The same molecular mechanism at the maternal meiosis I produces mono- and dicentric 8p duplications
- Universita di Pavia (Italy); and others
We studied 16 cases of 8p duplications, with a karyotype 46,XX or XY,dup(8p), associated with mental retardation, facial dysmorphisms, and brain defects. We demonstrate that these 8p rearrangements can be either dicentric (6 cases) with the second centromere at the tip of the short arm or monocentric (10 cases). The distal 8p23 region, from D8S349 to the telomere, including the defensin 1 locus, is deleted in all the cases. The region spanning from D8S252 to D8S265, at the proximal 8p23 region, is present in single copy, and the remaining part of the abnormal 8 short arm is duplicated in the dicentric cases and partially duplicated in the monocentric ones. The distal edge of the duplication always spans up to D8S552 (8p23.1), while its proximal edge includes the centromere in the dicentric cases and varies from case to case in the monocentric ones. The analysis of DNA polymorphisms indicates that the rearrangement is consistently of maternal origin. In the deleted region, only paternal alleles were present in the patient. In the duplicated region, besides one paternal allele, some loci showed two different maternal alleles, while others, which were duplicated by FISH analysis, showed only one maternal allele. We hypothesize that, at maternal meiosis I, there was abnormal pairing of chromosomes 8 followed by anomalous crossover at the regions delimited by D8S552 and D8S35 and by D8S252 and D8S349, which presumably contain inverted repeated sequences. The resulting dicentric chromosome, 8qter-8p23.1 (D8S552)::8p23.1-(D8S35)-8qter, due to the presence of two centromeres, breaks at anaphase I, generating an inverted duplicated 8p, dicentric if the breakage occurs at the centromere or monocentric if it occurs between centromeres. 44 refs., 7 figs., 2 tabs.
- OSTI ID:
- 285061
- Journal Information:
- American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: 4 Vol. 58; ISSN AJHGAG; ISSN 0002-9297
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
BASIC STUDIES
BANDING TECHNIQUES
BIOLOGICAL MARKERS
CENTROMERES
CHROMOSOMAL ABERRATIONS
CONGENITAL MALFORMATIONS
CROSSING-OVER
DICENTRIC CHROMOSOMES
DNA HYBRIDIZATION
FLUORESCENCE
GENE MUTATIONS
GENES
GENETIC MAPPING
HEREDITARY DISEASES
HUMAN CHROMOSOME 8
KARYOTYPE
MEIOSIS
MENTAL DISORDERS
PATIENTS
PROBES