Intragenic sex-chromosomal crossover of Xmrk oncogene alleles affect pigment pattern formation and the severity of melanoma in Xiphophorus

Abstract

The X and Y chromosomes of the platyfish (Xiphophorus maculatus) contain a region that encodes several important traits, including the determination of sex, pigment pattern formation, and predisposition to develop malignant melanoma. Several sex-chromosomal crossovers were identified in this region. As the melanoma-inducing oncogene Xmrk is the only molecularly identified constituent, its genomic organization on both sex chromosomes was analyzed in detail. Using X and Y allele-specific sequence differences a high proportion of the crossovers was found to be intragenic in the oncogene Xmrk, concentrating in the extracellular domain-encoding region. The genetic and molecular data allowed establishment of an order of loci over ~0.6 cM. It further revealed a sequence located within several kilobases of the extracellular domain-encoding region of Xmrk that regulates overexpression of the oncogene.