Forensic STRs as potential disease markers: A study of VWA and von Willebrand's Disease

Abstract 

In recent years it has been established that non-coding variants may be in linkage disequilibrium (LD) with coding variants up to several thousand base pairs away forming haplotype blocks. These non-coding markers may be haplotype specific and, therefore, informative regarding the surrounding coding sequence. In this study, we chose to study the VWA short tandem repeat (STR) as it is targeted in all major commercial kits utilized in routine forensic DNA profiling and is located in the von Willebrand Factor (vWF) gene; a gene associated with von Willebrand's Disease (vWD). We examined the VWA STR together with single nucleotide polymorphisms (SNPs) located throughout the vWF gene to identify haplotype structures and the extent of LD between markers in the region. Several areas exhibiting LD were identified by population data analysis in the 178kilobase (178kb) vWF gene, which was supported by family studies. However, there appeared to be no evidence of LD blocks surrounding the VWA STR and evidence for recombination within 3kb of VWA, hence, it is unlikely that VWA STR alleles could be used to predict haplotypes within the vWF gene that are associated with different forms of vWD.

Keywords: DNA profiling, VWA, vWF, vWD, Linkage disequilibrium, Haplotypes