Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
QIMR Home Page
GenEpi Home Page
Publications
Contacts
Research
Staff Index
Collaborators
Software Tools
Computing Resources
Studies
Search
GenEpi Intranet
PMID
17063143
TITLE
A genome-wide scan for naevus count: linkage to CDKN2A and to other chromosome regions.
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.
DATE PUBLISHED
2007 Jan
HISTORY
PUBSTATUS PUBSTATUSDATE
aheadofprint 2006/10/25
pubmed 2006/10/26 09:00
medline 2007/03/30 09:00
entrez 2006/10/26 09:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Zhu G Zhu Gu G Queensland Institute of Medical Research, Brisbane, Queensland, Australia.
Montgomery GW Montgomery Grant W GW
James MR James Michael R MR
Trent JM Trent Jeff M JM
Hayward NK Hayward Nicholas K NK
Martin NG Martin Nicholas G NG
Duffy DL Duffy David L DL
INVESTIGATORS
JOURNAL
VOLUME: 15
ISSUE: 1
TITLE: European journal of human genetics : EJHG
ISOABBREVIATION: Eur. J. Hum. Genet.
YEAR: 2007
MONTH: Jan
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Print
ISSN: 1018-4813
ISSNTYPE: Print
MEDLINE JOURNAL
MEDLINETA: Eur J Hum Genet
COUNTRY: England
ISSNLINKING: 1018-4813
NLMUNIQUEID: 9302235
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Twin Study
COMMENTS AND CORRECTIONS
GRANTS
GRANTID AGENCY COUNTRY
CA88363 NCI NIH HHS United States
N01-HG-65403 NHGRI NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adolescent
Australia
Female
Genes, p16
Genome, Human
Humans
Lod Score
Male
Melanoma epidemiology
Multifactorial Inheritance epidemiology
Multivariate Analysis epidemiology
Nevus, Pigmented pathology
Risk Factors pathology
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's