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pmokeefe
01-07-2021, 03:20 PM
A common 1.6 Mb Y-chromosomal inversion predisposes to subsequent deletions and severe spermatogenic failure in humans (https://www.medrxiv.org/content/10.1101/2020.12.08.20245928v1)

Pille Hallast, Laura Kibena, Margus Punab, Elena Arciero, Siiri Rootsi, Marina Grigorova, Rodrigo Flores, Mark A. Jobling, Olev Poolamets, Kristjan Pomm, Paul Korrovits, Kristiina Rull, Yali Xue, Chris Tyler-Smith, Maris Laan

Abstract
Male infertility is a prevalent condition, concerning 5-10% of men. So far, only some recurrent genetic factors have been described as confident 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 and Y-haplogroup determination. In analysing 2,324 Estonian men, we uncovered a novel structural variant as a high-penetrant risk factor to male infertility. The Y lineage R1a1-M458, reported at >20% frequency in several European populations, carries a fixed ∼1.6 Mb long r2/r3 inversion destabilizing the AZFc region and predisposing to recurrent microdeletions. Such complex rearrangements were significantly enriched among severe oligozoospermia cases. The carrier vs non-carrier risk to spermatogenic failure was increased 8.6-fold (p = 6.0 10−4). The finding contributes to improved molecular diagnostics and clinical management of infertility. Carrier identification in young age will facilitate timely counselling and reproductive decision-making

J Man
01-07-2021, 03:25 PM
Oufff lol

JoeyP37
01-07-2021, 05:39 PM
I think I speak for all M458 carriers when I say, is this some kind of sick joke? Although it would explain the extreme bottleneck.

Riverman
01-07-2021, 06:02 PM
I think I speak for all M458 carriers when I say, is this some kind of sick joke? Although it would explain the extreme bottleneck.

Even if true, it would just mean a significantly higher risk for one specific cause of infertility.

pmokeefe
04-13-2021, 12:20 AM
The published version of that preprint is out (https://elifesciences.org/articles/65420):
A common 1.6 mb Y-chromosomal inversion predisposes to subsequent deletions and severe spermatogenic failure in humans

Pille Hallast Is a corresponding author, Laura Kibena, Margus Punab, Elena Arciero, Siiri Rootsi, Marina Grigorova, Rodrigo Flores, Mark A Jobling, Olev Poolamets, Kristjan Pomm, Paul Korrovits, Kristiina Rull, Yali Xue, Chris Tyler-Smith, Maris Laan Is a corresponding author