Molecular characterisation of SGCE-associated myoclonus-dystonia ...

More documents

Recommendations

Info

List of figures V LIST OF FIGURES Fig 1 Projects and levels of investigation in the present thesis. ......................................... 1 Fig 2 Scheme of neuronal traces in the basal ganglia for motor control. .......................... 2 Fig 3 Potential connection between environmental and genetic factors, and PD............ 17 Fig 4 Pedigree of Family W. ............................................................................................. 22 Fig 5 Principle of the MLPA analysis............................................................................... 33 Fig 6 Scheme to illustrate the apparatus used to determine GSH by reverse-phase HPLC and electrochemical detection. ................................................................................ 35 Fig 7 Projects and levels of investigation in the present thesis [Project A]..................... 46 Fig 8 (previous page) Relevant pedigrees of families with M-D of index patients (A) IP15916; (B) IP16535; (C) IP15624; (D) IP15251 and (E) IP2141. ..................... 50 Fig 9 (previous page) Screening for exon rearrangements. ............................................. 52 Fig 10 Scheme of the genomic region, surrounding SGCE, with relevant markers and qPCRs. ..................................................................................................................... 53 Fig 11 Schematic representation of the SGCE gene and identified mutations. .................. 55 Fig 12 Projects and levels of investigation in the present thesis [Project B]..................... 56 Fig 13 Electropherograms of genomic DNA and cDNA..................................................... 57 Fig 14 PINK1 haplotype analysis. ...................................................................................... 58 Fig 15 Histograms displaying results of the quantitative PINK1 mRNA analysis.............. 59 Fig 16 Box-and-Whisker Plot showing clustered results of the mRNA expression analysis for each mutational status in Family W................................................................... 60 Fig 17 The human PINK1 gene and identified mutations................................................... 61 Fig 18 Projects and levels of investigation in the present thesis [Project C]..................... 62 Fig 19 Respiratory chain enzyme complexes I-IV............................................................... 63 Fig 20 Mitochondria content and mtDNA levels. ............................................................... 64 Fig 21 Protein expression of the respiratory chain enzyme complexes.............................. 65 Fig 22 Membrane potential under basal and stress conditions.......................................... 66 Fig 23 ATP levels under normal conditions........................................................................ 66 Fig 24 Indicators of oxidative stress................................................................................... 67 Fig 25 Mitochondrial network in primary fibroblasts. ....................................................... 68 Fig 26 Mitochondrial morphology in fibroblasts................................................................ 69 Fig S1 Determination of the optimal number of control genes for normalization............ 112 Fig S2 Average expression stability values (M) of reference genes calculated by the geNorm VBA applet. .............................................................................................. 112
List of tables VI LIST OF TABLES Table 1 Genetic causes of dystonia ...................................................................................... 4 Table 2 Genetic causes of parkinsonism .............................................................................. 8 Table 3 Classification criteria of M-D phenotypes in the SGCE study.............................. 19 Table 4 Genotypic and phenotypic characterization of Family W..................................... 21 Table 5 Demographic, clinical and genetic data of index patients and affected family members investigated in the M-D study ................................................................ 48 Table 6 Summary of the mitochondrial function and morphology data............................. 69 Table S1 Primer for PCR-amplification of SGCE genomic fragments .............................. 113 Table S2 Primer for gene dosage quantification of SGCE exons ...................................... 113 Table S3 Primer for PCR-amplification of PINK1 genomic fragments............................. 113 Table S4 Primer for the quantification of the PINK1 expression level.............................. 114
Page 1 and 2: Aus der Klinik für Neurologie (Pro
Page 3 and 4: This thesis is dedicated to my fami
Page 5 and 6: List of content II 2.2.6 Equipment
Page 7: List of content IV 4 DISCUSSION ...
Page 11 and 12: Introduction 2 The EPS has been imp
Page 13 and 14: Introduction 4 7, 9, 10, 13, and 15
Page 15 and 16: Introduction 6 chromosome contained
Page 17 and 18: Introduction 8 PD is the most commo
Page 19 and 20: Introduction 10 results in a p.W437
Page 21 and 22: Introduction 12 showed good respons
Page 23 and 24: Introduction 14 sequentially from o
Page 25 and 26: Introduction 16 favourable (Boyer,
Page 27 and 28: Introduction 18 1.5 Hypotheses The
Page 29 and 30: Patients, material and methods 20 T
Page 31 and 32: III:1 F2129 II:1 IP2123 III:2 F2130
Page 33 and 34: Patients, material and methods 24 E
Page 35 and 36: Patients, material and methods 26 H
Page 37 and 38: Patients, material and methods 28 S
Page 39 and 40: Patients, material and methods 30 s
Page 41 and 42: Patients, material and methods 32 2
Page 45 and 46: Patients, material and methods 36 b
Page 49 and 50: Patients, material and methods 40 c
Page 55 and 56: Results 46 3 RESULTS This thesis is
Page 57 and 58: Table 5 Demographic, clinical and g
Page 59 and 60:
Results 50 Fig 8 (previous page) Re
Page 61 and 62:
Results 52 Fig 9 (previous page) Sc
Page 63 and 64:
Results 54 3.1.4 Qualitative mutati
Page 65 and 66:
Results 56 3.2 Parkinson’s diseas
Page 67 and 68:
Results 58 3.2.2 Haplotype analysis
Page 69 and 70:
Results 60 sequence alterations wer
Page 71 and 72:
Results 62 3.3 Parkinson’s diseas
Page 73 and 74:
Results 64 activity in the nonsense
Page 75 and 76:
Results 66 4.00 3.50 Basal conditio
Page 77 and 78:
Results 68 3.3.7 Mitochondrial netw
Page 79 and 80:
Discussion 70 4 DISCUSSION The outc
Page 81 and 82:
Discussion 72 reports about genotyp
Page 83 and 84:
Discussion 74 4.2 Parkinson’s dis
Page 85 and 86:
Discussion 76 4.2.4 Genotype-phenot
Page 87 and 88:
Discussion 78 cellular ATP levels (
Page 89 and 90:
Discussion 80 However, the protein
Page 91 and 92:
Discussion 82 4.4 Conclusions Proje
Page 93 and 94:
Discussion 84 overall increase of t
Page 95 and 96:
Perspectives 86 In addition, mutant
Page 97 and 98:
Summary 88 1.0 in mutation-negative
Page 99 and 100:
Zusammenfassung 90 mutationspositiv
Page 101 and 102:
References 92 8 REFERENCES Abou-Sle
Page 103 and 104:
References 94 Butler AG, Duffey PO,
Page 105 and 106:
References 96 Exner N, Treske B, Pa
Page 107 and 108:
References 98 Hedrich K, Hagenah J,
Page 109 and 110:
References 100 Klein C, Lohmann-Hed
Page 111 and 112:
References 102 Martin MA, Molina JA
Page 113 and 114:
References 104 Piccoli C, Sardanell
Page 115 and 116:
References 106 Schüle B, Kock N, S
Page 117 and 118:
References 108 Wharton DC, Tzagolof
Page 119 and 120:
Appendix 110 FL - Fluorescence emis
Page 121 and 122:
Appendix 112 9.2 Supplementary mate
Page 123 and 124:
Appendix 114 Table S4 Primer for th
Page 125 and 126:
Appendix 116 04 - 06/2006 Erasmus M
Page 127 and 128:
Appendix 118 ABSTRACTS 1. Grünewal
Page 129 and 130:
Appendix 120 I would like to thank
show all

Molecular characterisation of SGCE-associated myoclonus-dystonia ...

Create successful ePaper yourself

Delete template?

Save as template?