Pitfall of identifying a disease locus by using low-resolution SNP arrays

Until recently, a whole-genome scan using a set of 300400 polymorphic DNA microsatellite markers was considered the most favoured strategy for gene mapping in Mendelian disorders. In many situations, however, it has not been possible to unravel significant disease loci by using DNA markers spaced across the genome at 10 cM intervals. Nowadays, to facilitate gene mapping or genome-wide association studies, several high-density SNP genotyping arrays with different SNP marker densities have been developed. These technologies offer highly-automated and rapid methods of genotyping as compared with genotyping microsatellites by PCR. For disease locus identification these data could be analysed by various methods, such as parametric multipoint linkage analysis and, in particular, homozygosity mapping for autosomal recessive inherited disorders in consanguineous families (Hugun et al, 2010). Homozygosity mapping is a powerful tool to detect disease loci, particularly in consanguineous pedigrees. Here, we have discussed a pitfall of this approach, namely the incapacity to detect the disease locus by the use of an Affymetrix 50K Xba I SNP array (50K array) in a highly-informative pedigree.