Developmental and temporal characteristics of clonal sperm mosaicism.
Cell
; 184(18): 4772-4783.e15, 2021 09 02.
Article
en En
| MEDLINE
| ID: mdl-34388390
ABSTRACT
Throughout development and aging, human cells accumulate mutations resulting in genomic mosaicism and genetic diversity at the cellular level. Mosaic mutations present in the gonads can affect both the individual and the offspring and subsequent generations. Here, we explore patterns and temporal stability of clonal mosaic mutations in male gonads by sequencing ejaculated sperm. Through 300× whole-genome sequencing of blood and sperm from healthy men, we find each ejaculate carries on average 33.3 ± 12.1 (mean ± SD) clonal mosaic variants, nearly all of which are detected in serial sampling, with the majority absent from sampled somal tissues. Their temporal stability and mutational signature suggest origins during embryonic development from a largely immutable stem cell niche. Clonal mosaicism likely contributes a transmissible, predicted pathogenic exonic variant for 1 in 15 men, representing a life-long threat of transmission for these individuals and a significant burden on human population health.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Espermatozoides
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Crecimiento y Desarrollo
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Mosaicismo
Tipo de estudio:
Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Adolescent
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Adult
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Humans
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Male
Idioma:
En
Año:
2021
Tipo del documento:
Article