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Non-random asynchronous replication at 22q11.2 favours unequal meiotic crossovers leading to the human 22q11.2 deletion
- Source :
- Journal of Medical Genetics. 41:413-420
- Publication Year :
- 2004
- Publisher :
- BMJ, 2004.
-
Abstract
- Background: Analyses of the replication timing at 22q11.2 were prompted by our finding of a statistically significant bias in the origin of the regions flanking the deletion site in patients with 22q11.2 deletions, the proximal region being in the majority of cases of grandmaternal origin. We hypothesised that asynchronous replication may be involved in the formation of the 22q11.2 deletion, the most frequently occurring interstitial deletion in humans, by favouring the mispairing of low-copy repeats. Methods: Replication timing during S phase at 22q11.2 was investigated by fluorescent in situ hybridisation on interphase nuclei. We report on the detection of non-random asynchronous replication at the human chromosome region 22q11.2, an autosomal locus believed not to contain imprinted genes. Results: Asynchronous replication at 22q11.2 was observed without exception in all 20 tested individuals; these comprised individuals with structurally normal chromosomes 22 (10 cases), individuals with translocations involving the locus 22q11.2 (eight cases), and patients with a 22q11.2 deletion (two cases). The non-random nature of the asynchronous replication was observed in all individuals for whom the chromosomes 22 were distinguishable. The earlier replicating allele was found to be of paternal origin in all cases where the parental origin of the translocation or deletion was known.
- Subjects :
- DNA Replication
Male
2716 Genetics (clinical)
22q11.2 deletion
10039 Institute of Medical Genetics
Chromosomes, Human, Pair 22
610 Medicine & health
Chromosomal translocation
Locus (genetics)
Biology
Chromosomal crossover
1311 Genetics
Meiosis
Genetics
Humans
Crossing Over, Genetic
Allele
In Situ Hybridization, Fluorescence
Genetics (clinical)
Replication timing
Models, Genetic
DNA replication
Pedigree
LCR
570 Life sciences
biology
Female
Original Article
Chromosome Deletion
Genomic imprinting
Microsatellite Repeats
Subjects
Details
- ISSN :
- 14686244
- Volume :
- 41
- Database :
- OpenAIRE
- Journal :
- Journal of Medical Genetics
- Accession number :
- edsair.doi.dedup.....3684fbd89cdb3361ea879b8b9ad34691