Genome-wide screening for smallest regions of overlaps in cryptorchidism

Cryptorchidism is a urogenital abnormality associated with increased rates of testicular neoplasia and impaired spermatogenesis. The field is facing expansion of genomics data; however, it lacks protocols for biomarker prioritization. Identification of smallest regions of overlap (SRO) presents an approach for candidate gene identification but has not yet been systematically conducted in cryptorchidism. The aim of this study was to conduct a genome-wide screening for SRO (GW-SRO) associated with cryptorchidism development. We updated the Cryptorchidism Gene Database to version 3, remapped genomic coordinates of loci from older assemblies to the GRCh38 and performed genome-wide screening for overlapping regions associated with cryptorchidism risk. A total of 73 chromosomal loci (68 involved in chromosomal mutations and five copy number variations) described in 37 studies associated with cryptorchidism risk in humans were used for SRO identification. Analysis resulted in 18 SRO, based on deletions, duplications, inversions, derivations and copy number variations. Screening for SRO was challenging owing to heterogeneous reporting of genomic locations. To our knowledge, this is the first GW-SRO study for cryptorchidism and it presents the basis for further narrowing of critical regions for cryptorchidism and planning functional experiments. The developed protocol could also be applied to other multifactorial diseases.