The cumulative impact of rare variants on common diseases is currently unknown, but recent studies have implicated rare genetic variants in many complex diseases. Consequently, it has been suggested that the combined effect of rare deleterious mutations could explain a substantial fraction of genetic susceptibility to many common diseases. Genome-wide association studies (GWAS) can interrogate the association of up to 1 million common single nucleotide polymorphisms (SNPs) with risk for disease or other phenotypes. However, the GWAS approach can only identify common variation; it is not designed to detect multiple rare variants in the same gene.
Only by resequencing candidate genes in a large population these variants can be identified. In the lab we are using the second-generation sequencing technology to identify rare variants implicated in Alzheimer’s and Parkinson’s disease. We are using both, targeted and whole-exome sequencing to identify novel pathogenic variants and sequences variants that influence age at onset and disease progression.