Meiotic segregation analysis of RB1 alleles in retinoblastoma pedigrees by use of single-sperm typing

Détails

ID Serval
serval:BIB_31B716E3C2F0
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Meiotic segregation analysis of RB1 alleles in retinoblastoma pedigrees by use of single-sperm typing
Périodique
American Journal of Human Genetics
Auteur⸱e⸱s
Girardet  A., McPeek  M. S., Leeflang  E. P., Munier  F., Arnheim  N., Claustres  M., Pellestor  F.
ISSN
0002-9297 (Print)
Statut éditorial
Publié
Date de publication
01/2000
Volume
66
Numéro
1
Pages
167-75
Notes
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S. --- Old month value: Jan
Résumé
In hereditary retinoblastoma, different epidemiological studies have indicated a preferential paternal transmission of mutant retinoblastoma alleles to offspring, suggesting the occurrence of a meiotic drive. To investigate this mechanism, we analyzed sperm samples from six individuals from five unrelated families affected with hereditary retinoblastoma. Single-sperm typing techniques were performed for each sample by study of two informative short tandem repeats located either in or close to the retinoblastoma gene (RB1). The segregation probability of mutant RB1 alleles in sperm samples was assessed by use of the SPERMSEG program, which includes experimental parameters, recombination fractions between the markers, and segregation parameters. A total of 2,952 single sperm from the six donors were analyzed. We detected a significant segregation distortion in the data as a whole (P=.0099) and a significant heterogeneity in the segregation rate across donors (.0092). Further analysis shows that this result can be explained by segregation distortion in favor of the normal allele in one donor only and that it does not provide evidence of a significant segregation distortion in the other donors. The segregation distortion favoring the mutant RB1 allele does not seem to occur during spermatogenesis, and, thus, meiotic drive may result either from various mechanisms, including a fertilization advantage or a better mobility in sperm bearing a mutant RB1 gene, or from the existence of a defectively imprinted gene located on the human X chromosome.
Mots-clé
Adult Aged Aged, 80 and over Alleles Genotype Humans Male Meiosis Microsatellite Repeats/genetics Middle Aged Pedigree Polymerase Chain Reaction Retinal Neoplasms/*genetics Retinoblastoma/*genetics Retinoblastoma Protein/analysis/*genetics Spermatozoa/chemistry/cytology
Pubmed
Web of science
Open Access
Oui
Création de la notice
28/01/2008 12:54
Dernière modification de la notice
20/08/2019 13:17
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