From genes to function: the next challenge to understanding multiple sclerosis
Tóm tắt
Từ khóa
Tài liệu tham khảo
Lopez-Diego, R. S. & Weiner, H. L. Novel therapeutic strategies for multiple sclerosis — a multifaceted adversary. Nature Rev. Drug Discov. 7, 909–925 (2008).
Correale, J., Fiol, M. & Gilmore, W. The risk of relapses in multiple sclerosis during systemic infections. Neurology 67, 652–659 (2006).
Ascherio, A. & Munger, K. L. Environmental risk factors for multiple sclerosis. Part II: noninfectious factors. Ann. Neurol. 61, 504–513 (2007).
Oksenberg, J. R., Baranzini, S. E., Sawcer, S. & Hauser, S. L. The genetics of multiple sclerosis: SNPs to pathways to pathogenesis. Nature Rev. Genet. 9, 516–526 (2008).
Bertrams, J., Kuwert, E. & Liedtke, U. HL-A antigens and multiple sclerosis. Tissue Antigens 2, 405–408 (1972).
Jersild, C., Svejgaard, A. & Fog, T. HL-A antigens and multiple sclerosis. Lancet 1, 1240–1241 (1972).
Naito, S., Namerow, N., Mickey, M. R. & Terasaki, P. I. Multiple sclerosis: association with HL-A3. Tissue Antigens 2, 1–4 (1972).
Jersild, C. et al. Histocompatibility determinants in multiple sclerosis, with special reference to clinical course. Lancet 2, 1221–1225 (1973).
Lincoln, M. R. et al. A predominant role for the HLA class II region in the association of the MHC region with multiple sclerosis. Nature Genet. 37, 1108–1112 (2005).
Oksenberg, J. R. et al. Mapping multiple sclerosis susceptibility to the HLA-DR locus in African Americans. Am. J. Hum. Genet. 74, 160–167 (2004).
Barcellos, L. F. et al. Heterogeneity at the HLA-DRB1 locus and risk for multiple sclerosis. Hum. Mol. Genet. 15, 2813–2824 (2006).
Dyment, D. A., Ebers, G. C. & Sadovnick, A. D. Genetics of multiple sclerosis. Lancet Neurol. 3, 104–110 (2004).
Fogdell-Hahn, A., Ligers, A., Gronning, M., Hillert, J. & Olerup, O. Multiple sclerosis: a modifying influence of HLA class I genes in an HLA class II associated autoimmune disease. Tissue Antigens 55, 140–148 (2000).
Harbo, H. F. et al. Genes in the HLA class I region may contribute to the HLA class II-associated genetic susceptibility to multiple sclerosis. Tissue Antigens 63, 237–247 (2004).
Brynedal, B. et al. HLA-A confers an HLA-DRB1 independent influence on the risk of multiple sclerosis. PLoS ONE 2, e664 (2007).
Yeo, T. W. et al. A second major histocompatibility complex susceptibility locus for multiple sclerosis. Ann. Neurol. 61, 228–236 (2007).
Hafler, D. A. et al. Risk alleles for multiple sclerosis identified by a genome-wide study. N. Engl. J. Med. 357, 851–862 (2007). This study shows that multiple sclerosis is associated with several genetic variants in or around immunologically relevant genes. The MHC region confers the largest risk, whereas the contributions from other risk genes, such as IL7R and IL2R , are small by comparison.
Lundmark, F. et al. Variation in interleukin 7 receptor α chain (IL7R) influences risk of multiple sclerosis. Nature Genet. 39, 1108–1113 (2007).
Ban, M. et al. Replication analysis identifies TYK2 as a multiple sclerosis susceptibility factor. Eur. J. Hum. Genet. 18 Mar 2009 (doi:10.1038/ejhg.2009.41).
Reich, D. et al. A whole-genome admixture scan finds a candidate locus for multiple sclerosis susceptibility. Nature Genet. 37, 1113–1118 (2005).
Hafler, J. P. et al. CD226 Gly307Ser association with multiple autoimmune diseases. Genes Immun. 10, 305–310 (2009).
Bernardinelli, L. et al. Association between the ACCN1 gene and multiple sclerosis in central east Sardinia. PLoS ONE 2, e480 (2007).
Aulchenko, Y. S. et al. Genetic variation in the KIF1B locus influences susceptibility to multiple sclerosis. Nature Genet. 40, 1402–1403 (2008).
Wemmie, J. A., Price, M. P. & Welsh, M. J. Acid-sensing ion channels: advances, questions and therapeutic opportunities. Trends Neurosci. 29, 578–586 (2006).
Nangaku, M. et al. KIF1B, a novel microtubule plus end-directed monomeric motor protein for transport of mitochondria. Cell 79, 1209–1220 (1994).
Donnelly, P. Progress and challenges in genome-wide association studies in humans. Nature 456, 728–731 (2008).
Vavouri, T., McEwen, G. K., Woolfe, A., Gilks, W. R. & Elgar, G. Defining a genomic radius for long-range enhancer action: duplicated conserved non-coding elements hold the key. Trends Genet. 22, 5–10 (2006).
Feuk, L., Carson, A. R. & Scherer, S. W. Structural variation in the human genome. Nature Rev. Genet. 7, 85–97 (2006).
Nejentsev, S., Walker, N., Riches, D., Egholm, M. & Todd, J. A. Rare variants of IFIH1, a gene implicated in antiviral responses, protect against type 1 diabetes. Science 5 Mar 2009 (doi:10.1126/science.1167728). This paper shows that re-sequencing studies can pinpoint disease-causing genes in genomic regions initially identified by genome-wide association studies.
Madsen, L. S. et al. A humanized model for multiple sclerosis using HLA-DR2 and a human T-cell receptor. Nature Genet. 23, 343–347 (1999).
Molberg, O. et al. Tissue transglutaminase selectively modifies gliadin peptides that are recognized by gut-derived T cells in celiac disease. Nature Med. 4, 713–717 (1998).
Cookson, W., Liang, L., Abecasis, G., Moffatt, M. & Lathrop, M. Mapping complex disease traits with global gene expression. Nature Rev. Genet. 10, 184–194 (2009).
Chen, Y. et al. Variations in DNA elucidate molecular networks that cause disease. Nature 452, 429–435 (2008).
Emilsson, V. et al. Genetics of gene expression and its effect on disease. Nature 452, 423–428 (2008). This study assesses the relationship between DNA sequence variants and gene expression. For a recent review on this subject see reference 34.
Goring, H. H. et al. Discovery of expression QTLs using large-scale transcriptional profiling in human lymphocytes. Nature Genet. 39, 1208–1216 (2007).
Moffatt, M. F. et al. Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma. Nature 448, 470–473 (2007).
Maier, L. M. et al. Soluble IL-2RA levels in multiple sclerosis subjects and the effect of soluble IL-2RA on immune responses. J. Immunol. 182, 1541–1547 (2009).
Maier, L. M. et al. IL2RA genetic heterogeneity in multiple sclerosis and type 1 diabetes susceptibility and soluble interleukin-2 receptor production. PLoS Genet. 5, e1000322 (2009).
De Jager, P. L. et al. The role of the CD58 locus in multiple sclerosis. Proc. Natl Acad. Sci. USA 106, 5264–5269 (2009).
Gregory, S. G. et al. Interleukin 7 receptor α chain (IL7R) shows allelic and functional association with multiple sclerosis. Nature Genet. 39, 1083–1091 (2007).
Nunnari, G. et al. Exogenous IL-7 induces Fas-mediated human neuronal apoptosis: potential effects during human immunodeficiency virus type 1 infection. J. Neurovirol. 11, 319–328 (2005).
Park, I. H. et al. Reprogramming of human somatic cells to pluripotency with defined factors. Nature 451, 141–146 (2008).
Takahashi, K. et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131, 861–872 (2007).
Yu, J. et al. Induced pluripotent stem cell lines derived from human somatic cells. Science 318, 1917–1920 (2007).
Aasen, T. et al. Efficient and rapid generation of induced pluripotent stem cells from human keratinocytes. Nature Biotechnol. 26, 1276–1284 (2008).
Loh, Y. H. et al. Generation of induced pluripotent stem cells from human blood. Blood 18 Mar 2009 (doi:10.1182/blood-2009-02-204800).
Kaji, K. et al. Virus-free induction of pluripotency and subsequent excision of reprogramming factors. Nature 58, 771–775 (2009).
Yamanaka, S. A fresh look at iPS cells. Cell 137, 13–17 (2009). This is mandatory reading for those wishing to catch up with the iPS cell field.
Dimos, J. T. et al. Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons. Science 321, 1218–1221 (2008).
Ebert, A. D. et al. Induced pluripotent stem cells from a spinal muscular atrophy patient. Nature 457, 277–280 (2009). This is the first study to show that human iPS cells can be used to model the specific pathology seen in a genetically inherited disease.
Soldner, F. et al. Parkinson's disease patient-derived induced pluripotent stem cells free of viral reprogramming factors. Cell 136, 964–977 (2009).
Borrelli, E., Nestler, E. J., Allis, C. D. & Sassone-Corsi, P. Decoding the epigenetic language of neuronal plasticity. Neuron 60, 961–974 (2008).
Chao, M. J. et al. Epigenetics in multiple sclerosis susceptibility: difference in transgenerational risk localizes to the major histocompatibility complex. Hum. Mol. Genet. 18, 261–266 (2009).
Zhang, X. et al. Genome-wide high-resolution mapping and functional analysis of DNA methylation in arabidopsis. Cell 126, 1189–1201 (2006).
Mockler, T. C. et al. Applications of DNA tiling arrays for whole-genome analysis. Genomics 85, 1–15 (2005).
Shen, S. et al. Age-dependent epigenetic control of differentiation inhibitors is critical for remyelination efficiency. Nature Neurosci. 11, 1024–1034 (2008). References 54 and 58 suggest that investigating dysregulated posttranslational modifications in multiple sclerosis may contribute to our understanding of its pathogenesis.
Friese, M. A. et al. The value of animal models for drug development in multiple sclerosis. Brain 129, 1940–1952 (2006).
Steinman, L. Blocking adhesion molecules as therapy for multiple sclerosis: natalizumab. Nature Rev. Drug Discov. 4, 510–518 (2005).
Gregersen, J. W. et al. Functional epistasis on a common MHC haplotype associated with multiple sclerosis. Nature 443, 574–577 (2006).
Caillier, S. J. et al. Uncoupling the roles of HLA-DRB1 and HLA-DRB5 genes in multiple sclerosis. J. Immunol. 181, 5473–5480 (2008).
Polman, C. H. et al. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N. Engl. J. Med. 354, 899–910 (2006).
Coles, A. J. et al. Alemtuzumab vs. interferon β-1a in early multiple sclerosis. N. Engl. J. Med. 359, 1786–1801 (2008).
Friese, M. A. et al. Opposing effects of HLA class I molecules in tuning autoreactive CD8+ T cells in multiple sclerosis. Nature Med. 14, 1227–1235 (2008). This study exemplifies how functional genetics can be used to understand disease-association studies that are directly relevant to multiple sclerosis.
Bell, G. I., Horita, S. & Karam, J. H. A polymorphic locus near the human insulin gene is associated with insulin-dependent diabetes mellitus. Diabetes 33, 176–183 (1984).
Vafiadis, P. et al. Insulin expression in human thymus is modulated by INS VNTR alleles at the IDDM2 locus. Nature Genet. 15, 289–292 (1997).
Pugliese, A. et al. The insulin gene is transcribed in the human thymus and transcription levels correlated with allelic variation at the INS VNTR-IDDM2 susceptibility locus for type 1 diabetes. Nature Genet. 15, 293–297 (1997).
Chentoufi, A. A. & Polychronakos, C. Insulin expression levels in the thymus modulate insulin-specific autoreactive T-cell tolerance: the mechanism by which the IDDM2 locus may predispose to diabetes. Diabetes 51, 1383–1390 (2002).
Lunemann, J. D. et al. EBNA1-specific T cells from patients with multiple sclerosis cross react with myelin antigens and co-produce IFN-γ and IL-2. J. Exp. Med. 205, 1763–1773 (2008).
Harkiolaki, M. et al. T cell-mediated autoimmune disease due to low-affinity crossreactivity to common microbial peptides. Immunity 30, 348–357 (2009).
Quintana, F. J. et al. Control of Treg and TH17 cell differentiation by the aryl hydrocarbon receptor. Nature 453, 65–71 (2008).
Veldhoen, M. et al. The aryl hydrocarbon receptor links TH17-cell-mediated autoimmunity to environmental toxins. Nature 453, 106–109 (2008). References 73 and 74 show the role of the environmental toxin dioxin in affecting T Reg and T H 17 cell activation and provide a potentially useful clue about the possible role of environmental triggers in disease initiation.
Bettelli, E., Korn, T., Oukka, M. & Kuchroo, V. K. Induction and effector functions of T H17 cells. Nature 453, 1051–1057 (2008).
Tzartos, J. S. et al. Interleukin-17 production in central nervous system-infiltrating T cells and glial cells is associated with active disease in multiple sclerosis. Am. J. Pathol. 172, 146–155 (2008).
Ramagopalan, S. V. et al. Expression of the multiple sclerosis-associated MHC class II allele HLA-DRB1*1501 is regulated by vitamin D. PLoS Genet. 5, e1000369 (2009).
Friese, M. A. et al. Acid-sensing ion channel-1 contributes to axonal degeneration in autoimmune inflammation of the central nervous system. Nature Med. 13, 1483–1489 (2007).
Gimeno, R. et al. Monitoring the effect of gene silencing by RNA interference in human CD34+ cells injected into newborn RAG2−/− γc−/− mice: functional inactivation of p53 in developing T cells. Blood 104, 3886–3893 (2004).
Traggiai, E. et al. Development of a human adaptive immune system in cord blood cell-transplanted mice. Science 304, 104–107 (2004).
Shultz, L. D., Ishikawa, F. & Greiner, D. L. Humanized mice in translational biomedical research. Nature Rev. Immunol. 7, 118–130 (2007).
Baranzini, S. E. et al. Pathway and network-based analysis of genome-wide association studies in multiple sclerosis. Hum. Mol. Genet. 13 Mar 2009 (doi:10.1093/hmg/ddp120).
Baranzini, S. E. et al. Genome-wide association analysis of susceptibility and clinical phenotype in multiple sclerosis. Hum. Mol. Genet. 18, 767–778 (2009).
McFarland, H. F. & Martin, R. Multiple sclerosis: a complicated picture of autoimmunity. Nature Immunol. 8, 913–919 (2007).
Frischer, J. M. et al. The relation between inflammation and neurodegeneration in multiple sclerosis brains. Brain 31 Mar 2009 (doi:10.1093/brain/awp070).
Frohman, E. M., Racke, M. K. & Raine, C. S. Multiple sclerosis — the plaque and its pathogenesis. N. Engl. J. Med. 354, 942–955 (2006).