Editor's Choice Academic Journal Main Category: Parkinson's Disease Also Included In: Genetics Article Date: 08 Oct 2012 - 0:00 PDT
Current ratings for: Parkinson's Risk Linked To Specific Genetic Variants
The researchers say they have carried out the first ever genome-wide evaluation of genetic variants linked to Parkinson's disease.
Jeanne Latourelle, DSc, and Richard H. Myers, PhD, explained that a recent study published by the PDGC (PD Genome Wide Association Study Consortium) had shown that people with genetic variants in or close to the genes HLA, MAPT, SNCA, RIT2, and GAK/DGKQ had a higher-than-average risk of developing Parkinson's disease. However, in that study, the mechanism behind the higher risk had not been determined.
Boston University School of Medicine reported in PLOS ONE in July 2012 that the FOXO1 gene plays an important part in the pathological mechanisms of Parkinson's disease. That study is said to have used the largest number of brain samples used in a wide-genome expression study of PD.
Latourelle suggested that perhaps a genetic variant might change how a gene is expressed in the brain, resulting in a higher risk of developing Parkinson's.
The scientists say that their findings may pave the way for treatments to correct the genetic variants and thus possibly reverse the effects of Parkinson's disease.
They determined gene expression by using a microarray that screened what the effects of genetic variants were on the expression of genes located very near the variant - called cis-effects - and genes that were far from the variant, such as genes on a totally different chromosome, called trans-effect. To recap - cis-effects are those on very nearby genes, while trans-effect are those on distant genes.
When they analyzed the cis-effects, it was observed that many genetic variants in the MAPT region showed a significant association with the expression of multiple nearby genes, including gene LOC644246, the duplicated genes LRRC37A and LRRC37A2, and the gene DCAKD.
They also observed significant cis-effects between variants in the HLA region on chromosome 6 and HLA-DQA1 and HLA-DQA1, two genes that were very near. When examining for trans-effects, they found 23 DNA sequence variations that were statistically significant in variants from the RIT2, MAPT, and SNCA genes.
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Parkinson's Risk Linked To Specific Genetic Variants
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