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Antoni Matilla Dueñas
Director Unidad Básica, Traslacional y Neurogenética Molecular en
Neurociencias y Coordinador Red Iberoamericana RIBERMOV
Editor Genética Revista “The Cerebellum”
Instituto de Investigación Germans Trias y Pujol (IGTP)
Universitat Autònoma de Barcelona
Badalona (Barcelona)
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Environmental
Risk
Factors
Genetic
Risk
Factors
Epigenome
+
Proteome
Complex Neurological
diseases
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Genetic Analysis in Neurology: The Next 10 Years.
Genetic Analysis in Neurology: The Next 10 Years. Pittman, Alan; Hardy, John JAMA Neurology. 70(6):696-702, June 2013. DOI: 10.1001/jamaneurol.2013.2068
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Genetic Analysis in Neurology: The Next 10 Years. Pittman, Alan; Hardy, John JAMA Neurology. 70(6):696-702, June 2013. DOI: 10.1001/jamaneurol.2013.2068
Genetic Analysis in Neurology: The Next 10 Years.
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Genetic Analysis in Neurology: The Next 10 Years.
Genetic Analysis in Neurology: The Next 10 Years. Pittman, Alan; Hardy, John JAMA Neurology. 70(6):696-702, June 2013. DOI: 10.1001/jamaneurol.2013.2068
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Variant classification according to their consequence or position on
transcripts. The set of consequence terms, defined by the Sequence
Ontology (http://www.sequenceontology.org/)
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The Neurogenomics View of Neurological Diseases. Tsuji, Shoji; MD, PhD JAMA Neurology. 70(6):689-694, June 2013. DOI: 10.1001/jamaneurol.2013.734
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The Neurogenomics View of Neurological Diseases. Tsuji, Shoji; MD, PhD JAMA Neurology. 70(6):689-694, June 2013. DOI: 10.1001/jamaneurol.2013.734
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Genes & Disease
OMIM, 27 Septiembre 2013
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Las ataxias espinocerebelosas
Las ataxias espinocerebelosas son genéticamente heterogéneas
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EA7
SCA25
SCA29 SCA15
SCA30
SCA12
SCA1
SCA17
SCA21
SCA18
SCA20SCA5
1 2 3 4 5 6 7 8 9 10 11 X
12
DRPLA
SCA2
16
SCA31 SCA4
13
SCA8
SCA27SCA3
14
SCA11
15 17
SCA28
18
SCA26
SCA6EA2
SCA13SCA14
19
SCA23
20 21
SCA10
22 Y
SCA7
ADSA
ADHD
EA1
EA3
EA5
EA6 ADNOA
SPAX1
SCA32
SCA34
SCA35
SCA36
SCA19/SCA22
SCA37
Las ataxias espinocerebelosas
Las ataxias espinocerebelosas son genéticamente heterogéneas
A Matilla-Dueñas. The ever expanding spinocerebellar ataxias.
Editorial. Cerebellum 11 (4), 821-827 (2012)
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I
II
III
IV
V
VI
MarkersD1S319D1S2661
D1S417D1S2652
D1S475D1S200D1S2742
D1S2690D1S2867
rs151062149
VI:1
V:1
II:1 II:2
?
III:1 III:3III:2 III:5III:4
IV:1
2 11 23 22 11 11 11 42 11 11 1
IV:2 IV:5
1 22 12 12 21 22 14 62 23 11 2
IV:6
1 22 12 11 21 21 14 61 21 11 2
IV:7
1 22 12 12 21 22 14 62 23 11 2
IV:8
2 42 12 11 21 23 49 21 11 11 1
V:6
1 42 12 12 21 22 44 22 13 11 1
V:7
2 21 21 22 12 11 36 92 11 12 1
IV:10
2 21 12 11 21 21 16 61 21 11 1
IV:9 IV:11
2 21 12 11 21 21 16 61 21 11 1
IV:12
1 42 22 21 21 11 34 41 21 11 1
IV:13
1 42 22 21 21 11 34 41 21 11 1
IV:14
V:3
IV:4
4 21 11 22 12 21 37 71 24 21 1
V:538
2 41 13 12 21 21 11 72 11 41 1
IV:3
2 11 23 22 11 11 11 42 11 11 1
V:2 V:4 V:8
3 22 12 21 21 21 17 62 21 11 1
V:10
3 22 12 11 21 21 12 61 21 11 1
VI:2 VI:3
?
I:1
?
I:2
II:4II:3
III:6 III:7 III:8 III:9 III:10
4 22 12 11 21 23 16 62 22 11 2
IV:15
1 31 12 21 11 15 34 63 21 21 1
IV:16
3 11 12 12 21 25 14 63 21 11 2
IV:18
3 11 12 22 11 15 34 63 21 21 1
IV:17
5 21 11 12 21 21 16 93 11 11 1
V:12
3 21 12 12 21 25 14 93 11 11 1
V:13
3 21 12 12 21 25 14 93 11 11 1
II:5 II:6
III:11 III:12
IV:21
2 22 12 12 22 24 19 62 24 11 2
IV:22
2 32 22 22 22 24 19 62 14 51 1
V:18
2 22 22 22 22 24 49 92 24 41 1
V:17
2 32 22 22 22 24 19 62 14 51 1
IV:19
2 22 11 12 21 24 14 62 21 11 2
V:15
2 41 41 12 22 11 26 52 11 52 1
V:14
2 42 41 12 21 14 24 52 11 51 1
V:16
1 11 22 12 21 32 24 92 21 21 1
VI:6
4 14 21 12 21 31 25 91 25 12 1
VI:7
2 11 11 22 22 11 26 42 21 11 1
V:9 V:11
VI:4 VI:5
IV:23IV:20
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New Subtype of Spinocerebellar Ataxia With Altered Vertical Eye Movements Mapping to Chromosome 1p32. Serrano-Munuera, Carmen; Corral-Juan, Marc; Stevanin, Giovanni; San Nicolas, Hector; Roig, Carles; MD, PhD; Corral, Jordi; Campos, Berta; de Jorge, Laura; Morcillo-Suarez, Carlos; Navarro, Arcadi; Forlani, Sylvie; MD, PhD; Durr, Alexandra; MD, PhD; Kulisevsky, Jaime; MD, PhD; Brice, Alexis; MD, PhD; Sanchez, Ivelisse; Volpini, Victor; MD, PhD; Matilla-Duenas, Antoni JAMA Neurology. 70(6):764-771, June 2013. DOI: 10.1001/jamaneurol.2013.2311
Figure 2. A and B, Sagittal and coronal T1-weighted magnetic resonance imaging scans of the brain of patient IV:5. The eye movements during vertical fixed saccades (C) (20[degrees] amplitude; top line, upward saccades; bottom line, downward saccades [arrows]) and smooth pursuit (D) (0.4 Hz; 16[degrees] amplitude; and peak velocity, 40[degrees]/s) are shown for patient IV:6. The asterisks indicate saccadic intrusions.
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Ataxias no sindrómicas
Secuenciación masiva panel de 30 genes: ADCK3, AFG3L2, ANO10, APTX, BEAN, CACNA1A, CACNB4, FGF14, FXN, IFRD1, ITPR1, KCNA1, KCNC3, MTP, MTPAP, PDYN, PIK3R5, PLEKHG4, PRKCG, SACS, SETX, SLC1A3, SPTBN2, SYNE1, SYT14, TDP1, TGM6, TTBK2, TTPA, ZNF592
Ataxias Sindrómicas
Secuenciación masiva panel de 55 genes: ABCB7, ABHD12, ADCK3, ALS2, ANG, ATCAY, ATM, ATR, CA8, CEP290, C10orf2, COQ2, COQ9, CYP27A1, DNAJC19, EIF2B1, EIF2B2, EIF2B3, EIF2B4, EIF2B5, FIG4, FLVCR1, FMR1, FUS, GJC2, GPR56, HSPD1, ITM2B, KCNJ10, KIAA0226, MRE11A, NPHP1, OPA1, PAX6, PC, PDHA1, PDSS1, PDSS2, PEX7, PHYH, PLP, POLG, POLR3A, PRNP, PRPS1, RPGRIP1L, SCN8A, SETX, SIL1, SLC9A6, SOD1, TARDBP, TMEM67, VAPB, VLDLR
Ataxias Sindrómicas y No Sindrómicas
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Parkinson, Enfermedad, tipos 1, 4, 5, 8, 11, 13, 17, 18, autosómica dominante
Secuenciación masiva panel de 7 genes: EIF4G1, GIGYF2, HTRA2, LRRK2, SNCA, UCHL1, VPS35
Parkinson, enfermedad, tipos 2, 6, 7, 9, 14, 15, autosómica recesiva, de inicio temprano
Secuenciación masiva panel de 6 genes: ATP13A2, FBXO7, PARK2, PARK7, PINK1, PLA2G6
Parkinson asociado a demencia frontotemporal, Enfermedad de Pick y parálisis supranuclear progresivay Demencia con cuerpos de Lewy
Secuenciación masiva panel de 2 genes: MAPT, SNCB
Parkinson, Enfermedad sindrómica y no sindrómica
Secuenciación masiva panel de 23 genes: ADH1C, ATP13A2, ATP1A3, DCTN1, EIF4G1, FBXO7, GBA, GCH1, GIGYF2, HTRA2, LRRK2, MAPT, PARK2, PARK7, PDXK, PINK1, PLA2G6, POLG1, SNCA, SNCAIP, SNCB, UCHL1, VPS35
Enfermedad de Parkinson
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SCA1* SCA2 SCA3 HD
AO/expanded 60.6%
(p<0.0001) 64%
(p= 0.0002) 60.5%
(p<0.0001) 63.4%
(p<2x10-16)
AO/expanded+ normal
66.4% (p<0.003)
65% (p=0.1300)
- 63.8%
(p<2x10-16)*
AO/expanded+ normal + gender
78.5% (p<0.0001)
- 61.1%
(p<0.0001) -
*Matilla-Dueñas, ..., Volpini. Hum Mol Gen 1993. AO: Edad de inicio
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Scatterplot of SCA2 CAG repeat length and age of onset in Cuban SCA2 patients; red and yellow lines denote one standard deviation boundaries for age of onset.
Pulst S et al. Brain 2005;128:2297-2303
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Understanding Neurological Disease Mechanisms in the Era of Epigenetics. Qureshi, Irfan; Mehler, Mark JAMA Neurology. 70(6):703-710, June 2013. DOI: 10.1001/jamaneurol.2013.1443
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JAMA Neurology. 70(6):703-710, June 2013. DOI: 10.1001/jamaneurol.2013.1443
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Farmacogenética
Fármacos a la carta
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A.Matilla-Dueñas, M.Corral-Juan & I.Sánchez.
Cerebellum 9 (2), 148-166 (2010)
Molecular pathways triggering
neurodegeneration in the
spinocerebellar ataxias
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Tipos de muerte celular [programada]: MCP
APOPTOSIS (MCP tipo I): Intrínseca (Mitocondria/apoptosoma) y Extrínseca
AUTOFAGIA (MCP tipo II): incluye mitofagia
MUERTE CELULAR CITOPLÁSMICA (MCP tipo III):
NECROSIS PROGRAMADA
NECROPTOSIS*
PARAPTOSIS
PARTHANATOS: mediada por poly ADP-ribose polimerasa-1 (PARP1) y AIF
DEGENERACIÓN NEURONAL OSCURA (DARK CELL DEGENERATION)
ANOIKIS
ENTOSIS
PIROPTOSIS: respuesta antimicrobiana durante inflamación (caspasa-1)
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Cerebellum. 2012 September; 11(3): 630–639.
doi: 10.1007/s12311-010-0182-9
PCs in aging SCA2 transgenic mice die by dark cell degeneration)
( 10 months old SCA2-58Q)
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Rutas Celulares y Moleculares en Neurodegeneración
apoptosis, necroptosis, DCD, etc.
2. Agregación proteica: plegado, insolubilidad
3. Degradación: proteasoma, autofagia
5. Excitotoxicidad: Glutamato
7. Homeostasis Calcio
10. Transporte axonal
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- 54 interacciones proteicas relacionadas con ataxias hereditarias:
recesivas (AF) y dominantes.
Factores modificadores
Muchas regulatorias (directa o indirectamente) de transcripción.
Las ataxias están causadas por alteraciones
de rutas moleculares y proteínas comunes
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Figure 1. Strategy for constructing tissue-specific networks and predicting phenotype-associated
genes.
Guan Y, Gorenshteyn D, Burmeister M, Wong AK, et al. (2012) Tissue-Specific Functional Networks for Prioritizing Phenotype and
Disease Genes. PLoS Comput Biol 8(9): e1002694. doi:10.1371/journal.pcbi.1002694
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Figure 6. Top connected genes to Atcay in the cerebellum-specific network reveals likely ataxia
candidates.
Guan Y, Gorenshteyn D, Burmeister M, Wong AK, et al. (2012) Tissue-Specific Functional Networks for Prioritizing Phenotype and
Disease Genes. PLoS Comput Biol 8(9): e1002694. doi:10.1371/journal.pcbi.1002694
http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1002694
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y = 0,0002x R² = 0,984
0,00
0,05
0,10
0,15
0,20
0,25
0 400 800 1200
OD
65
0 n
m
pmoles Phosphate
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Pp2a holoenzyme composition and signalling are altered in SCA1.
Sánchez I et al. Hum. Mol. Genet. 2013;22:3425-3437
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The proposed model of the ataxin-1 induced alterations of Pp2a activity and holoenzyme composition in the cerebellum of 5-week-old mice.
Sánchez I et al. Hum. Mol. Genet. 2013;22:3425-3437
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Neuronal morphological alterations in ATXN1[30Q] and ATXN1[80Q] expressing differentiated SH-SY5Y cells and the effects of ANP32A co-expression on neurite morphology.
Sánchez I et al. Hum. Mol. Genet. 2013;22:3425-3437
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Identification of ATXN1 toxicity and aggregation modifiers using cell-based assays. Petrakis et al. 2011
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Sacsin knockdown reduces the incidence
of cells with large nuclear inclusions of
polyglutamine-expanded ataxin-1.
Hum Mol Genet. 2009 May 1; 18(9): 1556–1565.
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Cribados in vivo para identificar y/o validar moduladores fenotipo atáxico
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Selective Positive Modulator of
Calcium-Activated Potassium
Channels Exerts Beneficial
Effects in a Mouse Model of
Spinocerebellar Ataxia Type 2.
Chemistry & Biology Volume 19,
Issue 10 2012 1340 - 1353
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Large-Scale Screen for Modifiers of Ataxin-3-Derived Polyglutamine-Induced Toxicity in Drosophila
PLoS ONE 7(11): 2012
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PLoS ONE 7(11): 2012
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Hum Mol Genet. 2012 Jan 1;21(1):76-84. Epub 2011 Sep 23.
Modifiers of spinocerebellar ataxia 3-associated neurodegeneration in Drosophila
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IFNγ induces frataxin accumulation in FRDA cells.
Tomassini B et al. Hum. Mol. Genet. 2012;21:2855-2861
![Page 50: Environmental Genetic Risk Factors€¦ · Factors Genetic Risk Factors Epigenome + Proteome Complex Neurological diseases . Genetic Analysis in Neurology: The Next 10 Years](https://reader035.vdocuments.us/reader035/viewer/2022071004/5fc0cb19644912595730ccb9/html5/thumbnails/50.jpg)
In vivo IFNγ treatment upregulates human frataxin in DRG of FRDA mice.
Tomassini B et al. Hum. Mol. Genet. 2012;21:2855-2861
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In vivo IFNγ treatment improves locomotor and motor coordination performances and prevents neurodegeneraton in FRDA mice.
Tomassini B et al. Hum. Mol. Genet. 2012;21:2855-2861
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Chintawar, S. et al. J. Neurosci. 2009;29:13126-13135
Injertos de Precursores neuronales en el
cerebelo atáxico
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Pandolfo, M. et al. Grafting neural precursor cells promotes functional recovery in
an SCA1 mouse model. The Journal of Neuroscience. 29, 13126-13135 (2009).
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