CENTROMERE ANNOTATION 147CONCLUSIONSCurrent studies <strong>of</strong> the genomic organization <strong>of</strong> the centromericregions <strong>of</strong> human chromosomes reveal severalfeatures, despite the large gaps that are apparent in thecurrent genome sequence assemblies (e.g., Fig. 2). <strong>The</strong>most proximal contigs on several chromosome arms inthe genome have reached α-satellite DNA, includingthose on chromosomes 7 (Hillier et al. 2003; Scherer et al.2003), 16 (Horvath et al. 2000), 21 (Brun et al. 2003), 22(Dunham et al. 1999), and the Y chromosome (Skaletskyet al. 2003), in addition to our work on the X chromosomeand chromosome 17, as summarized here. Other fully sequencedcontigs (chromosome 10, Guy et al. 2003) terminatein other types <strong>of</strong> satellite DNA, short <strong>of</strong> connectingto α satellite at the centromere. However, only thecontigs on Xp and 17p span from euchromatin <strong>of</strong> thechromosome arm to higher-order α-satellite repeat arraysthat have been annotated functionally with centromereassays (Fig. 7). Others (like the chromosome 21q junctionillustrated in Fig. 7) terminate in monomeric α satellite,but are separated by a gap <strong>of</strong> undetermined size from thehigher-order sequences <strong>of</strong> the functional centromere.Thus, chromosome arm/centromere junctions remain importantgoals for future research, requiring a combination<strong>of</strong> directed efforts to extend existing contigs and suitablefunctional assays to provide validation and functional annotation.As we move toward an understanding <strong>of</strong> the organization,function, and evolution <strong>of</strong> the human genome, anyclaims <strong>of</strong> a “complete” sequence will need to include fullanalysis <strong>of</strong> the pericentromeric and other heterochromaticregions <strong>of</strong> our chromosomes. <strong>The</strong> data presented here andelsewhere (Schueler et al. 2001) suggest that, notwithstandingtheir repetitive content, the satellite-containingcentromeric regions <strong>of</strong> human chromosomes can beFigure 7. <strong>Genom</strong>e assembly <strong>of</strong> the centromeric regions <strong>of</strong> the Xchromosome, and chromosomes 17 and 21. Both the X and 17centromeres have contiguous sequence on the short-arm sides,connecting euchromatin to monomeric α satellite (green) tohigher-order repeat α satellite (red). Orange indicates othersatellite sequences. A chromosome 21q contig has reachedmonomeric α satellite but has not connected to higher-order αsatellite (gap indicated by question marks). For these three humanchromosomes, the centromere activity <strong>of</strong> their respectivehigher-order repeat α satellites has been functionally annotatedusing a human artificial chromosome assay (Harrington et al.1997; Ikeno et al. 1998; Schueler et al. 2001).mapped, sequenced, assembled, and annotated functionally.Complete assembly <strong>of</strong> centromere contigs should,therefore, be feasible and will provide an importantsource <strong>of</strong> genomic and functional data for studies <strong>of</strong> chromosomebiology, as well as genome evolution.Scientific arguments aside, there is also a strong historicaland philosophical imperative for including centromeresin the final stages <strong>of</strong> gap closure in the archival,truly complete sequence <strong>of</strong> the genome <strong>of</strong> <strong>Homo</strong> <strong>sapiens</strong>.After all, which part <strong>of</strong> the Rosetta Stone would onechoose to omit?ACKNOWLEDGMENTSWe thank Evan Eichler, Jeff Bailey, Devin Locke, andEric Green for helpful discussions and assistance. 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GENETIC EPIDEMIOLOGY 361lytic epide
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GENETIC EPIDEMIOLOGY 363curate risk
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A Model System for Identifying Gene
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PTC TASTE GENETICS 367Figure 2. Hap
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PTC TASTE GENETICS 369Table 2. Hapl
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PTC TASTE GENETICS 371the emergence
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374 MCCALLION ET AL.Figure 1. Schem
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376 MCCALLION ET AL.lier (Carrasqui
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378 MCCALLION ET AL.Table 3. HSCR A
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380 MCCALLION ET AL.Figure 3. Trans
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Genetics of Schizophrenia and Bipol
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SCHIZOPHRENIA AND BIPOLAR AFFECTIVE
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SCHIZOPHRENIA AND BIPOLAR AFFECTIVE
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SCHIZOPHRENIA AND BIPOLAR AFFECTIVE
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SCHIZOPHRENIA AND BIPOLAR AFFECTIVE
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SCHIZOPHRENIA AND BIPOLAR AFFECTIVE
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The Genetics of Common Diseases: 10
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GENETICS OF COMMON DISEASES 397with
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GENETICS OF COMMON DISEASES 399SELE
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GENETICS OF COMMON DISEASES 401F.,
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404 CHEUNG ET AL.netic analysis. Ex
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406 CHEUNG ET AL.Figure 3. The expr
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Regulation of α-Synuclein Expressi
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α-SYNUCLEIN EXPRESSION AND PD 411T
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1. The levels of α-synuclein prote
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α-SYNUCLEIN EXPRESSION AND PD 415g
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418 BOTSTEINFigure 1. (A) Blectron
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420 BOTSTEINFigure 3. Cluster diagr
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422 BOTSTEINFigure 6. Kaplan-Meier
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424 BOTSTEINGarber M.E., Troyanskay
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426 ANTONARAKIS ET AL.1316192225283
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428 ANTONARAKIS ET AL.Figure 5. Sam
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430 ANTONARAKIS ET AL.POPULATION VA
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432 JORGENSEN ET AL.tive small mole
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434 JORGENSEN ET AL.FLAG-tagged pro
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436 JORGENSEN ET AL.visualization t
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438 JORGENSEN ET AL.AArp2/3 Complex
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Pathway40S440 JORGENSEN ET AL.ANutr
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442 JORGENSEN ET AL.Giaever G., Chu
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Genomic Disorders: Genome Architect
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GENOME ARCHITECTURE AND GENOMIC DIS
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GENOME ARCHITECTURE AND GENOMIC DIS
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GENOME ARCHITECTURE AND GENOMIC DIS
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GENOME ARCHITECTURE AND GENOMIC DIS
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Human Versus Chimpanzee Chromosome-
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HUMAN VS. CHIMP CHROMOSOME COMPARIS
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HUMAN VS. CHIMP CHROMOSOME COMPARIS
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Novel Transcriptional Units and Unc
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TRANSCRIPTIONAL UNITS AND GENE PAIR
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TRANSCRIPTIONAL UNITS AND GENE PAIR
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TRANSCRIPTIONAL UNITS AND GENE PAIR
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TRANSCRIPTIONAL UNITS AND GENE PAIR
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mtDNA Variation, Climatic Adaptatio
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mtDNA VARIATION 473Figure 3. Region
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ANALYSIS OF ADAPTIVE SELECTION FORR
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mtDNA VARIATION 477Figure 8. Temper
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Positive Selection in the Human Gen
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HUMAN-SPECIFIC EVOLUTIONARY CHANGES
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HUMAN-SPECIFIC EVOLUTIONARY CHANGES
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HUMAN-SPECIFIC EVOLUTIONARY CHANGES
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488 UNDERHILLorigin episodes, each
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490 UNDERHILLhaplogroups C through
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492 UNDERHILLO (Fig. 2e) that share
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The New Quantitative BiologyM.V. OL
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NEW QUANTITATIVE BIOLOGY 497alone.
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NEW QUANTITATIVE BIOLOGY 499There w
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NEW QUANTITATIVE BIOLOGY 501ceded,