The “faulty male” hypothesis: implications for evolution and disease DOI Creative Commons
Matthew W. Hahn, Yadira Peña-García, Richard Wang

et al.

Published: May 11, 2023

Biological differences between males and females lead to many in physiology, disease, overall health. One of the most prominent disparities is number germline mutations passed offspring: human transmit three times as do females. While classic explanation for this pattern invokes post-puberty replication sexes, recent whole-genome evidence humans other mammals has cast doubt on mechanism. Here, we review work that inconsistent with a replication-driven model male-biased mutation, propose an alternative, “faulty male” hypothesis. Importantly, suggest new mutation may also help explain several pronounced sexes cancer, aging, DNA repair. Although detailed contributions genetic, epigenetic, hormonal influences biological sex remain be fully understood, reconsideration mechanisms underlying these will deeper understanding evolution disease.

Language: Английский

A de novo nonsense variant in the DMD gene associated with X‐linked dystrophin‐deficient muscular dystrophy in a cat DOI Creative Commons
Nozomu Yokoyama, Yuki Matsumoto, Takahisa Yamaguchi

et al.

Journal of Veterinary Internal Medicine, Journal Year: 2024, Volume and Issue: 38(3), P. 1418 - 1424

Published: April 13, 2024

Abstract Background X‐linked dystrophin‐deficient muscular dystrophy (MD) is a form of MD caused by variants in the DMD gene. It fatal disease characterized progressive weakness and degeneration skeletal muscles. Hypothesis/Objectives Identify deleterious genetic whole‐genome sequencing (WGS) using next‐generation sequencer. Animals One MD‐affected cat, its parents, 354 cats from breeding colony. Methods We compared WGS data affected cat with available National Center for Biotechnology Information database searched candidate high‐impact silico analyses. Next, we confirmed Sanger samples parents used 2 genome assemblies, standard felCat9 (from an Abyssinian cat) novel AnAms1.0 American Shorthair cat), to evaluate assembly differences. Results found variants: 1‐bp deletion identical nonsense variant AnAms1.0. Whole validation showed that was false positive because misassembly. Among 357 cats, only which indicated it de novo variant. Conclusion Clinical Importance identified sequencing‐based genotyping whole gene determined be necessary did not have risk

Language: Английский

Citations

2
Naturally occurring genetic diseases caused by de novo variants in domestic animals DOI Creative Commons
Luı́sa Azevedo, Andreia P. Amaro, João Niza‐Ribeiro

et al.

Animal Genetics, Journal Year: 2024, Volume and Issue: 55(3), P. 319 - 327

Published: Feb. 7, 2024

Abstract With the advent of next‐generation sequencing, an increasing number cases de novo variants in domestic animals have been reported scientific literature primarily associated with clinically severe phenotypes. The emergence new at each generation is a crucial aspect understanding pathology early‐onset diseases and can provide valuable insights into similar humans. aim collecting deleterious animals, we searched compiled reports on 42 31 genes animals. No clear disease‐associated phenotype has established humans for three these ( NUMB , ANKRD28 KCNG1 ). For remaining 28 genes, strong similarity between animal human phenotypes was recognized from available information OMIM OMIA, revealing importance comparative studies supporting use as natural models diseases, line One Health approach.

Language: Английский

Citations

1
Characterization and distribution of de novo mutations in the zebra finch DOI Creative Commons
Xixi Liang, Shuai Yang, Daiping Wang

et al.

Communications Biology, Journal Year: 2024, Volume and Issue: 7(1)

Published: Oct. 2, 2024

Language: Английский

Citations

1
“Evolution of the mutation spectrum across a mammalian phylogeny” DOI Creative Commons
Annabel C. Beichman, Jacqueline A. Robinson, Meixi Lin

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: June 1, 2023

Little is known about how the spectrum and etiology of germline mutagenesis might vary among mammalian species. To shed light on this mystery, we quantify variation in mutational sequence context biases using polymorphism data from thirteen species mice, apes, bears, wolves, cetaceans. After normalizing mutation for reference genome accessibility

Language: Английский

Citations

3
The “faulty male” hypothesis: implications for evolution and disease DOI Creative Commons
Matthew W. Hahn, Yadira Peña-García, Richard Wang

et al.

Published: May 11, 2023

Biological differences between males and females lead to many in physiology, disease, overall health. One of the most prominent disparities is number germline mutations passed offspring: human transmit three times as do females. While classic explanation for this pattern invokes post-puberty replication sexes, recent whole-genome evidence humans other mammals has cast doubt on mechanism. Here, we review work that inconsistent with a replication-driven model male-biased mutation, propose an alternative, “faulty male” hypothesis. Importantly, suggest new mutation may also help explain several pronounced sexes cancer, aging, DNA repair. Although detailed contributions genetic, epigenetic, hormonal influences biological sex remain be fully understood, reconsideration mechanisms underlying these will deeper understanding evolution disease.

Language: Английский

Citations

2