Females are mosaics : X inactivation and sex differences in disease / Barbara R. Migeon.

Format:

Book

Author/Creator:

Migeon, Barbara R.

Language:

English

Subjects (All):

X chromosome.

Mosaicism.

Genetic sex determination.

Sex-linkage (Genetics).

X Chromosome Inactivation--physiology.

Genetic Diseases, X-Linked.

Sex Factors.

Medical Subjects:

Mosaicism.

X Chromosome Inactivation--physiology.

Genetic Diseases, X-Linked.

Sex Factors.

Physical Description:

xi, 271 pages, 8 unnumbered pages of plates : illustrations (partly color) ; 24 cm

Other Title:

X inactivation and sex differences in disease

Place of Publication:

Oxford ; New York : Oxford University Press, 2007.

Contents:

Chapter 1 Sex Differences in Disease 11

1.1 Males More Vulnerable at Every Age 11

1.2 Vulnerability of Males Leads to Sex-Specific Disease 15

1.3 Summary and Speculations 18

Chapter 2 Evolution of the Human Sex Chromosomes and a Portrait of the Human X 20

2.1 Chromosomal Basis of Sex Determination 20

2.2 The Human Sex Chromosomes Evolved from Reptilian Autosomes 22

2.3 Degeneration of the Y Chromosome 26

2.4 Ohno's Law and the Conservation of the Original X 26

2.5 Residual Homology and the Pseudoautosomal Regions 27

2.6 Genetic Portrait of the Human X 29

2.7 Summary and Speculations 33

Chapter 3 X Chromosome Dosage Compensation: An Overview 35

3.1 X Chromosome Dosage Compensation 35

3.2 Heterochromatin and Chromosome Silencing 38

3.3 Role in Sex Determination 40

3.4 Mechanisms of Dosage Compensation in Other Organisms 40

3.5 Mechanisms of Dosage Compensation in Mammals 43

3.6 Summary and Speculations 45

Chapter 4 The Discovery of X Chromosome Inactivation 47

4.1 The Lyon Hypothesis 51

4.2 General Scheme of Mammalian Dosage Compensation 54

4.3 Summary and Speculations 55

Chapter 5 Experimental Models for X Inactivation Studies 57

5.1 Spontaneous Human Mutations that Interfere with Inactivation 57

5.2 X-Linked Protein Variants Distinguish Parental Origin of X Chromosomes 61

5.3 Characterizing the Inactive X in Human Cell Cultures and Clones 62

5.4 Mouse-Human Hybrids Separate Inactive from Active X 64

5.5 Mouse Embryonic Stem Cells for Manipulating the Early Steps in X Inactivation 66

5.6 Transgenic Mice as a Functional Assay 68

5.7 Assays for X Inactivation Patterns in Heterozygotes 69

5.8 Summary and Speculations 70

Part II Themes and Variations of X Inactivation

Chapter 6 Theme 1: The Initial Steps-Creating the Active and Inactive X 73

6.1 Characteristics of the Inactive X Chromosome 74

6.2 Time of Initiation in the Embryo 77

6.3 Cis Inactivation 80

6.4 The Master Control Region: XIC and Xist 81

6.5 Silencing the Inactive X Chromosome 85

6.6 Choosing the Active X Chromosome 90

6.7 Summary and Speculations 96

Chapter 7 Theme 2: Subsequent Steps-Spreading and Maintaining Inactivation 98

7.1 Spreading Inactivation by Modifying Chromatin 99

7.2 Maintaining Inactivation by DNA Methylation of CpG Islands 106

7.3 Escape from Inactivation 109

7.4 Transient X Inactivation in Germ Cells 113

7.5 Induced X Reactivation in Placental Cells 115

7.6 Role of DNA Replication in X Inactivation 116

7.7 Summary and Speculations 117

Chapter 8 Variations 1: Stability of the Inactive X 119

8.1 Variations on the Themes of X Inactivation 120

8.2 Divergence in the Physical Map 120

8.3 Stability of X Inactivation 122

8.4 Summary and Speculations 126

Chapter 9 Variations 2: Choice of Active X 127

9.1 Primary Nonrandom X Inactivation 127

9.2 Paternal X Inactivation 131

9.3 Relationship of Paternal X Inactivation to Genomic Imprinting 133

9.4 Does Antisense Transcription Have a Role? 136

9.5 Evolution and Tinkering 140

9.6 Effect of Inactivation Timing 141

9.7 Summary and Speculations 143

Part III Medical Consequences of X Inactivation

Chapter 10 The Single Active X 147

10.1 Coping with a Monosomy X 147

10.2 Sex Differences in Susceptibility to Disease 149

10.3 Viability of Turner Syndrome, Klinefelter Syndrome, and X Chromosome Aneuploidy 150

10.4 X Deletions, Ring X Chromosomes, X Duplications, and Functional Disomy 156

10.5 X/Autosome Translocations and Spreading of Inactivation 158

10.6 Polyploidy and the Choice of Active X 161

10.7 Summary and Speculations 163

Chapter 11 Mosaicism 165

11.1 The X-Linked Phenotype Is Dominant at the Cellular Level 165

11.2 Females Are Mosaics 166

11.3 Interaction between Mosaic Cell Populations 168

11.4 Skewing of X Inactivation Patterns 176

11.5 Effect of X Inactivation on Clinical Phenotype 184

11.6 "Manifesting" Heterozygotes 199

11.7 Summary and Speculations 203

Chapter 12 Determinants of Female Phenotypes 206

12.1 The Dynamic Effect of Interacting Cell Populations on the Health of Females 207

12.2 The Effect of X Inactivation on Normal Female Phenotype and Cell Diversity 209

Appendix A Descriptions of Model X-linked and Other Relevant Diseases 213

Appendix B Sex Chromosome Aneuploidy, Polyploidy, and Parthenogenetic Conceptuses 227.

Notes:

Includes bibliographical references (pages 241-257) and index.

ISBN:

0195188128

9780195188127

OCLC:

65617406