Garcia-Velasco, J: Human Reproductive Genetics

Description

Human Reproductive Genetics: Emerging Technologies and Clinical Applications presents a great reference for clinicians and researchers in reproductive medicine. Part I includes a brief background of genetics and epigenetics, probability of disease, and the different techniques that are being used today for analysis and genetic counseling. Part II focuses on the analysis of the embryo, current controversies and future concepts. Part III comprises different clinical scenarios that clinicians frequently face in practice. The increasing amount of genetic tests available and the growing information that patients handle makes this section a relevant part of the fertility treatment discussion. Finally, Part IV concludes with the psychological aspects of genetic counseling and the role of counselor and bioethics in human reproduction. Cover HUMAN REPRODUCTIVE GENETICS: EMERGING TECHNOLOGIES AND CLINICAL APPLICATIONS Copyright Contents List of contributors About the editors Preface Part A: Fundamentals of genetics 1 Basic genetics: mitosis, meiosis, chromosomes, DNA, RNA, and beyond Introduction DNA, RNA, and protein Nucleic acids and DNA: the building blocks Messenger RNA: the DNA–protein intermediary Protein synthesis: translating the mRNA message into function Gametes uniquely rely on activation and translation of stored mRNAs Noncoding RNAs: not “genetic junk” Genes and chromosomes DNA is organized into chromosomes Mitochondria also contain DNA and chromosomes Regulation of gene expression: posttranslational modifications and imprinting DNA replication, mitosis, and meiosis: passing on genetic information DNA replication duplicates cellular DNA DNA replication is error-prone Mitosis Meiosis And beyond—is the human genome “editable”? References 2 Identification of genetic causes of gynecologic disorders Introduction The Human Genome Project, Mendelian and complex genetic inheritance Difference between mutations and polymorphisms Approaches for identifying the genetic cause of a disorder Candidate gene approach Linkage analysis Genome-wide association studies (polycystic ovary syndrome) Whole-genome sequencing/whole-exome sequencing Multimodal approaches and systems biology Genetic architecture of multifactorial diseases—area of artificial intelligence Summary References 3 Cytogenetics techniques Introduction Karyogram, karyotype, and idiogram Most frequent karyotype abnormalities Heteromorphisms, polymorphisms, or normal variants Tissue culture techniques and chromosome preparation Cell culture for standard karyotypes in peripheral blood Cell culture for high-resolution karyotypes in peripheral blood Chromosome banding techniques Bands distributed along the length of the whole chromosome Bands that stain specific chromosome structures Clinical indications for cytogenetic analysis Cytogenetic analysis in parents Cytogenetic analysis in Product Of Conception(POC) Prenatal diagnosis References 4 Molecular biology approaches utilized in preimplantation genetics: real-time PCR, microarrays, next-generation sequencing... The embryo factor: preimplantation genetic testing techniques for embryo selection against chromosomal abnormalities and mo... Karyotyping Fluorescence in situ hybridization Polymerase chain reaction High-resolution genome-wide approaches Comparative genomic hybridization arrays Single-nucleotide polymorphism array and karyomapping Karyomapping Next-generation sequencing The endometrial factor: gene expression diagnostic tools to assess endometrial receptivity Reverse-transcription real-time polymerase chain reaction DNA microarrays RNA-Seq General conclusion References Further reading 5 Epigenetics and imprinting in assisted reproduction Introduction Molecular mechanisms of epigenetic regulation DNA methylation Histone modifications Noncoding RNAs Epigenetics of aging Histone modifications and aging DNA methylation and aging Epigenetics and reproductive aging A special aspect of epigenetics: imprinting When imprinting goes bad Assisted reproductive treatment and the epigenome The epigenome as a tool to improve assisted reproductive treatment Summary and conclusions References Further reading Part B: Clinical scenarios 6 The quest for genetic sequence variants conferring risk of endometriosis Introduction A primer on genetic studies of complex diseases and a review of endometriosis genetics The proof for the existence of a genetic component Familial aggregation Twin studies Adoption studies Segregation analysis Identification of genes and/or genetic variants: recombination, linkage disequilibrium, and association Linkage analysis Affected sib-pair analysis Association and genome-wide association studies Layers of complexity Multifactorial? Polygenic? Omnigenic? Genetic architecture Epigenetic transmission Heterogeneity and misclassification Conclusion References 7 Genetics of polycystic ovarian syndrome Introduction Heritability Candidate gene studies Genome-wide association studies Functional studies Conclusion References 8 Male factor infertility: genetic and epigenetic aspects Introduction Genetic aspects of male infertility Klinefelter syndrome Y chromosome microdeletions Gene polymorphisms as a cause of male infertility The X chromosome and male infertility Epigenetic aspects of male infertility The roles of environment and lifestyle and transgenerational inheritance of epigenetic mutations Epigenetics and outcomes of assisted reproductive technology Implications References 9 Mitochondrial genetics Introduction Mitochondrial inheritance and replication Mitochondrial diseases Mitochondria in oocytes Mitochondria in sperm Mitochondria in embryos Conclusion References 10 Endometrial receptivity and genetics Introduction Genetic markers of endometrial function Beyond endometrial receptivity Micro-RNAs as markers of endometrial function Conclusions and clinical implications References 11 Genetics of premature ovarian insufficiency Introduction Premature ovarian insufficiency etiology Technical advances Genetics of the ovarian reserve Follicular development Syndromic premature ovarian insufficiency X chromosome defects Autoimmune polyendocrinopathy syndrome type I Blepharophimosis, ptosis, epicanthus inversus syndrome Galactosemia and carbohydrate-deficient glycoprotein syndromes Congenital disorders of glycosylation Pseudohypoparathyroidism type 1a Mitochondria Ovarioleukodystrophy Ataxia telangiectasia Demirhan syndrome Premature aging syndromes Fragile X syndrome Fragile X-associated premature ovarian insufficiency Protein expression and function Molecular mechanism Noncoding RNAs Role of telomeres in premature ovarian insufficiency Telomere history Telomere structure and function Telomeres and aging Telomeres in female reproduction Future diagnosis and treatment References Further reading 12 Prenatal testing Aneuploidy screening tests Nuchal translucency Background Limitations Other ultrasound markers Biochemical screening Serum analytes First trimester screen Maternal serum alpha-fetoprotein Quadruple screen Combination screening Integrated screening Sequential screen Twin gestations Cell-free fetal DNA screening Background Modalities of testing Counting Massive parallel shotgun sequencing Targeted massively parallel shotgun sequencing Single-nucleotide polymorphisms targeted sequencing Target population Counseling Limitations Summary Diagnostic prenatal genetic testing Chorionic villus sampling Amniocentesis Available testing modalities Karyotype Chromosomal microarray Whole-exome sequencing Targeted gene mutation analysis References 13 Expanded carrier screening in reproductive medicine Principles of carrier screening Historic perspectives Other aspects of traditional ethnicity-based screening Universal screening Role of expanded carrier screening Mutation screening versus gene sequencing Genotype–phenotype correlations Determination of residual risk Clinical utility of expanded carrier screening Options for carrier couples Carrier screening for X-linked disorders Counseling for consanguineous couples Counseling regarding variants of uncertain significance Gamete donors Ethical arguments in favor of expanded carrier screening Practical arguments opposing expanded carrier screening Genes on expanded carrier screening panels with additional implications Identifying individuals with two pathogenic variants Conclusion References Part C: How to analyze an embryo 14 Preimplantation genetic testing for monogenic diseases Introduction Indications for preimplantation genetic testing for monogenic diseases Mendelian conditions or single-gene disorders Late-onset diseases and cancer predisposition Human leukocyte antigen typing or testing for family matching Technologies and testing methods Polymerase chain reaction and capillary electrophoresis Whole-genome amplification for single or few embryo cells Single-nucleotide polymorphisms arrays Next-generation sequencing -based haplotyping Simultaneous embryo testing for preimplantation genetic testing for monogenic diseases and preimplantation genetic testing ... Limitations Conclusion References 15 Future technologies for preimplantation genetic applications Preimplantation genetic testing Noninvasive preimplantation genetic testing Future perspectives in preimplantation genetic testing for monogenic disease Preimplantation genetic testing for polygenic disease Whole-genome sequencing of the preimplantation embryo Germline genome editing How far are we from (safe) clinical application of genome editing? Ethical considerations for germline genome editing References Part D: Reproductive genetic counseling 16 Psychological aspects of reproductive genetic screening and diagnoses Reproductive genetic screening Preconception carrier screening Preimplantation genetic testing for monogenic defects Preimplantation genetic testing for aneuploidy The role of the infertility counselor Conclusions References 17 Bioethics in human reproduction (human reproductive genetics) Introduction Preconception genetic testing Preimplantation genetic testing Preimplantation genetic diagnosis Preimplantation genetic testing for aneuploidy screening Prenatal genetic testing References 18 The role of genetic counseling in the infertile patient Introduction Genetic counseling Psychological and emotional impacts of infertility and/or genetics Karyotype alterations as a cause of infertility Chromosomal heteromorphisms Sex chromosome aneuploides Structural rearrangements Reciprocal translocations Robertsonian translocations Inversions Genetic counseling in structural rearrangements Small supernumerary marker chromosomes Genetic counseling in preimplantation genetic testing Preimplantation genetic testing for aneuploidies Preimplantation genetic testing for structural rearrangements Preimplantation genetic testing for monogenic conditions Genetic counseling in preimplantation genetic testing Monogenic causes of infertility CFTR gene variants as a cause of male infertility FMR1 gene variants as a cause of female infertility Genetic counseling in expanded carrier screening Communication skills in genetics Taking a family history Frequent misconceptions about genetics Delivering genetic information Giving bad news Talking about risks References Index Back Cover