Ellen M. Wijsman
Research Program:ALS/PDC Guam
This project is not currently active, but is here to illustrate the advantages of use of genetic isolates for gene mapping.
Among the Chamorro people of Guam, there exists an unusual neurodegenerative disease known as amyotrophic lateral sclerosis (ALS) and Parkinsonian Dementia Complex (PDC) or ALS/PDC (each is considered a different clinical manifestation of the same disease). While the effects of ALS/PDC as observed in the Chamorro are similar (if not identical) to those observed in other parts of the world, this version is neuropathologically unique in that neurofibrillary tangles are observed in the cortex and spinal cord of the afflicted.
The goal of this study was to identify the genetic susceptibility factors involved in ALS/PDC.
To this end, we performed a genome screen of ALS/PDC in this population. Because of the unique
history of this population, which includes a recent population bottleneck, we used linkage
disequilibrium screening methods in addition to pedigree linkage analysis methods. The complexity
of the pedigree required use of computationallly intensive MCMC-based methods for analysis. We
found evidence for two loci contributing to disease risk. We also
found extensive cryptic relatedness in the population, which in retrospect is not surprising
in a relatively small population! This
lead to development of methods to accomodate such structure to allow case-control testing
The results for the genome scan are in: Sieh et al (2009) Human Molecular Genetics, 18:3725-3738.
The methods for accomodating cryptic relatedness are in: Choi et al (2009) Case-control association testing in the presence of unkown relationships. Genetic Epidemiology 35:668-678.