PURPOSE: 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.
PURPOSE: A recent experiment indicated that a loss of function mutation in the murineKatnal1 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 humanKATNAL1 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: Andrew D Johnson; Robert E Handsaker; Sara L Pulit; Marcia M Nizzari; Christopher J O'Donnell; Paul I W de Bakker Journal: Bioinformatics Date: 2008-10-30 Impact factor: 6.937
Authors: J J Hartman; J Mahr; K McNally; K Okawa; A Iwamatsu; S Thomas; S Cheesman; J Heuser; R D Vale; F J McNally Journal: Cell Date: 1998-04-17 Impact factor: 41.582
Authors: Anika H D M Dam; Isabelle Koscinski; Jan A M Kremer; Celine Moutou; Anne-Sophie Jaeger; Astrid R Oudakker; Herman Tournaye; Nicolas Charlet; Clotilde Lagier-Tourenne; Hans van Bokhoven; Stephane Viville Journal: Am J Hum Genet Date: 2007-08-21 Impact factor: 11.025
Authors: Miriam Cerván-Martín; Lara Bossini-Castillo; Andrea Guzmán-Jiménez; Rocío Rivera-Egea; Nicolás Garrido; Saturnino Lujan; Gema Romeu; Samuel Santos-Ribeiro; José Antonio Castilla; María Del Carmen Gonzalvo; Ana Clavero; Vicente Maldonado; Francisco Javier Vicente; Miguel Burgos; Rafael Jiménez; Sara González-Muñoz; Josvany Sánchez-Curbelo; Olga López-Rodrigo; Iris Pereira-Caetano; Patricia Isabel Marques; Filipa Carvalho; Alberto Barros; Lluís Bassas; Susana Seixas; João Gonçalves; Sara Larriba; Alexandra Manuel Lopes; Rogelio Jesús Palomino-Morales; Francisco David Carmona Journal: Andrology Date: 2022-07-08 Impact factor: 4.456