Lobular breast cancer: excess familiality observed in the Utah Population Database.

Family history of breast cancer (BC) is a strong predictor for developing female BC. Whether this excess familiality differs within morphological BC subgroups remains unclear. We assessed the risk of lobular breast cancer (LOB) and any BC among relatives of probands with LOB.

Examination of ELN as a candidate gene in the Utah intracranial aneurysm pedigrees.

Background And Purpose: A study of intracranial aneurysm (IA) sibpairs suggested association of an ELN haplotype with IA risk. 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.

Methods: We have investigated the ELN gene as a potential candidate gene for IA in Utah pedigrees.

Genome-wide linkage analyses of extended Utah pedigrees identifies loci that influence recurrent, early-onset major depression and anxiety disorders.

Major depressive disorder (MDD) is a common, clinically heterogeneous disorder often found comorbid with other disorders. We studied recurrent, early-onset MDD (MDD-RE) and anxiety disorders in combination to define powerful phenotypes for genetic study. We used 87 large, extended Utah pedigrees to investigate linkage to 3 phenotypes: "MDD-RE;" "MDD-RE or anxiety;" and "MDD-RE and anxiety;" where in the latter definition the disorders must appear comorbid within an individual.

Dissecting the genetic etiology of major depressive disorder using linkage analysis.

Major depressive disorder (MDD) is clinically and genetically heterogeneous. Studies suggest that recurrence, early onset and comorbid phenotypes define more genetically homogeneous sub-samples. The concordance of linkage findings in recent studies using such approaches is encouraging.

Characterization of linkage disequilibrium structure, mutation history, and tagging SNPs, and their use in association analyses: ELAC2 and familial early-onset prostate cancer.

In association analyses, it is critical that informative single-nucleotide polymorphisms (SNPs) be selected for study and utilized appropriately. We sequenced 38 kb, including exons of ELAC2, promoter region and conserved upstream intergenic sequences. A comprehensive characterization of linkage disequilibrium (LD) structure and mutation history was performed using our principal components analysis (PCA) method and a phylogenetic analysis.

Evidence for a heritable component in death resulting from aortic and mitral valve diseases.

Background: Cardiac valvular diseases contribute to >42,000 deaths yearly in the United States, but the role of genetics in these deaths is unknown. This study evaluated the familiality of death resulting from aortic, mitral, and all valvular diseases using a population-based genealogy linked to death records.

Methods And Results: The Utah Population Database contains >2 million individual records with genealogy data and 250,000 linked death certificates.

Longitudinal assessment of the nevus phenotype in a melanoma kindred.

Phenotypic characteristics of members of a melanoma prone kindred with a V126D CDKN2A gene mutation were monitored over approximately 15 y. Thirty-eight previously studied subjects were recruited. Participants underwent a complete skin examination by the same dermatologist who examined them initially.

Predisposition locus for major depression at chromosome 12q22-12q23.2.

Major depression disorder is a common psychiatric disease with a major economic impact on society. In many cases, no effective treatment is available. The etiology of major depression is complex, but it is clear that the disease is, to a large extent, determined genetically, especially among individuals with a familial history of major depression, presumably through the involvement of multiple predisposition genes in addition to an environmental component.

Confirmation of chromosome 7q11 locus for predisposition to intracranial aneurysm.

A significant linkage of intracranial aneurysm (IA) has recently been reported to chromosomal region 7q11 (MLS=3.22) in a genomic search of 85 Japanese nuclear families with at least two affected siblings (104 sib pairs). This region contains the elastin gene (ELN, OMIM 130160), which is a functional candidate gene for IA.

A genealogical assessment of heritable predisposition to aneurysms.

Object: This study was conducted to investigate the familial and genetic contribution to intracranial, abdominal aortic, and all other types of aneurysms, and to define familial relationships among patients who present with the different aneurysm types.

Methods: The authors used a unique Utah resource to perform population-based analysis of the familial nature of aneurysms. The Utah Population Data Base is a genealogy of the Utah population dating back eight generations, which is combined with death certificate data for the state of Utah dating back to 1904.

Characterization of common BRCA1 and BRCA2 variants.

Many missense variants identified in BRCA1 and BRCA2, two genes responsible for the majority of hereditary breast and ovarian cancer, are of unclear clinical significance. Characterizing the significance of such variants is important for medical management of patients in whom they are identified. The aim of this study was to characterize eight of the most common reported missense mutations in BRCA1 and BRCA2 occurring in patients tested for hereditary risk of breast and ovarian cancers.