Mammalian Genome

, Volume 22, Issue 5–6, pp 261–271 | Cite as

Transcript catalogs of human chromosome 21 and orthologous chimpanzee and mouse regions



A comprehensive representation of the gene content of the long arm of human chromosome 21 (Hsa21q) remains of interest for the study of Down syndrome, its associated phenotypic features, and mouse models. Here we compare transcript catalogs for Hsa21q, chimpanzee chromosome 21 (Ptr21q), and orthologous regions of mouse chromosomes 16, 17, and 10 for open reading frame (ORF) characteristics and conservation. The Hsa21q and mouse catalogs contain 552 and 444 gene models, respectively, of which only 162 are highly conserved. Hsa21q transcripts were used to identify orthologous exons in Ptr21q and assemble 533 putative transcripts. Transcript catalogs for all three organisms are searchable for nucleotide and amino acid sequence features of ORF length, repeat content, experimental support, gene structure, and conservation. For human and mouse comparisons, three additional summaries are provided: (1) the chromosomal distribution of novel ORF transcripts versus potential functional RNAs, (2) the distribution of species-specific transcripts within Hsa21q and mouse models of Down syndrome, and (3) the organization of sense–antisense and putative sense–antisense structures defining potential regulatory mechanisms. Catalogs, summaries, and nucleotide and amino acid sequences of all composite transcripts are available and searchable at These data sets provide comprehensive information useful for evaluation of candidate genes and mouse models of Down syndrome and for identification of potential functional RNA genes and novel regulatory mechanisms involving Hsa21q genes. These catalogs and search tools complement and extend information available from other gene annotation projects.



This work was supported by the Fondation Jerome Lejeune, the Anna and John J. Sie Foundation, the Coleman Institute for Cognitive Disabilities, and the National Institutes of Health (HD056235).

Supplementary material

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  1. Berto G, Camera P, Fusco C, Imarisio S, Ambrogio C, Chiarle R, Silengo L, Di Cunto F (2007) The Down syndrome critical region protein TTC3 inhibits neuronal differentiation via RhoA and Citron kinase. J Cell Sci 120:1859–1867PubMedCrossRefGoogle Scholar
  2. Bialowas-McGoey LA, Lesicka A, Whitaker-Azmitia PM (2008) Vitamin E increases S100B-mediated microglial activation in an S100B-overexpressing mouse model of pathological aging. Glia 56:1780–1790PubMedCrossRefGoogle Scholar
  3. CDC (Centers for Disease Control, Prevention) (2006) Improved National Prevalence Estimates for 18 Major Birth Defects. MMWR Morb Mortal Wkly Rep 54:6–12Google Scholar
  4. Denoeud F, Kapranov P, Ucla C, Frankish A, Castelo R, Drenkow J, Lagarde J, Alioto T, Manzano C, Chrast J, Dike S, Wyss C, Henrichsen CN, Holroyd N, Dickson MC, Taylor R, Hance Z, Foissac S, Myers RM, Rogers J, Hubbard T, Harrow J, Guigó R, Gingeras TR, Antonarakis SE, Reymond A (2007) Prominent use of distal 5’ transcription start sites and discovery of a large number of additional exons in ENCODE regions. Genome Res 17:746–759PubMedCrossRefGoogle Scholar
  5. Dinger ME, Pang KC, Mercer TR, Mattick JS (2008) Differentiating protein-coding and noncoding RNA: challenges and ambiguities. PLoS Comput Biol 4:e1000176PubMedCrossRefGoogle Scholar
  6. ENCODE Project Consortium, Birney E, Stamatoyannopoulos JA, Dutta A, Guigó R, Gingeras TR, Margulies EH, Weng Z, Snyder M, Dermitzakis ET, Thurman RE et al (2007) Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature 447:799–816PubMedCrossRefGoogle Scholar
  7. Faghihi MA, Wahlestedt C (2009) Regulatory roles of natural antisense transcripts. Nat Rev Mol Cell Biol 10:637–643PubMedCrossRefGoogle Scholar
  8. Gardiner KJ (2010) Molecular basis of pharmacotherapies for cognition in Down syndrome. Trends Pharmacol Sci 31:66–73PubMedCrossRefGoogle Scholar
  9. Gardiner K, Costa AC (2006) The proteins of human chromosome 21. Am J Med Genet C Semin Med Genet 142C:196–205PubMedCrossRefGoogle Scholar
  10. Gardiner K, Slavov D, Bechtel L, Davisson M (2002) Annotation of human chromosome 21 for relevance to Down syndrome: gene structure and expression analysis. Genomics 79:833–843PubMedCrossRefGoogle Scholar
  11. Gardiner K, Fortna A, Bechtel L, Davisson MT (2003) Mouse models of Down syndrome: how useful can they be? Comparison of the gene content of human chromosome 21 with orthologous mouse genomic regions. Gene 318:137–147PubMedCrossRefGoogle Scholar
  12. Griffith E, Walker S, Martin CA, Vagnarelli P, Stiff T, Vernay B, Al Sanna N, Saggar A, Hamel B, Earnshaw WC, Jeggo PA, Jackson AP, O’Driscoll M (2008) Mutations in pericentrin cause Seckel syndrome with defective ATR-dependent DNA damage signaling. Nat Genet 40:232–236PubMedCrossRefGoogle Scholar
  13. Harrow J, Denoeud F, Frankish A, Reymond A, Chen CK, Chrast J, Lagarde J, Gilbert JG, Storey R, Swarbreck D, Rossier C, Ucla C, Hubbard T, Antonarakis SE, Guigo R (2007) GENCODE: producing a reference annotation for ENCODE. Genome Biol 7(Suppl 1):S4.1–S4.9Google Scholar
  14. Hattori M, Fujiyama A, Taylor TD, Watanabe H, Yada T, Park HS, Toyoda A, Ishii K, Totoki Y, Choi DK, Groner Y, Soeda E, Ohki M, Takagi T, Sakaki Y, Taudien S, Blechschmidt K, Polley A, Menzel U, Delabar J, Kumpf K, Lehmann R, Patterson D, Reichwald K, Rump A, Schillhabel M, Schudy A, Zimmermann W, Rosenthal A, Kudoh J, Schibuya K, Kawasaki K, Asakawa S, Shintani A, Sasaki T, Nagamine K, Mitsuyama S, Antonarakis SE, Minoshima S, Shimizu N, Nordsiek G, Hornischer K, Brant P, Scharfe M, Schon O, Desario A, Reichelt J, Kauer G, Blocker H, Ramser J, Beck A, Klages S, Hennig S, Riesselmann L, Dagand E, Haaf T, Wehrmeyer S, Borzym K, Gardiner K, Nizetic D, Francis F, Lehrach H, Reinhardt R, Yaspo ML (2000) Chromosome 21 mapping and sequencing consortium: the DNA sequence of human chromosome 21. Nature 2000(405):311–319Google Scholar
  15. Kapranov P, Willingham AT, Gingeras TR (2007) Genome-wide transcription and the implications for genomic organization. Nat Rev Genet 8:413–423PubMedCrossRefGoogle Scholar
  16. Kuhn DE, Nuovo GJ, Terry AV Jr, Martin MM, Malana GE, Sansom SE, Pleister AP, Beck WD, Head E, Feldman DS, Elton TS (2010) Chromosome 21-derived microRNAs provide an etiological basis for aberrant protein expression in human Down syndrome brains. J Biol Chem 285:1529–1543PubMedCrossRefGoogle Scholar
  17. Li Z, Yu T, Morishima M, Pao A, LaDuca J, Conroy J, Nowak N, Matsui S, Shiraishi I, Yu YE (2007) Duplication of the entire 22.9 Mb human chromosome 21 syntenic region on mouse chromosome 16 causes cardiovascular and gastrointestinal abnormalities. Hum Mol Genet 16:1359–1366PubMedCrossRefGoogle Scholar
  18. Lott IT, Dierssen M (2010) Cognitive deficits and associated neurological complications in individuals with Down’s syndrome. Lancet Neurol 9:623–633PubMedCrossRefGoogle Scholar
  19. Mercer TR, Dinger ME, Mattick JS (2009) Long non-coding RNAs: insights into functions. Nat Rev Genet 10:155–159PubMedCrossRefGoogle Scholar
  20. Mushinski JF, Nguyen P, Stevens LM, Khanna C, Lee S, Chung EJ, Lee MJ, Kim YS, Linehan WM, Horisberger MA, Trepel JB (2009) Inhibition of tumor cell motility by the interferon-inducible GTPase MxA. J Biol Chem 284:15206–15214PubMedCrossRefGoogle Scholar
  21. Olson LE, Roper RJ, Sengstaken CL, Peterson EA, Aquino V, Galdzicki Z, Siarey R, Pletnikov M, Moran TH, Reeves RH (2007) Trisomy for the Down syndrome ‘critical region’ is necessary but not sufficient for brain phenotypes of trisomic mice. Hum Mol Genet 16:774–782PubMedCrossRefGoogle Scholar
  22. Parkhomchuk D, Borodina T, Amstislavskiy V, Banaru M, Hallen L, Krobitsch S, Lehrach H, Soldatov A (2009) Transcriptome analysis by strand-specific sequencing of complementary DNA. Nucleic Acids Res 37:e123PubMedCrossRefGoogle Scholar
  23. Pereira PL, Magnol L, Sahún I, Brault V, Duchon A, Prandini P, Gruart A, Bizot JC, Chadefaux-Vekemans B, Deutsch S, Trovero F, Delgado-García JM, Antonarakis SE, Dierssen M, Herault Y (2009) A new mouse model for the trisomy of the Abcg1–U2af1 region reveals the complexity of the combinatorial genetic code of down syndrome. Hum Mol Genet 18:4756–4769PubMedCrossRefGoogle Scholar
  24. Pritchard M, Reeves RH, Dierssen M, Patterson D, Gardiner KJ (2008) Down syndrome and the genes of human chromosome 21: current knowledge and future potentials. Report on the Expert workshop on the biology of chromosome 21 genes: towards gene–phenotype correlations in Down syndrome. Washington, D.C., September 28–October 1, 2007. Cytogenet Genome Res 121:67–77PubMedCrossRefGoogle Scholar
  25. Rauch A, Thiel CT, Schindler D, Wick U, Crow YJ, Ekici AB, van Essen AJ, Goecke TO, Al-Gazali L, Chrzanowska KH, Zweier C, Brunner HG, Becker K, Curry CJ, Dallapiccola B, Devriendt K, Dörfler A, Kinning E, Megarbane A, Meinecke P, Semple RK, Spranger S, Toutain A, Trembath RC, Voss E, Wilson L, Hennekam R, de Zegher F, Dörr HG, Reis A (2008) Mutations in the pericentrin (PCNT) gene cause primordial dwarfism. Science 319:816–819PubMedCrossRefGoogle Scholar
  26. Salehi A, Faizi M, Colas D, Valletta J, Laguna J, Takimoto-Kimura R, Kleschevnikov A, Wagner SL, Aisen P, Shamloo M, Mobley WC (2009) Restoration of norepinephrine-modulated contextual memory in a mouse model of Down syndrome. Sci Transl Med 1:7ra17Google Scholar
  27. Schwartz JC, Younger ST, Nguyen NB, Hardy DB, Monia BP, Corey DR, Janowski BA (2008) Antisense transcripts are targets for activating small RNAs. Nat Struct Mol Biol 15:842–848PubMedCrossRefGoogle Scholar
  28. Sérégaza Z, Roubertoux PL, Jamon M, Soumireu-Mourat B (2006) Mouse models of cognitive disorders in trisomy 21: a review. Behav Genet 36:387–404PubMedCrossRefGoogle Scholar
  29. Shibuya K, Obayashi I, Asakawa S, Minoshima S, Kudoh J, Shimizu N (2004) A cluster of 21 keratin-associated protein genes within introns of another gene on human chromosome 21q22.3. Genomics 83:679–693PubMedCrossRefGoogle Scholar
  30. Singer T, McConnell MJ, Marchetto MC, Coufal NG, Gage FH (2010) LINE-1 retrotransposons: mediators of somatic variation in neuronal genomes? Trends Neurosci 33:345–354PubMedCrossRefGoogle Scholar
  31. Tam W (2001) Identification and characterization of human BIC, a gene on chromosome 21 that encodes a noncoding RNA. Gene 274:157–167PubMedCrossRefGoogle Scholar
  32. Tibelius A, Marhold J, Zentgraf H, Heilig CE, Neitzel H, DucoMmun B, Rauch A, Ho AD, Bartek J, Krämer A (2009) Microcephalin and pericentrin regulate mitotic entry via centrosome-associated Chk1. J Cell Biol 185:1149–1157PubMedCrossRefGoogle Scholar
  33. van Bakel H, Nislow C, Blencowe BJ, Hughes TR (2010) Most “dark matter” transcripts are associated with known genes. PLoS Biol 8:e1000371PubMedCrossRefGoogle Scholar
  34. Walters RD, Kugel JF, Goodrich JA (2009) InvAluable junk: the cellular impact and function of Alu and B2 RNAs. IUBMB Life 61:831–837PubMedCrossRefGoogle Scholar
  35. Watanabe H, Fujiyama A, Hattori M, Taylor TD, Toyoda A, Kuroki Y, Noguchi H, BenKahla A, Lehrach H, Sudbrak R, Kube M, Taenzer S, Galgoczy P, Platzer M, Scharfe M, Nordsiek G, Blöcker H, Hellmann I, Khaitovich P, Pääbo S, Reinhardt R, Zheng HJ, Zhang XL, Zhu GF, Wang BF, Fu G, Ren SX, Zhao GP, Chen Z, Lee YS, Cheong JE, Choi SH, Wu KM, Liu TT, Hsiao KJ, Tsai SF, Kim CG, OOta S, Kitano T, Kohara Y, Saitou N, Park HS, Wang SY, Yaspo ML, Sakaki Y (2004) DNA sequence and comparative analysis of chimpanzee chromosome 22. Nature 429:382–388PubMedCrossRefGoogle Scholar
  36. Wetmore DZ, Garner CC (2010) Emerging pharmacotherapies for neurodevelopmental disorders. J Dev Behav Pediatr 31:564–581PubMedCrossRefGoogle Scholar
  37. Wilming LG, Gilbert JG, Howe K, Trevanion S, Hubbard T, Harrow JL (2008) The vertebrate genome annotation (Vega) database. Nucleic Acids Res 36:D753–D760PubMedCrossRefGoogle Scholar
  38. Wiseman FK, Alford KA, Tybulewicz VL, Fisher EM (2009) Down syndrome—recent progress and future prospects. Hum Mol Genet 18(R1):R75–R83PubMedCrossRefGoogle Scholar
  39. Yu T, Li Z, Jia Z, Clapcote SJ, Liu C, Li S, Asrar S, Pao A, Chen R, Fan N, Carattini-Rivera S, Bechard AR, Spring S, Henkelman RM, Stoica G, Matsui S, Nowak NJ, Roder JC, Chen C, Bradley A, Yu YE (2010) A mouse model of Down syndrome trisomic for all human chromosome 21 syntenic regions. Hum Mol Genet 19:2780–2791PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Department of Pediatrics, Computational Biosciences ProgramUniversity of Colorado DenverAuroraUSA
  2. 2.Intellectual and Developmental Disabilities Research Center, Neuroscience and Human Medical Genetics ProgramsUniversity of Colorado DenverAuroraUSA

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