Modifier Genes and the Plasticity of Genetic Networks in Mice
Modifier genes are an integral part of the genetic landscape in both humans and experimental organisms, but have been less well explored in mammals than other systems. A growing number of modifier genes in mouse models of disease nonetheless illustrate the potential for novel findings, while new technical advances promise many more to come. Modifier genes in mouse models include induced mutations and spontaneous or wild-derived variations captured in inbred strains. Identification of modifiers among wild-derived variants in particular should detect disease modifiers that have been shaped by selection and might therefore be compatible with high fitness and function. Here we review selected examples and argue that modifier genes derived from natural variation may provide a bias for nodes in genetic networks that have greater intrinsic plasticity and whose therapeutic manipulation may therefore be more resilient to side effects than conventional targets.
Vyšlo v časopise:
Modifier Genes and the Plasticity of Genetic Networks in Mice. PLoS Genet 8(4): e32767. doi:10.1371/journal.pgen.1002644
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Review
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1002644
Souhrn
Modifier genes are an integral part of the genetic landscape in both humans and experimental organisms, but have been less well explored in mammals than other systems. A growing number of modifier genes in mouse models of disease nonetheless illustrate the potential for novel findings, while new technical advances promise many more to come. Modifier genes in mouse models include induced mutations and spontaneous or wild-derived variations captured in inbred strains. Identification of modifiers among wild-derived variants in particular should detect disease modifiers that have been shaped by selection and might therefore be compatible with high fitness and function. Here we review selected examples and argue that modifier genes derived from natural variation may provide a bias for nodes in genetic networks that have greater intrinsic plasticity and whose therapeutic manipulation may therefore be more resilient to side effects than conventional targets.
Zdroje
1. CarlsonEA 1981 Genes, radiation and society: the life and work of H.J. Muller Ithaca Cornell Universtiy Press 457
2. SturtevantAH 1965 A history of genetics New York Harper & Row
3. CastleWE 1912 The inconstancy of unit-characters. Am Naturalist 46 352 362
4. CastleWE 1916 Further studies on piebald rats and selection. Carnegie Inst Wash Publ No 241 161 192
5. DexterJS 1914 The analysis of a case of continuous variation in Drosophila by a study of its linkage relationships. Am Naturalist 48 712 758
6. CastleWE 1919 Piebald rats and the theory of genes. Proc Natl Acad Sci U S A 5 126 130
7. CastleWE 1951 Variation in the hooded pattern of rats, and a new allele of hooded. Genetics 36 254 266
8. AltenburgEMullerHJ 1920 The genetic basis of truncate wing,-an inconstant and modifiable character in Drosophila. Genetics 5 1 59
9. CuttingGR 2010 Modifier genes in Mendelian disorders: the example of cystic fibrosis. Ann N Y Acad Sci 1214 57 69
10. WrightFAStrugLJDoshiVKCommanderCWBlackmanSM 2011 Genome-wide association and linkage identify modifier loci of lung disease severity in cystic fibrosis at 11p13 and 20q13.2. Nat Genet 43 539 546
11. GuYHarleyITHendersonLBAronowBJVietorI 2009 Identification of IFRD1 as a modifier gene for cystic fibrosis lung disease. Nature 458 1039 1042
12. RozmahelRGyomoreyKPlyteSNguyenVWilschanskiM 1997 Incomplete rescue of cystic fibrosis transmembrane conductance regulator deficient mice by the human CFTR cDNA. Hum Mol Genet 6 1153 1162
13. HastonCKCoreyMTsuiLC 2002 Mapping of genetic factors influencing the weight of cystic fibrosis knockout mice. Mamm Genome 13 614 618
14. HastonCKMcKerlieCNewbiggingSCoreyMRozmahelR 2002 Detection of modifier loci influencing the lung phenotype of cystic fibrosis knockout mice. Mamm Genome 13 605 613
15. HastonCKTsuiLC 2003 Loci of intestinal distress in cystic fibrosis knockout mice. Physiol Genomics 12 79 84
16. ZielenskiJCoreyMRozmahelRMarkiewiczDAznarezI 1999 Detection of a cystic fibrosis modifier locus for meconium ileus on human chromosome 19q13. Nat Genet 22 128 129
17. LouieCMCaridiGLopesVSBrancatiFKispertA 2010 AHI1 is required for photoreceptor outer segment development and is a modifier for retinal degeneration in nephronophthisis. Nat Genet 42 175 180
18. GirirajanSRosenfeldJACooperGMAntonacciFSiswaraP 2010 A recurrent 16p12.1 microdeletion supports a two-hit model for severe developmental delay. Nat Genet 42 203 209
19. EichersERLewisRAKatsanisNLupskiJR 2004 Triallelic inheritance: a bridge between Mendelian and multifactorial traits. Ann Med 36 262 272
20. BealesPLBadanoJLRossAJAnsleySJHoskinsBE 2003 Genetic interaction of BBS1 mutations with alleles at other BBS loci can result in non-Mendelian Bardet-Biedl syndrome. Am J Hum Genet 72 1187 1199
21. KatsanisNAnsleySJBadanoJLEichersERLewisRA 2001 Triallelic inheritance in Bardet-Biedl syndrome, a Mendelian recessive disorder. Science 293 2256 2259
22. NadeauJHTopolEJ 2006 The genetics of health. Nat Genet 38 1095 1098
23. PapetaNZhengZSchonEABroselSAltintasMM 2010 Prkdc participates in mitochondrial genome maintenance and prevents Adriamycin-induced nephropathy in mice. J Clinical Invest 120 4055 4064
24. SpinazzolaAViscomiCFernandez-VizarraECarraraFD'AdamoP 2006 MPV17 encodes an inner mitochondrial membrane protein and is mutated in infantile hepatic mitochondrial DNA depletion. Nat Genet 38 570 575
25. SweetHO 1983 Dilute suppressor, a new suppressor gene in the house mouse. J Hered 74 305 306
26. MooreKJSwingDACopelandNGJenkinsNA 1990 Interaction of the murine dilute suppressor gene (dsu) with fourteen coat color mutations. Genetics 125 421 430
27. MooreKJSwingDARinchikEMMucenskiMLBuchbergAM 1988 The murine dilute suppressor gene dsu suppresses the coat-color phenotype of three pigment mutations that alter melanocyte morphology, d, ash and ln. Genetics 119 933 941
28. O'SullivanTNWuXSRachelRAHuangJDSwingDA 2004 dsu functions in a MYO5A-independent pathway to suppress the coat color of dilute mice. Proc Natl Acad Sci U S A 101 16831 16836
29. Damek-PoprawaMDiemerTLopesVSLilloCHarperDC 2009 Melanoregulin (MREG) modulates lysosome function in pigment epithelial cells. J Biol Chem 284 10877 10889
30. KearneyJABuchnerDADe HaanGAdamskaMLevinSI 2002 Molecular and pathological effects of a modifier gene on deficiency of the sodium channel Scn8a (Na(v)1.6). Hum Mol Genet 11 2765 2775
31. HowellVMJonesJMBergrenSKLiLBilliAC 2007 Evidence for a direct role of the disease modifier SCNM1 in splicing. Hum Mol Genet 16 2506 2516
32. BuchnerDATrudeauMMeislerMH 2003 SCNM1, a putative RNA splicing factor that modifies disease severity in mice. Science 301 967 969
33. HowellVMde HaanGBergrenSJonesJMCuliatCT 2008 A targeted deleterious allele of the splicing factor SCNM1 in the mouse. Genetics 180 1419 1427
34. QuwailidMMHugillADearNVizorLWellsS 2004 A gene-driven ENU-based approach to generating an allelic series in any gene. Mamm Genome 15 585 591
35. ConcepcionDSeburnKLWenGFrankelWNHamiltonBA 2004 Mutation rate and predicted phenotypic target sizes in ethylnitrosourea-treated mice. Genetics 168 953 959
36. HiltonJMLewisMAGratiMInghamNPearsonS 2011 Exome sequencing identifies a missense mutation in Isl1 associated with low penetrance otitis media in dearisch mice. Genome Biol 12 R90
37. FairfieldHGilbertGJBarterMCorriganRRCurtainM 2011 Mutation discovery in mice by whole exome sequencing. Genome Biol 12 R86
38. ArnoldCNXiaYLinPRossCSchwanderM 2011 Rapid identification of a disease allele in mouse through whole genome sequencing and bulk segregation analysis. Genetics 187 633 641
39. BlewittMEGendrelAVPangZSparrowDBWhitelawN 2008 SmcHD1, containing a structural-maintenance-of-chromosomes hinge domain, has a critical role in X inactivation. Nat Genet 40 663 669
40. AsheAMorganDKWhitelawNCBruxnerTJVickaryousNK 2008 A genome-wide screen for modifiers of transgene variegation identifies genes with critical roles in development. Genome Biol 9 R182
41. ChongSVickaryousNAsheAZamudioNYoungsonN 2007 Modifiers of epigenetic reprogramming show paternal effects in the mouse. Nat Genet 39 614 622
42. BlewittMEVickaryousNKHemleySJAsheABruxnerTJ 2005 An N-ethyl-N-nitrosourea screen for genes involved in variegation in the mouse. Proc Natl Acad Sci U S A 102 7629 7634
43. YoungsonNAVickaryousNvan der HorstAEppTHartenS 2011 A missense mutation in the transcription factor Foxo3a causes teratomas and oocyte abnormalities in mice. Mamm Genome 22 235 248
44. MateraIWatkins-ChowDELoftusSKHouLIncaoA 2008 A sensitized mutagenesis screen identifies Gli3 as a modifier of Sox10 neurocristopathy. Hum Mol Genet 17 2118 2131
45. SilverDLWatkins-ChowDESchreckKCPierfeliceTJLarsonDM 2010 The exon junction complex component Magoh controls brain size by regulating neural stem cell division. Nature Neurosci 13 551 558
46. StevensJCBanksGTFestingMFFisherEM 2007 Quiet mutations in inbred strains of mice. Trends Mol Med 13 512 519
47. FestingMFW 1996 Origins and characteristics of inbred strains of mice. LyonMFRastanSBrownSDM Genetics variants and strains of the laboratory mouse. 3rd edition Oxford Oxford University Press 1537 1576
48. KirbyAKangHMWadeCMCotsapasCKostemE 2010 Fine mapping in 94 inbred mouse strains using a high-density haplotype resource. Genetics 185 1081 1095
49. FrazerKAEskinEKangHMBogueMAHindsDA 2007 A sequence-based variation map of 8.27 million SNPs in inbred mouse strains. Nature 448 1050 1053
50. WadeCMDalyMJ 2005 Genetic variation in laboratory mice. Nat Genet 37 1175 1180
51. CristRCRothJJLisantiMPSiracusaLDBuchbergAM 2011 Identification of Mom12 and Mom13, two novel modifier loci of Apc (Min) -mediated intestinal tumorigenesis. Cell Cycle 10 1092 1099
52. OikarinenSIClevelandAGCorkKMBynoteKKRafterJJ 2009 Genetic mapping of Mom5, a novel modifier of Apc(Min)-induced intestinal tumorigenesis. Carcinogenesis 30 1591 1596
53. KwongLNShedlovskyABiehlBSClipsonLPaschCA 2007 Identification of Mom7, a novel modifier of Apc(Min/+) on mouse chromosome 18. Genetics 176 1237 1244
54. HainesJJohnsonVPackKSuraweeraNSlijepcevicP 2005 Genetic basis of variation in adenoma multiplicity in ApcMin/+ Mom1S mice. Proc Natl Acad Sci U S A 102 2868 2873
55. SilvermanKAKoratkarRSiracusaLDBuchbergAM 2002 Identification of the modifier of Min 2 (Mom2) locus, a new mutation that influences Apc-induced intestinal neoplasia. Genome Res 12 88 97
56. CormierRTBilgerALillichAJHalbergRBHongKH 2000 The Mom1AKR intestinal tumor resistance region consists of Pla2g2a and a locus distal to D4Mit64. Oncogene 19 3182 3192
57. DietrichWFLanderESSmithJSMoserARGouldKA 1993 Genetic identification of Mom-1, a major modifier locus affecting Min-induced intestinal neoplasia in the mouse. Cell 75 631 639
58. PerreaultNSackettSDKatzJPFurthEEKaestnerKH 2005 Foxl1 is a mesenchymal Modifier of Min in carcinogenesis of stomach and colon. Genes Dev 19 311 315
59. MacPheeMChepenikKPLiddellRANelsonKKSiracusaLD 1995 The secretory phospholipase A2 gene is a candidate for the Mom1 locus, a major modifier of ApcMin-induced intestinal neoplasia. Cell 81 957 966
60. CormierRTHongKHHalbergRBHawkinsTLRichardsonP 1997 Secretory phospholipase Pla2g2a confers resistance to intestinal tumorigenesis. Nat Genet 17 88 91
61. LeungSYChenXChuKMYuenSTMathyJ 2002 Phospholipase A2 group IIA expression in gastric adenocarcinoma is associated with prolonged survival and less frequent metastasis. Proc Natl Acad Sci U S A 99 16203 16208
62. KeaneTMGoodstadtLDanecekPWhiteMAWongK 2011 Mouse genomic variation and its effect on phenotypes and gene regulation. Nature 477 289 294
63. YangHWangJRDidionJPBuusRJBellTA 2011 Subspecific origin and haplotype diversity in the laboratory mouse. Nat Genet 43 648 655
64. WheelerFCFernandezLCarlsonKMWolfMJRockmanHA 2005 QTL mapping in a mouse model of cardiomyopathy reveals an ancestral modifier allele affecting heart function and survival. Mamm Genome 16 414 423
65. WheelerFCTangHMarksOAHadnottTNChuPL 2009 Tnni3k modifies disease progression in murine models of cardiomyopathy. PLoS Genet 5 e1000647 doi:10.1371/journal.pgen.1000647
66. BeckJALloydSHafezparastMLennon-PierceMEppigJT 2000 Genealogies of mouse inbred strains. Nat Genet 24 23 25
67. WiltshireSALeiva-TorresGAVidalSM 2011 Quantitative trait locus analysis, pathway analysis, and consomic mapping show genetic variants of Tnni3k, Fpgt, or H28 control susceptibility to viral myocarditis. J Immunol 186 6398 6405
68. HamiltonBASmithDJMuellerKLKerrebrockAWBronsonRT 1997 The vibrator mutation causes neurodegeneration via reduced expression of PITP alpha: positional complementation cloning and extragenic suppression. Neuron 18 711 722
69. FloydJAGoldDAConcepcionDPoonTHWangX 2003 A natural allele of Nxf1 suppresses retrovirus insertional mutations. Nat Genet 35 221 228
70. ConcepcionDFlores-GarciaLHamiltonBA 2009 Multipotent genetic suppression of retrotransposon-induced mutations by Nxf1 through fine-tuning of alternative splicing. PLoS Genet 5 e1000484 doi:10.1371/journal.pgen.1000484
71. JohnsonKRLanePWWard-BaileyPDavissonMT 1995 Mapping the mouse dactylaplasia mutation, Dac, and a gene that controls its expression, mdac. Genomics 29 457 464
72. ChaiCK 1981 Dactylaplasia in mice a two-locus model for development anomalies. J Hered 72 234 237
73. SidowABulotskyMSKerrebrockAWBirrenBWAltshulerD 1999 A novel member of the F-box/WD40 gene family, encoding dactylin, is disrupted in the mouse dactylaplasia mutant. Nat Genet 23 104 107
74. KanoHKurahashiHTodaT 2007 Genetically regulated epigenetic transcriptional activation of retrotransposon insertion confers mouse dactylaplasia phenotype. Proc Natl Acad Sci U S A 104 19034 19039
75. SheXChengZZollnerSChurchDMEichlerEE 2008 Mouse segmental duplication and copy number variation. Nat Genet 40 909 914
76. YalcinBWongKAgamAGoodsonMKeaneTM 2011 Sequence-based characterization of structural variation in the mouse genome. Nature 477 326 329
77. PhilipVMSokoloffGAckert-BicknellCLStrizMBranstetterL 2011 Genetic analysis in the Collaborative Cross breeding population. Genome Res 21 1223 1238
78. ShaoHBurrageLCSinasacDSHillAEErnestSR 2008 Genetic architecture of complex traits: large phenotypic effects and pervasive epistasis. Proc Natl Acad Sci U S A 105 19910 19914
79. SingerJBHillAEBurrageLCOlszensKRSongJ 2004 Genetic dissection of complex traits with chromosome substitution strains of mice. Science 304 445 448
80. LiMAPettittSJYusaKBradleyA 2010 Genome-wide forward genetic screens in mouse ES cells. Method Enzymol 477 217 242
81. VoehringerDWuDLiangHELocksleyRM 2009 Efficient generation of long-distance conditional alleles using recombineering and a dual selection strategy in replicate plates. BMC Biotechnol 9 69
82. van der WeydenLShaw-SmithCBradleyA 2009 Chromosome engineering in ES cells. Methods in molecular biology 530 49 77
83. ten BergeDKurekDBlauwkampTKooleWMaasA 2011 Embryonic stem cells require Wnt proteins to prevent differentiation to epiblast stem cells. Nat Cell Biol 13 1070 1075
84. NadeauJH 2001 Modifier genes in mice and humans. Nat Rev Genet 2 165 174
85. HamiltonBAFrankelWN 2001 Of mice and genome sequence. Cell 107 13 16
86. EppigJTBlakeJABultCJKadinJARichardsonJE 2011 The Mouse Genome Database (MGD): comprehensive resource for genetics and genomics of the laboratory mouse. Nucleic Acids Res 40 D881 D886
87. BlakeJABultCJKadinJARichardsonJEEppigJT 2011 The Mouse Genome Database (MGD): premier model organism resource for mammalian genomics and genetics. Nucleic Acids Res 39 D842 D848
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Genetika Reprodukčná medicínaČlánok vyšiel v časopise
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