Greater prevalence of Y chromosome Q1a3a haplogroup in Y-microdeleted Chilean men: a case-control study

Abstract

Purpose: To determine the prevalence of South Amerindian Y chromosome in Chilean patients with spermatogenic failure and their association with classical and/or AZFc-partial Y chromosome deletions.

Methods: We studied 400 men, 218 with secretory azo/oligozoospermia (cases) and 182 controls (116 fertile and/or normozoospermic, and 66 azoospermic with normal spermatogenesis). After a complete testicular characterization (physical evaluation, hormonal and/or biopsy) peripheral blood was drawn to obtain DNA for Y chromosome microdeletions, AZFc-partial deletions and biallelic analysis by allele specific polymerase chain reaction (PCR) of the M3 (rs3894) single nucleotide polymorphism (SNP).

Results: Classical AZF microdeletions were found in 23 cases (Y-microdeleted). AZFc-partial deletions were observed in 10 cases (6 "gr/gr", 3 "b2/b3" and 1 "b1/b3") and 4 controls (4 "gr/gr"). The AZFc-partial deletions were mainly associated with the absence of DAZ1/DAZ2 (64 %). No significant differences in the prevalence of AZFc-partial deletions were observed between cases and controls. We observed a significant higher proportion of the Q1a3a haplogroup in Y-microdeleted men compared to patients with spermatogenic failure without deletions and control men (P<0.01 and P<0.05, respectively by Bonferroni test). Among them, patients with AZFb deletions had an increased prevalence of the Q1a3a haplogroup compared to controls, cases without deletions and to those with complete or partial-AZFc deletions (P<0.01, Bonferroni test).

Conclusions: The Q1a3a South Amerindian lineage seems to increase the susceptibility to non AZFc microdeletions. On the other hand, in Chilean population the AZFc-partial deletions ("gr/gr", "b1/b3" and/or "b2/b3") does not seem to predispose to severe spermatogenic impairment.

Fig. 1

Schematic Y chromosome structure and STS employed to detect deletions. a Schematic view of the Y-chromosome with pseudoautosomal regions (PAR) 1 and 2, palindromes 1–8, centromere, heterochromatin regions, inverted repeat IR and the chromosomal position of the DYS199 locus as depicted in Lange et al. [28]. b Expanded view of AZFs regions. c The AZFb and AZFc amplicon structure is drawn according to the color code of Kuroda-Kawaguchi et al. [27]. In (a) and (c) are shown the location of the principal STS and locus analyzed for the screening of AZFs microdeletion and AZFc partial deletions of the Y chromosome. d Exemplary results of PCR-based analysis in patients with AZFa, AZFb, AZFc or AZFb+c microdeletion. Black bar: STS/locus present. Lines: STS/locus absent. Gray lines: STS/locus that normally amplifies by PCR but assumed to be absent in the context of deletion pattern