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
1 Department of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, 23298, VA, USA
2 Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, 23298, VA, USA
3 Department of Biomedical Sciences, Applied Biology Section; Interdepartmental Centre for Research and Therapy of Male Infertility, University of Siena, Policlinico Le Scotte, Siena, 53100, Italy
4 Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, USA
5 MCV Campus, Sanger Hall, 1st Floor, Room 1-071, 1101 East Marshall Street, PO Box 980565, Richmond, 23298, VA, USA
BMC Urology 2012, 12:27 doi:10.1186/1471-2490-12-27Published: 10 September 2012
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.
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).
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.
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.