Y-haplotypes and idiopathic male infertility in an Indian population

Abstract

Infertility being a multifactorial disorder, both genetic and environmental factors contribute to the etiology of infertile phenotype. Chromosomal anomalies and Y-microdeletion are the established genetic risk factors of male infertility. Y-haplotypes has been found as risk factor for male infertility in certain populations, though in certain others no association has been reported, suggesting a population-specific association of these variations with male infertility. In a case-control study, 165 azoo-/oligospermic patients and 200 controls were haplotyped for certain Y-haplogroups for a possible association with idiopathic male infertility in an Indian population. Analysed Y-haplogroups showed no association with infertile phenotype. Thus this genetic factor is not a risk for infertility in the studied Indian population but that does not rule out the possibility of any of them, to be a risk in other populations.

Keywords: Male infertility; Y-haplotypes; single nucleotide polymorphism.

Figure 1

A representative illustration of haplotype analysis using 12f2 Indel marker. Haplotyping was done by PCR.[16] PCR assay generates a 427 bp product from chromosomes carrying the Taq I/10 kb allele but this product is absent from Taq I/8-kb allele chromosomes. An 800 bp amplicon from the SRY region, present in all the chromosomes, is amplified as a control. In the above agarose gel in pt #55 and pt #58 12f2 is deleted

Figure 2

M9 (C→G) haplotype was detected by PCR-RFLP.[11] The 340 bp PCR product after digestion with Hinf I yields 172 bp, 100 bp and 68 bp product for the wild type C allele and 240 bp and 100 bp products for mutant G allele (a). 92R7 (C→T) was also haplotyped by PCR-RFLP.[12] The 709 bp PCR product was digested with Hind III. 709bp, 512 bp and 197bp fragments were obtained for the wild type C allele whereas 709 bp product for the mutant T allele as it was not cut by the enzyme (b)

Figure 3

SRY 1532 (A→G→A) was haplotyped by PCR-RFLP method.[1314] 167 bp PCR product after digestion with Dra III yields 112bp and 55 bp products for the wild type A allele and the mutant G allele was not cut by the enzyme (c). RPS4Y (C→T) was haplotyped by PCR-RFLP.[15] 528 bp PCR product was digested with Bsl I and after digestion for wild type C allele 234 bp, 154 bp and 140 bp products were obtained whereas for mutant T allele 388bp and 140 bp products

Figure 4

Phylogenetic tree of SNPs’ and Indel marker used in the study and the haplogroup they define