|
Systemic lupus erythematosus (SLE) is a serious, chronic
disease characterized by familial aggregation suggesting a
strong genetic component. Indeed, eleven genetic linkages
have been established (lod>3.3 or p<0.00002), demonstrating
the complexity of the genetics of SLE. Most of these
linkages are race specific. The unique history and
population characteristics of Puerto Rico, with genetic
admixture and geographic isolation, combine to provide an
opportunity for investigating the etiology of SLE. The
population of Puerto Rico experienced a bottleneck soon
after Western contact when there may have been as few as
2500 founders. Subsequent episodic immigration of Europeans
and Africans has resulted in a current population of 4
million composed of 18% Taino Indians, 45% European and 37%
African. We will use capture-recapture methods to identify
probands to determine population-based estimates of
incidence and prevalence, relationship-specific recurrence
rates, confirmation of birth order and other observations
concerning family structure and environmental exposure of
SLE in Puerto Rico. We propose a genetic association study
that will take advantage of the unique history and
population characteristics of Puerto Rico. A genome scan
using 330 standard micro satellite markers will be perform
to discover markers and haplotypes associated with the SLE
in the Puerto Rican population. We will confirm these
initial genetic associations by using estimating association
with neighboring genetic markers and work toward gene
identification in these areas of genetic association. Also,
we will compare evidence of association at those chromosome
regions suggested to be associated with SLE in the US
population with the evidence in the Puerto Rican population.
This study will provide new observations concerning SLE, and
perhaps, new genetic effects. In addition, this study has
the potential to establish that the unique history and
population characteristics of Puerto Rico can be used for
genetic discovery in any phenotype and will help to build
genetic studies in Puerto Rico.
|
