title: Genetic variation in SPAG16 regions encoding the WD40 repeats is not associated with reduced sperm motility and axonemal defects in a population of infertile males.
abstract: BACKGROUND
  SPAG16 is a critical structural component of motile cilia and flagella. In the eukaryotic unicellular algae Chlamydomonas, loss of gene function causes flagellar paralysis and prevents assembly of the "9 + 2" axoneme central pair. In mice, we have previously shown that loss of Spag16 gene function causes male infertility and severe sperm motility defects. We have also reported that a heterozygous mutation of the human SPAG16 gene reduces stability of the sperm axonemal central apparatus.
  
  
  METHODS
  In the present study, we analyzed DNA samples from 60 infertile male volunteers of Western European (Italian) origin, to search for novel SPAG16 gene mutations, and to determine whether increased prevalence of SPAG16 single nucleotide polymorphisms (SNPs) was associated with infertility phenotypes. Semen parameters were evaluated by light microscopy and sperm morphology was comprehensively analyzed by transmission electron microscopy (TEM).
  
  
  RESULTS
  For gene analysis, sequences were generated covering exons encoding the conserved WD40 repeat region of the SPAG16 protein and the flanking splice junctions. No novel mutations were found, and the four SNPs in the assessed gene region were present at expected frequencies. The minor alleles were not associated with any assessed sperm parameter in the sample population.
  
  
  CONCLUSIONS
  Analysis of the SPAG16 regions encoding the conserved WD repeats revealed no evidence for association of mutations or genetic variation with sperm motility and ultrastructural sperm characteristics in a cohort of Italian infertile males.
authors.affiliation: Department of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, VA 23298, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Nagarkatti-Gude
authors.forename: Giulia
authors.initials: G
authors.lastname: Collodel
authors.forename: Lori D
authors.initials: LD
authors.lastname: Hill
authors.forename: Elena
authors.initials: E
authors.lastname: Moretti
authors.forename: Michela
authors.initials: M
authors.lastname: Geminiani
authors.forename: Zhibing
authors.initials: Z
authors.lastname: Zhang
authors.forename: Jerome F
authors.initials: JF
authors.lastname: Strauss
mesh_terms: D000595:Amino Acid Sequence; D015331:Cohort Studies; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D007248:Infertility, Male / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics*; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D013081:Sperm Motility / Q000235:genetics*
chemical_list: D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins; C450619:SPAG16 protein, human; C118067:WDR1 protein, human