title: Lack of association of KATNAL1 gene sequence variants and azoospermia in humans.
abstract: OBJECTIVE
  A recent experiment indicated that a loss of function mutation in the murine Katnal1 gene resulted in male factor infertility due to premature exfoliation of spermatids. This study investigated the relevance of this gene to infertility in humans.
  
  
  METHODS
  Multiple methods of genetic analysis were employed to investigate whether mutations in human KATNAL1 have a causative role in male infertility. This was a genetic association study, which included DNA samples from 105 men with non-obstructive azoospermia (NOA) and 242 anonymous sperm donor controls. 28 commercially available TaqMan SNP assays were used to haplotype samples from both groups and genetically tag regions of interest across the entire gene. AmpliSeq primers were then designed for identified regions so that targeted next-generation sequencing (NGS) could be used to identify causative variants.
  
  
  RESULTS
  Four SNPs in the 3'UTR demonstrated a putative association with NOA. The AmpliSeq primers designed for the 3'UTR provided 83 % coverage of the 7,202 basepairs within the regions of interest. Variant sites were analyzed against genetic models to identify sequence polymorphisms which associated with NOA. No variants met standard criteria for significance when tested between the groups.
  
  
  CONCLUSIONS
  This study suggests a lack of association of KATNAL1 gene sequence variants and azoospermia in humans.
authors.affiliation: Department of Microbiology and Molecular Genetics, UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ, 08854-5635, USA, afedick@rmanj.com.
authors.forename: Anastasia M
authors.initials: AM
authors.lastname: Fedick
authors.forename: Kyle
authors.initials: K
authors.lastname: Eckert
authors.forename: Katharine
authors.initials: K
authors.lastname: Thompson
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Forman
authors.forename: Batsal
authors.initials: B
authors.lastname: Devkota
authors.forename: Nathan R
authors.initials: NR
authors.lastname: Treff
authors.forename: Deanne
authors.initials: D
authors.lastname: Taylor
authors.forename: Richard T
authors.initials: RT
authors.lastname: Scott
mesh_terms: D053713:Azoospermia / Q000235:genetics*; D016022:Case-Control Studies; D004247:DNA / Q000235:genetics; D010450:Endopeptidases / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007248:Infertility, Male / Q000235:genetics*; D000074201:Katanin; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D055101:Semen Analysis
chemical_list: D004247:DNA; D010450:Endopeptidases; C000600349:KATNAL1 protein, human; D000074201:Katanin