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“Beijing Region” (3pter-D3S3397) of the Human Genome: Complete sequence and analysis

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Abstract

The goal of the Human Genome Project (HGP) is to determine a complete and high-quality sequence of the human genome. China, as one of the six member states, takes a region between 3pter and D3S3397 of the human chromosome 3 as its share of this historic project, referred as “Beijing Region”. The complete sequence of this region comprises of 17.4 megabasepairs (Mb) with an average GC content of 42% and an average recombination rate of 2.14 cM/Mb. Within Beijing Region, 122 known and 20 novel genes are identified, as well as 42607 single nucleotide polymorphisms (SNPs). Comprehensive analyses also reveal: (i) gene density and GC-content of Beijing Region are in agreement with human cytogenetic maps, i.e. G-minus bands are GC-rich and of a high gene density, whereas G-plus bands are GC-poor and of a relatively low gene density; (ii) the average recombination rate within Beijing Region is relatively high compared with other regions of chromosome 3, with the highest recombination rate of 6.06 cM/Mb in the subtelomeric area; (iii) it is most likely that a large gene, associated with the mammary gland, may reside in the 1.1 Mb gene-poor area near the telomere; (iv) many disease-related genes are genetically mapped to Beijing Region, including those associated with cancers and metabolic syndromes. All make Beijing Region an important target for in-depth molecular investigations with a purpose of medical applications.

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References

  1. The International Human Genome Sequencing Consortium, Initial sequencing and analysis of the human genome, Nature, 2001, 409: 860–921.

    Article  Google Scholar 

  2. Ewing, B., Green, P., Base-calling of automated sequencer traces using phred. II Error probabilities, Genome Res., 1998, 8: 186–194.

    PubMed  CAS  Google Scholar 

  3. Ewing, B., Hillier, L. M., Wendl, C. et al., Base-calling of automated sequencer traces using phred. I. Accuracy assessment, Genome Res., 1998, 8: 175–185.

    PubMed  CAS  Google Scholar 

  4. Gordon, D., Abajian, C., Green, P., Consed: A graphical tool for sequence finishing, Genome Res., 1998, 8: 195–202.

    PubMed  CAS  Google Scholar 

  5. Benson, G., Tandem repeats finder: A program to analyze DNA sequences, Nucleic Acids Res., 1999, 27: 573–580.

    Article  PubMed  CAS  Google Scholar 

  6. Pruitt, K. D., Maglott, D. R., RefSeq and LocusLink: NCBI gene-centered resources, Nucleic Acids Res., 2001, 29: 137–140.

    Article  PubMed  CAS  Google Scholar 

  7. Imanishi, T., Itoh, T., Suzuki, Y. et al., Integrative Annotation of 21, 037 Human Genes Validated by Full-Length cDNA Clones, PLoS Bio., 2004, 2(6): e162.

    Article  Google Scholar 

  8. Kent, W. J., BLAT—The BLAST-Like Alignment Tool, Genome Res., 2002, 12:656–664.

    PubMed  CAS  Google Scholar 

  9. Salamov, A. A., Solovyev, V. V., Ab initio gene finding in Drosophila genomic DNA, Genome Res., 2000, 10: 516–522.

    Article  PubMed  CAS  Google Scholar 

  10. Boeckmann, B., Bairoch, A., Apweiler, R. et al., The SWISS-PROT protein knowledgebase and its supplement TrEMBL in 2003, Nucleic Acids Res., 2003, 31: 365–370.

    Article  PubMed  CAS  Google Scholar 

  11. Zdobnov, E. M., Apweiler, Rolf, InterProScan—An integration platform for the signature-recognition methods in InterPro, Bioinformatics, 2001, 17: 847–848.

    Article  PubMed  CAS  Google Scholar 

  12. Lowe, T. M., Eddy, S. R., tRNAscan-SE: A program for improved detection of transfer RNA genes in genomic sequence, Nucleic Acids Res., 1997, 25: 955–964.

    Article  PubMed  CAS  Google Scholar 

  13. Griffiths-Jones, S., Bateman, A., Marshall, M., et al., An RNA family database, Nucleic Acids Res., 2003, 31:439–441.

    Article  PubMed  CAS  Google Scholar 

  14. Griffiths-Jones, S., The microRNA Registry, Nucleic Acids Res., 2004, 32: 109–111.

    Article  Google Scholar 

  15. Ambros, V., Bartel, B., Bartel, D. P., A uniform system for microRNA annotation, RNA, 2003, 9: 277–279.

    Article  PubMed  CAS  Google Scholar 

  16. Schwartz, S., Kent, W. J., Smit, A. et al., Human-mouse alignments with BLASTZ, Genome Res., 2003, 13: 103–107.

    Article  PubMed  CAS  Google Scholar 

  17. Felsenfeld, A., Peterson, J., Schloss, J. et al., Assessing the quality of the DNA sequence from the Human Genome Project, Genome Res., 1999, 9: 1–4.

    PubMed  CAS  Google Scholar 

  18. Patel, A., Rochelle, J. M., Jones, J. M. et al., Mapping of the taurine transporter gene to mouse chromosome 6 and to the short arm of human chromosome 3, Genomics, 1995, 25: 314–317.

    Article  PubMed  CAS  Google Scholar 

  19. Heilig, R., Eckenberg, R., Petit, J. L. et al., The DNA sequence and analysis of human chromosome 14, Nature, 2003, 421: 601–607.

    Article  PubMed  CAS  Google Scholar 

  20. Woolfe, A., Goodson, M., Goode, D. K. et al., Highly conserved non-coding sequences are associated with vertebrate development, PLoS Biol., 2005, 3: e7.

    Article  PubMed  Google Scholar 

  21. Deloukas, P., Matthews, L. H., Ashurst, J. et al., The DNA sequence and comparative analysis of human chromosome 20, Nature, 2001, 414: 865–871.

    Article  PubMed  CAS  Google Scholar 

  22. Dunham, I., Shimizu, N., Roe, B. A. et al., The DNA sequence of human chromosome 22, Nature, 1999, 402: 489–495.

    Article  PubMed  CAS  Google Scholar 

  23. Mironov, A. A., Fickett, J. W., Gelfand, M. S., Frequent alternative splicing of human genes, Genome Res., 1999, 9: 1288–1293.

    Article  PubMed  CAS  Google Scholar 

  24. The Gene Ontology Consortium, Gene Ontology: Tool for the unification of biology. Nat. Genet., 2000, 25: 25–29.

    Article  Google Scholar 

  25. Gardiner, K., Human genome organization, Curr. Opin. Genet., 1995, 5:315–322.

    Article  CAS  Google Scholar 

  26. Kruglyak, S., Durrett, R. T., Schug, M. D. et al., Equilibrium distributions of microsatellite repeat length resulting from a balance between slippage events and point mutations, Proc. Natl. Acad. Sci. USA, 1998, 95: 10774–10778.

    Article  PubMed  CAS  Google Scholar 

  27. The International HapMap Consortium, The international Hap-Map project, Nature, 2003, 426: 789–796.

    Article  Google Scholar 

  28. Schwartz, S., Kent, W. J., Smit, A. et al., Human-mouse alignments with BLASTZ, Genome Res., 2003, 13: 103–107.

    Article  PubMed  CAS  Google Scholar 

  29. Riethman, H. C., Moyzis, R. K., Meyne, J. et al., Cloning human telomeric DNA fragments into Saccharomyces cerevisiae using a yeast-artificial-chromosome vector, Proc. Natl. Acad. Sci. USA, 1989, 86:6240–6244.

    Article  PubMed  CAS  Google Scholar 

  30. Riethman, H., Ambrosini, A., Castaneda, C. et al., Mapping and initial analysis of human subtelomeric sequence assemblies, Genome Res., 2004, 14: 18–28.

    Article  PubMed  CAS  Google Scholar 

  31. Purrello, M., Alhadeff, B., Whittington, E. et al., Comparison of cytologic and genetic distances between long arm subtelomeric markers of human autosome 14 suggests uneven distribution of crossing-over, Cytogenet. Cell Genet., 1987, 44: 32–40.

    Article  PubMed  CAS  Google Scholar 

  32. Mohrenweiser, H. W., Tsujimoto, S., Gordon, L. et al., Regions of sex-specific hypo and hyper-recombination identified through integration of 180 genetic markers into the metric physical map of human chromosome 19, Genomics, 1998, 472: 153–162.

    Article  Google Scholar 

  33. Broman, K. W., Murray, J.C., Sheffield, V. C. et al., Comprehensive human genetic maps: Individual and sex-specific variation in recombination, Am. J. Hum. Genet., 1998, 63: 861–869.

    Article  PubMed  CAS  Google Scholar 

  34. Dib, C., Faure, S., Fizames, C. et al., A comprehensive genetic map of the human genome based on 5,264 microsatellites, Nature, 1996, 380:152–154.

    Article  PubMed  CAS  Google Scholar 

  35. Gerton, J. L., DeRisi, J., Shroff, R. et al., Global mapping of meiotic recombination hotspots and coldspots in the yeast Saccharomyces cerevisiae, Proc. Natl. Acad. Sci. USA, 2000, 97: 11383–11390.

    Article  PubMed  CAS  Google Scholar 

  36. Wang, J., Li, S. T., Zhang, Y. et al., Vertebrate gene predictions and the problem of large genes, Nature, 2003, 4: 741–749.

    CAS  Google Scholar 

  37. Burge, C., Karlin, S., Prediction of complete gene structures in human genomic DNA, J. Mol. Biol., 1997, 268: 78–94.

    Article  PubMed  CAS  Google Scholar 

  38. Birn, E., Clamp, M., Durbin, R., GeneWise and Genomewise, Genome Res., 2004, 14: 988–995.

    Article  Google Scholar 

  39. Fortna, A., Gardiner, K., Genomic sequence analysis tools: A user’s guide, Trends Genet., 2001, 17: 158–164.

    Article  PubMed  CAS  Google Scholar 

  40. International Human Genome Sequencing Consortium, Finishing the euchromatic sequence of the human genome, Nature, 2004, 431:931–945.

    Article  Google Scholar 

  41. Wong, G. K., Passey, D. A., Yu, J., Most of the human genome is transcribed, Genome Res., 2001, 11: 1975–1977.

    Article  PubMed  CAS  Google Scholar 

  42. Wong, G. K., Passey, D. A., Huang, Y. et al., Is “junk” DNA mostly intron DNA? Genome Res., 2000, 10: 1672–1678.

    Article  PubMed  CAS  Google Scholar 

  43. Venkatesh, B., Gilligan, P., Brenner, S., Fugu: A compact vertebrate reference genome, FEBS Lett., 2000, 476: 3–7.

    Article  PubMed  CAS  Google Scholar 

  44. Venter, J. C., Adams, M. D., Myers, E. W. et al., The sequence of the human genome, Science, 2001, 291: 1304–1351.

    Article  PubMed  CAS  Google Scholar 

  45. Wu, Q., Dong, W., Qi, X., Genomic Structure of Metabotropic glutamate receptor 7 and comparison of genomic structures of extracellular domains of mGluR family, Chinese Science Bulletin, 2002, 47: 1330–1336.

    Article  CAS  Google Scholar 

  46. Makoff, A., Pilling, C., Harrington, K. et al., Human metabotropic glutamate receptor type 7: Molecular cloning and mRNA distribution in the CNS, Brain Res. Mol. Brain Res., 1996, 40: 165–170.

    Article  PubMed  CAS  Google Scholar 

  47. Phillips, T., Makoff, A., Murrison, E. et al., Immunohistochemical localisation of mGluR7 protein in the rodent and human cerebellar cortex using subtype specific antibodies, Brain Res. Mol. Brain Res., 1998, 57:132–141.

    Article  PubMed  CAS  Google Scholar 

  48. Monaghan, D. T., Bridges, R. J., Cotman, C. W., The excitatory amino acid receptors: Their classes, pharmacology, and distinct properties in the function of the central nervous system, Annu. Rev. Pharmacol. Toxicol., 1989, 29: 365–402.

    Article  PubMed  CAS  Google Scholar 

  49. Huang, F., Shi, L. J., Heng, H. H. et al., Assignment of the human GABA transporter gene (GABATHG) locus to chromosome 3p24-p25, Genomics, 1995, 29: 302–304.

    Article  PubMed  CAS  Google Scholar 

  50. Borden, L. A., Dhar, T. G., Smith, K. E. et al., Cloning of the human homologue of the GABA transporter GAT-3 and identification of a novel inhibitor with selectivity for this site, Receptors Channels, 1994, 2: 207–213.

    PubMed  CAS  Google Scholar 

  51. Huebner, K., Tumor suppressors on 3p: A neoclassic quartet, Proc. Natl. Acad. Sci. USA, 2001, 98: 14763–14765.

    Article  PubMed  CAS  Google Scholar 

  52. Kondo, K., William, G., Kaelin, J. R., The von Hippel-Lindau tumor suppressor gene, Exp. Cell Res., 2001, 264: 117–125.

    Article  PubMed  CAS  Google Scholar 

  53. Friedrich, C. A., Von Hippel-Lindau syndrome. A pleomorphic condition, Cancer, 1999, 86: 2478–2482.

    Article  PubMed  CAS  Google Scholar 

  54. Duan, D. R., Pause, A., Burgess, W. H. et al., Inhibition of transcription elongation by the VHL tumor suppressor protein, Science, 1995, 269: 1402–1406.

    Article  PubMed  CAS  Google Scholar 

  55. Kibel, A., Iliopoulos, O., DeCaprio, J. A., et al., Binding of the von Hippel-Lindau tumor suppressor protein to Elongin B and C, Science, 1995, 269: 1444–1446.

    Article  PubMed  CAS  Google Scholar 

  56. Gnarra, J. R., Zhou, S., Merrill, M. J., et al., Post-transcriptional regulation of vascular endothelial growth factor mRNA by the product of the VHL tumor suppressor gene, Proc. Natl. Acad. Sci. USA, 1996, 93: 10589–10594.

    Article  PubMed  CAS  Google Scholar 

  57. Iliopoulos, O., Levy, A. P., Jiang, C., et al., Negative regulation of hypoxia-inducible genes by the von Hippel-Lindau protein, Proc. Natl. Acad. Sci. USA, 1996, 93: 10595–10599.

    Article  PubMed  CAS  Google Scholar 

  58. Pause, A., Lee, S., Lonergan, K. M. et al., The von Hippel-Lindau tumor suppressor gene is required for cell cycle exit upon serum withdrawal, Proc. Natl. Acad. Sci. USA, 1998, 95: 993–998.

    Article  PubMed  CAS  Google Scholar 

  59. Ohh, M., Yauch, R. L., Lonergan, K. M. et al., The von Hippel-Lindau tumor suppressor protein is required for proper assembly of an extracellular fibronectin matrix, Mol. Cell, 1998, 1: 959:968.

    Article  PubMed  Google Scholar 

  60. Kamura, T., Koepp, D. M., Conrad, M. N. et al., Rbx1, a component of the VHL tumor suppressor complex and SCF ubiquitin ligase, Science, 1999, 284: 657–661.

    Article  PubMed  CAS  Google Scholar 

  61. Timmers, C., Taniguchi, T., Hejna, J. et al., Positional cloning of a novel Fanconi anemia gene, FANCD2, Mol. Cell, 2001, 7–241:248.

    Google Scholar 

  62. Garcia-Higuera, I., Taniguchi, T., Ganesan, S. et al., Interaction of the Fanconi anemia proteins and BRCA1 in a common pathway, Mol. Cell, 2001, 7: 249–262.

    Article  PubMed  CAS  Google Scholar 

  63. Galbiati, F., Volonte, D., Minetti, C. et al., Phenotypic behavior of caveolin-3 mutations that cause autosomal dominant limb girdle muscular dystrophy (LGMD-1C). Retention of LGMD-1C caveolin-3 mutants within the golgi complex, J. Biol. Chem., 1999, 274: 25632–25641.

    Article  PubMed  CAS  Google Scholar 

  64. Wang, M., Liu, Y. E., Greene, J. et al., Inhibition of tumor growth and metastasis of human breast cancer cells transfected with tissue inhibitor of metalloproteinase 4, Oncogene, 1997, 14: 2767–2774.

    Article  PubMed  CAS  Google Scholar 

  65. Collins, F. S., Positional cloning moves from perditional to traditional, Nat. Genet., 1995, 9: 347–350.

    Article  PubMed  CAS  Google Scholar 

  66. Drumheller, T., McGillivray, B. C., Behrner, D. et al., Precise localisation of 3p25 breakpoints in four patients with the 3p-syndrome, J. Med. Genet., 1996, 33: 842–847.

    Article  PubMed  CAS  Google Scholar 

  67. Angeloni, D., Lindor, N. M., Pack, S. et al., CALL gene is haploinsufficient in a 3p-syndrome patient, Am. J. Med. Genet., 1999, 86:482–485.

    Article  PubMed  CAS  Google Scholar 

  68. Dan, M., Niebuhr, A., Zhang, X. X., Critical region for cri-du-chat syndrome is located in the 5p15.2, a region flanked by DNA markers D5S713 and D5S18, Chinese Journal of Medical Genetics, 1997, 14:263–267.

    Google Scholar 

  69. Church, D. M., Bengtsson, U., Nielsen, K. V. et al., Molecular definition of deletions of different segments of distal 5p that result in distinct phenotypic features, Am. J. Hum. Genet., 1995, 56: 1162–1172.

    PubMed  CAS  Google Scholar 

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    The Chinese Human Genome Sequencing Consortium. “Beijing Region” (3pter-D3S3397) of the Human Genome: Complete sequence and analysis. Sci. China Ser. C.-Life Sci. 48, 311–329 (2005). https://doi.org/10.1360/062005-173

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