6.3　A Novel Disease-Causing Gene Conversion Mutati...

6.3　A Novel Disease-Causing Gene Conversion Mutation in the PRSS1 Gene

Gene conversion，one of the two mechanisms of homologous recombination，involves the unidirectional transfer of genetic material from a‘donor’sequence to a highly homologous‘acceptor’（Chen et al.2007）.The PRSS1 gene and four of its five paralogs are tandemly linked on chromosome 7q35（see below for PRSS3 translocated to chromosome 9）.These clustered paralogs share approximately 91%nucleotide sequence similarity，providing the molecular basis for gene conversion occurring between them（Chen et al.2013a）.Several chronic pancreatitis-causing mutations in the PRSS1 gene have been previously considered to result from gene conversion（Chen et al.2000；Chen and Férec 2000a，b；Teich et al.2005）.Recently，a new gene conversion affecting the PRSS1 gene was found in two unrelated patients with chronic pancreatitis.This event resulted in the replacement of 24-71 nucleotides in exon 3 of the PRSS1 gene by the corresponding sequence of PRSS3P2，one of the pseudo-trypsinogen genes.The mutant PRSS1 allele was predicted to encode a protein with three missense mutations including the diseasecausing p.Argl22His（Rygiel et al.2015）.(https://www.daowen.com)