Bioinformatics and Functional Genomics 3rd Edition

Chapter 20: The Human Genome

In 1953 Francis Crick and James Watson described the double-helical nature of DNA. By 2003, 50 years later, the human genome sequence was essentially completed. In the following decade the introduction of next-generation sequencing has allowed tens of thousands of genomes (and perhaps hundreds of thousands of exomes) to be sequenced. We can ask two fundamentally different questions:

  • What makes us different than other creatures? We can compare the human and chicken genomes, focusing on the few regions that are perfectly conserved (see Chapter 8 where we do this as an exercise).
  • What makes us different than each other? We can sequence the genomes of people from diverse geographic regions, focusing on the few regions that are different among humans (such as single nucleotide polymorphisms).
  • In this chapter we explore the human genome in terms of its basic features. We follow the outline of two key 2001 papers on the completion of the human genome, one from the HumAsan Genome Project (a public, multinational consortium) and one from Celera Genomics. We survey the chromosomes (1-22, X, Y, and the mitochondrial genome) and we discuss major initiatives such as HapMap and the 1000 Genomes Project.

    Publications reporting the sequence of the human genomes and chromosomes
    Project Reference PMID Accession
    Human genome (public) International Human Genome Sequencing Consortium. Initial sequencing and analysis of the human genome. Nature 409, 860–921 (2001)

    11237011

     
    Human genome (public, finished) International Human Genome Sequencing Consortium. Finishing the euchromatic sequence of the human genome. Nature 431, 931-945 (2004). 15496913  
    Human genome (Celera) Venter, J. C., et al. The sequence of the human genome. Science 291, 1304–1351 (2001). 11181995  
    Individual diploid genome Levy, S., et al. The diploid genome sequence of an individual human. PLoS Biol. 5, e254 (2007). 17803354  
    chromosome 1 Gregory, S.G., et al.  The DNA sequence and biological annotation of human chromosome 1. Nature 441, 315-321 (2006). 16710414 NC_000001   

    AC_000133

    CH003496
    chromosome 2 Hillier, L. W. et al. Generation and annotation of the DNA sequences of human chromosomes 2 and 4. Nature 434, 724-731 (2005). 15815621 NC_000002
    chromosome 3 Muzny, D.M. et al. The DNA sequence, annotation and analysis of human chromosome 3. Nature 440, 1194-1198 (2006). 16641997 CM000464
    chromosome 4 Hillier, L. W. et al. Generation and annotation of the DNA sequences of human chromosomes 2 and 4. Nature 434, 724-731 (2005). 15815621 CM000465
    chromosome 5 Schmutz, J. et al. The DNA sequence and comparative analysis of human chromosome 5. Nature 431, 268-274 (2004). 15372022 CM000466
    chromosome 6 Mungall, A.J. et al. The DNA sequence and analysis of human chromosome 6. Nature 425, 805-811 (2003). 14574404 CM000467
    chromosome 7 Hillier, L. W. et al. The DNA sequence of human chromosome 7. Nature 424, 157-164 (2003). 12853948 CM000468
    chromosome 7 Scherer et al. Human chromosome 7: DNA sequence and biology. Science 300(5620), 767-772 (2003). 12690205 BL000001
    chromosome 8 Nusbaum, C. et al. DNA sequence and analysis of human chromosome 8. Nature 439, 331-335 (2006). 16421571 CM000469
    chromosome 9 Humphray, S. J. et al. DNA sequence and analysis of human chromosome 9. Nature 429, 369-375 (2004). 15164053 CM000470
    chromosome 10 Deloukas, P. et al. The DNA sequence and comparative analysis of human chromosome 10. Nature 429, 375-382 (2004). 15164054 CM000471
    chromosome 11 Taylor, T. D. et al. Human chromosome 11 DNA sequence and analysis including novel gene identification. Nature 440, 497-500 (2006). 16554811 CM000472
    chromosome 12 Scherer, S. E. et al. The finished DNA sequence of human chromosome 12. Nature 440, 346-351 (2006). 16541075  
    chromosome 13

    Dunham, A. et al. The DNA sequence and analysis of human chromosome 13. Nature 428, 522-528(2004).

    15057823  
    chromosome 14 Heilig, R. et al. The DNA sequence and analysis of human chromosome 14. Nature 421, 601-607 (2003). 12508121  
    chromosome 15 Zody, M. C. et al. Analysis of the DNA sequence and duplication history of human chromosome 15. Nature 440, 671-675 (2006). 16572171  
    chromosome 16 Martin, J. et al. The sequence and analysis of duplication-rich human chromosome 16. Nature 432, 988-994 (2004). 15616553  
    chromosome 17 Muzny, D. M. et al. DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage. Nature 440, 1045-1049 (2006). 16625196  
    chromosome 18      
    chromosome 19 Grimwood, J. et al. The DNA sequence and biology of human chromosome 19. Nature 428, 529-625 (2003). 15057824  
    chromosome 20 Deloukas, P., et al. The DNA sequence and comparative analysis of human chromosome 20. Nature 414, 865–871 (2001). 11780052  
    chromosome 21 Hattori, M. et al. The DNA sequence of human chromosome 21. Nature 405, 311-319 (2000). 10830953  
    chromosome 22 Dunham, I., et al. The DNA sequence of human chromosome 22. Nature 402, 489–495 (1999). 10591208  
    chromosome X Ross, M.T. et al. The DNA sequence of the human X chromosome. Nature 434, 325-337 (2005). 15772651  
    chromosome Y      
    To find accession numbers of chromosomes from 100 to 200 Mb, use the Entrez Nucleotide command txid9606[Organism:exp] 100000000:200000000[slen]. To see a list of chromosomal accession numbers, visit this NCBI site.