Lisa A Cannon-Albright

..This report confirms that linkage analysis for common disorders can be successful in analysis of high-density markers in sets of singly informative high-risk pedigrees...

..CONCLUSION: In this set of high-risk prostate cancer pedigrees with at least nominal linkage evidence to BRCA2, we saw no evidence for segregating BRCA2 protein truncating mutations in heritable prostate cancer...

..Our results do indicate there exists potential to augment our current knowledge about the relationships among genes associated with complex diseases using expression data...

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..Example analyses and high-risk pedigrees are presented. Finally we briefly review ways this resource, or others like it, may expand in future...

..abstract:..

..34, at D7S2421, corrected P=0.001). This study is the first to confirm the linkage of the 7q11 locus for IA...

..The recently developed sumLINK and sumLOD statistics are powerful tools for linkage analysis in the presence of heterogeneity...

..In addition to potential allelic heterogeneity, 8q24 exhibits strong linkage disequilibrium over vast distances and is prone to chromosomal aberrations...

..From this information, one can identify possible genetic targets for future therapies...

..We also nominally replicated the association of prostate cancer with rs5945619 (Xp11). In particular, it seems that the susceptibility locus at 10q11 maybe involved in familial, early-onset disease...

..Our results suggest that XRCC4 may play a role in the age at diagnosis and risk of breast cancer in non-BRCA1/2, heritable breast cancer cases...

..Continued accumulation of nevi in mutation carriers supports a nevogenic role for this CDKN2A mutation. An intermediate nevus phenotype in non-carrier family members suggests the presence of additional modifier genes...

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..This study evaluated the familiality of death resulting from aortic, mitral, and all valvular diseases using a population-based genealogy linked to death records...

..Subsequent linkage analysis of the ELN region on chromosome 7q11 in high-risk Utah IA pedigrees significantly confirmed linkage between IA and the ELN region...

..This population-based description of cancer clustering describes patterns of cancer coaggregation suggestive of a genetic predisposition...

..We report familial relative risk (FRR) in probands with various combinations, or constellations, of affected relatives, extending to third-degree...

..Further, it supports the hypothesis that MDD and anxiety disorders have over-lapping genetic etiologies and suggests that comorbid diagnoses may be useful in defining more genetically homogeneous forms of MDD for linkage mapping...

..A retrospective, population-based study cross-referencing a genealogic database of over 2 million Utah residents with 10 years of clinical diagnosis data from a large tertiary hospital...

..Using a large, retrospective cohort from the Utah Population Database, we assess how well family history predicts who will acquire colorectal cancer during a 20-year period...

..Asthma is a multifactorial disease; genetic factors have been suggested but have not been well defined...

..We describe a patient from a familial melanoma pedigree with 7 primary melanomas on the right side of her body, the first occurring 5 years after exposure to atmospheric nuclear bomb testing in the 1950s...

..The increased risks for five additional cancer types in first-degree relatives of melanoma cases suggest that individuals with a family history of melanoma should strictly adhere to recommended screenings for all cancers...

..2). CONCLUSION: These data suggest that melanomas occurring in the context of an underlying inherited susceptibility do not have a significantly different biologic behavior...

..Relatives of women with LOB are at higher risk for BC than relatives of other BC subtypes; a more rigorous BC screening regime may be warranted for these individuals...

..We observed a significantly elevated rate of pancreatic cancer in one of four families with a deleterious CDKN2A mutation...

..To compare colonoscopy screening/surveillance rates by level of risk for colorectal cancer based on age, personal history of adenomatous polyps or colorectal cancer, or family history of colorectal cancer...

..Using a genealogical database, we examined risk of endometrial cancer among family members of individuals with endometrial cancer...

..We are mutation screening candidate genes in this region to identify specific genetic variants segregating in these pedigrees...

..The Utah Population Database (UPDB) has provided important illumination of the familial contribution to cancer risk by cancer site...

..Several familial pancreatic cancer syndromes have been identified. However, the prevalence of familial pancreatic cancers in the general population has not been well defined...

..41 under a recessive model. Seventeen pedigrees (53%) had at least nominal evidence for linkage on a by-pedigree basis at this region. These results provide evidence for a predisposition gene for PFDs on chromosome 9q...

..The evidence of linkage at the 5q13 region represents the first significant evidence for linkage on a genome-wide basis for this locus. Linked pedigrees localize the region to approximately between 92.3-105.5 Mb...

..This study provides an optimal set of tSNPs for association analyses of CETP. The observed complexity of LD structure highlights the importance of using methods, such as PCA, that allow for multiple dynamics in intragenic LD structure...

..This study evaluated deaths caused by CAD, MI, hypertensive heart disease (HtnHD), and congestive heart failure (CHF) among close and distant relatives...

..This collaborative study by the ICPCG illustrates the value of consortium efforts and the continued utility of linkage analysis using informative pedigrees to localize genes for complex diseases...

..CONCLUSIONS: Our genome-wide search in the informative, extended Utah pedigrees continues to illustrate an ability to identify and replicate linkage peaks, and supports four regions of interest for PrCa predisposition genes...

..abstract:..

..We used a population-based resource combining genealogical data for Utah with clinical diagnosis data from a large Utah hospital to test the hypothesis of excess familial clustering for rotator cuff disease...

..The Utah Population Database (UPDB) is unique; it links genealogy for over 2 million Utah individuals to a statewide Cancer Registry. We have investigated the familial nature of rectal cancer, considered independently from colon cancer...

..The low incidence of sarcomas in the general population makes heritable contribution to disease risk difficult to discern beyond highly penetrant Mendelian syndromes...

..Genes found might influence specific subtypes of MDD or broader phenotypes, leading to enhanced clinical characterization and management of MDD...

..To define a risk haplotype and map the CASP8 gene region with respect to underlying susceptibility variant/s, we screened four genes in the CASP8 region on 2q33-q34 for breast cancer risk...

..The purpose of the present study was to define population-based familial clustering among individuals with a diagnosis of, or treated for, lumbar disc herniation or disc degeneration...

..Although our sample size is small, this study is population based, lacks ascertainment and recall bias, and benefits from uniform, consistent diagnoses of all cancers in a statewide registry...

..These data provide strong support for a heritable contribution to predisposition to death due to influenza...

..Pelvic organ prolapse (POP) in women is a common condition whose etiology is poorly understood. There is increasing evidence that POP is heritable. The aim of our study was to define and evaluate familial clustering of POP...

..In particular, the correlation analysis of IBD expression patterns might hint to possible gene-gene interactions and the filtering might be a fruitful approach to distinguish true correlation signals from noise...

..K. case-control cohorts (Sheffield and Leeds) and a U.S. case-control study of CRC cases from high-risk Utah pedigrees...

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..This GenoMEL study provides the most extensive characterization of mutations in high-risk melanoma susceptibility genes in families with three or more melanoma patients yet available...

..component to many health and disease related traits not previously studied, and will eventually lead to the identification and understanding of disease predisposition, risk-modifying, and disease-associated and health-associated genes ..

..abstract_text> ..

..Someday, identification of these high risk populations may be as general as familial risk, or as specific as specific gene screening. ..

..component to many health and disease related traits not previously studied, and will eventually lead to the identification and understanding of disease predisposition, risk-modifying, and disease-associated and health-associated genes ..

..This proposal supports the University of Utah high-risk pedigree collection and analysis, and some Myriad genotyping effort towards this goal. ..

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..Someday, identification of these high risk populations may be as general as familial risk, or as specific as specific gene screening. ..