Genetic Analysis Of Familial Cryptorchidism By Whole Exome Sequencing

Background: Cryptorchidism represents the most common congenital malformation in newborn boys. It is of public health importance because it may cause infertility in the human male, and it is a high risk factor for testicular cancer. Exome sequencing is a powerful strategy that can be applied to relatively few cases. To refine our knowledge of the genetic mechanisms involved in testicular descent, we carry out a strategy of exome sequencing to analyze the genetic inheritance in a cryptorchidism family.Methodology/Principal Findings: We sequenced the whole exome of two affected members of cryptorchidism family and one normal member of this family. Exon-enriched DNA was sequenced by the Illumina Genome Analyser II platform. As a result, 23,989 SNPs were detected in the patient sample, while 26,171 SNPs in patient's younger brother and 24,427 in patient's father. 14,597 SNPs were position shared between these three samples which including 3 SNPs of GREAT gene. Considering that GREAT gene involves in the pathway of neuroactive ligand-receptor interaction, we also found another 7 genes in the same pathway as GREAT gene were prone to mutate in cryptorchidism patients by clustering analysis. By excluding those SNPs present in the patient's younger brother from the shared SNPs and using the CHB/JPT data released as a part of 1000 Genome Project, we detected 39 non- synonymous SNPs. We then screened these SNPs in 10 other samples diagnosed with the same condition. As a result, one specific-mutation at gene FCGR3A is shown to mutate in all these 10 samples.Conclusions: Exome sequencing can be established as a good tool for uncovering the genetic causes of familial cryptorchidism. The specific-mutant in FCGR3A gene found can play an important role as disorder-specific mutant/gene in the genetic inheritance of familial cryptorchidism.