Disease‐related Genes: Identification


The identification of a disease gene is a crucial step in the development of diagnostic procedures and in the understanding of the pathogenetic mechanisms underlying the disease. Strategies for the identification of genes involved in the pathogenesis of human disease can involve either those used in the presence of known loci (mainly positional candidate genes) or those used when the locus is unknown (functional cloning and candidate genes).

Keywords: disease gene; candidate gene; positional candidate genes; functional cloning; mutation analysis

Figure 1.

Schematic of the strategies most commonly used for disease gene identification.

Figure 2.

Schematic of the positional candidate approach. When a new disease locus is assigned to a chromosomal region (see middle panel), candidate genes from the same region are evaluated. The features of these candidate genes are compared with the features of that particular disease in order to determine possible matches. Similarly, when a new gene is assigned to a chromosomal region, candidate diseases are analyzed by an analogous process. (Reprinted with permission from Ballabio .)



Adams MD, Kelley JM, Gocayne JD, et al. (1991) Complementary DNA sequencing: expressed sequence tags and human genome project. Science 252: 1651–1656.

Ballabio A (1993) The rise and fall of positional cloning? Nature Genetics 3: 277–279.

Ballabio A, Brown S, and Fisher E (1998) Strategies for gene discovery in mammalian systems. In: Green ED, Birren B, Klapholz S, Myers RM and Hieter P (eds.) Genome Analysis: A Laboratory Manual, vol. 2, pp. 1–48. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press.

Collins FS (1992) Positional cloning: let's not call it reverse anymore. Nature Genetics 1: 3–6.

Collins FS (1995) Positional cloning moves from state of the art. Nature Genetics 9: 347–350.

Deloukas P, Schuler GD, Gyapay G, et al. (1998) A physical map of 30 000 human genes. Science 282: 744–746.

Dryja TP, McGee TL, Reichel E, et al. (1990) A point mutation of the rhodopsin gene in one form of retinitis pigmentosa. Nature 343: 364–366.

Fickett JW (1996) Finding genes by computer: the state of the art. Trends in Genetics 12: 316–320.

Fishel R and Wilson T (1997) MutS homologs in mammalian cells. Current Opinion in Genetics and Development 7: 105–113.

Gitschier J, Wood WI, Goralka TM, et al. (1984) Characterization of the human factor VIII gene. Nature 312: 326–330.

Lander ES, Linton LM, Birren B, et al. (2001) Initial sequencing and analysis of the human genome. Nature 409: 860–921.

Price DL, Sisodia SS and Borchelt DR (1998) Genetic neurodegenerative diseases: the human illness and transgenic models. Science 282: 1079–1083.

Schuler GD, Boguski MS, Stewart EA, et al. (1996) A gene map of the human genome. Science 274: 540–546.

Semina EV, Ferrell RE, Mintz‐Hittner HA, et al. (1998) A novel homeobox gene PITX3 is mutated in families with autosomal‐ dominant cataracts and ASMD. Nature Genetics 19: 167–170.

Venter JC, Adams MD, Myers EW, et al. (2001) The sequence of the human genome. Science 291: 1304–1351.

Whitney M, Thayer M, Reifsteck C, et al. (1995) Microcell mediated chromosome transfer maps the Fanconi anaemia group D gene to chromosome 3p. Nature Genetics 11: 341–343.

Yamamoto S, Sippel KC, Berson EL and Dryja TP (1997) Defects in the rhodopsin kinase gene in the Oguchi form of stationary night blindness. Nature Genetics 15: 175–178.

Zhu Z, Yao J, Johns T, et al. (1998) SURF1, encoding a factor involved in the biogenesis of cytochrome c oxidase, is mutated in Leigh syndrome. Nature Genetics 20: 337–343.

Web Links

Human Genome Browser Gateway (University of California Santa Cruz) http://genome.ucsc.edu/cgi‐bin/hgGateway?org=Human

Ensembl Genome Browser (Sanger Institute) http://www.ensembl.org/Homo_sapiens/

Both these sites provide a detailed annotation of the human genome NIX server at Human Genome Mapping Resource Centre (UK MRC HGMP‐RC) NIX is a tool to view the results of running many DNA analysis programs on a given DNA sequence. http://www.hgmp.mrc.ac.uk/Registered/Webapp/nix/

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Banfi, Sandro, and Ballabio, Andrea(Jan 2006) Disease‐related Genes: Identification. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0005484]