Human Genome Project: Importance in Clinical Genetics

Abstract

The Human Genome Project is impacting upon clinical genetics by defining the complexity of genes in humans, by developing technology at ‘genome‐wide’ scale, by underpinning the search for the genetic origins of complex disorders and by driving the development of new sequencing technologies of great power. Here we review these developments and argue that the greatest benefit of the Human Genome Project is yet to come.

Keywords: genome; common genetic disorders; personal genome; genome scale; DNA arrays; predictive genetic information

Figure 1.

Copy number variations (CNVs) in human DNA. Red bars to left of chromosome indicate frequency and blue or green bars to right indicate size (see key above). Reprinted by permission from Macmillan Publisers Ltd, Redon et al..

Figure 2.

SNPs and haplotypes in the human genome. Displays are for chromosomes 18‐Y only. See original figure for legend and data from remainder of genome. LD is linkage disequilibrium and is a measure of haplotype ‘lengths’. From Hinds DA et al. Whole‐genome patterns of common DNA variation in three human populations. Science 307: 1072–1079. Reproduced with permission from AAAS. http://www.sciencemag.org. Readers may view, browse and/or download material for temporary copying purposes only, provided these uses are for noncommercial personal purposes. Except as provided by the law, this material may not be further reproduced, distributed, transmitted, modified, adapted, performed, displayed, published, or sold in whole or in part, without prior written permission from the publisher.

close

References

Babak T, Blencowe BJ and Hughes TR (2005) A systematic search for new mammalian noncoding RNAs indicates little conserved intergenic transcription. BMC Genomics 5: 104.

Bentley DR (2006) Whole‐genome re‐sequencing. Current Opinion in Genetics and Development 16: 545–552.

Bulyk ML (2006) DNA microarray technologies for measuring protein‐DNA interactions. Current Opinion in Biotechnology 17: 422–430.

Carninci P (2006) Tagging mammalian transcription complexity. Trends in Genetics 22: 501–510.

Chen K and Rajewsky N (2007) The evolution of gene regulation by transcription factors and microRNAs. Nature Reviews. Genetics 8: 93–103.

Crawford GE, Davis S, Scacheri PC et al. (2006) DNase‐chip: a high‐resolution method to identify DNase I hypersensitive sites using tiled microarrays. Nature Methods 3: 503–509.

Easton DF, Pooley KA, Dunning AM et al. (2007) Genome‐wide association study identifies novel breast cancer susceptibility loci. Nature 447(May 27): 1087–1093. (Epub ahead of print).

Ein‐Dor L, Kela I, Getz G, Givol D and Domany E (2005) Outcome signature genes in breast cancer: is there a unique set? Bioinformatics 21: 171–178.

ENCODE Project Consortium (2007) Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature 447: 799–816.

Esteller M (2007) Cancer epigenomics: DNA methylomes and histone‐modification maps. Nature Reviews. Genetics 8: 286–298.

Frayling TM, Timpson NJ, Weedon MN et al. (2007) A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 316: 889–994.

Freeman JL, Perry GH, Feuk L et al. (2006) Copy number variation: new insights in genome diversity. Genome Research 16: 949–961.

Greenman C, Stephens P, Smith R et al. (2007) Patterns of somatic mutation in human cancer genomes. Nature 446: 153–158.

Guigo R, Flicek P, Abril JF et al. (2006) EGASP: the human ENCODE Genome Annotation Assessment Project. Genome Biology 7(suppl. 1): S2.1–S31.

Hinds DA, Stuve LL, Nilsen GB et al. (2005) Whole‐genome patterns of common DNA variation in three human populations. Science 307: 1072–1079.

Huttenhofer A, Schattner P and Polacek N (2005) Non‐coding RNAs: hope or hype? Trends in Genetics 21: 289–297.

International Haplotype Map Consortium (2005) A haplotype map of the human genome. Nature 437: 1299–1320.

Jackson RJ and Standart N (2007) How do microRNAs regulate gene expression? Science STKE 2007(367): re1, 2 January.

Juric D, Sale S, Hromas RA et al. (2005) Gene expression profiling differentiates germ cell tumors from other cancers and defines subtype‐specific signatures. Proceedings of the National Academy of Sciences of the USA 102: 17763–17768.

Lacayo NJ, Meshinchi S, Kinnunen P et al. (2004) Gene expression profiles at diagnosis in de novo childhood AML patients identify FLT3 mutations with good clinical outcomes. Blood 104: 2646–2654.

Lu J, Getz G, Miska EA et al. (2005) MicroRNA expression profiles classify human cancers. Nature 435: 834–838.

Nelson WG, Yegnasubramanian S, Agoston AT et al. (2007) Abnormal DNA methylation, epigenetics, and prostate cancer. Frontiers in Bioscience 12: 4254–4266.

O'Connor TP and Crystal RG (2006) Genetic medicines: treatment strategies for hereditary disorders. Nature Reviews. Genetics 7: 261–276.

Ohlsson R and Gondor A (2007) The 4C technique: the ‘Rosetta stone’ for genome biology in 3D? Current Opinion in Cell Biology 19: 1–5.

Pinkel D and Albertson DG (2005) Comparative genomic hybridization. Annual Reviews of Genomics and Human Genetics 6: 331–354.

Redon R, Ishikawa S, Fitch KR et al. (2006) Global variation in copy number in the human genome. Nature 444: 444–454.

Saxena R, Voight BF, Lyssenko V et al. (2007) Genome‐wide association analysis identifies loci for type 2 diabetes and triglyceride levels. Science 316(April 26): 1331–1336. (Epub ahead of print).

Sladek R, Rocheleau G, Rung J et al. (2007) A genome‐wide association study identifies novel risk loci for type 2 diabetes. Nature 445: 881–885.

The Human Genome Structural Variation Working Group (2007) Completing the map of human genetic variation. Nature 447: 161–165.

Ventura M, Weigl S, Carbone L et al. (2004) Recurrent sites for new centromere seeding. Genome Research 14: 1696–1703.

Wiemer EA (2007) The role of microRNAs in cancer: no small matter. European Journal of Cancer 43(May 23): 1529–1544. (Epub ahead of print).

Further Reading

Church GM (2005) The personal Genome Project, Molecular Systems Biology 1:2005.0030. (Epub December 13).

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Little, Peter FR, and Williams, Rohan BH(Apr 2008) Human Genome Project: Importance in Clinical Genetics. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0005485]