The centromeric regions of all human chromosomes are characterized by distinct subsets of a diverse tandemly repeated DNA family, alpha satellite. On human chromosome 17, the predominant form of alpha satellite is a 2.7-kilobase-pair higher-order repeat unit consisting of 16 alphoid monomers. We present the complete nucleotide sequence of the 16-monomer repeat, which is present in 500 to 1,000 copies per chromosome 17, as well as that of a less abundant 15-monomer repeat, also from chromosome 17. These repeat units were -98% identical in sequence, differing by the exclusion of precisely 1 monomer from the 15-monomer repeat. Homologous unequal crossing-over is suggested as a probable mechanism by which the different repeat lengths on chromosome 17 were generated, and the putative site of such a recombination event is identified. The monomer organization of the chromosome 17 higher-order repeat unit is based, in part, on tandemly repeated pentamers. A similar pentameric suborganization has been previously demonstrated for alpha satellite of the human X chromosome. Despite the organizational similarities, substantial sequence divergence distinguishes these subsets. Hybridization experiments indicate that the chromosome 17 and X subsets are more similar to each other than to the subsets found on several other human chromosomes. We suggest that the chromosome 17 and X alpha satellite subsets may be related components of a larger alphoid subfamily which have evolved from a common ancestral repeat into the contemporary chromosome-specific subsets.Alpha satellite (alphoid DNA) is a complex family of tandemly repeated DNA found in primate genomes. Long tandem arrays of alpha satellite DNA based on a monomer repeat length of -171 base paiirs (bp) are located principally at the centromeres of primate chromosomes (3,15,16,19,20). In the human genome, these sequences have been identified at the centromeric regions of each human chromosome and constitute some 5% of total human DNA. Human alpha satellite was initially described as a 340-bp EcoRI repeat, comprising two diverged monomer halves of 169 and 171 bp (16,34). However, more recent studies have indicated that this DNA family is substantially more heterogeneous than was once believed. The dimeric EcoRI repeat itself is made up of several distinct subfamilies (11,22), and a number of different molecular configurations in the human genome have been described (7,10,18,28,29,32,33,35). Alpha satellite subsets have been identified on several human chromosomes, and the suggestion has been made that individual human chromosomes may each be characterized by distinct alpha satellite subsets defined by restriction enzyme periodicity and primary sequence (15,18,29).Alpha satellite DNA specific for the human X chromosome (alphaX) has been cloned and extensively characterized (28, 32, 35). The 2.0-kilobase-pair (kb) BamHI higherorder repeat unit from this chromosome consists of 12 tandem but diverged alpha satellite monomers arranged as two adjacent and related pentamer blocks plus ...

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Tandemly repeated DNA families appear to undergo concerted evolution, such that repeat units within a species have a higher degree of sequence similarity than repeat units from even closely related species. While intraspecies homogenization of repeat units can be explained satisfactorily by repeated rounds of genetic exchange processes such as unequal crossing over and/or gene conversion, the parameters controlling these processes remain largely unknown. Alpha satellite DNA is a noncoding tandemly repeated DNA family found at the centromeres of all human and primate chromosomes. We have used sequence analysis to investigate the molecular basis of 13 variant alpha satellite repeat units, allowing comparison of multiple independent recombination events in closely related DNA sequences. The distribution of these events within the 171-bp monomer is nonrandom and clusters in a distinct 20-to 25-bp region, suggesting possible effects of primary sequence and/or chromatin structure. The position of these recombination events may be associated with the location within the higher-order repeat unit of the binding site for the centromere-specific protein CENP-B.These studies have implications for the molecular nature of genetic recombination, mechanisms of concerted evolution, and higher-order structure of centromeric heterochromatin.The complex genomes of eukaryotes contain large amounts of tandemly repeated DNA, often comprising several percent of an organism's genetic complement. These DNA families contain as many as several thousand repeat units at a given location, arranged in a head-to-tail fashion. Noncoding tandemly repeated DNAs are possible candidates for providing some of the structural requirements for proper chromosome function (14,20), while multigene families such as ribosomal DNA (rDNA) and immunoglobulin genes are important for the development and biology of complex organisms (16). One interesting but poorly understood property of these DNA families is the high degree of sequence similarity observed among repeat units within a species compared with the relatively low similarity of repeat units between closely related species (5, 16). Models to explain this phenomenon of concerted evolution invoke repeated rounds of homologous genetic exchange processes such as unequal crossing over and conversion, such that mutations arising in individual repeat units can be duplicated and eventually spread throughout the DNA family within a species (24, 30). Genetic exchange processes are thought to be important in shaping complex genomes, resulting in gene duplication, deletion, or fusion (reviewed in reference 15) and contributing to genetic diversity between populations during evolution (8,32 tinct linear arrangements that form highly homologous chromosome-specific higher-order repeat units (6, 50). These have presumably been homogenized on their particular chromosomes by genetic exchanges between misaligned arrays aligned on the register of the higher-order repeat units (31,38,50). Within a particular chromosomal subse...

The mechanism of X-inactivation in man is thought to involve a specific cis-acting locus within the X-inactivation centre at Xq13 (1,2). The XIST gene (X inactive specific transcript) at Xq13 is ubiquitously expressed only from the inactive X and as such may be involved in or influenced by the X-inactivation process (3,4). We have localised the breakpoints on two acquired isodicentric X chromosomes associated with leukaemia to a 450 kilobase region of DNA within Xq13, which result in deletion of the XIST gene. We have demonstrated that these chromosomes remain inactive and that there is no evidence of XIST expression from the remaining intact X chromosomes. The data suggest that XIST is not required for the maintenance of X-inactivation on these somatically rearranged X chromosomes.