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

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{prime} end of the FMR1 gene was also assessed in 141 control chromosomes and correlated with their haplotypes. Significant linkage disequilibrium between some {open_quotes}major{close_quotes} haplotypes and fragile X was observed, while other {open_quotes}minor{close_quotes} 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{sup -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{sup -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,more » or fragile X mutations might occur more frequently on certain background haplotypes. 59 refs., 4 figs.« less

Authors:
; ; ;  [1]
  1. Universita Cattolica and Centro Ricerche per la Disabilita Mentale e Motoria, Roma (Italy); and others
Publication Date:
OSTI Identifier:
476935
Resource Type:
Journal Article
Journal Name:
American Journal of Medical Genetics
Additional Journal Information:
Journal Volume: 64; Journal Issue: 1; Other Information: PBD: 12 Jul 1996
Country of Publication:
United States
Language:
English
Subject:
55 BIOLOGY AND MEDICINE, BASIC STUDIES; HUMAN X CHROMOSOME; BIOLOGICAL EVOLUTION; GENETIC MAPPING; CHROMOSOMAL ABERRATIONS; MUTATION FREQUENCY; NUCLEOTIDES; MUTATIONS; MENTAL DISORDERS; ETIOLOGY; PATIENTS; HEREDITARY DISEASES; GENES; GENE MUTATIONS; GENE RECOMBINATION; DNA SEQUENCING; ITALY; BIOLOGICAL MARKERS; POLYMERASE CHAIN REACTION; RFLPS

Citation Formats

Chiurazzi, P, Genuardi, M, Kozak, L, and Neri, G. Fragile X founder chromosomes in Italy: A few initial events and possible explanation for their heterogeneity. United States: N. p., 1996. Web. doi:10.1002/(SICI)1096-8628(19960712)64:1<209::AID-AJMG38>3.0.CO;2-P.
Chiurazzi, P, Genuardi, M, Kozak, L, & Neri, G. Fragile X founder chromosomes in Italy: A few initial events and possible explanation for their heterogeneity. United States. https://doi.org/10.1002/(SICI)1096-8628(19960712)64:1<209::AID-AJMG38>3.0.CO;2-P
Chiurazzi, P, Genuardi, M, Kozak, L, and Neri, G. 1996. "Fragile X founder chromosomes in Italy: A few initial events and possible explanation for their heterogeneity". United States. https://doi.org/10.1002/(SICI)1096-8628(19960712)64:1<209::AID-AJMG38>3.0.CO;2-P.
@article{osti_476935,
title = {Fragile X founder chromosomes in Italy: A few initial events and possible explanation for their heterogeneity},
author = {Chiurazzi, P and Genuardi, M and Kozak, L and Neri, G},
abstractNote = {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{prime} end of the FMR1 gene was also assessed in 141 control chromosomes and correlated with their haplotypes. Significant linkage disequilibrium between some {open_quotes}major{close_quotes} haplotypes and fragile X was observed, while other {open_quotes}minor{close_quotes} 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{sup -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{sup -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. 59 refs., 4 figs.},
doi = {10.1002/(SICI)1096-8628(19960712)64:1<209::AID-AJMG38>3.0.CO;2-P},
url = {https://www.osti.gov/biblio/476935}, journal = {American Journal of Medical Genetics},
number = 1,
volume = 64,
place = {United States},
year = {Fri Jul 12 00:00:00 EDT 1996},
month = {Fri Jul 12 00:00:00 EDT 1996}
}