POSTER NO: 393

Genome-scan and fine mapping for quantitative-trait loci for mole density and other phenotypes from Brisbane Twin Mole Study

Gu Zhu, David L. Duffy, Grant Montgomery, Nicholas K. Hayward, Nicholas G. Martin
Queensland Institute of Medical Research, Post Office, Royal Brisbane Hospital, Brisbane 4029, Australia

The Brisbane Twin Mole Study started in 1992, and is still going on. All twins have two visits at 12 and 14 years old. We have collected 636 families of twins, parents and their sibs, and 533 pair of twins have completed both their visits. Phenotype information was collected for skin characters such as mole count, skin reflectance, freckle, acne, sun-exposure time and used protection methods. The blood samples collected were used to obtain immunological data, biochemistry measurements and genotype marker information. We have conducted a genome-scan using the ABI PRISM Linkage Mapping Set Version 2 (400 markers that define a ~10cM resolution human index map) for 274 families with 642 individuals. Also we have done fine mapping on Chromosome 9 at p16 (CDKN2A) gene region with another 25 markers and 6 SNPs. We hypothesized that some of the genetic variance for mole count might be due to variation in the p16 gene. Analysis of linkage to a highly polymorphic marker (D9S942), located close to p16, detected quantitative-trait-loci (QTL) effects accounting for 27% of variance in total mole count, rising to 33% if flat but not raised moles were considered. Total heritability was higher for raised (.69) than for flat (.42) moles, but variance due to a linked QTL was zero for raised moles, whereas it accounted for 80% of the heritability of flat moles; additionally, family environment accounted for only 15% of variance in raised versus 46% in flat moles.