Abstract for presentation at 11th International Congress of Human Genetics

We have examined the organisational properties of a number of the key components of the mammalian centromere. Our study is based on the use of human and mouse centromeres, and a fully sequenced human neocentromere. We have used chromatin isolation and genomic array analysis to define the distribution pattern of the chromosome scaffold at the centromere and those of a number of essential centromere proteins. We have investigated the DNA methylation profile of a functional human centromere in relation to the mapped domains, and to the transcriptionally active sites within the centromere. Our data indicate an overall hypermethylation of the centromeric DNA, with pockets of hypomethylation that are associated with sites of active transcription and/or the boundaries of specific centromeric chromatin domains. Using electron microscopy, we have determined the higher order organisation of the centromere protein-A (CENP-A)-binding domain. In addition, we have sequenced the centromere-to-telomere regions of the mouse telocentric chromosomes, and have defined a structure that promotes interchromosomal recombination exchanges that ensures the stable maintenance of the mouse telocentric karyotype, as well as allows the occasional Robertsonian translocations to occur. These studies inform us on the properties of a number of the important organisational components of the mammalian centromeres.