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Fragile X founder chromosomes in Italy: A few initial events and possible explanation for their heterogeneity

Fragile X founder chromosomes in Italy: A few initial events and possible explanation for their... A total of 137 fragile X and 235 control chromosomes from various regions of Italy were haplotyped by analyzing two neighbouring marker microsatellites, FRAXAC1 and DXS548. The number of CGG repeats at the 5′ end of the FMR1 gene was also assessed in 141 control chromosomes and correlated with their haplotypes. Significant linkage disequilibrium between some “major” haplotypes and fragile X was observed, while other “minor” haplotypes may have originated by subsequent mutation at the marker microsatellite loci and/or recombination between them. Recent evidence suggests that the initial mechanism leading to CGG instability might consist of rare (10 6/‐7) CGG repeat slippage events and/or loss of a stabilizing AGG via A‐to‐C transversion. Also, the apparently high variety of fragile X chromosomes may be partly due to the relatively high mutation rate (10 −4/‐5) of the microsatellite markers used in haplotyping. Our fragile X sample also showed a higher than expected heterozygosity when compared to the control sample and we suggest that this might be explained by the chance occurrence of the few founding events on different chromosomes, irrespective of their actual frequency in the population. Alternatively, a local mechanism could enhance the microsatellite mutation rate only on fragile X chromosomes, or fragile X mutations might occur more frequently on certain background haplotypes. © 1996 Wiley‐Liss, Inc. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png American Journal of Medical Genetics Part A Wiley

Fragile X founder chromosomes in Italy: A few initial events and possible explanation for their heterogeneity

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References (59)

Publisher
Wiley
Copyright
Copyright © 1996 Wiley Subscription Services, Inc., A Wiley Company
ISSN
1552-4825
eISSN
1552-4833
DOI
10.1002/(SICI)1096-8628(19960712)64:1<209::AID-AJMG38>3.0.CO;2-P
pmid
8826478
Publisher site
See Article on Publisher Site

Abstract

A total of 137 fragile X and 235 control chromosomes from various regions of Italy were haplotyped by analyzing two neighbouring marker microsatellites, FRAXAC1 and DXS548. The number of CGG repeats at the 5′ end of the FMR1 gene was also assessed in 141 control chromosomes and correlated with their haplotypes. Significant linkage disequilibrium between some “major” haplotypes and fragile X was observed, while other “minor” haplotypes may have originated by subsequent mutation at the marker microsatellite loci and/or recombination between them. Recent evidence suggests that the initial mechanism leading to CGG instability might consist of rare (10 6/‐7) CGG repeat slippage events and/or loss of a stabilizing AGG via A‐to‐C transversion. Also, the apparently high variety of fragile X chromosomes may be partly due to the relatively high mutation rate (10 −4/‐5) of the microsatellite markers used in haplotyping. Our fragile X sample also showed a higher than expected heterozygosity when compared to the control sample and we suggest that this might be explained by the chance occurrence of the few founding events on different chromosomes, irrespective of their actual frequency in the population. Alternatively, a local mechanism could enhance the microsatellite mutation rate only on fragile X chromosomes, or fragile X mutations might occur more frequently on certain background haplotypes. © 1996 Wiley‐Liss, Inc.

Journal

American Journal of Medical Genetics Part AWiley

Published: Dec 12, 1996

Keywords: ; ; ; ;

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