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View Full Version : R1a1-M458 linked to male infertility



traveller
31-03-21, 07:26
A common 1.6 mb Y-chromosomal inversion predisposes to subsequent deletions and severe spermatogenic failure in humans


Abstract

Male infertility is a prevalent condition, affecting 5–10% of men. So far, few genetic factors have been described as contributors to spermatogenic failure. Here, we report the first re-sequencing study of the Y-chromosomal Azoospermia Factor c (AZFc) region, combined with gene dosage analysis of the multicopy DAZ, BPY2, and CDYgenes and Y-haplogroup determination. In analysing 2324 Estonian men, we uncovered a novel structural variant as a high-penetrance risk factor for male infertility. The Y lineage R1a1-M458, reported at >20% frequency in several European populations, carries a fixed ~1.6 Mb r2/r3 inversion, destabilizing the AZFc region and predisposing to large recurrent microdeletions. Such complex rearrangements were significantly enriched among severe oligozoospermia cases. The carrier vs non-carrier risk for spermatogenic failure was increased 8.6-fold (p=6.0×10−4). This finding contributes to improved molecular diagnostics and clinical management of infertility. Carrier identification at young age will facilitate timely counselling and reproductive decision-making.

https://elifesciences.org/articles/65420

traveller
31-03-21, 07:32
Considering how widespread M458 is, it appears our ancestors have successfully navigated around the genetic risks...

Maciamo
31-03-21, 12:20
It depends on the deep clade too.

https://iiif.elifesciences.org/lax:65420%2Felife-65420-fig2-v1.tif/full/617,/0/default.jpg