Identification of ASAH1 as a susceptibility gene for familial keloids.

Keloids result from abnormal proliferative scar formation with scar tissue expanding beyond the margin of the original wound and are mostly found in individuals of sub-Saharan African descent. The etiology of keloids has not been resolved but previous studies suggest that keloids are a genetically heterogeneous disorder. Although possible candidate genes have been suggested by genome-wide association studies using common variants, by upregulation in keloids or their involvement in syndromes that include keloid formation, rare coding variants that contribute to susceptibility in non-syndromic keloid formation have not been previously identified. Through analysis of whole-genome data we mapped a locus to chromosome 8p23.3-p21.3 with a statistically significant maximum multipoint LOD score of 4.48. This finding was followed up using exome sequencing and led to the identification of a c.1202T>C (p.(Leu401Pro)) variant in the N-acylsphingosine amidohydrolase (ASAH1) gene that co-segregates with the keloid phenotype in a large Yoruba family. ASAH1 is an acid ceramidase known to be involved in tumor formation by controlling the ratio of ceramide and sphingosine. ASAH1 is also involved in cell proliferation and inflammation, and may affect the development of keloids via multiple mechanisms. Functional studies need to clarify the role of the ASAH1 variant in wound healing.

Genome-editing technologies and patent landscape overview.

Unlike with zinc finger nuclease and transcriptional activator-like effector nuclease DNA modification technologies that rely on lead proteins, developed through expensive and time-consuming processes, the clustered regularly interspaced short palindromic repeat (CRISPR)/Cas system has rapidly emerged as the most promising gene-editing technology to date for the modification of any selected DNA sequence. CRISPR is receiving tremendous fanfare due, in part, to its potential to provide a means to fundamentally alter medical genetics and especially cancer medicine. In this review, we compare key technologies of genome-editing zinc finger nucleases, transcriptional activator-like effector nucleases and CRISPR, with a focus on the race to acquire lucrative intellectual property rights, the current CRISPR patent dispute and potential repercussions on innovation and the adoption of this promising technology by the medical community.