- Reiter, L. T., Potocki, L., Chien, S., Gribskov, M. & Bier, E. A systematic analysis of human disease-associated gene sequences in Drosophila melanogaster. Genome Res. 11, 1114–1125 (2001). This systematic cross-genomic analysis of human disease homologues in D. melanogaster revealed that 75% of human disease genes, covering a broad range of disorders, have homologues in flies.
CAS PubMed PubMed Central Google Scholar
- Chien, S., Reiter, L. T., Bier, E. & Gribskov, M. Homophila: human disease gene cognates in Drosophila. Nucleic Acids Res. 30, 149–151 (2002).
CAS PubMed PubMed Central Google Scholar
- Adams, M. D. et al. The genome sequence of Drosophila melanogaster. Science 287, 2185–2195 (2000).
Article PubMed Google Scholar
- Fortini, M. E., Skupski, M. P., Boguski, M. S. & Hariharan, I. K. A survey of human disease gene counterparts in the Drosophila genome. J. Cell Biol. 150, F23–30 (2000).
CAS PubMed Google Scholar
- Inlow, J. K. & Restifo, L. L. Molecular and comparative genetics of mental retardation. Genetics 166, 835–881 (2004).
CAS PubMed PubMed Central Google Scholar
- Bier, E. & McGinnis, W. in Molecular Basis of Inborn Errors of Development (eds Epstein C. J., Erikson, R. P. & Wynshaw-Boris, A.) 25–45 (Oxford Univ. Press, New York, 2004).
Google Scholar
- Jiang, J., Kosman, D., Ip, Y. T. & Levine, M. The dorsal morphogen gradient regulates the mesoderm determinant twist in early Drosophila embryos. Genes Dev. 5, 1881–1891 (1991).
CAS PubMed Google Scholar
- Kosman, D., Ip, Y. T., Levine, M. & Arora, K. Establishment of the mesoderm-neuroectoderm boundary in the Drosophila embryo. Science 254, 118–122 (1991).
CAS PubMed Google Scholar
- Leptin, M. twist and snail as positive and negative regulators during Drosophila mesoderm development. Genes Dev. 5, 1568–1576 (1991).
CAS PubMed Google Scholar
- Rao, Y., Vaessin, H., Jan, L. Y. & Jan, Y. N. Neuroectoderm in Drosophila embryos is dependent on the mesoderm for positioning but not for formation. Genes Dev. 5, 1577–1588 (1991).
CAS PubMed Google Scholar
- Ray, R. P., Arora, K., Nusslein-Volhard, C. & Gelbart, W. M. The control of cell fate along the dorsal-ventral axis of the Drosophila embryo. Development 113, 35–54 (1991).
CAS PubMed Google Scholar
- Beiman, M., Shilo, B. Z. & Volk, T. Heartless, a Drosophila FGF receptor homolog, is essential for cell migration and establishment of several mesodermal lineages. Genes Dev. 10, 2993–3002 (1996).
CAS PubMed Google Scholar
- Gisselbrecht, S., Skeath, J. B., Doe, C. Q. & Michelson, A. M. heartless encodes a fibroblast growth factor receptor (DFR1/DFGF-R2) involved in the directional migration of early mesodermal cells in the Drosophila embryo. Genes Dev. 10, 3003–3017 (1996).
CAS PubMed Google Scholar
- Rice, D. P. et al. Integration of FGF and TWIST in calvarial bone and suture development. Development 127, 1845–1855 (2000).
CAS PubMed Google Scholar
- Sosic, D., Richardson, J. A., Yu, K., Ornitz, D. M. & Olson, E. N. Twist regulates cytokine gene expression through a negative feedback loop that represses NF-κB activity. Cell 112, 169–180 (2003).
CAS PubMed Google Scholar
- Ip, Y. T., Park, R. E., Kosman, D., Yazdanbakhsh, K. & Levine, M. dorsal-twist interactions establish snail expression in the presumptive mesoderm of the Drosophila embryo. Genes Dev. 6, 1518–1530 (1992).
CAS PubMed Google Scholar
- Irvine, K. D. & Vogt, T. F. Dorsal-ventral signaling in limb development. Curr. Opin. Cell Biol. 9, 867–876 (1997).
CAS PubMed Google Scholar
- Wu, J. Y. & Rao, Y. Fringe: defining borders by regulating the Notch pathway. Curr. Opin. Neurobiol. 9, 537–543 (1999).
CAS PubMed Google Scholar
- Bridges, C. B. & Morgan, T. H. The third-chromosome group of mutant characters in Drosophila melanogaster. Carnegie Inst. Washington Publ. 327, 197–201 (1923).
Google Scholar
- Kusumi, K. et al. The mouse pudgy mutation disrupts Delta homologue Dll3 and initiation of early somite boundaries. Nature Genet. 19, 274–278 (1998).
CAS PubMed Google Scholar
- Evrard, Y. A., Lun, Y., Aulehla, A., Gan, L. & Johnson, R. L. lunatic fringe is an essential mediator of somite segmentation and patterning. Nature 394, 377–381 (1998).
CAS PubMed Google Scholar
- Zhang, N. & Gridley, T. Defects in somite formation in _lunatic fringe_-deficient mice. Nature 394, 374–377 (1998).
CAS PubMed Google Scholar
- Li, L. et al. Alagille syndrome is caused by mutations in human Jagged1, which encodes a ligand for Notch1. Nature Genet. 16, 243–251 (1997).
CAS PubMed Google Scholar
- Oda, T. et al. Mutations in the human Jagged1 gene are responsible for Alagille syndrome. Nature Genet. 16, 235–242 (1997).
CAS PubMed Google Scholar
- Bulman, M. P. et al. Mutations in the human Delta homologue, DLL3, cause axial skeletal defects in spondylocostal dysostosis. Nature Genet. 24, 438–441 (2000). Showed that the human DLL3 gene is mutated in individuals with spondylocostal dysostosis, which is phenotypically similar to loss of Dll3 function in the pudgy mouse mutant.
CAS PubMed Google Scholar
- Bodai, L., Pallos, J., Thompson, L. M. & Marsh, J. L. Altered protein acetylation in polyglutamine diseases. Curr. Med. Chem. 10, 2577–2587 (2003).
CAS PubMed Google Scholar
- Bonini, N. M. & Fortini, M. E. Human neurodegenerative disease modeling using Drosophila. Annu. Rev. Neurosci. 26, 627–656 (2003).
CAS PubMed Google Scholar
- Driscoll, M. & Gerstbrein, B. Dying for a cause: invertebrate genetics takes on human neurodegeneration. Nature Rev. Genet. 4, 181–194 (2003).
CAS PubMed Google Scholar
- Muqit, M. M. & Feany, M. B. Modelling neurodegenerative diseases in Drosophila: a fruitful approach? Nature Rev. Neurosci. 3, 237–243 (2002).
CAS Google Scholar
- Shulman, J. M., Shulman, L. M., Weiner, W. J. & Feany, M. B. From fruit fly to bedside: translating lessons from Drosophila models of neurodegenerative disease. Curr. Opin. Neurol. 16, 443–449 (2003).
PubMed Google Scholar
- Rubinsztein, D. C. Lessons from animal models of Huntington's disease. Trends Genet. 18, 202–209 (2002).
CAS PubMed Google Scholar
- Ghosh, S. & Feany, M. B. Comparison of pathways controlling toxicity in the eye and brain in Drosophila models of human neurodegenerative diseases. Hum. Mol. Genet. 13, 2011–2018 (2004).
CAS PubMed Google Scholar
- Warrick, J. M. et al. Suppression of polyglutamine-mediated neurodegeneration in Drosophila by the molecular chaperone HSP70. Nature Genet. 23, 425–428 (1999). Showed that human HSP70 could suppress the effect of polyglutamine-mediated retinal degeneration in flies, which was also shown subsequently to be the case in mice.
CAS PubMed Google Scholar
- Kazemi-Esfarjani, P. & Benzer, S. Genetic suppression of polyglutamine toxicity in Drosophila. Science 287, 1837–1840 (2000).
CAS PubMed Google Scholar
- Fernandez-Funez, P. et al. Identification of genes that modify _ataxin-1_-induced neurodegeneration. Nature 408, 101–106 (2000).
CAS PubMed Google Scholar
- Steffan, J. S. et al. Histone deacetylase inhibitors arrest polyglutamine-dependent neurodegeneration in Drosophila. Nature 413, 739–743 (2001).
CAS PubMed Google Scholar
- Shulman, J. M. & Feany, M. B. Genetic modifiers of tauopathy in Drosophila. Genetics 165, 1233–1242 (2003).
CAS PubMed PubMed Central Google Scholar
- Cummings, C. J. et al. Chaperone suppression of aggregation and altered subcellular proteasome localization imply protein misfolding in SCA1. Nature Genet. 19, 148–154 (1998).
CAS PubMed Google Scholar
- Cummings, C. J. et al. Over-expression of inducible HSP70 chaperone suppresses neuropathology and improves motor function in SCA1 mice. Hum. Mol. Genet. 10, 1511–1518 (2001).
CAS PubMed Google Scholar
- Hay, D. G. et al. Progressive decrease in chaperone protein levels in a mouse model of Huntington's disease and induction of stress proteins as a therapeutic approach. Hum. Mol. Genet. 13, 1389–1405 (2004).
CAS PubMed Google Scholar
- Hockly, E. et al. Suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, ameliorates motor deficits in a mouse model of Huntington's disease. Proc. Natl Acad. Sci. USA 100, 2041–2046 (2003).
CAS PubMed PubMed Central Google Scholar
- Mutsuddi, M., Marshall, C. M., Benzow, K. A., Koob, M. D. & Rebay, I. The spinocerebellar ataxia 8 noncoding RNA causes neurodegeneration and associates with staufen in Drosophila. Curr. Biol. 14, 302–308 (2004).
CAS PubMed Google Scholar
- Auluck, P. K. & Bonini, N. M. Pharmacological prevention of Parkinson disease in Drosophila. Nature Med. 8, 1185–1186 (2002).
CAS PubMed Google Scholar
- Maroteaux, L., Campanelli, J. T. & Scheller, R. H. Synuclein: a neuron-specific protein localized to the nucleus and presynaptic nerve terminal. J. Neurosci. 8, 2804–2815 (1988).
CAS PubMed PubMed Central Google Scholar
- Spillantini, M. G. et al. α-synuclein in Lewy bodies. Nature 388, 839–840 (1997).
CAS PubMed Google Scholar
- Feany, M. B. & Bender, W. W. A Drosophila model of Parkinson's disease. Nature 404, 394–398 (2000). Showed that mis-expression of mutant, but not normal, forms of human α-synuclein in flies causes phenotypes similar to those observed in Parkinson disease, including loss of dopaminergic neurons and the formation of filamentous intraneuronal inclusions that are reminiscent of Lewy bodies.
CAS PubMed Google Scholar
- Shimura, H. et al. Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase. Nature Genet. 25, 302–305 (2000).
CAS PubMed Google Scholar
- Shimura, H. et al. Ubiquitination of a new form of α-synuclein by parkin from human brain: implications for Parkinson's disease. Science 293, 263–269 (2001).
CAS PubMed Google Scholar
- Pesah, Y. et al. Drosophila parkin mutants have decreased mass and cell size and increased sensitivity to oxygen radical stress. Development 131, 2183–2194 (2004).
CAS PubMed Google Scholar
- Haywood, A. F. & Staveley, B. E. Parkin counteracts symptoms in a Drosophila model of Parkinson's disease. BMC Neurosci. 5, 14 (2004).
PubMed PubMed Central Google Scholar
- Yang, Y., Nishimura, I., Imai, Y., Takahashi, R. & Lu, B. Parkin suppresses dopaminergic neuron-selective neurotoxicity induced by Pael-R in Drosophila. Neuron 37, 911–924 (2003).
CAS PubMed Google Scholar
- Levy-Lahad, E. et al. A familial Alzheimer's disease locus on chromosome 1. Science 269, 970–973 (1995).
CAS PubMed Google Scholar
- Sherrington, R. et al. Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease. Nature 375, 754–760 (1995).
CAS PubMed Google Scholar
- Kopan, R. & Goate, A. A common enzyme connects Notch signaling and Alzheimer's disease. Genes Dev. 14, 2799–2806 (2000).
CAS PubMed Google Scholar
- Chartier-Harlin, M. C. et al. Early-onset Alzheimer's disease caused by mutations at codon 717 of the β-amyloid precursor protein gene. Nature 353, 844–846 (1991).
CAS PubMed Google Scholar
- Murrell, J., Farlow, M., Ghetti, B. & Benson, M. D. A mutation in the amyloid precursor protein associated with hereditary Alzheimer's disease. Science 254, 97–99 (1991).
CAS PubMed Google Scholar
- Goate, A. et al. Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease. Nature 349, 704–706 (1991).
CAS PubMed Google Scholar
- Leissring, M. A. et al. A physiologic signaling role for the α-secretase-derived intracellular fragment of APP. Proc. Natl Acad. Sci. USA 99, 4697–702 (2002).
CAS PubMed PubMed Central Google Scholar
- Kimberly, W. T., Zheng, J. B., Guenette, S. Y. & Selkoe, D. J. The intracellular domain of the β-amyloid precursor protein is stabilized by Fe65 and translocates to the nucleus in a Notch-like manner. J. Biol. Chem. 276, 40288–40292 (2001).
CAS PubMed Google Scholar
- Gao, Y. & Pimplikar, S. W. The α-secretase-cleaved C-terminal fragment of amyloid precursor protein mediates signaling to the nucleus. Proc. Natl Acad. Sci. USA 98, 14979–14984 (2001).
CAS PubMed PubMed Central Google Scholar
- Cupers, P., Orlans, I., Craessaerts, K., Annaert, W. & De Strooper, B. The amyloid precursor protein (APP)-cytoplasmic fragment generated by α-secretase is rapidly degraded but distributes partially in a nuclear fraction of neurones in culture. J. Neurochem. 78, 1168–1178 (2001).
CAS PubMed Google Scholar
- Cao, X. & Sudhof, T. C. A transcriptionally active complex of APP with Fe65 and histone acetyltransferase Tip60. Science 293, 115–120 (2001).
CAS PubMed Google Scholar
- Kamal, A., Almenar-Queralt, A., LeBlanc, J. F., Roberts, E. A. & Goldstein, L. S. Kinesin-mediated axonal transport of a membrane compartment containing α-secretase and presenilin-1 requires APP. Nature 414, 643–648 (2001).
CAS PubMed Google Scholar
- Gunawardena, S. & Goldstein, L. S. Disruption of axonal transport and neuronal viability by amyloid precursor protein mutations in Drosophila. Neuron 32, 389–401 (2001).
CAS PubMed Google Scholar
- White, A. R. et al. Contrasting, species-dependent modulation of copper-mediated neurotoxicity by the Alzheimer's disease amyloid precursor protein. J. Neurosci. 22, 365–376 (2002).
CAS PubMed PubMed Central Google Scholar
- Kopan, R. & Goate, A. Aph-2/Nicastrin: an essential component of α-secretase and regulator of Notch signaling and Presenilin localization. Neuron 33, 321–324 (2002).
CAS PubMed Google Scholar
- Francis, R. et al. aph-1 and pen-2 are required for Notch pathway signaling, α-secretase cleavage of βAPP, and presenilin protein accumulation. Dev. Cell 3, 85–97 (2002).
CAS PubMed Google Scholar
- Lopez-Schier, H. & St Johnston, D. Drosophila nicastrin is essential for the intramembranous cleavage of Notch. Dev. Cell. 2, 79–89 (2002).
CAS PubMed Google Scholar
- Hu, Y., Ye, Y. & Fortini, M. E. Nicastrin is required for γ-secretase cleavage of the Drosophila Notch receptor. Dev. Cell 2, 69–78 (2002).
CAS PubMed Google Scholar
- Chung, H. M. & Struhl, G. Nicastrin is required for Presenilin-mediated transmembrane cleavage in Drosophila. Nature Cell Biol. 3, 1129–1132 (2001).
CAS PubMed Google Scholar
- Yu, G. et al. Nicastrin modulates presenilin-mediated Notch/glp-1 signal transduction and βAPP processing. Nature 407, 48–54 (2000).
CAS PubMed Google Scholar
- Siomi, H., Ishizuka, A. & Siomi, M. C. RNA interference: a new mechanism by which FMRP acts in the normal brain? What can Drosophila teach us? Ment. Retard. Dev. Disabil. Res. Rev. 10, 68–74 (2004).
PubMed Google Scholar
- Zhang, Y. Q. et al. Drosophila fragile X-related gene regulates the MAP1B homolog Futsch to control synaptic structure and function. Cell 107, 591–603 (2001).
CAS PubMed Google Scholar
- Lee, A. et al. Control of dendritic development by the Drosophila fragile X-related gene involves the small GTPase Rac1. Development 130, 5543–5552 (2003).
CAS PubMed Google Scholar
- Ishizuka, A., Siomi, M. C. & Siomi, H. A Drosophila fragile X protein interacts with components of RNAi and ribosomal proteins. Genes Dev. 16, 2497–2508 (2002). Makes the link between the gene mutated in Fragile-X syndrome – FMR1 – and the RNAi pathway by showing that the D. melanogaster FMR1 homologue ( Fmr1 ) is present in a complex with several essential components of the RNAi pathway such as AGO1, p68 RNA helicase and Dicer.
CAS PubMed PubMed Central Google Scholar
- Jin, P. et al. Biochemical and genetic interaction between the fragile X mental retardation protein and the microRNA pathway. Nature Neurosci. 7, 113–117 (2004).
CAS PubMed Google Scholar
- Jin, P. et al. RNA-mediated neurodegeneration caused by the fragile X premutation rCGG repeats in Drosophila. Neuron 39, 739–747 (2003).
CAS PubMed Google Scholar
- Simon, M. A., Bowtell, D. D., Dodson, G. S., Laverty, T. R. & Rubin, G. M. Ras1 and a putative guanine nucleotide exchange factor perform crucial steps in signaling by the Sevenless protein tyrosine kinase. Cell 67, 701–716 (1991).
CAS PubMed Google Scholar
- Dickson, B. J., van der Straten, A., Dominguez, M. & Hafen, E. Mutations modulating Raf signaling in Drosophila eye development. Genetics 142, 163–171 (1996).
CAS PubMed PubMed Central Google Scholar
- Margolis, B. & Skolnik, E. Y. Activation of Ras by receptor tyrosine kinases. J. Am. Soc. Nephrol. 5, 1288–1299 (1994).
CAS PubMed Google Scholar
- Han, M. & Sternberg, P. W. let-60, a gene that specifies cell fates during C. elegans vulval induction, encodes a Ras protein. Cell 63, 921–931 (1990).
CAS PubMed Google Scholar
- Aroian, R. V., Koga, M., Mendel, J. E., Ohshima, Y. & Sternberg, P. W. The let-23 gene necessary for Caenorhabditis elegans vulval induction encodes a tyrosine kinase of the EGF receptor subfamily. Nature 348, 693–699 (1990).
CAS PubMed Google Scholar
- Hill, R. J. & Sternberg, P. W. The gene lin-3 encodes an inductive signal for vulval development in C. elegans. Nature 358, 470–476 (1992).
CAS PubMed Google Scholar
- Han, M., Golden, A., Han, Y. & Sternberg, P. W. C. elegans lin-45 Raf gene participates in let-60 Ras-stimulated vulval differentiation. Nature 363, 133–140 (1993).
CAS PubMed Google Scholar
- Huang, L. S., Tzou, P. & Sternberg, P. W. The lin-15 locus encodes two negative regulators of Caenorhabditis elegans vulval development. Mol. Biol. Cell 5, 395–411 (1994).
CAS PubMed PubMed Central Google Scholar
- Pan, D., Dong, J., Zhang, Y. & Gao, X. Tuberous sclerosis complex: from Drosophila to human disease. Trends Cell Biol. 14, 78–85 (2004).
CAS PubMed Google Scholar
- Gao, X. & Pan, D. TSC1 and TSC2 tumor suppressors antagonize insulin signaling in cell growth. Genes Dev. 15, 1383–1392 (2001).
CAS PubMed PubMed Central Google Scholar
- Potter, C. J., Huang, H. & Xu, T. Drosophila Tsc1 functions with Tsc2 to antagonize insulin signaling in regulating cell growth, cell proliferation, and organ size. Cell 105, 357–368 (2001).
CAS PubMed Google Scholar
- Tapon, N., Ito, N., Dickson, B. J., Treisman, J. E. & Hariharan, I. K. The Drosophila tuberous sclerosis complex gene homologs restrict cell growth and cell proliferation. Cell 105, 345–355 (2001).
CAS PubMed Google Scholar
- Kamada, Y., Sekito, T. & Ohsumi, Y. Autophagy in yeast: a TOR-mediated response to nutrient starvation. Curr. Top. Microbiol. Immunol. 279, 73–84 (2004).
CAS PubMed Google Scholar
- Neufeld, T. P. Body building: regulation of shape and size by PI3K/TOR signaling during development. Mech. Dev. 120, 1283–1296 (2003).
CAS PubMed Google Scholar
- Saucedo, L. J. & Edgar, B. A. Why size matters: altering cell size. Curr. Opin. Genet. Dev. 12, 565–571 (2002).
CAS PubMed Google Scholar
- Sutcliffe, J. E., Korenjak, M. & Brehm, A. Tumour suppressors—a fly's perspective. Eur. J. Cancer 39, 1355–1362 (2003).
CAS PubMed Google Scholar
- Justice, R. W., Zilian, O., Woods, D. F., Noll, M. & Bryant, P. J. The Drosophila tumor suppressor gene warts encodes a homolog of human myotonic dystrophy kinase and is required for the control of cell shape and proliferation. Genes Dev. 9, 534–546 (1995).
CAS PubMed Google Scholar
- Xu, T., Wang, W., Zhang, S., Stewart, R. A. & Yu, W. Identifying tumor suppressors in genetic mosaics: the Drosophila lats gene encodes a putative protein kinase. Development 121, 1053–1063 (1995).
CAS PubMed Google Scholar
- Tapon, N. et al. salvador promotes both cell cycle exit and apoptosis in Drosophila and is mutated in human cancer cell lines. Cell 110, 467–478 (2002). Identified mutations in the D. melanogaster salvador gene that resulted in tissue overgrowth and found that the human homologue of this gene was mutated in cancer cell lines.
CAS PubMed Google Scholar
- Harvey, K. F., Pfleger, C. M. & Hariharan, I. K. The Drosophila Mst ortholog, hippo, restricts growth and cell proliferation and promotes apoptosis. Cell 114, 457–467 (2003).
CAS PubMed Google Scholar
- Starz-Gaiano, M. & Montell, D. J. Genes that drive invasion and migration in Drosophila. Curr. Opin. Genet. Dev. 14, 86–91 (2004).
CAS PubMed Google Scholar
- Pagliarini, R. A. & Xu, T. A genetic screen in Drosophila for metastatic behavior. Science 302, 1227–1231 (2003). Showed that mutations in the D. melanogaster scribbled gene, which is involved in maintaining cell polarity, can cause cells that express an activated oncogenic form of RAS to metastasize. See also reference 96.
CAS PubMed Google Scholar
- Brumby, A. M. & Richardson, H. E. scribble mutants cooperate with oncogenic Ras or Notch to cause neoplastic overgrowth in Drosophila. EMBO J. 22, 5769–5779 (2003).
CAS PubMed PubMed Central Google Scholar
- Fang, P. et al. The spectrum of mutations in UBE3A causing Angelman syndrome. Hum. Mol. Genet. 8, 129–135 (1999).
CAS PubMed Google Scholar
- Kishino, T., Lalande, M. & Wagstaff, J. UBE3A/E6-AP mutations cause Angelman syndrome. Nature Genet. 15, 70–73 (1997).
CAS PubMed Google Scholar
- Matsuura, T. et al. De novo truncating mutations in E6-AP ubiquitin-protein ligase gene (UBE3A) in Angelman syndrome. Nature Genet. 15, 74–77 (1997).
CAS PubMed Google Scholar
- Netto, L. E. S., Chae, H. Z., Kang, S. W., Rhee, S. G. & Stadtman, E. R. Removal of hydrogen peroxide by thiol-specific antioxidant enzyme (TSA) is involved with its antioxidant properties. TSA possesses thiol peroxidase activity. J. Biol. Chem. 271, 15315–15321 (1996).
CAS Google Scholar
- Lim, Y. S. et al. Removals of hydrogen peroxide and hydroxyl radical by thiol-specific antioxidant protein as a possible role in vivo. Biochem. Biophys. Res. Commun. 192, 273–280 (1993).
CAS PubMed Google Scholar
- Kim, K., Kim, I. H., Lee, K. Y., Rhee, S. G. & Stadtman, E. R. The isolation and purification of a specific 'protector' protein which inhibits enzyme inactivation by a thiol/Fe(III)/O2 mixed-function oxidation system. J. Biol. Chem. 263, 4704–4711 (1988).
CAS PubMed Google Scholar
- Zhou, Y. et al. Presenilin-1 protects against neuronal apoptosis caused by its interacting protein PAG. Neurobiol. Dis. 9, 126–138 (2002).
CAS PubMed Google Scholar
- Bejjani, B. A. et al. Mutations in CYP1B1, the gene for cytochrome P4501B1, are the predominant cause of primary congenital glaucoma in Saudi Arabia. Am. J. Hum. Genet. 62, 325–333 (1998).
CAS PubMed PubMed Central Google Scholar
- Stoilov, I., Akarsu, A. N. & Sarfarazi, M. Identification of three different truncating mutations in cytochrome P4501B1 (CYP1B1) as the principal cause of primary congenital glaucoma (Buphthalmos) in families linked to the GLC3A locus on chromosome 2p21. Hum. Mol. Genet. 6, 641–647 (1997).
CAS PubMed Google Scholar
- Gibbs, R. A. et al. The International HapMap Project. Nature 426, 789–796 (2003). This paper by the International HapMap Project consortium defines the goals and motivation for determining patterns of sequence variation in the human genome, which should provide crucial information for identifying genes involved in polygenic disorders.
CAS Google Scholar
- Aebi, M. & Hennet, T. Congenital disorders of glycosylation: genetic model systems lead the way. Trends Cell Biol. 11, 136–141 (2001).
CAS PubMed Google Scholar
- Imbach, T. et al. A mutation in the human ortholog of the Saccharomyces cerevisiae ALG6 gene causes carbohydrate-deficient glycoprotein syndrome type-Ic. Proc. Natl Acad. Sci. USA 96, 6982–6987 (1999).
CAS PubMed PubMed Central Google Scholar
- Imbach, T. et al. Deficiency of dolichol-phosphate-mannose synthase-1 causes congenital disorder of glycosylation type Ie. J. Clin. Invest. 105, 233–239 (2000).
CAS PubMed PubMed Central Google Scholar
- Grubenmann, C. E. et al. Deficiency of the first mannosylation step in the N–glycosylation pathway causes congenital disorder of glycosylation type Ik. Hum. Mol. Genet. 13, 535–542 (2004).
CAS PubMed Google Scholar
- Westphal, V. et al. A frequent mild mutation in ALG6 may exacerbate the clinical severity of patients with congenital disorder of glycosylation Ia (CDG-Ia) caused by phosphomannomutase deficiency. Hum. Mol. Genet. 11, 599–604 (2002).
CAS PubMed Google Scholar
- Bodmer, R. Heart development in Drosophila and its relationship to vertebrate systems. Trends Cardiovasc. Med. 5, 21–28 (1995).
CAS PubMed Google Scholar
- Wessells, R. J. & Bodmer, R. Screening assays for heart function mutants in Drosophila. Biotechniques 37, 58–60, 62, 64 passim (2004).
CAS PubMed Google Scholar
- Wessells, R. J., Fitzgerald, E., Cypser, J. R., Tatar, M. & Bodmer, R. Insulin regulation of heart function in aging fruit flies. Nature Genetics (in the press).
- Kosman, D. et al. Multiplex detection of RNA expression in Drosophila embryos. Science 305, 846 (2004).
CAS PubMed Google Scholar
- Elefant, F. & Palter, K. B. Tissue-specific expression of dominant negative mutant Drosophila HSC70 causes developmental defects and lethality. Mol. Biol. Cell 10, 2101–2017 (1999).
CAS PubMed PubMed Central Google Scholar
- Pinsky, L. et al. Androgen resistance due to mutation of the androgen receptor. Clin. Invest. Med. 15, 456–472 (1992).
CAS PubMed Google Scholar
- Buchanan, R. L. & Benzer, S. Defective glia in the Drosophila brain degeneration mutant drop-dead. Neuron 10, 839–850 (1993).
CAS PubMed Google Scholar
- Rogina, B., Benzer, S. & Helfand, S. L. Drosophila drop-dead mutations accelerate the time course of age-related markers. Proc. Natl Acad. Sci. USA 94, 6303–6306 (1997).
CAS PubMed PubMed Central Google Scholar
- Zinsmaier, K. E., Eberle, K. K., Buchner, E., Walter, N. & Benzer, S. Paralysis and early death in cysteine string protein mutants of Drosophila. Science 263, 977–980 (1994).
CAS PubMed Google Scholar
- Kretzschmar, D., Hasan, G., Sharma, S., Heisenberg, M. & Benzer, S. The swiss cheese mutant causes glial hyperwrapping and brain degeneration in Drosophila. J. Neurosci. 17, 7425–7432 (1997).
CAS PubMed PubMed Central Google Scholar
- Lin, Y. J., Seroude, L. & Benzer, S. Extended life-span and stress resistance in the Drosophila mutant methuselah. Science 282, 943–946 (1998).
CAS PubMed Google Scholar
- Tatar, M. et al. A mutant Drosophila insulin receptor homolog that extends life-span and impairs neuroendocrine function. Science 292, 107–110 (2001).
CAS PubMed Google Scholar
- Tatar, M., Bartke, A. & Antebi, A. The endocrine regulation of aging by insulin-like signals. Science 299, 1346–1351 (2003).
CAS PubMed Google Scholar
- Tatar, M. Unearthing loci that influence life span. Sci. Aging Knowledge Environ. 2003, PE5 (2003).
PubMed Google Scholar
- Antebi, A. Inside insulin signaling, communication is key to long life. Sci. Aging Knowledge Environ. 2004, PE25 (2004).
PubMed Google Scholar
- Kapahi, P. et al. Regulation of lifespan in Drosophila by modulation of genes in the TOR signaling pathway. Curr. Biol. 14, 885–890 (2004).
CAS PubMed PubMed Central Google Scholar
- Tower, J. There's a problem in the furnace. Sci. Aging Knowledge Environ. 2004, PE1 (2004).
PubMed Google Scholar
- Jabs, E. M. in Molecular Basis of Inborn Errors of Development (eds Epstein C. J., Erikson, R. P. & Wynshaw-Boris, A.) 401–409 (Oxford Univ. Press, New York, 2004).
Google Scholar
- Lai, E. C., Deblandre, G. A., Kintner, C. & Rubin, G. M. Drosophila neuralized is a ubiquitin ligase that promotes the internalization and degradation of Delta. Dev. Cell 1, 783–794 (2001).
CAS PubMed Google Scholar
- Fryer, C. J., Lamar, E., Turbachova, I., Kintner, C. & Jones, K. A. Mastermind mediates chromatin-specific transcription and turnover of the Notch enhancer complex. Genes Dev. 16, 1397–1411 (2002).
CAS PubMed PubMed Central Google Scholar
- Saga, Y. & Takeda, H. The making of the somite: molecular events in vertebrate segmentation. Nature Rev. Genet. 2, 835–845 (2001).
CAS PubMed Google Scholar
- Aulehla, A. & Herrmann, B. G. Segmentation in vertebrates: clock and gradient finally joined. Genes Dev. 18, 2060–2067 (2004).
CAS PubMed Google Scholar
- Bessho, Y. & Kageyama, R. Oscillations, clocks and segmentation. Curr. Opin. Genet. Dev. 13, 379–384 (2003).
CAS PubMed Google Scholar
- Kim, H. J. & Bar-Sagi, D. Modulation of signalling by Sprouty: a developing story. Nature Rev. Mol. Cell Biol. 5, 441–450 (2004).
CAS Google Scholar
- Muragaki, Y., Mundlos, S., Upton, J. & Olsen, B. R. Altered growth and branching patterns in synpolydactyly caused by mutations in HOXD13. Science 272, 548–551 (1996).
CAS PubMed Google Scholar
- Akarsu, A. N., Stoilov, I., Yilmaz, E., Sayli, B. S. & Sarfarazi, M. Genomic structure of HOXD13 gene: a nine polyalanine duplication causes synpolydactyly in two unrelated families. Hum. Mol. Genet. 5, 945–952 (1996).
CAS PubMed Google Scholar
- Goodman, F. R. et al. Synpolydactyly phenotypes correlate with size of expansions in HOXD13 polyalanine tract. Proc. Natl Acad. Sci. USA 94, 7458–7463 (1997).
CAS PubMed PubMed Central Google Scholar
- Del Campo, M. et al. Monodactylous limbs and abnormal genitalia are associated with hemizygosity for the human 2q31 region that includes the HOXD cluster. Am. J. Hum. Genet. 65, 104–110 (1999).
CAS PubMed PubMed Central Google Scholar
- Goodman, F. et al. Deletions in HOXD13 segregate with an identical, novel foot malformation in two unrelated families. Am. J. Hum. Genet. 63, 992–1000 (1998).
CAS PubMed PubMed Central Google Scholar
- Goodman, F. R. et al. Novel HOXA13 mutations and the phenotypic spectrum of Hand-Foot–Genital syndrome. Am. J. Hum. Genet. 63S, A18 (1998).
Google Scholar
- Goodman, F. R. et al. Novel HOXA13 mutations and the phenotypic spectrum of hand-foot-genital syndrome. Am. J. Hum. Genet. 67, 197–202 (2000).
CAS PubMed PubMed Central Google Scholar
- Mortlock, D. P. & Innis, J. W. Mutation of HOXA13 in hand-foot-genital syndrome. Nature Genet. 15, 179–180 (1997).
CAS PubMed Google Scholar
- Mortlock, D. P., Post, L. C. & Innis, J. W. The molecular basis of hypodactyly (Hd): a deletion in Hoxa 13 leads to arrest of digital arch formation. Nature Genet. 13, 284–289 (1996). The first study to show that a reduction in Hox gene function leads to digit malformation in vertebrates
CAS PubMed Google Scholar
- Devriendt, K. et al. Haploinsufficiency of the HOXA gene cluster, in a patient with hand-foot-genital syndrome, velopharyngeal insufficiency, and persistent patent Ductus botalli. Am. J. Hum. Genet. 65, 249–251 (1999).
CAS PubMed PubMed Central Google Scholar
- Czerny, T. et al. twin of eyeless, a second Pax-6 gene of Drosophila, acts upstream of eyeless in the control of eye development. Mol. Cell 3, 297–307 (1999).
CAS PubMed Google Scholar
- Jiao, R. et al. Headless flies generated by developmental pathway interference. Development 128, 3307–3319 (2001).
CAS PubMed Google Scholar
- Quiring, R., Walldorf, U., Kloter, U. & Gehring, W. J. Homology of the eyeless gene of Drosophila to the small eye gene in mice and aniridia in humans. Science 265, 785–789 (1994).
CAS PubMed Google Scholar
- van Heningen, V. & Williamson, K. in Molecular Basis of Inborn Errors of Development (eds Epstein C. J., Erikson, R. P. & Wynshaw-Boris, A.) 649–657 (Oxford Univ. Press, New York, 2004).
Google Scholar
- Kohlhase, J. SALL1 mutations in Townes-Brocks syndrome and related disorders. Hum. Mutat. 16, 460–466 (2000).
CAS PubMed Google Scholar
- Kohlhase, J. & Engel, W. in Molecular Basis of Inborn Errors of Development (eds Epstein C. J., Erikson, R. P. & Wynshaw-Boris, A.) 265–271 (Oxford Univ. Press, New York, 2004).
Google Scholar
- Dong, P. D., Dicks, J. S. & Panganiban, G. Distal-less and homothorax regulate multiple targets to pattern the Drosophila antenna. Development 129, 1967–1974 (2002).
CAS PubMed Google Scholar
- Cohen, M. M. in Molecular Basis of Inborn Errors of Development (eds Epstein C. J., Erikson, R. P. & Wynshaw-Boris, A.) 380–400 (Oxford Univ. Press, New York, 2004).
Google Scholar
- Spinner, N. B. & Krantz, I. D. in Molecular Basis of Inborn Errors of Development (eds Epstein C. J., Erikson, R. P. & Wynshaw-Boris, A.) 461–469 (Oxford Univ. Press, New York, 2004).
Google Scholar
- Turnpenny, P. D. & Kusumi, K. in Molecular Basis of Inborn Errors of Development (eds Epstein C. J., Erikson, R. P. & Wynshaw-Boris, A.) 470–481 (Oxford Univ. Press, New York, 2004).
Google Scholar
- Prall, O. W., Elliott, D. A. & Harvey, R. P. Developmental paradigms in heart disease: insights from tinman. Ann. Med. 34, 148–156 (2002).
PubMed Google Scholar
- Schott, J. J. et al. Congenital heart disease caused by mutations in the transcription factor NKX2-5. Science 281, 108–111 (1998).
CAS PubMed Google Scholar
- Jay, P. Y., Powell, A. J., Sherwood, M. C. & Izumo, S. in Molecular Basis of Inborn Errors of Development (eds Epstein C. J., Erikson, R. P. & Wynshaw-Boris, A. A.) 607–614 (Oxford Univ. Press, New York, 2004).
Google Scholar
- Garg, V. et al. GATA4 mutations cause human congenital heart defects and reveal an interaction with TBX5. Nature 424, 443–447 (2003).
CAS PubMed Google Scholar
- Klinedinst, S. L. & Bodmer, R. Gata factor Pannier is required to establish competence for heart progenitor formation. Development 130, 3027–3038 (2003).
CAS PubMed Google Scholar
- Patient, R. K. & McGhee, J. D. The GATA family (vertebrates and invertebrates). Curr. Opin. Genet. Dev. 12, 416–422 (2002).
CAS PubMed Google Scholar
- Bamshad, M. J. & Jorde, L. B. in Molecular Basis of Inborn Errors of Development (eds Epstein C. J., Erikson, R. P. & Wynshaw-Boris, A.) 705–718 (Oxford Univ. Press, New York, 2004).
Google Scholar
- Hamaguchi, T., Yabe, S., Uchiyama, H. & Murakami, R. _Drosophila Tbx6_-related gene, Dorsocross, mediates high levels of Dpp and Scw signal required for the development of amnioserosa and wing disc primordium. Dev. Biol. 265, 355–368 (2004).
CAS PubMed Google Scholar
- Reim, I., Lee, H. H. & Frasch, M. The T-box-encoding Dorsocross genes function in amnioserosa development and the patterning of the dorsolateral germ band downstream of Dpp. Development 130, 3187–3204 (2003).
CAS PubMed Google Scholar
- Klewer, S. E., Runyan, R. B. & Erickson, R. P. in Molecular Basis of Inborn Errors of Development (eds Epstein C. J., Erikson, R. P. & Wynshaw-Boris, A.) 699–704 (Oxford Univ. Press, New York, 2004).
Google Scholar
- Vikkula, M. et al. Vascular dysmorphogenesis caused by an activating mutation in the receptor tyrosine kinase TIE2. Cell 87, 1181–1190 (1996).
CAS PubMed Google Scholar
- Ross, C. A. Polyglutamine pathogenesis: emergence of unifying mechanisms for Huntington's disease and related disorders. Neuron 35, 819–822 (2002).
CAS PubMed Google Scholar
- Marsh, J. L., Pallos, J. & Thompson, L. M. Fly models of Huntington's disease. Hum. Mol. Genet. 12 Review issue 2, R187–193 (2003).
CAS PubMed Google Scholar
- Bates, G. P. & Hockly, E. Experimental therapeutics in Huntington's disease: are models useful for therapeutic trials? Curr. Opin. Neurol. 16, 465–470 (2003).
PubMed Google Scholar
- Gunawardena, S. et al. Disruption of axonal transport by loss of huntingtin or expression of pathogenic polyQ proteins in Drosophila. Neuron 40, 25–40 (2003).
CAS PubMed Google Scholar
- de Silva, R. & Farrer, M. Tau neurotoxicity without the lesions: a fly challenges a tangled web. Trends Neurosci. 25, 327–329 (2002).
CAS PubMed Google Scholar
- Valente, E. M. et al. Hereditary early-onset Parkinson's disease caused by mutations in PINK1. Science 304, 1158–1160 (2004).
CAS PubMed Google Scholar
- Chiurazzi, P., Neri, G. & Oostra, B. A. Understanding the biological underpinnings of fragile X syndrome. Curr. Opin. Pediatr. 15, 559–566 (2003).
PubMed Google Scholar
- Bakker, C. E. & Oostra, B. A. Understanding fragile X syndrome: insights from animal models. Cytogenet. Genome Res. 100, 111–123 (2003).
CAS PubMed Google Scholar
- Jiang, Y. H. & Beaudet, A. L. Human disorders of ubiquitination and proteasomal degradation. Curr. Opin. Pediatr. 16, 419–426 (2004).
PubMed Google Scholar
- Wagstaff, J. in Molecular Basis of Inborn Errors of Development (eds Epstein C. J., Erikson, R. P. & Wynshaw-Boris, A.) 823–827 (Oxford Univ. Press, New York, 2004).
Google Scholar
- Rosner, M., Hofer, K., Kubista, M. & Hengstschlager, M. Cell size regulation by the human TSC tumor suppressor proteins depends on PI3K and FKBP38. Oncogene 22, 4786–4798 (2003).
CAS PubMed Google Scholar
- Kwiatkowski, D. J. in Molecular Basis of Inborn Errors of Development (eds Epstein C. J., Erikson, R. P. & Wynshaw-Boris, A.) 920–930 (Oxford Univ. Press, New York, 2004).
Google Scholar
- Hengstschlager, M. & Rosner, M. The cell cycle and tuberous sclerosis. Prog. Cell. Cycle Res. 5, 43–48 (2003).
PubMed Google Scholar
- Narayanan, V. Tuberous sclerosis complex: genetics to pathogenesis. Pediatr. Neurol. 29, 404–409 (2003).
PubMed Google Scholar
- Tapon, N. Modeling transformation and metastasis in Drosophila. Cancer Cell 4, 333–335 (2003).
CAS PubMed Google Scholar
- El Ghouzzi, V. et al. Mutations of the TWIST gene in the Saethre-Chotzene syndrome. Nature Genet. 15, 42–46 (1997).
CAS PubMed Google Scholar
- Sturtevant, MA and Bier, E. Analysis of the genetic hierarchy guiding wing vein development in Drosophila. Development 121, 785–801 (1995).
CAS PubMed Google Scholar