Genetic Disorders

Cover......Page 1
GENETIC DISORDERS......Page 2
©......Page 3
Contents......Page 5
Preface......Page 7
1.2. Classification and types of OI......Page 9
1.3. Sillence classification......Page 10
1.5. Recessively inherited OI......Page 12
2.2. Brittle II mouse: A model for type II OI......Page 13
2.4. Brittle IV mouse: A model for type IV OI......Page 14
3.1.1. Bisphosphonates......Page 15
3.1.3. Parathyroid hormone......Page 17
3.2. Cell-based therapies......Page 18
3.2.2. Cellular replacement therapy......Page 19
4. MSC-based therapy......Page 20
5. HSC-based therapy......Page 21
7. Conclusions and future perspectives......Page 23
Author details......Page 24
References......Page 25
1.1. The nuclear envelope......Page 35
1.2. The lamins......Page 36
2.1.1. Emery-dreifuss muscular dystrophy......Page 38
2.1.3. Dilated cardiomyopathy with conduction defect 1......Page 40
2.2.1. Familial partial lipodystrophy type 2......Page 41
2.3.2. Charcot-Marie-Tooth disorder......Page 42
2.4.2. Restrictive dermopathy......Page 43
2.5.3. Reynolds syndrome......Page 44
3. Linking genotype and phenotype of laminopathies......Page 45
4. Mouse models......Page 50
5. Treatment......Page 53
Author details......Page 55
References......Page 56
1. Introduction......Page 73
2. Signs and symptoms......Page 74
3. Genetic basis......Page 76
4. Animal models......Page 80
References......Page 83
5. Treatments......Page 84
References......Page 87
1. Introduction......Page 97
2.1. Genetics of HR trait in humans......Page 99
2.2. Genetic studies of HR trait in rodents......Page 102
2.3. Challenges and future directions in the genetic studies on HR variation......Page 104
Acknowledgments......Page 105
Author details......Page 106
References......Page 107
1. Introduction......Page 113
2.1. Malignant hyperthermia......Page 115
2.2. Core myopathies......Page 116
3. Functional studies......Page 117
3.2. Methods......Page 118
3.3. Highlight of the results......Page 119
References......Page 121
References......Page 122
4. Structural studies of RyRs......Page 123
4.1. Cryo-EM studies of RyRs......Page 124
4.2. X-ray crystallographic studies of RyRs......Page 127
4.3. Homology models for RyR domains......Page 131
5. Conclusion......Page 134
References......Page 135
1. Introduction......Page 151
2. The causes of mental retardation......Page 152
2.1. Chromosomal abnormalities......Page 154
2.2. Contigous gene syndromes associated with cognitive deficits......Page 159
2.3. Monogenic mental retardation......Page 163
2.4. Mental retardation in metabolic disorders......Page 170
2.5. Multifactorial inheritance and mental retardation......Page 174
3. Establishing the diagnosis of mental retardation......Page 175
References......Page 178
1. Introduction......Page 183
2. Ataxia telangiectasia pathology......Page 184
4. ATM function: The DNA damage response......Page 185
4.2. Identification of ATM substrates: Proteomic studies......Page 187
5. ATM kinase: Other functions......Page 188
5.1. ATM and oxidative stress......Page 189
5.2. ATM and mitochondria......Page 190
5.3. ATM, hypoxia and autophagy......Page 191
5.4. ATM and metabolic syndrome......Page 192
5.5. ATM and growth factors......Page 193
5.6. ATM and death receptors......Page 194
6. Molecular mechanisms that ensure the modulation of ATM kinase activity......Page 195
7.1. ATM expression and cancer......Page 198
7.2. ATM and the DDR as barrier to tumor development......Page 199
7.3. ATM kinase inhibition and cancer therapy......Page 200
8. Functional links between ATM kinase and the immune system defects......Page 201
9. Functional links between ATM kinase, neurodegeneration and other neurological features......Page 203
9.1. ATM and neuronal stem cells......Page 204
10. General conclusions, remarks and future perspectives......Page 205
References......Page 206
1. Introduction......Page 219
2. Generalized epilepsies......Page 221
3. Partial epilepsies......Page 223
4. Pharmacogenetics and epilepsy......Page 225
References......Page 226
1. Introduction......Page 231
2. Clinical features......Page 232
3. Diagnostic criteria......Page 233
4. Physical features and pathophysiology......Page 235
5. Genetics and MeCP2......Page 237
6. MeCP2 function......Page 238
8. Treatment options......Page 239
List of abbreviations......Page 242
References......Page 243
1. Introduction......Page 251
2.1. Glycoenzymes involved in N-glycan biosynthesis......Page 252
2.2. Disorders in N-glycan biosynthesis: CDG-I and CDG-II......Page 254
3.1. Deficiency in O-mannosylation: congenital muscular dystrophies and dystroglycopathies......Page 255
3.2.2.2. GalNAc-T2 as a regulator of plasma lipid levels......Page 257
3.2.3. Tn syndrome caused by Cosmc mutations......Page 259
4.2. Lysosomal multienzyme complex for carbohydrate degradation......Page 260
References......Page 261
6. Conclusions......Page 264
References......Page 265
1. Introduction......Page 279
2. Hypothesis for etiology of the obesity epidemic......Page 280
3. Genetic research methods used for identification of obesity susceptibility genes......Page 282
4. The influential role of genes in obesity......Page 283
5. Epigenetics......Page 291
6. Assessment of the obese child......Page 292
7. Conclusions......Page 293
References......Page 294
2. Epidemiology......Page 301
3. Environmental and genetic factors in myopia......Page 302
References......Page 305
1. Introduction......Page 313
3. Murine models of FA......Page 314
4. Bone marrow microenvironmental abnormalities in hematopoietic diseases......Page 316
5. Dysregulated bone marrow microenvironment in FA patients and FA murine models......Page 317
7. Biology of MSPCs and their potential clinical application in transplantation therapy for FA patients......Page 318
Author details......Page 319
References......Page 320
1. Introduction......Page 327
2.1. The pancreas......Page 328
2.2. The lungs......Page 330
3.1. Michael Welsh and Jeffrey Smith, University of Iowa, Iowa City, IA......Page 332
3.2. Robert Bridges, Rosalind Franklin University......Page 333
3.3. Shmuel Muallem, University of Texas Southwestern, Dallas, TX......Page 334
3.4. Alan Verkman, University of California San Francisco, San Francisco, CA......Page 335
3.5. Paul Quinton and Malla Reddy, University of California, La Jolla, CA......Page 336
3.6. Steve Ballard, University of South Alabama, Mobile, AL......Page 337
3.7. Terry Machen and Horst Fischer, University of California Berkeley, Berkeley CA......Page 338
3.8. Lane Clarke, University of Missouri, Columbia, MO......Page 339
3.9. Mike Knowles and Richard Boucher, University of North Carolina, Chapel Hill, NC......Page 340
3.10. Jeffrey Wine and Mauri Krouse, Stanford University, Stanford, CA......Page 341
4. Final context: What's new, what's next?......Page 343
References......Page 344