Genetic Predisposition to Disease

RASopathy Gene Mutations in Melanoma.

Next-generation sequencing of melanomas has unraveled critical driver genes and genomic abnormalities, mostly defined as occurring at high frequency. In addition, less abundant mutations are present that link melanoma to a set of disorders, commonly …

Germline MC1R status influences somatic mutation burden in melanoma.

The major genetic determinants of cutaneous melanoma risk in the general population are disruptive variants (R alleles) in the melanocortin 1 receptor (MC1R) gene. These alleles are also linked to red hair, freckling, and sun sensitivity, all of …

Exome sequencing identifies recurrent mutations in NF1 and RASopathy genes in sun-exposed melanomas.

We report on whole-exome sequencing (WES) of 213 melanomas. Our analysis established NF1, encoding a negative regulator of RAS, as the third most frequently mutated gene in melanoma, after BRAF and NRAS. Inactivating NF1 mutations were present in 46% …

Exome sequencing identifies recurrent somatic RAC1 mutations in melanoma.

We characterized the mutational landscape of melanoma, the form of skin cancer with the highest mortality rate, by sequencing the exomes of 147 melanomas. Sun-exposed melanomas had markedly more ultraviolet (UV)-like CtextgreaterT somatic mutations …

Rare nonsynonymous variants in alpha-4 nicotinic acetylcholine receptor gene protect against nicotine dependence.

BACKGROUND: Several studies report association of alpha-4 nicotinic acetylcholine receptors (encoded by CHRNA4) with nicotine dependence (ND). A meta-analysis of genomewide linkage studies for ND implicated a single chromosomal region, which includes …

Genomewide linkage scan for nicotine dependence: identification of a chromosome 5 risk locus.

BACKGROUND: Nicotine dependence (ND) is costly to societies worldwide, moderately heritable, and genetically complex. Risk loci can be identified with genetic linkage analysis independent of prior physiological hypotheses. METHODS: We completed a …