Low-frequency protamine 1 gene transversions c.102GT and c.–107GC do not correlate with male infertility.

Correspondence in Journal of Medical Genetics 2008 vol. 45 n°4Note/ Correspondenc dans J. Med. Genet.Iguchi et al,1 and Ravel et al.2 have proposed that, in the heterozygous state, the c.102GT and the c.-107GC transversions in the protamine 1 gene (PRM1), could be causes of human male infertility. Deleterious mutations in one allele of the human PRM1 gene are reasonably expected to have a dominant negative effect on male fertility, because in the mouse, germ cells carrying one null Prm1 allele do not produce viable gametes.3 In human PRM1 studies,1 2 however, several infertile men carried one of the two transversions, evoking the possibility of founder effects and therefore efficient transmission. To explore this apparent paradox, we screened 1195 infertile and control men for these two transversions, and conclude that neither has a significant effect on male fertility

HSFY genes and the P4 palindrome in the AZFb interval of the human Y chromosome are not required for spermatocyte maturation

International audienceBACKGROUND: Recurrent AZFb deletions on the human Y chromosome are associated with an absence of ejaculated spermatozoa consequent to a meiotic maturation arrest that prevents the progression of germ cells to haploid stages. The extreme rarity of partial deletions has hampered the identification of the AZFb genes required for normal meiotic stages. The critical interval, refined by two overlapping deletions associated with full spermatogenesis (AZFc and b1/b3), measures over 4 Mb and contains 13 coding genes: CDY2, XKRY, HSFY1, HSFY2, CYORF15A, CYORF15B, KDM5D, EIF1AY, RPS4Y2 and four copies of RBMY. METHODS AND RESULTS: We screened 1186 men from infertile couples for Y chromosome deletions, and identified three unrelated oligozoospermic men and one azoospermic man who carry an identical 768 kb deletion resulting in loss of the entire P4 palindrome, including both HSFY genes, the only coding genes within the deletion interval. This 768 kb deletion was not found in 1179 control men. The deletion breakpoints share only 4 bp of nucleotide identity, revealing that the deletions are not recurrent, but are descendants of a founding deletion. Confirming this, we find that all four men carry a Y chromosome of the same highly defined haplogroup (R1b1b1a1b) (incidence 30% in Southern France), although further haplotype analyses showed that they were not closely related. CONCLUSIONS: Although the HSFY deletion is restricted to our infertile group, it has been transmitted naturally over many generations, indicating that HSFY genes make only a slight contribution to male fertility. Importantly, our study formally excludes HSFY genes as the AZFb factor required for progression through meiosis