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The most comprehensive analysis to date of a single pericentromeric segmental duplication in primate genomes. It uses fluorescence in situ hybridisation, library screening, sequencing, phylogenetics and somatic cell hybrid analyses in an effort to map all of the known human PIR4 variants and to establish their origin. The duplication dynamics that are uncovered conform to the two-step model of pericentromeric-directed duplication, whereas analyses of human loci highlight the poor representation of PIR4 in the current human draft sequence. A further 15 novel PIR4 bacterial artificial chromosomes are identified that can be used to enhance existing sequence data.
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The first cytogenetic analysis of a human pericentromeric segmental duplication family to catalogue the extent of polymorphic variation in a control population. It establishes the size and marker order in the segmental duplications (~1 Mb), confirms that no phenotype is associated with the observed copy number variations, and highlights the difficulty in mapping pericentromeric duplications accurately.
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This analysis of a gene-derived family of primate-specific segmental duplications provides some of the clearest evidence that interchromosomal and intrachromosomal duplication mechanisms are distinct. Paralogues of this gene fall into two distinct classes with different distributions and duplication dynamics; a centromere-specific class linked to pericentromeric satellites and a chromosome-specific family linked to other chromosome-specific segmental duplications.
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This fluorescence in situ hybridisation based phylogenetic analysis of human chromosome 6 identifies two centromere-repositioning events. The historical location of one of the ancestral centromeres, present in the common ancestor of apes, is delineated by the same methodology to a region of ~9 Mb on 6p22.1, which contains a dense cluster of primarily chromosome-specific segmental duplications.
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Eder V., Ventura M., Ianigro M., Teti M., Rocchi M., Archidiacono N. Chromosome 6 phylogeny in primates and centromere repositioning. Mol Biol Evol. 20:2003;1506-1512 This fluorescence in situ hybridisation based phylogenetic analysis of human chromosome 6 identifies two centromere-repositioning events. The historical location of one of the ancestral centromeres, present in the common ancestor of apes, is delineated by the same methodology to a region of ~9 Mb on 6p22.1, which contains a dense cluster of primarily chromosome-specific segmental duplications.
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•] that establishes the recent phylogeny of human chromosomes 14 and 15, and delineates the site of an ancestral centromere in 15q25. This analysis also delineates the position of two neocentromeres in the same region and establishes that they do not map to the site of the ancestral centromere. All three centromeres (one ancestral, two neo), however, map within 500 kb of chromosome-specific segmental duplications that are enriched in this region. The authors propose that the segmental-duplication- rich architecture is a by-product of centromere inactivation.
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•] that establishes the recent phylogeny of human chromosomes 14 and 15, and delineates the site of an ancestral centromere in 15q25. This analysis also delineates the position of two neocentromeres in the same region and establishes that they do not map to the site of the ancestral centromere. All three centromeres (one ancestral, two neo), however, map within 500 kb of chromosome-specific segmental duplications that are enriched in this region. The authors propose that the segmental-duplication-rich architecture is a by-product of centromere inactivation.
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The most comprehensive in silico analysis of recent duplications in the human genome so far. Although not the most recent [34], this analysis is extremely powerful because the depth of sequence coverage obtained during the private whole shotgun sequencing effort (which should show no copy number bias) is used as an independent estimator of copy number in an analysis of the public sequence (which is directed and non-random in nature). This identifies a strong relationship between segmental duplication position and disease, identifies numerous candidate areas of instability, and flags for more detailed analysis regions in the public sequence that appear to be multiple copy.
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The second of two back-to-back papers from the same group that meticulously analyse ~600 kb of sequence flanking the site of the most recent chromosome fusion event within the human genome using both experimental and in silico approaches. The patchwork nature of subtelomeric and pericentromeric sequences is clearly presented, and the extent and speed of gene creation, particularly at subtelomeric locations, are striking.
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