A genome-wide scan for naevus count

Linkage to CDKN2A and to other chromosome regions

Gu Zhu, Grant W. Montgomery, Michael R. James, Jeff M. Trent, Nicholas K. Hayward, Nicholas G. Martin, David L. Duffy

Research output: Contribution to journalArticle

Abstract

High numbers of melanocytic naevi (moles), and mutations in the p16 gene (CDKN2A), are two strong risk factors for cutaneous malignant melanoma. We have previously reported linkage of mole count to the CDKN2A locus. Here, we report genome-wide scans for mole counts (differentiated into flat, raised and atypical subtypes) with a total of 796 microsatellite markers for 424 families with 1024 twins and siblings, plus genotypes for 690 parents. Inclusion of 221 pairs of MZ twins enabled separation of shared environmental and polygenic influences, so placing an upper limit to estimates of QTL variance. Maximum likelihood multipoint variance component methods were used to assess linkage of naevus count. Sex, age, body surface area, skin colour, hair colour, sunburn and facial freckles were included as covariates. Peak linkage of flat mole count was to regions on chromosomes 2, 9, 8 and 17 with lod scores 2.95, 2.95, 2.50 and 2.15, respectively. The support for linkage to the CDKN2A gene region (9p21) increased to 3.42 when additional fine mapping markers were added. For raised mole count, there was suggestive evidence of linkage in our sample to chromosome 16 (lod = 1.87), and for atypical mole count on chromosomes 1, 6 and X with lod scores of 2.20, 2.00 and 2.00, respectively. The multivariate linkage peaks generally match those from individual trait analyses, with the exception of a new peak on chromosome 4 (point-wise empirical P-value = 0.001). We replicate our earlier finding of linkage to CDKN2A and discovering linkage to several novel regions that may also influence risk of the development of malignant melanoma.

Original languageEnglish (US)
Pages (from-to)94-102
Number of pages9
JournalEuropean Journal of Human Genetics
Volume15
Issue number1
DOIs
StatePublished - Jan 2007
Externally publishedYes

Fingerprint

p16 Genes
Lod Score
Nevus
Chromosomes
Hair Color
Genome
Sunburn
Skin Pigmentation
Chromosomes, Human, Pair 16
Melanosis
Pigmented Nevus
Chromosomes, Human, Pair 9
Chromosomes, Human, Pair 17
Chromosomes, Human, Pair 4
Chromosomes, Human, Pair 6
Chromosomes, Human, Pair 2
Chromosomes, Human, Pair 1
Body Surface Area
Microsatellite Repeats
Melanoma

ASJC Scopus subject areas

  • Genetics(clinical)

Cite this

Zhu, G., Montgomery, G. W., James, M. R., Trent, J. M., Hayward, N. K., Martin, N. G., & Duffy, D. L. (2007). A genome-wide scan for naevus count: Linkage to CDKN2A and to other chromosome regions. European Journal of Human Genetics, 15(1), 94-102. https://doi.org/10.1038/sj.ejhg.5201729

A genome-wide scan for naevus count : Linkage to CDKN2A and to other chromosome regions. / Zhu, Gu; Montgomery, Grant W.; James, Michael R.; Trent, Jeff M.; Hayward, Nicholas K.; Martin, Nicholas G.; Duffy, David L.

In: European Journal of Human Genetics, Vol. 15, No. 1, 01.2007, p. 94-102.

Research output: Contribution to journalArticle

Zhu, G, Montgomery, GW, James, MR, Trent, JM, Hayward, NK, Martin, NG & Duffy, DL 2007, 'A genome-wide scan for naevus count: Linkage to CDKN2A and to other chromosome regions', European Journal of Human Genetics, vol. 15, no. 1, pp. 94-102. https://doi.org/10.1038/sj.ejhg.5201729
Zhu, Gu ; Montgomery, Grant W. ; James, Michael R. ; Trent, Jeff M. ; Hayward, Nicholas K. ; Martin, Nicholas G. ; Duffy, David L. / A genome-wide scan for naevus count : Linkage to CDKN2A and to other chromosome regions. In: European Journal of Human Genetics. 2007 ; Vol. 15, No. 1. pp. 94-102.
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