Can the male germline offer insight into mammalian brain size expansion? DOI
Stephen J. Bush, Anne Goriely

Andrology, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 18, 2024

Abstract Recent advances in single‐cell transcriptomic data have greatly expanded our understanding of both spermatogenesis and the molecular mechanisms male infertility. However, this growing wealth could also shed light on a seemingly unrelated biological problem: genetic basis mammalian brain size expansion throughout evolution. It is now increasingly recognized that testis share many cellular similarities including pivotal roles for RAS/MAPK PI3K/AKT/mTOR pathways, mutations which are known to pronounced impact cell proliferation. Most notably, stem lineages organs, new been shown increase output over time. These include ‘selfish’ spermatogonial cells, disproportionately proportion mutant sperm, and—to draw parallel—human‐specific neural cells which, by increasing number neurons, implicated neocortical expansion. Here we speculate origin ‘expansion’‐associated germline as such, deeper controlling testicular turnover may yield fresh insight into biology evolution brain.

Language: Английский

SMAD4 Pathogenic Variants in Seven New Brazilian Individuals With Myhre Syndrome Including a New Family DOI Creative Commons

Samira Spineli‐Silva,

Larissa Bretanha Pontes,

Nicole de Leeuw

et al.

American Journal of Medical Genetics Part A, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 15, 2025

Myhre syndrome is a rare disorder caused by pathogenic gain-of-function variants in the SMAD4 gene. Most of patients have had de novo variants. There are several instances autosomal dominant inheritance, and penetrance appears to be complete. We describe seven Brazilian patients, three whom siblings carrying recurrent c.1486C>T p.(Arg496Cys) variant inherited from father. The other unrelated simplex cases. All affected individuals clinical features commonly found syndrome, including typical dysmorphic facial features, with intra- interfamilial heterogeneity. Five developmental delay and/or signs intellectual disability. However, only one neuropsychological testing. Only patient diagnosis autism spectrum disorder. As previously reported families, this new family has same variant. This first study describing highlighting variability disease. reinforce need investigate parents provide appropriate genetic counseling.

Language: Английский

Citations

0
Thick skin and thicker arteries: case report on a rare cause of hypertension DOI
Georgie Mathew, Srinivasavaradan Govindarajan,

Swathi Kiran Shiri

et al.

Pediatric Nephrology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 27, 2025

Language: Английский

Citations

0
Sperm sequencing reveals extensive positive selection in the male germline DOI Creative Commons
Matthew D. C. Neville, Andrew Lawson, Rashesh Sanghvi

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 1, 2024

Abstract Mutations that occur in the cell lineages of sperm or eggs can be transmitted to offspring. In humans, positive selection driver mutations during spermatogenesis is known increase birth prevalence certain developmental disorders. Until recently, characterising extent this has been limited by error rates sequencing technologies. Using duplex method NanoSeq, we sequenced 81 bulk samples from individuals aged 24 75 years. Our findings revealed a linear accumulation 1.67 (95% CI = 1.41-1.92) per year haploid genome, driven two mutational signatures associated with human ageing. Deep targeted and exome NanoSeq identified over 35,000 germline coding mutations. We detected 40 genes (31 novel) under significant male germline, implicating both activating loss-of-function mechanisms diverse cellular pathways. Most positively selected are cancer predisposition disorders children, while four exhibit elevated frequencies protein-truncating variants healthy populations. find drives 2-3 fold risk disease-causing sperm, resulting 3-5% middle-aged elderly carrying pathogenic mutation across exome. These shed light on dynamics highlight broader increased disease for children born fathers advanced age than previously appreciated.

Language: Английский

Citations

2
Can the male germline offer insight into mammalian brain size expansion? DOI
Stephen J. Bush, Anne Goriely

Andrology, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 18, 2024

Abstract Recent advances in single‐cell transcriptomic data have greatly expanded our understanding of both spermatogenesis and the molecular mechanisms male infertility. However, this growing wealth could also shed light on a seemingly unrelated biological problem: genetic basis mammalian brain size expansion throughout evolution. It is now increasingly recognized that testis share many cellular similarities including pivotal roles for RAS/MAPK PI3K/AKT/mTOR pathways, mutations which are known to pronounced impact cell proliferation. Most notably, stem lineages organs, new been shown increase output over time. These include ‘selfish’ spermatogonial cells, disproportionately proportion mutant sperm, and—to draw parallel—human‐specific neural cells which, by increasing number neurons, implicated neocortical expansion. Here we speculate origin ‘expansion’‐associated germline as such, deeper controlling testicular turnover may yield fresh insight into biology evolution brain.

Language: Английский

Citations

0