期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 101, 期 7, 页码 1939-1944出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0308336100
关键词
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资金
- NCI NIH HHS [R01 CA078836, U01 CA089600, P50 CA058236, R01 CA58236, K05CA90754, R01 CA089600, T32 CA080416, R01 CA080122, R01 CA78836, K05 CA090754, R01 CA80122] Funding Source: Medline
Results from over a dozen prostate cancer susceptibility genome-wide scans, encompassing some 1,500 hereditary prostate cancer families, indicate that prostate cancer is an extremely heterogeneous disease with multiple loci contributing to overall susceptibility. In an attempt to reduce locus heterogeneity, we performed a genomewide linkage scan for prostate cancer susceptibility genes with 36 Jewish families, which represent a stratification of hereditary prostate cancer families with potentially increased locus homogeneity. The 36 Jewish families represent a combined dataset of 17 Jewish families from the Fred Hutchinson Cancer Research Center-based Prostate Cancer Genetic Research Study dataset and 19 Ashkenazi Jewish families collected at Johns Hopkins University. All available family members, including 94 affected men, were genotyped at markers distributed across the genome with an average interval of <10 centimorgans. Nonparametric multipoint linkage analyses were the primary approach, although parametric analyses were performed as well. Our strongest signal was a significant linkage peak at 7q11-21, with a nonparametric linkage (NPL) score of 3.01 (P = 0.0013). Simulations indicated that this corresponds to a genomewide empirical P = 0.006. All other regions had NPL P values greater than or equal to0.02. After genotyping additional markers within the 7q11-21 peak, the NPL score increased to 3.35 (P = 0.0004) at D7S634 with an allele-sharing logarithm of odds of 3.12 (P = 0.00007). These studies highlight the utility of analyzing defined sets of families with a common origin for reducing locus heterogeneity problems associated with studying complex traits.
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