title: Genomic and genetic definition of a functional human centromere.
abstract: The definition of centromeres of human chromosomes requires a complete genomic understanding of these regions. Toward this end, we report integration of physical mapping, genetic, and functional approaches, together with sequencing of selected regions, to define the centromere of the human X chromosome and to explore the evolution of sequences responsible for chromosome segregation. The transitional region between expressed sequences on the short arm of the X and the chromosome-specific alpha satellite array DXZ1 spans about 450 kilobases and is satellite-rich. At the junction between this satellite region and canonical DXZ1 repeats, diverged repeat units provide direct evidence of unequal crossover as the homogenizing force of these arrays. Results from deletion analysis of mitotically stable chromosome rearrangements and from a human artificial chromosome assay demonstrate that DXZ1 DNA is sufficient for centromere function. Evolutionary studies indicate that, while alpha satellite DNA present throughout the pericentromeric region of the X chromosome appears to be a descendant of an ancestral primate centromere, the current functional centromere based on DXZ1 sequences is the product of the much more recent concerted evolution of this satellite DNA.
authors.affiliation: Department of Genetics, Case Western Reserve University School of Medicine and Center for Human Genetics, and, Research Institute, University Hospitals of Cleveland, Cleveland, OH 44106, USA.
authors.forename: M G
authors.initials: MG
authors.lastname: Schueler
authors.forename: A W
authors.initials: AW
authors.lastname: Higgins
authors.forename: M K
authors.initials: MK
authors.lastname: Rudd
authors.forename: K
authors.initials: K
authors.lastname: Gustashaw
authors.forename: H F
authors.initials: HF
authors.lastname: Willard
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002503:Centromere / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D020090:Chromosome Segregation; D022202:Chromosomes, Artificial, Bacterial; D022222:Chromosomes, Artificial, Human; D003198:Computer Simulation; D020451:Contig Mapping; D003434:Crossing Over, Genetic; D004276:DNA, Satellite / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D019143:Evolution, Molecular; D006801:Humans; D020071:Interspersed Repetitive Sequences; D008957:Models, Genetic; D010802:Phylogeny; D012091:Repetitive Sequences, Nucleic Acid; D015183:Restriction Mapping; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D016324:Sequence Tagged Sites; D014162:Transfection; D014424:Turner Syndrome / Q000235:genetics; D014960:X Chromosome / Q000235:genetics / Q000502:physiology* / Q000648:ultrastructure
chemical_list: D004276:DNA, Satellite