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West Virginia IDeA Network of Biomedical
Research Excellence |
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Mark Flood
Fairmont State UniversityGenetic
Basis for Familial Combined Hyperlipidemia
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 Abstract: Familial Combined
Hyperlipidemia (FCHL) affects 1-2% of the population on Westernized
societies and is most common genetic lipid disorder in patients with
coronary artery disease (CAD). Because of their high incidence of
CAD West Virginians may be at greater risk for this disorder
compared to the general US population. Our long-range goal is to
gain an understanding of the molecular and cellular events that lead
to disregulation of cholesterol and lipid levels and how the events
predispose to atherosclerosis. The overall objective of this project
is to identify gene(s) that predispose to FCHL using family-based
linkage analysis and population-based association methods. The
central hypotheses are that there are specific genes that confer
susceptibility to FCHL and that there is genetic heterogeneity (i.e.
more than one gene or set of genes can give rise to the disease).
Our first specific aim is to identify FCHL susceptibility loci by
linkage analysis on a genome-wide set of makers and on a small set
of previously identified FCHL candidate loci. Families with FCHL
will be ascertained by identifying individuals with a defined
phenotype. Parametric and nonparametric linkage analysis methods
will be utilized to determine which loci contribute to FCHL in WV
population. Our second aim is to obtain a genetic fine mapping on
the susceptibility loci in order to narrow the region of interest.
Association of the disease phenotype with single nucleotide
polymorphisms (SNPs) that are known to map to the region of interest
will be assessed using the Pedigree Disequilibrium Test (PDT) and
TRANSMIT. Finally we will screen for positional candidate genes
within the region of interest using molecular and bioinformatics
approaches. It is expected that this study will uncover novel loci
and specific genes at those loci that contribute to the development
of FCHL. The results of this proposal will be significant because
they will further the understanding of the pathogenesis of vascular
disease and because these susceptibility genes represent new targets
for preventative and therapeutic interventions. |
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