Implications for medical genetics of the House of Commons Science and Technology Committee's report on human genetics.
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We have developed 21 new microsatellites in the model diploid perennial species Fragaria vesca from an enriched genomic library developed using F. vesca 'Ruegen'. The transferability of the primer pairs to other Fragaria species was high; all 31 primer pairs produced amplicons in 3 accessions of the octoploid strawberry Fragaria x ananassa, whereas 24 (77%) amplified a product in 7 other diploid Fragaria species. We analysed the allelic variation among 15 F. vesca accessions using the 21 microsatellites reported here and 10 F. vesca microsatellites described previously. The level of polymorphism detected at these microsatellite loci was high; five loci were monomorphic. Only two microsatellites were required to unambiguously discriminate among the 15 F. vesca accessions. A preliminary survey of segregation in an F2 progeny indicates that 20 of the 26 polymorphic loci (77%) could be mapped.
Association studies of quantitative traits have often relied on methods in which a normal distribution of the trait is assumed. However, quantitative phenotypes from complex human diseases are often censored, highly skewed, or contaminated with outlying values. We recently developed a rank-based association method that takes into account censoring and makes no distributional assumptions about the trait. In this study, we applied our new method to age-at-onset data on ALDX1 and ALDX2. Both traits are highly skewed (skewness > 1.9) and often censored. We performed a whole genome association study of age at onset of the ALDX1 trait using Illumina single-nucleotide polymorphisms. Only slightly more than 5% of markers were significant. However, we identified two regions on chromosomes 14 and 15, which each have at least four significant markers clustering together. These two regions may harbor genes that regulate age at onset of ALDX1 and ALDX2. Future fine mapping of these two regions with densely spaced markers is warranted.
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