A whole-exome sequencing study of polymorphic teratozoospermia in multiplex consanguineous families

Almost half of the male infertility cases remain idiopathic indicating that despite careful physical and molecular examinations, no definitive cause can be identified. Due to its heterogenous nature, examination of various genes used to be an obstacle but with the advent of next-generation sequencing technology it is now a feasible option. We have identified a large family with a host of consanguineous marriages in which seven people have been diagnosed with polymorphic teratozoospermia whom share relatively similar phenotypes of sperm cells. Our objective is to determine a novel pathogenic variant by performing a family-based exome sequencing study.MethodsWhole-exome sequencing (WES) was performed on six people including four affected and two unaffected who are parents to affected. Sequencing run was performed on Illumina nextseq 500 platform. Resulting FASTQ files were checked for quality via FASTQC software. Burrows-Wheeler Aligner (BWA) was used to map the files against the hg19 reference genome provided by the UCSC Genome Browser. Output files were validated and sorted using the Picard tools package. Next steps of the analyses were performed in accordance with GATK best practices. Annotation of finalized VCF files was done via ANNOVAR.Results Candidate variants that co-segregate with the disease phenotype were double-checked by Sanger Sequencing and will be published very soon.Conclusion Since infertility involves various proteins working in concordance with each other, we hope our data can provide a new insight into its pathogenesis

Keywords:

Male infertility , teratozoospermia , Whole Exome Sequencing , family-based study , Next-generation Sequencing