The Sins of Our Forefathers: Paternal Impacts on De Novo Mutation Rate and Development.
Annu Rev Genet
; 54: 1-24, 2020 11 23.
Article
en En
| MEDLINE
| ID: mdl-32663048
ABSTRACT
Spermatogonial stem cells (SSCs) are generally characterized by excellent DNA surveillance and repair, resulting in one of the lowest spontaneous mutation rates in the body. However, the barriers to mutagenesis can be overwhelmed under two sets of circumstances. First, replication errors may generate age-dependent mutations that provide the mutant cells with a selective advantage, leading to the clonal expansions responsible for dominant genetic diseases such as Apert syndrome and achondroplasia. The second mechanism centers on the vulnerability of the male germline to oxidative stress and the induction of oxidative DNA damage in spermatozoa. Defective repair of such oxidative damage in the fertilized oocyte results in the creation of mutations in the zygote that can influence the health and well-being of the offspring. A particular hot spot for such oxidative attack on chromosome 15 has been found to align with several mutations responsible for paternally mediated disease, including cancer, psychiatric disorders, and infertility.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Enfermedades Genéticas Congénitas
/
Mutación
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Annu Rev Genet
Año:
2020
Tipo del documento:
Article