The centromere is an important region of the chromosome which ensures correct segregation at cell division. The DNA sequences which make up human centromeres are poorly understood. An analysis of the human Y chromosome centromere DNA has therefore been undertaken. The structures of 23 yeast artificial chromosomes (YAC) clones and 4 cosmid clones have been determined and these have contributed to a map of ~7Mb of DNA which span the centromere. The centromeric region of the human Y chromosome contains a single major block of tandemly repeating alphoid DNA which is variable in size. The 5.7kb alphoid subunits are all orientated in one direction and become diverged at the edges of the array. Flanking the alphoid DNA are small blocks of other known tandemly repeated sequences, the 5bp, 48bp and 68bp satellites. These satellites are arranged in an asymmetric manner and are interspersed with a range of low to moderate copy number repeats. Only one putative single copy sequence has been detected. Nearby lie two regions of X-Y homology: a more proximal region which contains a gene (amelogenin) and a more distal region which has previously been shown to result from a recent X-Y transposition event. These results show that the centromeric region of the human Y chromosome is a complex mosaic of tandem repeats and other repeats. Furthermore, they provide a detailed map of the region and thus provide a solid basis for functional studies of candidate centromere determining sequences.

Mapping studies of the centromeric region of the human Y chromosome Construction of a map of a human centromeric region is very important in order to understand the organisation of this essential part of the chromosome. A YAC contig map has been assembled of the pericentric 10 Mb of the human Y chromosome, giving coverage of Yp from the large X-Y homologous region through to the alphoid satellite of the centromere, and from the alphoid DNA to the proximal unique sequences on Yq. The Yp map has one remaining gap between TSPY1 and the AMELY region, while two gaps separate the satellite region on Yq from the other two contigs. After constructing the map, the known genes were localised to the region. One Yq gene, DFFRY, was discounted as a potential anti-Turner syndrome gene by analysis of rearranged Y chromosomes. Detection of a block of duplicated sequence on Yp led to the confirmation of the existence of an inversion polymorphism, which was then found to be correlated with a major subclass of sex-reversed individuals, who have X-Y chromosomal breakpoints within the inverted region. These results not only give a far more extensive and detailed map of this region than before, but also show that understanding the organisation of the region has important consequences for a number of genetic disorders.