Population WGS-based spinal muscular atrophy carrier screening in a cohort of 1076 healthy Polish individuals.

Spinal muscular atrophy is a severe neuromuscular disorder with an autosomal recessive inheritance pattern. The disease-causing gene is SMN1, and its paralogue, SMN2, is a disease course modifier. Both genes SMN1 and SMN2 show over 99.9% sequence identity and a high rate of crossing over in the genomic region. Due to this reason, SMN1/SMN2 is usually excluded from the whole-genome sequencing (WGS) analysis and investigated with traditional methods, such as MLPA and qPCR. Recently, novel bioinformatic algorithms dedicated to analyzing this particular genomic region have been developed. Here, we analyze the SMN1/SMN2 genomic region with a dedicated program, SMNCopyNumberCaller. We report a similar prevalence of SMN1 gene deletion carrier status (1 per 41 people) to published data from the Polish population (1 per 35 people). Additionally, SMNCopyNumberCaller can identify SMN2 CNVs and SMN2Δ7-8 present in 153 healthy Polish individuals. Two other programs for the CNV analysis in standard genomic regions were not able to provide reliable results. Using WGS-based tools for SMN1/2 genomic region analysis is not only an efficient method in terms of time but will also enable more complex analysis such screening for markers related with a silent carrier status and identification of further genetic modifiers. Although still an experimental method, soon WGS-based SMN1/SMN2 carrier identification may become a standard method for patients screened with WGS for other purposes.