Reproductive Genetics

Title page
......Page 4
Contents......Page 6
Participants......Page 8
Declarations of personal interest
......Page 10
Preface......Page 12
Female infertility......Page 14
Evidence of a genetic contribution......Page 15
Genetic causes......Page 16
Chromosome disorders......Page 17
Three Y chromosome microdeletions......Page 18
Autosomal genes......Page 19
Genetics and epigenetics......Page 20
Conclusion......Page 21
References......Page 22
Introduction......Page 28
Chromosomal sex......Page 29
Gonadal and phenotypic sex......Page 30
Other sexually dimorphic processes: germ cell fate and gonad position......Page 31
Disorders of sex development......Page 33
Classification and diagnosis......Page 34
Sex chromosome DSD......Page 36
Gonadal (testicular) dysgenesis......Page 39
Ovarian development defects......Page 40
Prenatal karyotyping/genotyping and CAH treatment......Page 41
The multidisciplinary team......Page 42
Fertility......Page 43
References......Page 44
PGD as a clinical service......Page 48
Why do people request PGD?......Page 49
Preparation for PGD......Page 50
Embryo biopsy......Page 51
Embryo transfer......Page 52
Number of cycles and pregnancy rates......Page 53
Regulation of PGD......Page 54
Funding......Page 55
Single-gene disorders......Page 56
Sex selection......Page 60
PGD for HLA matching......Page 63
Non fully penetrant disorders......Page 64
Acknowledgements......Page 65
References......Page 66
4 Ethical aspects of saviour siblings :procreative reasons and the treatment of children......Page 72
Third-party intervention......Page 73
How do we deal with bad reasons?......Page 74
Two further thoughts......Page 76
Conclusions: judging reasons......Page 77
The treatment of saviour siblings......Page 78
Live organ donation by children......Page 79
Conclusion......Page 80
References......Page 81
Genomic imprinting......Page 84
DNA methylation controls genomic imprinting......Page 85
Assisted reproductive technologies......Page 86
Embryo culture......Page 87
Superovulation......Page 88
Genomic imprinting and the placenta......Page 89
ART and genomic imprinting syndromes......Page 90
Summary......Page 91
References......Page 92
Sources of stem cells......Page 96
Bone marrow, liver and blood......Page 97
Amniotic fluid......Page 99
Development of in utero transplantation......Page 100
Preclinical development in wild types......Page 101
Muscular dystrophy......Page 102
Osteogenesis imperfecta......Page 103
Fetal experience......Page 104
Barriers to engraftment......Page 105
Rescue treatment......Page 106
References......Page 107
Summary......Page 114
The advantage......Page 115
Candidate diseases......Page 116
Vectors for prenatal gene therapy......Page 118
The evidence: preclinical proof-of-principle studies......Page 120
Manipulating the vector......Page 122
Methods and timing of delivery to the fetus......Page 123
Choice of disease......Page 124
Integrating vectors and insertional mutagenesis......Page 125
Reversion to wild type vector......Page 126
Ethical concerns......Page 127
Fetal somatic gene therapy in practice......Page 128
The future of prenatal gene therapy......Page 129
References
......Page 130
Introduction......Page 136
Implication in evil......Page 137
Blurring of the line between research and treatment......Page 139
Consent for fetuses and children......Page 140
Cost-effectiveness and resource allocation......Page 141
References......Page 142
Introduction......Page 144
Holoprosencephaly......Page 146
Omphalocele......Page 147
Skeletal dysplasias......Page 148
Cardiac abnormalities......Page 150
Arthrogryposis......Page 151
Hydrops......Page 152
Sex reversal......Page 153
Gastrointestinal disorders......Page 154
Renal disorders......Page 155
References......Page 156
Background......Page 160
Current PND service delivery models in the UK......Page 162
New technologies and PND......Page 163
aCGH and PND......Page 165
Potential PND service reconfiguration driven by aCGH......Page 167
References......Page 170
Introduction......Page 172
Fetal sex determination......Page 173
Diagnosis of aneuploidy......Page 176
Ethics, education and counselling......Page 181
References......Page 182
Introduction......Page 186
Molecular basis for D polymorphism......Page 187
Fetal D testing in alloimmunised (high-risk) pregnant women......Page 188
The problem of including internal controls......Page 190
Fetal testing to ascertain the requirement for antenatal anti-D immunoglobulin prophylaxis......Page 191
Fetal genotyping for other blood groups......Page 192
Conclusion......Page 193
References......Page 194
Introduction......Page 196
The severity of a condition: whose interests?......Page 197
Termination of pregnancy......Page 199
PGD......Page 203
Conclusion......Page 204
References......Page 205
The UK approach to genetic test evaluation......Page 206
Analytical validity......Page 207
Ethical legal and social issues......Page 208
Are the UKGTN systems future-proof?......Page 209
What changes or new systems should be considered?......Page 210
References......Page 211
ARC’s contact with parents making decisions about invasive
diagnostic tests......Page 212
Implications for parents of the future implementation of NIPD......Page 213
NIPD and the challenge of informed consent......Page 214
New techniques in preimplantation genetic screening and diagnosis......Page 215
Conclusion......Page 216
References......Page 217
Introduction: consent, choices and decisions......Page 218
Information......Page 219
Decision making......Page 220
Evaluating the performance of prenatal screening and testing programmes......Page 221
Knowledge......Page 222
Values and attitudes......Page 223
Behaviour and the predictive power of attitudes......Page 224
Evaluating screening programmes: what else can we do?......Page 226
References......Page 227
Health policy......Page 230
Saviour siblings......Page 231
Development of existing technology......Page 232
Other recommendations......Page 233
Index......Page 234