Meiotic Chromosome Structure, the Synaptonemal Complex, and Infertility.
Annu Rev Genomics Hum Genet
; 24: 35-61, 2023 08 25.
Article
em En
| MEDLINE
| ID: mdl-37159901
ABSTRACT
In meiosis, homologous chromosome synapsis is mediated by a supramolecular protein structure, the synaptonemal complex (SC), that assembles between homologous chromosome axes. The mammalian SC comprises at least eight largely coiled-coil proteins that interact and self-assemble to generate a long, zipper-like structure that holds homologous chromosomes in close proximity and promotes the formation of genetic crossovers and accurate meiotic chromosome segregation. In recent years, numerous mutations in human SC genes have been associated with different types of male and female infertility. Here, we integrate structural information on the human SC with mouse and human genetics to describe the molecular mechanisms by which SC mutations can result in human infertility. We outline certain themes in which different SC proteins are susceptible to different types of disease mutation and how genetic variants with seemingly minor effects on SC proteins may act as dominant-negative mutations in which the heterozygous state is pathogenic.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Complexo Sinaptonêmico
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Infertilidade
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article