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De novo cytogenetically balanced reciprocal non-Robertsonian translocations are rare findings in clinical cytogenetics and might be associated with an abnormal phenotype. Knowledge of the parental origin and mechanisms of formation is still limited. By microdissection of the derivative chromosomes and their normal homologs from metaphases followed by microsatellite-mediated marker analysis we identified 7 cases of paternal and 3 cases of maternal origin in a cohort of 10 patients with de novo cytogenetically balanced reciprocal non-Robertsonian translocations. Neither in the maternal nor in the paternal group of our study parental age seems to be increased. Together with the data from the literature our results confirm that the majority of de novo cytogenetically balanced reciprocal translocations are of paternal origin, but the preponderance does not appear to be as distinct as previously thought and the paternal age does not seem to be necessarily a major contributing factor.

Low copy repeats (LCRs) are stretches of duplicated DNA that are more than 1 kb in size and share a sequence similarity that exceeds 90%. Non-allelic homologous recombination (NAHR) between highly similar LCRs has been implicated in numerous genomic disorders. This study aimed at defining the impact of LCRs on the generation of balanced and unbalanced chromosomal rearrangements in mentally retarded patients. A cohort of 22 patients, preselected for the presence of submicroscopic imbalances, was analysed using submegabase resolution tiling path array CGH and the results were compared with a set of 41 patients with balanced translocations and breakpoints that were mapped to the BAC level by FISH. Our data indicate an accumulation of LCRs at breakpoints of both balanced and unbalanced rearrangements. LCRs with high sequence similarity in both breakpoint regions, suggesting NAHR as the most likely cause of rearrangement, were observed in 6/22 patients with chromosomal imbalances, but not in any of the balanced translocation cases studied. In case of chromosomal imbalances, the likelihood of NAHR seems to be inversely related to the size of the aberration. Our data also suggest the presence of additional mechanisms coinciding with or dependent on the presence of LCRs that may induce an increased instability at these chromosomal sites.

Mobile elements are most abundant in the mammalian genome, comprising at least 40–50% of the DNA. They are differentiated into two most prominent families: the LINE elements, which are preferentially located in the G-bands, and SINES, which are clustered in the R-bands. We report here a novel mammalian non-L1-retroposon, which invaded the genome of Microtus agrestis in a very short time from an evolutionary viewpoint. No relevant sequence homology could be demonstrated to known sequences in the NCBI database. However, cross-hybridizing sequences exist in the genomes of all other Microtus species analyzed, but not in Mus musculus, indicating the recent evolutionary origin of this element. This retroposon is enriched in the entire heterochromatin of the X and Y chromosomes, but is also interspersed in autosomal locations in euchromatic portions of the genome. We show that the retroposon is heavily transcribed from the heterochromatin during female meiosis prerequisite for the subsequent retrotransposition. The estimated rate of retrotransposition is at least 1–2 × 10–2 per generation, which is hundred-fold higher than that of the majority of invertebrate retroposons and also higher than the transposition rate of a murine L1 element, which was calculated to be 3 × 10–3 per generation.

We report on an 18-year-old female with de novo tandem duplication Xq23→Xq27–28. The breakpoints of the duplication segment have been mapped by FISH using a panel of locus specific YACs. Despite selective inactivation of the aberrant X chromosome, proven by a combination of molecular and cytogenetic studies, the patient exhibits mental retardation, dysmorphic features and short stature. Possible mechanisms explaining this unexpected finding are discussed.

The sex chromosomes of Microtus agrestis are extremely large due to the accumulation of constitutive heterochromatin. We have cloned and characterized a 2,999-bp (GATA)n-positive sequence, following Haelll digestion, that is confined to the noncentromeric heterochromatin of the X chromosome. The cloned element exhibits an accumulation of certain oligomers, which are scattered throughout its entire length, and several copies of Chi-related sequence motifs, which are thought to be implicated in recombination. The latter might have been responsible for the extensive amplification of homologous genomic elements. The sequence has been amplified to a copy number of 1–2 × 104 within the genome of M. agrestis. In contrast to many satellite DNAs, which are thought to be an inevitable constituent of constitutive heterochromatin, the sequence exhibits a tissue-specific methylation pattern and is organized, not as a simple tandem array, but as a component of an extremely large, multimeric, higher-order repeat unit with a length of over 20 kb. This higher-order repeat accounts for at least 15–30 % of the gonosomal heterochromatin in M. agrestis. Sequences homologous to pMAHAE2 are abundant in the genomes of all Microtus species. The copy number varies from ∼100 per diploid genome in M. arvalis, M. oeconomus, and M. cabrerae to –500 per diploid genome in M. guentheri and up to 1–2 × 104 in M. agrestis. Our molecular data indicate that the sequences of the pMAHAE2 family probably arose during the evolution of the common ancestor of Microtus and have subsequently been amplified extensively in the X chromosomes of M. agrestis in the phylogenetically very short period of less than 1 million years.