Somatic mutation processes at a human minisatellite.
Hum Mol Genet
; 6(1): 129-32; 134-6, 1997 Jan.
Article
em En
| MEDLINE
| ID: mdl-9002681
ABSTRACT
Germline instability at human minisatellites frequently involves complex inter-allelic transfers of repeat units usually restricted to one end of the repeat array and apparently regulated by flanking DNA. In contrast, nothing is known about the structural basis of somatic instability at minisatellites. An electrophoretic size-enrichment strategy was therefore developed at minisatellite MS32 (D1S8) to enable rare abnormal-length mutants to be detected, validated and quantitated in blood DNA by single molecule PCR. Structural analysis of rare mutant alleles in blood revealed simple deletions/duplications of repeat unit blocks located at random along the tandem repeat array, a mode of mutation completely different from that seen in sperm. Furthermore, allele-specific suppression of sperm instability at MS32 did not affect somatic instability. These data suggest that conversion-based minisatellite mutation in sperm is completely germline-specific and most likely meiotic in origin. Somatic instability appears to occur by a separate pathway involving replication slippage or, more likely, intra-allelic unequal crossing over.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
DNA Satélite
/
Mutagênese
/
Repetições de Microssatélites
Limite:
Humans
/
Male
Idioma:
En
Revista:
Hum Mol Genet
Assunto da revista:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Ano de publicação:
1997
Tipo de documento:
Article
País de afiliação:
Reino Unido