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

Journal Article · Fri Jul 12 00:00:00 EDT 1996 · American Journal of Medical Genetics

DOI:https://doi.org/10.1002/(SICI)1096-8628(19960712)64:1<209::AID-AJMG38>3.0.CO;2-P· OSTI ID:476935

Chiurazzi, P; Genuardi, M; Kozak, L; Neri, G ^[1]

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1. Universita Cattolica and Centro Ricerche per la Disabilita Mentale e Motoria, Roma (Italy); and others

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.

• OSTI ID: 476935
• Journal Information: American Journal of Medical Genetics, Vol. 64, Issue 1; Other Information: PBD: 12 Jul 1996
• Country of Publication: United States
• Language: English

Related Subjects

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