Faculty Research

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Yvette P. Conley, PhD

Keywords:

• Genetics

Currently Funded Projects:

• The Genetic Basis of a Disease Free Model of Aging
• Dopamine Genetic Variants Modulating Recovery after TBI (Wagner)
• Biomarkers Evaluating and Treating Acute Chronic TBI
• Genetics of Age Related Maculopathy (Gorin)

Conley, Y.
07/15/05 –06/30/09

The Genetic Basis of a Disease Free Model of Aging

 Information is limited about the genetic factors participating in or mediating the pace of aging in humans. Such information would be valuable to our understanding of the biology of individual variation in the aging process, which could help us understand the mechanisms of longevity and have an impact on improving the health span of individuals. A significant problem in this regard is the lack of adequate disease independent biomarkers of aging to define as phenotypes. The aims of this exploratory project will assess the feasibility of utilizing the normal decline in lens transparency as a disease independent model of aging from the perspective of a genetic based study. The aims of this exploratory assessment will establish the feasibility, rationale, and research design details that will be utilized to inform the basis for a line of investigation that will involve identifying gene(s) and gene-environment interactions that participate in the aging process and rate of the aging process in humans using a disease independent model of aging. To accomplish the goals of this exploratory project,

quantitative lens transparency measurements, health, exposure and demographic data, and DNA will be collected from multigenerational families. The proband for each family will be recruited from an ongoing population based study, the Cardiovascular Health Study (CHS), which is a population based longitudinal study being conducted in adults aged 65 and older. Preliminary data from active CHS participants indicate that they are willing to contact their family members to participate in a study involving the genetics of aging; the majority have family structures that will be conducive to conducting this exploratory study. Approximately half of the active participants will have both of their original lens intact and available for measurement. This is the first study to propose lens transparency as a continuous, quantitative measure of the human aging process that will be suitable for genetic linkage and gene identification.

Conley, Y.
09*01/1993-03/31/2010
NEI

Genetics of Age Related Maculopathy (Gorin)

Age-related Maculopathy (ARM) is the leading cause of vision loss in the elderly population in the United States and Western world and is a major public health issue. Epidemiologic studies have indicated that heredity is a significant risk factor and family studies have further substantiated that ARM can be inherited as a dominant disease with late age of onset and variable expressivity. ARM is not well suited for traditional genetic investigations due to difficulties of clinical ascertainment and the small pedigrees because of its late onset. However, nonparametric Linkage methods including Affected Pedigree Member method and simIBD provide a means of determining genetic loci that contribute to ARM susceptibility using small and intermediate-sized families.

In our previous project we ascertained over 200 ARM families and are in the process of completing a candidate locus screening as well as a genome-wide scan of the first 120 families with 161 autosomal markers (average spacing of 20cM). We have established a classification system that allows us to evaluate a stringently defined ARM population as well as larger sets of patients with less severe and/or ambiguous phenotypes. Several markers used in the initial candidate gene screening and chromosome-wide panels have provided results that suggest linkage with ARM. These will be investigated during the next grant period.

We are proposing to expand our recruitment of ARM families to 1000 families and pursue a combination of genome-wide scans (200 and 350 families) with 20 cM resolution and focused genotyping based upon the tentative positively linked loci determined during the first grant period. The large number of families is necessary to confirm and further resolve potential ARM loci so that we can undertake candidate gene screening of our ARM population. The families that are not used in the genome-wide scans will be used for the focused genotyping effort, in the candidate gene screening program, and for disequilibrium linkage studies.

Co-Investigator:

Conley, Y.
09/24/04-06/30/09
NEI

NIH/NICHD, R01, “Dopamine Genetic Variants Modulating Recovery after TBI,” (Principal Investigator: A. Wagner, School of Health and Rehabilitation Sciences)

Conley, Y.
1/1/2008—11/30/2009
ARMY

U.S. Army, “Biomarkers Evaluating and Treating Acute and Chronic TBI,” (Principal Investigator: A. Wagner, School of Health and Rehabilitation Sciences)