic groups are more likely to develop keloids than others imply that certain genes may predispose people to keloid formation. Surprisingly, little is known about the genetic factors contributing to keloids in individuals of African or Hispanic ancestry, which are the two ethnic groups most likely to develop keloids. There is also little known about the differences between the normal skin of those who keloid and the normal skin of those that do not. The research aims of this application will test the hypothesis that specific genetic variations confer susceptibility to keloid formation in those individuals at greatest risk: subjects of African and Hispanic ancestry. They will also test the hypothesis that there exist uncharacterized genes and gene isoforms, in keloids as well as in the normal skin of individuals that keloid that are critical to keloid pathogenesis. A keloid registry has been established to better characterize subjects and families of African and Hispanic descent with keloids. The registry has 117 families and 136 unrelated individuals with sporadic keloids to date and enrollment is ongoing. As part of enrollment a medical history, dermatologic evaluation and venipuncture are performed. Plasma and serum are aliquoted and genomic DNA is extracted and stored. In participants with a family history of keloids, the other family members (both affected and unaffected individuals) are invited to participate. Specific Aim 1 is to Identify Susceptibility Loci in Families with Keloids. Linkage analysis will be performed on all of the members of a family with familial keloids. The location of disease-causing loci within each family will be found by identifying the genetic markers that are co-inherited with the keloid phenotype. A logarithm of the odds (LOD) score will be calculated based upon the genetic markers co-segregating with the keloid phenotype within the family. A LOD score of three or more will be used to determine if a region is linked with the keloid phenotype. Candidate genes within these identified loci will be examined to identify variants that co-segregate with keloid formation. Specific Aim 2 is to Identify Genetic Variations Associated with Keloids. All exons in the genome (i.e. the exome) will be sequenced using high-throughput sequencing in selected members of families with keloids. Rare sequence variations identified in the affected family members will be further examined to identify variants that co-segregate with keloid formation. These candidate genes will be sequenced in other families that have ...