Linkage analysis of extended high-risk pedigrees replicates a cutaneous malignant melanoma predisposition locus on chromosome 9q21.

Three predisposition genes have been identified for cutaneous malignant melanoma (CMM), but they account for only ∼25% of melanoma clusters/pedigrees. Linkage analyses of melanoma pedigrees from many countries have failed to identify significant linkage evidence for the remaining predisposition genes that must exist. The Utah linkage analysis approach of using singly informative extended high-risk pedigrees combined with high-density single-nucleotide polymorphism (SNP) markers has successfully identified significant linkage evidence for two regions. This is, to our knowledge, the first genome-wide linkage analysis of the extended Utah high-risk CMM pedigrees, and it provides confirmation of linkage for a chromosome 9q region previously reported in Danish pedigrees. This report confirms that linkage analysis for common disorders can be successful in analysis of high-density markers in sets of singly informative high-risk pedigrees.