Constitutive heterochromatin polymorphisms in human chromosomes identified by whole comparative genomic hybridization

Abstract

Whole comparative genomic hybridization (W-CGH) is a new technique that reveals cryptic differences in highly repetitive DNA sequences, when different genomes are compared using metaphase or interphase chromosomes. W-CGH provides a quick approach to identify differential expansion of these DNA sequences at the single-chromosome level in the whole genome. In this study, we have determined the frequency of constitutive chromatin polymorphisms in the centromeric regions of human chromosomes using a whole-genome in situ cross-hybridization method to compare the whole genome of five different unrelated individuals. Results showed that the pericentromeric constitutive heterochromatin of chromosome 6 exhibited a high incidence of polymorphisms in repetitive DNA families located in pericentromeric regions. The constitutive heterochromatin of chromosomes 5 and 9 was also identified as highly polymorphic. Although further studies are necessary to corroborate and assess the overall incidence of these polymorphisms in human populations, the use of W-CGH could be pertinent and of clinical relevance to assess rapidly, from a chromosomal viewpoint, genome similarities and differences in closely related genomes such as those of relatives, or in more specific situations such as bone marrow transplantation where chimerism is produced in the recipient.

Mate pair sequencing outperforms fluorescence in situ hybridization in the genomic characterization of multiple myeloma

“…Since the centromere regions that are targeted by the FISH probes are not covered by MPseq, it is unclear whether a small gain or presence of a polymorphism of these regions are present without evidence of a bona fide trisomy or whether the trisomy was present at a subclonal level below the limit of detection by MPseq (<25% for CNAs) 18 . Polymorphisms of the acrocentric chromosome 15 have also been reported 39 and are observed in FISH analysis of PCNs in our laboratory (data not shown). Discrepancies involving chromosome 15 are present in 6 of 70 cases in this study demonstrated by either a monosomy 15 FISH result with normal chromosome 15 s by MPseq or either a normal or monosomy 15 FISH result with trisomy 15 by MPseq.…”

Precarious maintenance of simple DNA repeats in eukaryotes

“…Replication of centromeres is associated with chromosome fragility and double strand breaks, which may be due to the collapse of replication forks [112][113][114]. Pericentromeric and alpha satellite repeats evolve at a faster pace than the rest of the primate genome and also display length polymorphisms amongst humans, suggesting they are very prone to instability [106,[115][116][117]. Studies in fission yeast (which have different centromere sequences but similar centromeric chromatin to humans) have identified several of the replication fork restart proteins, including Smc5/6 and Brc1, as crucial to duplicating and suppressing crossover recombination within centromeric regions (for a recent review see [118]).…”

Chronic Exposure to Particulate Nickel Induces Neoplastic Transformation in Human Lung Epithelial Cells

“…Fragmentation was not observed in any of the other chromosomes that exhibit smaller regions of heterochromatic DNA. In humans, the centromeric and telomeric regions of all chromosomes along with larger portions of the 1, 9, 16, Y and second X chromosomes are heterochromatic [24]. Besides the second X chromosome, no other chromosomes are primarily heterochromatin.…”