Of flies and man: Drosophila as a model for human complex traits

Annual Review of Genomics and Human Genetics

Volumn 7, Issue , 2006, Pages 339-367

  Mackay, Trudy F C ^a   Anholt, Robert R H ^a  

^a NORTH CAROLINA STATE UNIVERSITY   (United States)

Author keywords

Epistasis; Genotype by environment interaction; Pleiotropy; Quantitative trait loci; Transgenic models of human disease

Indexed keywords

ALCOHOLISM; ALLELE; ALZHEIMER DISEASE; DEGENERATIVE DISEASE; DROSOPHILA MELANOGASTER; ENVIRONMENTAL FACTOR; GENE EXPRESSION; GENETIC CONSERVATION; GENETIC MODEL; GENETIC TRAIT; GENETIC VARIABILITY; HEREDITY; HUMAN; HUNTINGTON CHOREA; MOLECULAR EVOLUTION; NONHUMAN; PARKINSON DISEASE; PHENOTYPE; QUANTITATIVE TRAIT LOCUS; REVIEW; SEX DIFFERENCE; SLEEP DISORDER;

ANIMALS; DROSOPHILA; EVOLUTION; HUMANS; MODELS, ANIMAL; MULTIFACTORIAL INHERITANCE; QUANTITATIVE TRAIT, HERITABLE;

DROSOPHILA MELANOGASTER;

EID: 33750330814     PISSN: 15278204     EISSN: None     Source Type: Book Series    
DOI: 10.1146/annurev.genom.7.080505.115758     Document Type: Review

References (204)

1. Adams MD, Celniker S, Holt RA, Evans CA, Gocayne JD, et al. 2000. The genome sequence of Drosophila melanogaster. Science 287:2185-95
2. Agrawal N, Pallos J, Slepko N, Apostol BL, Bodai L, et al. 2005. Identification of combinatorial drug regimens for treatment of Huntington's disease using Drosophila. Proc. Natl. Acad. Sci. USA 102:3777-81
3. Alzheimer A. 1906. Über einen eigenartigen schweren Krankheitsprozess der Hirnrinde. Zentralblatt für Nervenkrankheiten 25:1134
4. Andretic R, van Swinderen B, Greenspan RJ. 2005. Dopaminergic modulation of arousal in Drosophila. Curr. Biol. 15:1165-75
5. Anholt RRH, Dilda CL, Chang S, Fanara JJ, Kulkarni NH, et al. 2003. The genetic architecture of odor-guided behavior in Drosophila: epistasis and the transcriptome. Nat. Genet. 35:180-84
6. Anholt RRH, Lyman RF, Mackay TFC. 1996. Effects of single P element insertions on olfactory behavior in Drosophila melanogaster. Genetics 143:293-301
7. Auluck PK, Bonini NM. 2002. Pharmacological prevention of Parkinson disease in Drosophila. Nat. Med. 8:1185-86
8. Auluck PK, Chan HY, Trojanowski JQ, Lee VM, Bonini NM. 2002. Chaperone suppression of α-synuclein toxicity in a Drosophila model for Parkinson's disease. Science 295:865-68
9. Auluck PK, Meulener MC, Bonini NM. 2005. Mechanisms of suppression of α-synuclein neurotoxicity by geldanamycin in Drosophila. J. Biol. Chem. 280:2873-78
10. Bainton RJ, Tsai LT, Singh CM, Moore MS, Neckameyer WS, et al. 2000. Dopamine modulates acute responses to cocaine, nicotine and ethanol in Drosophila. Curr. Biol. 10:187-94
11. Bates G, Lehrach H. 1994. Trinucleotide repeat expansions and human genetic disease. BioEssays 16:277-84
12. Bates G. 2003. Huntingtin aggregation and toxicity in Huntington's disease. Lancet 361:1642-44
13. Bates GP, Hockly E. 2003. Experimental therapeutics in Huntington's disease: are models useful for therapeutic trials? Curr. Opin. Neurol. 16:465-70
14. th, pp. 252-68
15. Bellen HJ, Levis RW, Liao G, Carlson YJW, Tsang G, et al. 2004. The BDGP gene disruption project: single transposon insertions associated with 40% of Drosophila genes. Genetics 167:761-81
16. Berger J, Suzuki T, Senti KA, Stubbs J, Schaffner G, et al. 2001. Genetic mapping with SNP markers in Drosophila. Nat. Genet. 29:475-81
17. Bilder D, Perrimon N. 2000. Localization of apical epithelial determinants by the basolateral PDZ domain protein Scribble. Nature 403:676-80
18. Borrás T, Morozova TV, Heinsohn SL, Lyman RF, Mackay TF, et al. 2003. Transcription profiling in Drosophila eyes that overexpress the human glaucoma-associated trabecular meshwork-inducible glucocorticoid response protein/myocilin (TIGR/MYOC). Genetics 163:637-45
19. Brand AH, Perrimon N. 1993. Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development 118:401-15
20. Breese EL, Mather K. 1957. The organization of polygenic activity within a chromosome of Drosophila. I. Hair characters. Heredity 11:373-95
21. Caligari PDS, Mather K. 1975. Genotype-environment interaction III. Interactions in Drosophila melanogaster. Genetics 191:387-411
22. Caspi A, McClay J, Moffitt TE, Mill J, Martin J, et al. 2002. Role of genotype in the cycle of violence in maltreated children. Science 297:851-54
23. Caspi A, Sugden K, Moffitt TE, Taylor A, Craig IW, et al. 2003. Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science 301:386-89
24. Chen L, Feany MB. 2005. α-synuclein phosphorylation controls neurotoxicity and inclusion formation in a Drosophila model of Parkinson disease. Nat. Neurosci. 8:657-63
25. Cheng Y, Endo K, Wu K, Rodan AR, Heberlein U, et al. 2001. Drosophila fasciclinII is required for the formation of odor memories and for normal sensitivity to alcohol. Cell 105:757-68
26. Chung HM, Struhl G. 2001. Nicastrin is required for Presenilin-mediated transmembrane cleavage in Drosophila. Nat. Cell Biol. 3:1129-32
27. Cirelli C. 2003. Searching for sleep mutants of Drosophila melanogaster. BioEssays 25:940-49
28. Cirelli C, Bushey D, Hill S, Huber R, Kreber R, et al. 2005. Reduced sleep in Drosophila Shaker mutants. Nature 434:1087-92
29. Cirelli C, LaVaute TM, Tononi G. 2005. Sleep and wakefulness modulate gene expression in Drosophila. J. Neurochem. 94:1411-19
30. Clark AG, Wang L. 1997. Epistasis in measured genotypes: Drosophila P element insertions. Genetics 147:157-63
31. Clark AG, Wang L, Hulleberg T. 1995. P-element-induced variation in metabolic regulation in Drosophila. Genetics 139:337-48
32. Cohan FM, Hoffman AA 1986. Genetic divergence under uniform selection. II. Different responses to selection for knockdown resistance to ethanol among Drosophila melanogaster populations and their replicate lines. Genetics 114:145-63
33. Cornett J, Cao F, Wang CE, Ross CA, Bates GP, et al. 2005. Polyglutamine expansion of huntingtin impairs its nuclear export. Nat. Genet. 37:198-204
34. Crowther DC, Kinghorn KJ, Page R, Lomas DA. 2004. Therapeutic targets from a Drosophila model of Alzheimer's disease. Curr. Opin. Pharmacol. 4:513-16
35. De Benedictis G, Caratenuto L, Carrieri G, De Luca M, Falcone E, et al. 1998. Gene/longevity association studies at four autosomal loci (REN, THO, PARP, SOD2). Eur. J. Hum. Genet. 6:534-41
36. De Luca M, Roshina NV, Geiger-Thornsberry GL, Lyman RF, Pasyukova EG, et al. 2003. Dopa-decarboxylase affects variation in Drosophila longevity. Nat. Genet. 34:429-33
37. Dilda CL, Mackay TFC. 2002. The genetic architecture of Drosophila sensory bristle number. Genetics 162:1655-74
38. Ding Q, Lewis JJ, Strum KM, Dimayuga E, Bruce-Keller AJ, et al. 2002. Polyglutamine expansion, protein aggregation, proteasome activity, and neural survival. J. Biol. Chem. 277:13935-42
39. Drysdale RA, Crosby MA, FlyBase Consortium. 2005. FlyBase: genes and gene models. Nucleic. Acids Res. 33:D390-95. http://flybase.org/
40. Evert BO, Wullner U, Klockgether T. 2000. Cell death in polyglutamine diseases. Cell Tissue Res. 301:189-204
41. Falconer DS. 1965. The inheritance of liability to certain diseases, estimated from the incidence among relatives. Ann. Hum. Genet. 29:51-76
42. Falconer DS, Mackay TFC. 1996. Introduction to Quantitative Genetics. Harlow, Essex: Addison Wesley Longman
43. Fanara JJ, Robinson KO, Rollmann SM, Anholt RRH, Mackay TFC. 2002. Vanaso is a candidate quantitative trait gene for Drosophila olfactory behavior. Genetics 162:1321-28
44. Feany MB, Quinn WG. 1995. A neuropeptide gene defined by the Drosophila memory mutant amnesiac. Science 268:869-73
45. Feany MB, Bender WW. 2000. A Drosophila model of Parkinson's disease. Nature 404:394-98
46. Fedorowicz GM, Fry JD, Anholt RRH, Mackay TFC. 1998. Epistatic interactions between smell-impaired loci in Drosophila melanogaster. Genetics 148:1885-91
47. Florez JC, Hirschhorn J, Altshuler D. 2003. The inherited basis of diabetes mellitus: implications for the genetic analysis of complex traits. Annu. Rev. Genomes Hum. Genet. 4:257-91
48. Francis R, McGrath G, Zhang J, Ruddy DA, Sym M, et al. 2002. aph-1 and pen-2 are required for Notch pathway signaling, gamma-secretase cleavage of beta-APP, and presenilin protein accumulation. Dev. Cell 3:85-97
49. Fujiwara H. 2002. α-Synuclein is phosphorylated in synucleinopathy lesions. Nat. Cell Biol. 4:160-64
50. Ganguly I, Mackay TFC, Anholt RRH. 2003. Scribble is essential for olfactory behavior in Drosophila. Genetics 164:1447-57
51. Gleason JM, Nuzhdin SV, Ritchie MG. 2002. Quantitative trait loci affecting a courtship signal in Drosophila melanogaster. Heredity 89:1-6
52. Goellner GM, Rechsteiner M. 2003. Are Huntington's and polyglutamine-based ataxias proteasome storage diseases? Int. J. Biochem. Cell Biol. 35:562-71
53. Greene JC, Whitworth AJ, Kuo I, Andrews LA, Feany MB, et al. 2003. Mitochondrial pathology and apoptotic muscle degeneration in Drosophila parkin mutants. Proc. Natl. Acad. Sci. USA 100:4078-83
54. Greenspan R. 2004. Fly Pushing: The Theory and Practice of Drosophila Genetics. Cold Spring Harbor: Cold Spring Harbor Lab. Press
55. Greeve I, Kretzschmar D, Tschape JA, Beyn A, Brellinger C, et al. 2004. Age-dependent neurodegeneration and Alzheimer-amyloid plaque formation in transgenic Drosophila. J. Neurosci. 24:3899-906
56. Guarneri DJ, Heberlein U. 2003. Drosophila melanogaster, a genetic model system for alcohol research. Int. Rev. Neurobiol. 54:199-228
57. Guillen E, Sanchez-Canete FJ, Garrido JJ, Dorado G, Barbancho M. 1987. Intergenotypic effect of isopropanol ingestion in the further detoxification of ethanol and isopropanol in Drosophila melanogaster. Heredity 59:405-11
58. Gunawardena S, Goldstein LS. 2001. Disruption of axonal transport and neuronal viability by amyloid precursor protein mutations in Drosophila. Neuron 32:389-401
59. Gunawardena S, Her LS, Brusch RG, Laymon RA, Niesman IR, et al. 2003. Disruption of axonal transport by loss of huntingtin or expression of pathogenic polyQ proteins in Drosophila. Neuron 40:25-40
60. Gurganus MC, Fry JD, Nuzhdin SV, Pasyukova EG, Lyman RF, et al. 1998. Genotype-environment interaction at quantitative trait loci affecting sensory bristle number in Drosophila melanogaster. Genetics 149:1883-98
61. Gurganus MC, Nuzhdin SV, Leips JW, Mackay TFC. 1999. High-resolution mapping of quantitative trait loci for sternopleural bristle number in Drosophila melanogaster. Genetics 152:1585-604
62. Harbison ST, Yamamoto AH, Fanara JJ, Norga KK, Mackay TFC. 2004. Quantitative trait loci affecting starvation resistance in Drosophila melanogaster. Genetics 166:1807-23
63. Hay DG, Sathasivam K, Tobaben S, Stahl B, Marber M, et al. 2004. 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
64. Haywood AF, Staveley BE. 2004. Parkin counteracts symptoms in a Drosophila model of Parkinson's disease. BMC Neurosci. 5:14
65. Heinstra PW, Scharloo W, Thorig GE. 1989. Alcohol dehydrogenase polymorphism in Drosophila: enzyme kinetics of product inhibition. J. Mol. Evol. 28:145-50
66. Hendricks JC, Finn SM, Panckeri KA, Chavkin J, Williams JA, et al. 2000. Rest in Drosophila is a sleep-like state. Neuron. 25:129-38
67. Hendricks JC, Williams JA, Panckeri K, Kirk D, Tello M, et al. 2001. A non-circadian role for cAMP signaling and CREB activity in Drosophila rest homeostasis. Nat. Neurosci. 4:1108-15
68. Hendricks JC, Kirk D, Panckeri K, Miller MS, Pack AL. 2003. Modafinil maintains waking in the fruit fly Drosophila melanogaster. Sleep 26:139-46
69. Hockly E, Richon VM, Woodman B, Smith DL, Zhou X, et al. 2003. Suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, ameliorates motor deficits in a mouse model of Huntington's disease. Proc Natl. Acad. Sci. USA 100:2041-46
70. Huber R, Hill SL, Holladay C, Biesiadecki M, Tononi G, et al. 2004. Sleep homeostasis in Drosophila melanogaster. Sleep 27:628-39
71. Huntington G. 1872. On chorea. Med. Surg. Reporter 26:317
72. Huntington's Disease Collaborative Research Group 1993. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell 72:971-83
73. Iijima K, Liu HP, Chiang AS, Hearn SA, Konsolaki M, et al. 2004. Dissecting the pathological effects of human Abeta40 and Abeta42 in Drosophila: a potential model for Alzheimer's disease. Proc. Natl. Acad. Sci. USA 101:6623-28
74. Jackson GR, Salecker I, Dong X, Yao X, Arnheim N, et al. 1998. Polyglutamine-expanded human huntingtin transgenes induce degeneration of Drosophila photoreceptor neurons. Neuron. 21:633-42
75. Jackson GR, Wiedau-Pazos M, Sang TK, Wagle N, Brown CA, et al. 2002. Human wild-type tau interacts with wingless pathway components and produces neurofibrillary pathology in Drosophila. Neuron 34:509-19
76. Kazantsev A, Walker HA, Slepko N, Bear JE, Preisinger E, et al. 2002. A bivalent Huntingtin binding peptide suppresses polyglutamine aggregation and pathogenesis in Drosophila. Nat. Genet. 30:367-76
77. Kegel KB, Sapp E, Yoder J, Cuiffo B, Sobin L, et al. 2005. Huntingtin associates with acidic phospholipids at the plasma membrane. J. Biol. Chem. 280:36464-73
78. Kidwell JF. 1969. A chromosomal analysis of egg production and abdominal chaeta number in Drosophila melanogaster. Can. J. Genet. Cytol. 11:547-57
79. Kitada T, Asakawa S, Hattori N, Matsumine H, Yamamura Y, et al. 1998. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature 392:605-8
80. Klos KL, Kardia SL, Hixson JE, Turner ST, Hanis C, et al. 2005. Linkage analysis of plasma ApoE in three ethnic groups: multiple genes with context-dependent effects. Ann. Hum. Genet. 69(Pt. 2):157-67
81. Kopan R, Goate A. 2002. Aph-2/Nicastrin: an essential component of gamma-secretase and regulator of Notch signaling and Presenilin localization. Neuron 33:321-24
82. Kruger R, Kuhn W, Muller T, Woitalla D, Graeber M, et al. 1998. Ala30Pro mutation in the gene encoding α-synuclein in Parkinson's disease. Nat. Genet. 18:106-8
83. Kume K, Kume S, Park SK, Hirsh J, Jackson FR. 2005. Dopamine is a regulator of arousal in the fruit fly. J. Neurosci. 25:7377-84
84. Lai C, Lyman RF, Long AD, Langley CH, Mackay TFC. 1994. Naturally occurring variation in bristle number and DNA polymorphisms at the scabrous locus of Drosophila melanogaster. Science 266:1697-702
85. Laurie CC, Stam LF. 1994. The effect of an intronic polymorphism on alcohol dehydrogenase expression in Drosophila melanogaster. Genetics 138:379-85
86. Laviolette SR, van der Kooy D. 2004. The neurobiology of nicotine addiction: bridging the gap from molecules to behaviour. Nat. Rev. Neurosci. 5:55-65
87. Lee WC, Yoshihara M, Littleton JT. 2004. Cytoplasmic aggregates trap polyglutamine-containing proteins and block axonal transport in a Drosophila model of Huntington's disease. Proc. Natl. Acad. Sci. USA 101:3224-29
88. Leips J, Mackay TFC. 2000. Quantitative trait loci for life span in Drosophila melanogaster: interactions with genetic background and larval density. Genetics 155:1773-88
89. Leips J, Mackay TFC. 2002. The complex genetic architecture of Drosophila life span. Exp. Aging Res. 28:361-90
90. Leyssen M, Ayaz D, Hebert SS, Reeve S, De Strooper B, et al. 2005. Amyloid precursor protein promotes post-developmental neurite arborization in the Drosophila brain. EMBO J. 24:2944-55
91. Li Z, Karlovich CA, Fish MP, Scott MP, Myers RM. 1999. A putative Drosophila homolog of the Huntington's disease gene. Hum. Mol. Genet. 8:1807-15
92. Lievens JC, Rival T, Iche M, Chneiweiss H, Birman S. 2005. Expanded polyglutamine peptides disrupt EGF receptor signaling and glutamate transporter expression in Drosophila. Hum. Mol. Genet. 14:713-24
93. Long AD, Langley CH. 1999. Power of association studies to detect the contribution of candidate genetic loci to complexly inherited phenotypes. Genome Res. 9:720-31
94. Long AD, Lyman RF, Langley CH, Mackay TFC. 1998. Two sites in the Delta gene region contribute to naturally occurring variation in bristle number in Drosophila melanogaster. Genetics 149:999-1017
95. Long AD, Lyman RF, Morgan AH, Langley CH, Mackay TFC. 2000. Both naturally occurring insertions of transposable elements and intermediate frequency polymorphisms at the achaete-scute complex are associated with variation in bristle number in Drosophila melanogaster. Genetics 154:1255-69
96. Long AD, Mullaney SL, Mackay TFC, Langley CH. 1996. Genetic interactions between naturally occurring alleles at quantitative trait loci and mutant alleles at candidate loci affecting bristle number in Drosophila melanogaster. Genetics 114:1497-1510
97. Long AD, Mullaney SL, Reid LA, Fry JD, Langley CH, et al. 1995. High resolution mapping of genetic factors affecting abdominal bristle number in Drosophila melanogaster. Genetics 139:1273-91
98. Luo LQ, Martin-Morris LE, White K. 1990. Identification, secretion, and neural expression of APPL, a Drosophila protein similar to human amyloid protein precursor. J. Neurosci. 10:3849-61
99. Luo L, Tully T, White K. 1992. Human amyloid precursor protein ameliorates behavioral deficit of flies deleted for Appl gene. Neuron 9:595-605
100. Lyman RF, Lai C, Mackay TFC. 1999. Linkage disequilibrium mapping of molecular polymorphisms at the scabrous locus associated with naturally occurring variation in bristle number in Drosophila melanogaster. Genet. Res. 74:303-11
101. Lyman RF, Lawrence F, Nuzhdin SV, Mackay TFC. 1996. Effects of single P element insertions on bristle number and viability in Drosophila melanogaster. Genetics 143:277-92
102. Lyman RF, Mackay TFC. 1998. Candidate quantitative trait loci and naturally occurring phenotypic variation for bristle number in Drosophila melanogaster: the Delta-Hairless gene region. Genetics 149:983-98
103. Lynch M, Walsh B. 1998. Genetics and Analysis of Quantitative Traits. Sunderland, MA: Sinauer
104. Mackay TFC. 2001. Quantitative trait loci in Drosophila. Nat. Rev. Genet. 2:11-20
105. Mackay TFC, Lyman RF, Hill WG. 1995. Polygenic mutation in Drosophila melanogaster: Non-linear divergence among unselected strains. Genetics 139:849-59
106. Mackay TFC, Roshina NV, Leips JW, Pasyukova EG. 2005. Complex genetic architecture of Drosophila longevity, pp. 181-216. in Handbook of the Biology of Aging, Sixth Edition, ed. Masaro EJ, Austad SN. Burlington, MA: Academic Press
107. Marfany G, Del-Favero J, Valero R, De Jonghe C, Woodrow S, et al. 1998. Identification of a Drosophila presenilin homologue: evidence of alternatively spliced forms. J. Neurogenet. 12:41-54
108. Marsh JL, Pallos J, Thompson LM. 2003. Fly models of Huntington's disease. Hum. Mol. Genet. 12:R187-R193
109. Martin JR, Raabe T, Heisenberg M. 1999. Central complex substructures are required for the maintenance of locomotor activity in Drosophila melanogaster. J. Comp. Physiol. A 185:277-88
110. Martin-Morris LE, White K. 1990. The Drosophila transcript encoded by the β-amyloid protein precursor-like gene is restricted to the nervous system. Development 110:185-95
111. McClung C, Hirsh J. 1998. Stereotypic behavioral responses to free-base cocaine and the development of behavioral sensitization in Drosophila. Curr. Biol. 8:109-12
112. McClung C, Hirsh J. 1999. The trace amine tyramine is essential for sensitization to cocaine in Drosophila. Curr. Biol. 9:853-60
113. Merdes G, Soba P, Loewer A, Bilic MV, Beyreuther K, et al. 2004. Interference of human and Drosophila APP and APP-like proteins with PNS development in Drosophila. EMBO J. 23:4082-95
114. Micchelli CA, Esler WP, Kimberly WT, Jack C, Berezovska O, et al. 2003. Gamma-secretase/presenilin inhibitors for Alzheimer's disease phenocopy Notch mutations in Drosophila. FASEB J. 17:79-81
115. Moehring AJ, Mackay TFC. 2 004. The quantitative genetic basis of male mating behavior in Drosophila melanogaster. Genetics 167:1249-63
116. Monastirioti M, Linn CEJ, White K. 1996. Characterization of Drosophila tyramine-beta-hydroxylase gene and isolation of mutant flies lacking octopamine. J. Neurosci. 16:3900-11
117. Montooth KL, Marden JH, Clark AG. 2003. Mapping determinants of variation in energy metabolism, respiration and flight in Drosophila. Genetics 165:623-35
118. Moore MS, DeZazzo J, Luk AY, Tully T, Singh CM, et al. 1998. Ethanol intoxication in Drosophila: genetic and pharmacological evidence for regulation by the cAMP signaling pathway. Cell 93:997-1007
119. Mudher A, Shepherd D, Newman TA, Mildren P, Jukes JP, et al. 2004. GSK-3beta inhibition reverses axonal transport defects and behavioural phenotypes in Drosophila. Mol. Psychiatry 9:522-30
120. Mulligan CJ, Robin RW, Osler MV, Sambuughin N, Goldfarb LG, et al. 2003. Allelic variation at alcohol metabolism genes (ADH1B, ADH1C, ALDH2) and alcohol dependence in an American Indian population. Hum. Genet. 113:325-36
121. Nishimura I, Yang Y, Lu B. 2004. PAR-1 kinase plays an initiator role in a temporally ordered phosphorylation process that confers tau toxicity in Drosophila. Cell 116:671-82
122. Nitz DA, van Swinderen B, Tononi G, Greenspan RJ. 2002. Electrophysiological correlates of rest and activity in Drosophila melanogaster. Curr. Biol. 12:1934-40
123. Norga KK, Gurganus MC, Dilda CL, Yamamoto A, Lyman RF, et al. 2003. Quantitative analysis of bristle number in Drosophila mutants identifies genes involved in neural development. Curr. Biol. 13:1388-97
124. Nowotny P, Gorski SM, Han SW, Philips K, Ray WJ, et al. 2000. Posttranslational modification and plasma membrane localization of the Drosophila melanogaster presenilin. Mol. Cell. Neurosci. 15:88-98
125. Nuzhdin SV, Dilda CL, Mackay TFC. 1999. The genetic architecture of selection response: inferences from fine-scale mapping of bristle number quantitative trait loci in Drosophila melanogaster. Genetics 153:1317-31
126. Nuzhdin SV, Pasyukova EG, Dilda CL, Zeng Z-B, Mackay TFC. 1997. Sex-specific quantitative trait loci affecting longevity in Drosophila melanogaster. Proc. Natl. Acad. Sci. USA 94:9734-39
127. Ober C, Thompson EE. 2005. Rethinking genetic models of asthma: the role of environmental modifiers. Curr. Opin. Immunol. 7:670-78
128. Okochi M, Walter J, Koyama A, Nakajo S, Baba M, Iwatsubo T, et al. 2000. Constitutive phosphorylation of the Parkinson's disease associated α-synuclein. J. Biol. Chem. 275:390-97
129. Ostrander EA, Markianos K, Stanford JL. 2004. Finding prostate cancer susceptibility genes. Annu. Rev. Genomics Hum. Genet. 5:151-75
130. Papel I, Henderson M, Van Herrewege J, David J, Sofer W. 1979. Drosophila alcohol dehydrogenase activity in vitro and in vivo: effects of acetone feeding. Biochem. Genet. 17:553-63
131. Park SK, Sedore SA, Cronmiller C, Hirsh J. 2000. PKA-RII-deficient Drosophila are viable, but show developmental, circadian and drug response phenotypes. J. Biol. Chem. 275:20588-96
132. Parkinson J. 1817. An essay on the shaking palsy. London: Whittingham & Rowland
133. Parks AL, Cook KR, Belvin M, DompeNA, Fawcett R, et al. 2004. Systematic generation of high-resolution deletion coverage of the Drosophila melanogaster genome. Nat Genet. 36:288-92
134. Pasyukova EG, Roshina NV, Mackay TFC. 2004. shuttle craft: a candidate quantitative trait gene for Drosophila life span. Aging Cell 3:297-307
135. Pasyukova EG, Vieira C, Mackay TFC. 2000. Deficiency mapping of quantitative trait loci affecting longevity in Drosophila melanogaster. Genetics 156:1129-46
136. Pendleton RG, Parvez F, Sayed M, Hillman R. 2002. Effects of pharmacological agents upon a transgenic model of Parkinson's disease in Drosophila melanogaster. J. Pharmacol. Exp. Ther. 300:91-96
137. Penney JB Jr, Vonsattel JP, MacDonald ME, Gusella JF, Myers RH. 1997. CAG repeat number governs the development rate of pathology in Huntington's disease. Ann. Neurol. 41:689-92
138. Pesah Y, Pham T, Burgess H, Middlebrooks B, Verstreken P, et al. 2004. Drosophila parkin mutants have decreased mass and cell size and increased sensitivity to oxygen radical stress. Development 131:2183-94
139. Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, et al. 1997. Mutation in the α-synuclein gene identified in families with Parkinson's disease. Science 276:2045-47
140. Quinn WG, Sziber PP, Booker R. 1979. The Drosophila memory mutant amnesiac. Nature 277:212-14
141. Radel M, Goldman D. 2001. Pharmacogenetics of alcohol response and alcoholism: the interplay of genes and environmental factors in thresholds for alcoholism. Drug Metab. Dispos. 29:489-94
142. Ravikumar B, Vacher C, Berger Z, Davies JE, Luo S, et al. 2004. Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease. Nat. Genet. 36:585-95
143. Risch N, Merikangas K, 1996. The future of genetic studies of complex human diseases. Science 273:1516-17
144. Robertson A. 1967. The nature of quantitative genetic variation. In Heritage From Mendel, ed. A Brink, pp. 265-80. Madison, WI: Univ. Wise. Press
145. Robin C, Lyman RF, Long AD, Langley CH, Mackay TFC. 2002. hairy: a quantitative trait locus for Drosophila bristle number. Genetics 162:155-64
146. Rodan AR, Kiger JA Jr, Heberlein U. 2002. Functional dissection of neuroanatomical loci regulating ethanol sensitivity in Drosophila. J. Neurosci. 22:9490-501
147. Roeder T. 1999. Octopamine in invertebrates. Prog. Neurobiol. 59:533-61
148. Rothenfluh A, Heberlein U. 2002. Drugs, flies, and videotape: the effects of ethanol and cocaine on Drosophila locomotion. Curr. Opin. Neurobiol. 12:639-45
149. Rubin GM, Yandell MD, Wortman JR, Gabor Miklos GL, Nelson CR, et al. 2000. Comparative genomics of the eukaryotes. Science 287:2204-15
150. Saito Y, Kawashima A, Ruberu NN, Fujiwara H, Koyama S, et al. 2003. Accumulation of phosphorylated α-synuclein in aging human brain. J. Neuropathol. Exp. Neurol. 62:644-54
151. Sax K. 192 3. The association of size differences with seed-coat pattern and pigmentation in Phaseolus vulgaris. Genetics 8:552-60
152. Schapira AH, Cooper JM, Dexter D, Clark JB, Jenner P, et al. 1990. Mitochondrial complex I deficiency in Parkinson's Disease. J. Neurochem. 54:823-27
153. Scherzer CR, Jensen RV, Gullans SR, Feany MB. 2003. Gene expression changes presage neurodegeneration in a Drosophila model of Parkinson's disease. Hum. Mol. Genet. 12:2457-66
154. Scholz H. 2005. Influence of the biogenic amine tyramine on ethanol-induced behaviors in Drosophila. J. Neurobiol. 63:199-214
155. Scholz H, Ramond J, Singh CM, Heberlein U. 2000. Functional ethanol tolerance in Drosophila. Neuron. 28:261-71
156. Scholz H, Franz M, Heberlein U. 2005. The hangover gene defines a stress pathway required for ethanol tolerance development. Nature 436:845-47
157. Shaw PJ, Cirelli C, Greenspan RJ, Tononi G. 2000. Correlates of sleep and waking in Drosophila melanogaster. Science 287:1834-37
158. Shrimpton AE, Robertson A. 1988. The isolation of polygenic factors controlling bristle score in Drosophila melanogaster. I. Allocation of third chromosome bristle effects to chromosome sections. Genetics 118:437-4-3
159. Shrimpton AE, Robertson A. 1988. The isolation of polygenic factors controlling bristle score in Drosophila melanogaster. II. Distribution of third chromosome bristle effects within chromosome sections. Genetics 118:445-59
160. Shulman JM, Feany MB. 2003. Genetic modifiers of tauopathy in Drosophila. Genetics 165:1233-42
161. Singh CM, Heberlein U. 2000. Genetic control of acute ethanol-induced behaviors in Drosophila. Alcohol. Clin. Exp. Res. 24:1127-36
162. Singleton AB, Farrer M, Johnson J, Singleton A, Hague S, et al. 2003. α-Synuclein locus triplication causes Parkinson's disease. Science 302:841
163. Sklar P. 2002. Linkage analysis in psychiatric disorders: the emerging picture. Annu. Rev. Genomics Hum. Genet. 3:371-4-13
164. Stam LF, Laurie CC. 1996. Molecular dissection of a major gene effect on a quantitative trait: the level of alcohol dehydrogenase expression in Drosophila melanogaster. Genetics 144:1559-64
165. Steffan JS, Bodai L, Pallos J, Poelman M, McCampbell A, et al. 2001. Histone deacetylase inhibitors arrest polyglutamine-dependent neurodegeneration in Drosophila. Nature 413:739-43
166. Steffan JS, Agrawal N, Pallos J, Rockabrand E, Trotman LC, et al. 2004. SUMO modification of Huntingtin and Huntington's disease pathology. Science 304:100-4
167. Stine OC, Pleasant N, Franz ML, Abbott MH, Folstein SE, et al. 1993. Correlation between the onset age of Huntington's disease and length of the trinucleotide repeat in IT-15. Hum. Mol. Genet. 2:1547-19
168. Struhl G, Greenwald I. 1999. Presenilin is required for activity and nuclear access of Notch in Drosophila. Nature 398:522-25
169. Suster ML, Karunanithi S, Atwood HL, Sokolowski MB. 2004. Turning behavior in Drosophila larvae: a role for the small scribbler transcript. Genes Brain Behav. 3:273-86
170. Takasugi N, Takahashi Y, Morohashi Y, Tomita T, Iwatsubo T. 2002. The mechanism of gamma-secretase activities through high molecular weight complex formation of presenilins is conserved in Drosophila melanogaster and mammals. J. Biol. Chem. 277:50198-205
171. Takasugi N, Tomita T, Hayashi I, Tsuruoka M, Niimura M, et al. 2003. The role of presenilin cofactors in the gamma-secretase complex. Nature 422:438-41
172. Taru H, Iijima K, Hase M, Kirino Y, Yagi Y, et al. 2002. Interaction of Alzheimer's beta-amyloid precursor family proteins with scaffold proteins of the JNK signaling cascade. J. Biol. Chem. 277:20070-78
173. Templeton A. 1999. Uses of evolutionary theory in the human genome project. Annu. Rev. Ecol. Syst. 30:23-49
174. Terashima T, Kawai H, Fujitani M, Maeda K, Yasuda H. 2002. SUMO-1 co-localized with mutant atrophin-1 with expanded polyglutamines accelerates intranuclear aggregation and cell death. Neuroreport 13:2359-64
175. The International HapMap Consortium. 2005. A haplotype map of the human genome. Nature 437:1299-1320
176. Thibault ST, Singer MA, Miyazaki WY, Milash B, Dompe NA et al. 2004. A complementary transposon tool kit for Drosophila melanogaster using P and piggyBac. Nat. Genet. 36:283-87
177. Torroja L, Chu H, Kotovsky I, White K. 1999. Neuronal overexpression of APPL, the Drosophila homologue of the amyloid precursor protein (APP), disrupts axonal transport. Curr. Biol. 9:489-92
178. Tsuda H, Jafar-Nejad H, Patel AK, Sun Y, Chen H, et al. 2005. The AXH domain of ataxin-1 mediates neurodegeneration through its interaction with Gfi-1/Senseless Proteins. Cell 122:633-44
179. Ueda H, Goto J, Hashida H, Lin X, Oyanagi K, et al. 2002. Enhanced SUMOylation in polyglutamine diseases. Biochem. Biophys. Res. Commun. 293:307-13
180. van Swinderen B, Nitz DA, Greenspan RJ. 2004. Uncoupling of brain activity from movement defines arousal states in Drosophila. Curr. Biol. 14:81-87
181. van Swinderen B. 2005. The remote roots of consciousness in fruit-fly selective attention? BioEssays 27:321-30
182. Venken KJ, Bellen HJ. 2005. Emerging technologies for gene manipulation in Drosophila melanogaster. Nat. Rev. Genet. 6:167-78
183. Vieira C, Pasyukova EG, Zeng S, Hackett JB, Lyman RF et al. 2000. Genotype-environment interaction for quantitative trait loci affecting life span in Drosophila melanogaster. Genetics 154:213-27
184. Waddell S, Armstrong JD, Kitamoto T, Kaiser K, Quinn WG. 2000. The amnesiac gene product is expressed in two neurons in the Drosophila brain that are critical for memory. Cell 103:805-13
185. Waelter S, Boeddrich A, Lurz R, Scherzinger E, Lueder G, et al. 2001. Accumulation of mutant huntingtin fragments in aggresome-like inclusion bodies as a result of insufficient protein degradation. Mol. Biol. Cell. 12:1393-407
186. Wang P, Saraswati S, Guan Z, Watkins CJ, Wurtman RJ, et al. 2004. A Drosophila temperature-sensitive seizure mutant in phosphoglycerate kinase disrupts ATP generation and alters synaptic function. J. Neurosci. 24:4518-29
187. Warrick JM, Chan HYE, Gray-Board GL, Chai YH, Paulson HL, et al. 1999. Suppression of polyglutamine-mediated neurodegeneration in Drosophila by the molecular chaperone HSP70. Nat. Genet. 23:425-28
188. Wayne ML, Hackett JB, Dilda CL, Nuzhdin SV, Pasyukova EG, et al. 2001. Quantitative trait loci mapping of fitness-related traits in Drosophila melanogaster. Genet. Res. 77:107-16
189. Weber KE. 1988. An apparatus for measurement of resistance to gas-phase reagents. Dros. Info. Serv. 67:91-93
190. Weber K, Eisman R, Higgins S, Morey L, Patty A, et al. 2001. An analysis of polygenes affecting wing shape on chromosome 2 in Drosophila melanogaster. Genetics 159:1045-57
191. Weber K, Eisman R, Morey L, Patty A, Sparks J, et al. 1999. An analysis of polygenes affecting wing shape on chromosome 3 in Drosophila melanogaster. Genetics 153:773-86
192. Wei VL, Singh SM. 1988. Genetically determined response of hepatic aldehyde dehydrogenase activity to ethanol exposures may be associated with alcohol sensitivity in mouse genotypes. Alcohol Clin. Exp. Res. 12:39-45
193. Whitworth AJ, Theodore DA, Greene JC, Benes H, Wes PD, et al. 2005. Increased glutathione S-transferase activity rescues dopaminergic neuron loss in a Drosophila model of Parkinson's disease. Proc. Natl. Acad. Sci. USA 102:8024-29
194. Wittmann CW, Wszolek MF, Shulman JM, Salvaterra PM, Lewis J, et al. 2001. Tauopathy in Drosophila: neurodegeneration without neurofibrillary tangles. Science 293:711-14
195. Wolf FW, Rodan AR, Tsai LT, Heberlein U. 2002. High-resolution analysis of ethanol-induced locomotor stimulation in Drosophila. J. Neurosci. 22:11035-44
196. Wolfgang WJ, Miller TW, Webster JM, Huston JS, Thompson LM, et al. 2005. Suppression of Huntington's disease pathology in Drosophila by human single-chain Fv antibodies. Proc. Natl. Acad. Sci. USA. 102:11563-68
197. Yagi Y, Tomita S, Nakamura M, Suzuki T. 2000. Overexpression of human amyloid precursor protein in Drosophila. Mol. Cell Biol. Res. Commun. 4:43-49
198. Yang Y, Nishimura I, Imai Y, Takahashi R, Lu B. 2003. Parkin suppresses dopaminergic neuron-selective neurotoxicity induced by Pael-R in Drosophila. Neuron 37:911-24
199. Ye Y, Lukinova N, Fortini ME. 1999. Neurogenic phenotypes and altered Notch processing in Drosophila Presenilin mutants. Nature 398:525-29
200. Zarnescu DC, Shan G, Warren ST, Jin P. 2005. Come FLY with us: toward understanding fragile X syndrome. Genes Brain Behav. 4:385-92
201. Zarranz JJ, Alegre J, Gomez-Esteban JC, Lezcano E, Ros R, et al. 2004. The new mutation, E46K, of α-synuclein causes Parkinson and Lewy body dementia. Ann. Neurol. 55:164-73
202. Zhang X, Smith DL, Meriin AB, Engemann S, Russel DE, et al. 2005. A potent small molecule inhibits polyglutamine aggregation in Huntington's disease neurons and suppresses neurodegeneration in vivo. Proc. Natl. Acad. Sci. USA 102:892-97
203. Zimatkin SM, Liopo AV, Satanovskaya VI, Bardina LR, Deitrich RA. 2001. Relationship of brain ethanol metabolism to the hypnotic effect of ethanol. II: studies in selectively bred rats and mice. Alcohol Clin. Exp. Res. 25:982-88
204. Zoghbi HY, Orr HT. 2000. Glutamine repeats and neurodegeneration. Annu. Rev. Neurosci. 23:217-47