Associations of PYGO2 and PRDM9 Genes Single Nucleotide Polymorphisms with Idiopathic Azoospermia in Iranian Population

Background One cause of infertility is azoospermia which affects about 1% of men in the general population. Non-obstructive azoospermia can be due to genetic disorders. Pygo2 and PRDM9 are two genes involved in spermatogenesis process. The aim of this study was to assess two single nucleotide polymorphism (SNPs) rs61758740, rs61758741 and rs2973631, rs1874165 in these genes respectively. Methods In this case-control study, a total of 100 Iranian patients with idiopathic azoospermia and 100 fertile control subjects were genotyped for Pygo2 rs61758740 and rs61758741 and PRDM9 rs2973631 polymorphism using Tetra-ARMS PCR. PRDM9 rs1874165 polymorphism was assessed by PCR-RFLP method. LH, FSH and testosterone concentrations were measured with electrochemical luminescence (ECL) method. Results Our data indicated a significant increase only in the FSH and LH hormone levels of patients which suggest that the cause of azoospermia is not pre-testicular. rs61758740 (T>C) polymorphism in Pygo2 gene was associated with increased risk of azoospermia (OR, 2.359; 95% Cl (1.192 – 4.666); p= 0.012). Also based on dominant model analysis in rs2973631 of PRDM9 gene, we identified a significant gene frequency difference between cases and control in dominant, recessive and codominant models but dominant, codominant and overdominant models was confirmed for rs1874165. Conclusion Our findings provide evidence for an association between Pygo2 and RDM9 genetic variation and idiophatic azoospermia in Iranian populations. Therefore, SNPs of these genes can be cosidered as a risk factor for male infertility.

Deviation from Hardy–Weinberg proportions in finite populations

SummaryFor a finite diploid population with no mutation, migration and selection, equations for the deviation of observed genotype frequencies from Hardy–Weinberg proportions are derived in this paper for monoecious species and for autosomal and sex-linked loci in dioecious species. It is shown that the genotype frequency deviation in finite random-mating populations results from the difference between the gene frequencies of male and female gametes, which is determined by two independent causes: the gene frequency difference between male and female parents and the sampling error due to the finite number of offspring. Previous studies have considered only one of the causes and the equations derived by previous authors are applicable only in the special case of random selection. The general equations derived here for both causes incorporate the variances and covariances of family size and thus they reduce to previous equations for random selection. Stochastic simulations are run to check the predictions from different formulae. Non-random mating and variation in census size are considered and the applications of the derived formulae are exemplified.