Analysis of replication timing at the FRA10B and FRA16B fragile site loci

The molecular basis for the cytogenetic appearance of chromosomal fragile sites is not yet understood. Late replication and further delay of replication at fragile sites expressing alleles has been observed for FRAXA, FRAXE and FRA3B fragile site loci. We analysed the timing of replication at the FR...

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Bibliographic Details
Published in:Chromosome research 2000-01, Vol.8 (8), p.677-688
Main Authors: Handt, O, Baker, E, Dayan, S, Gartler, S M, Woollatt, E, Richards, R I, Hansen, R S
Format: Article
Language:English
Subjects:
Alleles
Cells, Cultured
Chromosome Fragile Sites
Chromosome Fragility - genetics
Chromosomes
DNA Replication - genetics
Flow Cytometry
Genetic Markers
Heterozygote
Humans
In Situ Hybridization, Fluorescence
Interphase - genetics
Lymphocytes - cytology
Lymphocytes - metabolism
Polymerase Chain Reaction
Repetitive Sequences, Nucleic Acid - genetics
Sequence Tagged Sites
Time Factors
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Summary:The molecular basis for the cytogenetic appearance of chromosomal fragile sites is not yet understood. Late replication and further delay of replication at fragile sites expressing alleles has been observed for FRAXA, FRAXE and FRA3B fragile site loci. We analysed the timing of replication at the FRA10B and FRA16B loci to determine whether late replication is a feature which is shared by all fragile sites and, therefore, is a necessary condition for chromosomal fragile site expression. The FRA10B locus was located in a transitional region between early and late zones of replication. Fragile and non-fragile alleles exhibit a similar replication pattern proximal to the repeat but fragile alleles are delayed relative to non-fragile ones on the distal side. Although fragility at FRA10B appears to be caused by expansion of an AT-rich repeat in the region, replication time near the repeat was similar in fragile and non-fragile alleles. The FRA16B locus was late replicating and appeared to replicate even later on fragile chromosomes. While these observations are compatible with the hypothesis that delayed replication may play a role in fragile site expression, they suggest that replication delay may not need to occur at the expanded repeat region itself in order to be permissive for fragility.
ISSN:0967-3849
1573-6849
DOI:10.1023/A:1026737203447