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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 CerebellumInstituto de Investigación Germans Trias y Pujol (IGTP) Universitat Autònoma de Barcelona Badalona (Barcelona)

Environmental Genetic Risk Factors€¦ · Factors Genetic Risk Factors Epigenome + Proteome Complex Neurological diseases . Genetic Analysis in Neurology: The Next 10 Years

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Page 1: Environmental Genetic Risk Factors€¦ · Factors Genetic Risk Factors Epigenome + Proteome Complex Neurological diseases . Genetic Analysis in Neurology: The Next 10 Years

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)

Page 2: Environmental Genetic Risk Factors€¦ · Factors Genetic Risk Factors Epigenome + Proteome Complex Neurological diseases . Genetic Analysis in Neurology: The Next 10 Years

Environmental

Risk

Factors

Genetic

Risk

Factors

Epigenome

+

Proteome

Complex Neurological

diseases

Page 3: Environmental Genetic Risk Factors€¦ · Factors Genetic Risk Factors Epigenome + Proteome Complex Neurological diseases . Genetic Analysis in Neurology: The Next 10 Years

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

Page 4: Environmental Genetic Risk Factors€¦ · Factors Genetic Risk Factors Epigenome + Proteome Complex Neurological diseases . 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

Genetic Analysis in Neurology: The Next 10 Years.

Page 5: Environmental Genetic Risk Factors€¦ · Factors Genetic Risk Factors Epigenome + Proteome Complex Neurological diseases . Genetic Analysis in Neurology: The Next 10 Years

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

Page 6: Environmental Genetic Risk Factors€¦ · Factors Genetic Risk Factors Epigenome + Proteome Complex Neurological diseases . Genetic Analysis in Neurology: The Next 10 Years

Variant classification according to their consequence or position on

transcripts. The set of consequence terms, defined by the Sequence

Ontology (http://www.sequenceontology.org/)

Page 7: Environmental Genetic Risk Factors€¦ · Factors Genetic Risk Factors Epigenome + Proteome Complex Neurological diseases . Genetic Analysis in Neurology: The Next 10 Years
Page 8: Environmental Genetic Risk Factors€¦ · Factors Genetic Risk Factors Epigenome + Proteome Complex Neurological diseases . Genetic Analysis in Neurology: The Next 10 Years

The Neurogenomics View of Neurological Diseases. Tsuji, Shoji; MD, PhD JAMA Neurology. 70(6):689-694, June 2013. DOI: 10.1001/jamaneurol.2013.734

Page 9: Environmental Genetic Risk Factors€¦ · Factors Genetic Risk Factors Epigenome + Proteome Complex Neurological diseases . Genetic Analysis in Neurology: The Next 10 Years

The Neurogenomics View of Neurological Diseases. Tsuji, Shoji; MD, PhD JAMA Neurology. 70(6):689-694, June 2013. DOI: 10.1001/jamaneurol.2013.734

Page 10: Environmental Genetic Risk Factors€¦ · Factors Genetic Risk Factors Epigenome + Proteome Complex Neurological diseases . Genetic Analysis in Neurology: The Next 10 Years

Genes & Disease

OMIM, 27 Septiembre 2013

Page 11: Environmental Genetic Risk Factors€¦ · Factors Genetic Risk Factors Epigenome + Proteome Complex Neurological diseases . Genetic Analysis in Neurology: The Next 10 Years
Page 12: Environmental Genetic Risk Factors€¦ · Factors Genetic Risk Factors Epigenome + Proteome Complex Neurological diseases . Genetic Analysis in Neurology: The Next 10 Years

Las ataxias espinocerebelosas

Las ataxias espinocerebelosas son genéticamente heterogéneas

Page 13: Environmental Genetic Risk Factors€¦ · Factors Genetic Risk Factors Epigenome + Proteome Complex Neurological diseases . Genetic Analysis in Neurology: The Next 10 Years

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)

Page 14: Environmental Genetic Risk Factors€¦ · Factors Genetic Risk Factors Epigenome + Proteome Complex Neurological diseases . Genetic Analysis in Neurology: The Next 10 Years

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

Page 15: Environmental Genetic Risk Factors€¦ · Factors Genetic Risk Factors Epigenome + Proteome Complex Neurological diseases . Genetic Analysis in Neurology: The Next 10 Years

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.

Page 16: Environmental Genetic Risk Factors€¦ · Factors Genetic Risk Factors Epigenome + Proteome Complex Neurological diseases . Genetic Analysis in Neurology: The Next 10 Years

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

Page 17: Environmental Genetic Risk Factors€¦ · Factors Genetic Risk Factors Epigenome + Proteome Complex Neurological diseases . Genetic Analysis in Neurology: The Next 10 Years

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

Page 18: Environmental Genetic Risk Factors€¦ · Factors Genetic Risk Factors Epigenome + Proteome Complex Neurological diseases . Genetic Analysis in Neurology: The Next 10 Years

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

Page 19: Environmental Genetic Risk Factors€¦ · Factors Genetic Risk Factors Epigenome + Proteome Complex Neurological diseases . Genetic Analysis in Neurology: The Next 10 Years

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

Page 20: Environmental Genetic Risk Factors€¦ · Factors Genetic Risk Factors Epigenome + Proteome Complex Neurological diseases . Genetic Analysis in Neurology: The Next 10 Years
Page 21: Environmental Genetic Risk Factors€¦ · Factors Genetic Risk Factors Epigenome + Proteome Complex Neurological diseases . Genetic Analysis in Neurology: The Next 10 Years
Page 22: Environmental Genetic Risk Factors€¦ · Factors Genetic Risk Factors Epigenome + Proteome Complex Neurological diseases . Genetic Analysis in Neurology: The Next 10 Years
Page 23: Environmental Genetic Risk Factors€¦ · Factors Genetic Risk Factors Epigenome + Proteome Complex Neurological diseases . Genetic Analysis in Neurology: The Next 10 Years
Page 24: Environmental Genetic Risk Factors€¦ · Factors Genetic Risk Factors Epigenome + Proteome Complex Neurological diseases . Genetic Analysis in Neurology: The Next 10 Years

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

Page 25: Environmental Genetic Risk Factors€¦ · Factors Genetic Risk Factors Epigenome + Proteome Complex Neurological diseases . Genetic Analysis in Neurology: The Next 10 Years

JAMA Neurology. 70(6):703-710, June 2013. DOI: 10.1001/jamaneurol.2013.1443

Page 26: Environmental Genetic Risk Factors€¦ · Factors Genetic Risk Factors Epigenome + Proteome Complex Neurological diseases . Genetic Analysis in Neurology: The Next 10 Years

Farmacogenética

Fármacos a la carta

Page 27: Environmental Genetic Risk Factors€¦ · Factors Genetic Risk Factors Epigenome + Proteome Complex Neurological diseases . Genetic Analysis in Neurology: The Next 10 Years

A.Matilla-Dueñas, M.Corral-Juan & I.Sánchez.

Cerebellum 9 (2), 148-166 (2010)

Molecular pathways triggering

neurodegeneration in the

spinocerebellar ataxias

Page 28: Environmental Genetic Risk Factors€¦ · Factors Genetic Risk Factors Epigenome + Proteome Complex Neurological diseases . Genetic Analysis in Neurology: The Next 10 Years

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)

Page 29: Environmental Genetic Risk Factors€¦ · Factors Genetic Risk Factors Epigenome + Proteome Complex Neurological diseases . Genetic Analysis in Neurology: The Next 10 Years
Page 30: Environmental Genetic Risk Factors€¦ · Factors Genetic Risk Factors Epigenome + Proteome Complex Neurological diseases . Genetic Analysis in Neurology: The Next 10 Years

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)

Page 31: Environmental Genetic Risk Factors€¦ · Factors Genetic Risk Factors Epigenome + Proteome Complex Neurological diseases . Genetic Analysis in Neurology: The Next 10 Years

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

Page 32: Environmental Genetic Risk Factors€¦ · Factors Genetic Risk Factors Epigenome + Proteome Complex Neurological diseases . Genetic Analysis in Neurology: The Next 10 Years

- 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

Page 33: Environmental Genetic Risk Factors€¦ · Factors Genetic Risk Factors Epigenome + Proteome Complex Neurological diseases . Genetic Analysis in Neurology: The Next 10 Years

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

Page 34: Environmental Genetic Risk Factors€¦ · Factors Genetic Risk Factors Epigenome + Proteome Complex Neurological diseases . Genetic Analysis in Neurology: The Next 10 Years

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

Page 35: Environmental Genetic Risk Factors€¦ · Factors Genetic Risk Factors Epigenome + Proteome Complex Neurological diseases . Genetic Analysis in Neurology: The Next 10 Years

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

Page 36: Environmental Genetic Risk Factors€¦ · Factors Genetic Risk Factors Epigenome + Proteome Complex Neurological diseases . Genetic Analysis in Neurology: The Next 10 Years

Pp2a holoenzyme composition and signalling are altered in SCA1.

Sánchez I et al. Hum. Mol. Genet. 2013;22:3425-3437

Page 37: Environmental Genetic Risk Factors€¦ · Factors Genetic Risk Factors Epigenome + Proteome Complex Neurological diseases . Genetic Analysis in Neurology: The Next 10 Years

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

Page 38: Environmental Genetic Risk Factors€¦ · Factors Genetic Risk Factors Epigenome + Proteome Complex Neurological diseases . Genetic Analysis in Neurology: The Next 10 Years

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

Page 39: Environmental Genetic Risk Factors€¦ · Factors Genetic Risk Factors Epigenome + Proteome Complex Neurological diseases . Genetic Analysis in Neurology: The Next 10 Years
Page 40: Environmental Genetic Risk Factors€¦ · Factors Genetic Risk Factors Epigenome + Proteome Complex Neurological diseases . Genetic Analysis in Neurology: The Next 10 Years

Identification of ATXN1 toxicity and aggregation modifiers using cell-based assays. Petrakis et al. 2011

Page 41: Environmental Genetic Risk Factors€¦ · Factors Genetic Risk Factors Epigenome + Proteome Complex Neurological diseases . Genetic Analysis in Neurology: The Next 10 Years

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.

Page 42: Environmental Genetic Risk Factors€¦ · Factors Genetic Risk Factors Epigenome + Proteome Complex Neurological diseases . Genetic Analysis in Neurology: The Next 10 Years

Cribados in vivo para identificar y/o validar moduladores fenotipo atáxico

Page 43: Environmental Genetic Risk Factors€¦ · Factors Genetic Risk Factors Epigenome + Proteome Complex Neurological diseases . Genetic Analysis in Neurology: The Next 10 Years

Selective Positive Modulator of

Calcium-Activated Potassium

Channels Exerts Beneficial

Effects in a Mouse Model of

Spinocerebellar Ataxia Type 2.

Chemistry &amp; Biology Volume 19,

Issue 10 2012 1340 - 1353

Page 44: Environmental Genetic Risk Factors€¦ · Factors Genetic Risk Factors Epigenome + Proteome Complex Neurological diseases . Genetic Analysis in Neurology: The Next 10 Years

Large-Scale Screen for Modifiers of Ataxin-3-Derived Polyglutamine-Induced Toxicity in Drosophila

PLoS ONE 7(11): 2012

Page 45: Environmental Genetic Risk Factors€¦ · Factors Genetic Risk Factors Epigenome + Proteome Complex Neurological diseases . Genetic Analysis in Neurology: The Next 10 Years

PLoS ONE 7(11): 2012

Page 46: Environmental Genetic Risk Factors€¦ · Factors Genetic Risk Factors Epigenome + Proteome Complex Neurological diseases . Genetic Analysis in Neurology: The Next 10 Years

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

In vivo IFNγ treatment upregulates human frataxin in DRG of FRDA mice.

Tomassini B et al. Hum. Mol. Genet. 2012;21:2855-2861

Page 51: Environmental Genetic Risk Factors€¦ · Factors Genetic Risk Factors Epigenome + Proteome Complex Neurological diseases . Genetic Analysis in Neurology: The Next 10 Years

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

Page 54: Environmental Genetic Risk Factors€¦ · Factors Genetic Risk Factors Epigenome + Proteome Complex Neurological diseases . Genetic Analysis in Neurology: The Next 10 Years

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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Page 56: Environmental Genetic Risk Factors€¦ · Factors Genetic Risk Factors Epigenome + Proteome Complex Neurological diseases . Genetic Analysis in Neurology: The Next 10 Years

www.btnunit.org

Dra. Ivelisse Sánchez Díaz

Eudald Balagué Cabasés

Maria Queralt Caus Capdevila

Patricia Piñol Jurado

Marc Corral-Juan

Alba Bellot Sáez

Ariadna Navarro Aragall

Mireia Seró Torres

Ainània Tècul Torres

Unidad de Investigación Básica, Traslacional y de Neurogenética

Molecular en Neurociencias dirigida por el Dr. Matilla.

Page 57: Environmental Genetic Risk Factors€¦ · Factors Genetic Risk Factors Epigenome + Proteome Complex Neurological diseases . Genetic Analysis in Neurology: The Next 10 Years

Dr. Arcadi Navarro Dr. Carles Morcillo

Dra. Carmen Serrano

Dr. Antoni Dávalos Dr. Ramiro Álvarez Dr. Jaume Coll Dr. Domingo Escudero Dra. Lourdes Ispierto Dra. Pilar Latorre

Dr. Victor Volpini Berta Campos Laura de Jorge Jordi Corral Héctor SanNicolás

Dr. Alexis Brice Dra. Alexandra Durr Dr. Giovanni Stevanin

Dr. Massimo Pandolfo

Dr. Xavier Gomis-Rüth Dr. Iñaki de Diego

Dr. Manuel Posada

NEURODEGNET: www.neurodeg.net RARE-BESTpractices: en preparación REDAPED: en preparación RIBERMOV: www.ribermov.org

Departamento Neurociencias y Servicio Neurología:

Colaboraciones y Financiación

Dr. Javier Arpa

Page 58: Environmental Genetic Risk Factors€¦ · Factors Genetic Risk Factors Epigenome + Proteome Complex Neurological diseases . Genetic Analysis in Neurology: The Next 10 Years