Study of consanguineous populations can improve the annotation of SNP databases.

ABSTRACT

Our view of SNPs has evolved significantly from harmless mutational events that accumulated through the history of human race to important players in human health and disease. As a result, determining the pathologic vs. benign nature of SNPs on pure statistical basis is now viewed as too simplistic. Here, we show that two previously reported SNPs in COL6A2 and AGL represent disease-causing mutation for Ullrich Muscular Dystrophy and Glycogenosis type III, respectively, in homoallelic state. This report urges caution in interpreting SNPs in databases in the clinical genetics setting and calls for sequencing runs of homozygosity in healthy individuals as a promising approach to better annotate SNP databases.