| Description |
1 online resource |
| Contents |
Front Cover -- Progress in Genomic Medicine -- Copyright Page -- Dedication -- Contents -- Preface -- Acknowledgments -- Epigraph -- I. History and Growth of Genetic Medicine -- 1 Documentation of units of inheritance and their contribution to phenotype -- 1.1 Rediscovery of the laws of Mendel -- 1.2 Genes and genetics -- 1.3 Nucleic acids -- 1.4 The structure of DNA -- 1.5 DNA and chromatin -- 1.5.1 Consequences of determination of DNA structure -- 1.5.2 Modifications of DNA sequences -- 1.6 Applications of studies of chromosomes, genomes, genes, and gene expression to clinical medicine -- 1.6.1 Chromosome microarray analyses -- 1.7 Long-read sequencing for detection of genomic variants including structural chromosome abnormalities -- 1.8 Determination of the significance of structural variants in the genome -- 1.8.1 Clinical significance of structural genomic variants -- 1.9 Mosaicism -- 1.9.1 Chromosomal mosaicism -- 1.9.2 Mosaicism detection -- 1.9.3 Mosaicism and genetic diseases -- 1.10 Germline mutations -- 1.11 Genetic mosaicism in inborn errors of immunity -- References -- Further reading -- 2 Early documentation of inherited disorders through family studies -- 2.1 The Treasury of Human Inheritance -- 2.2 Ectrodactyly -- 2.3 Deafness -- 2.4 Hemophilia -- 2.5 Achondroplasia -- 2.6 Color blindness -- 2.7 Blue sclerotics and fragility of bone -- 2.8 Hereditary optic atrophy (Leber's disease) -- 2.9 Huntington's chorea -- 2.10 Duchenne muscular dystrophy -- 2.11 Determination of genetic causes of specific diseases and family studies -- References -- Further reading -- 3 Discoveries in physiology, biochemistry, protein, and enzyme studies between 1920 and 1970 -- References -- Further reading -- 4 Early translation of biochemical, metabolic, and genetic discoveries into clinical medicine -- 4.1 ABO |
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4.2 Further information on the ABO blood group system -- 4.3 Secretor status -- 4.4 Mapping of the ABO locus to a chromosome -- 4.5 Rh blood group system -- 4.6 RHD genotyping -- 4.7 Chemical analyses and metabolism incorporating information gathered across the decades -- References -- Further reading -- 5 Advances in methods of genome analyses, nucleotide analyses, and implications of variants -- 5.1 Introduction -- 5.2 DNA sequencing -- 5.3 Applications of long-read sequencing -- 5.4 Sequence variant interpretation -- 5.4.1 Sequencing in clinical diagnosis: reinterpretation of data and secondary findings -- 5.4.2 Long-range sequencing relevance to diagnosis of rare disorders -- 5.5 Additional evidence for digenic or complex inheritance -- 5.6 Variants in nonprotein coding genomic regions -- 5.7 Haplotype phasing -- 5.7.1 Noninvasive prenatal screening and haplotype phasing -- 5.8 Haplotype analysis -- 5.9 Long-range sequencing and identification of structural genomic variants leading to disease -- 5.10 Investigations of chromatin structure and genomic function -- 5.10.1 Chromatin conformation capture -- 5.11 Methylation analyses -- 5.12 Imprinted genomic regions -- 5.13 Genetic disorders where analysis of methylation is important -- 5.13.1 Methylation and cancer -- References -- II. Clinical Applications of Genomic Medicine -- 6 Expansion of use of genome analyses and sequencing in diagnosis of genetic diseases -- 6.1 Measurement toolkit for assessing the clinical utility of whole genome sequencing -- 6.1.1 Next generation sequencing in clinical neurology -- 6.2 One phenotype many genes -- 6.2.1 Incomplete penetrance -- 6.3 Genome sequencing in pediatric developmental defects -- 6.4 Optical DNA mapping in human genome studies -- 6.5 Transcriptome sequencing -- 6.6 Imprinting -- 6.7 Imprinting disorders |
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6.8 Prader−Willi syndrome and Angelman syndrome -- 6.9 Silver−Russell syndrome -- 6.10 GNAS locus -- 6.11 Epivariations -- 6.12 Multilocus imprinting disorders -- 6.13 Chromosomes genomes and sequence -- 6.14 Structural genomic variants -- 6.14.1 Population analyses -- 6.14.2 Dosage sensitivity and haploinsufficiency -- 6.14.3 ACMG recommendations regarding genomic copy number variants analysis and reporting -- 6.15 Assessment of copy number changes in different conditions and at different life stages -- 6.16 Prenatal exome sequence analysis -- 6.17 Deciphering Developmental Disorders Study -- 6.18 Investigations of causes of recurrent miscarriage -- 6.19 Sequencing in prenatal diagnosis: noninvasive prenatal testing -- References -- Further reading -- 7 Improved analyses of regulatory genome, transcriptome and gene function, mutation penetrance, and clinical applications -- 7.1 Introduction -- 7.1.1 Gene expression -- 7.2 Regulatory genome, gene expression, phenotype, and variability -- 7.2.1 Long noncoding RNAs (long nonprotein coding RNAs) -- 7.2.2 Defining functions of specific regulatory elements and their relationship to diseases -- 7.3 Epigenetic factors relevant to gene expression -- 7.3.1 Disorders of the epigenetic machinery leading to neurodevelopmental disorders -- 7.3.2 Cohesinopathies -- 7.4 Regulatory circuit: Epimap -- 7.4.1 Combinations of variants in different genes and impact of phenotype -- 7.5 Genotype phenotype axis -- 7.6 Promoters -- 7.7 Transcription initiation and promoters -- 7.7.1 Genes with more than one promoter -- 7.7.2 Ornithine transcarbamylase gene promoters and enhancers -- 7.8 Transcription factors -- 7.8.1 Transcription elongation and RNA polymerase II -- 7.9 Transcription termination -- 7.10 Polyadenylation -- 7.11 Alternate polyadenylation -- 7.11.1 Alternate splicing of transcripts -- 7.12 The spliceosome |
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7.12.1 Generation of microexons -- 7.13 MicroRNAs and posttranscriptional regulation -- 7.14 Translation, ribosomes biogenesis, functions, and defects -- 7.14.1 Human disorders associated with impaired ribosomal biogenesis or function -- 7.15 Translation of mRNA to proteins and associated defects leading to disease -- 7.15.1 Aminoacyl tRNA synthases -- 7.15.2 Noncanonical functions of aminoacyl tRNA synthetases -- 7.16 tRNAs -- 7.17 RNA surveillance -- 7.17.1 Posttranscriptional control and RNA binding proteins -- 7.17.2 RNA modifications and regulation of gene expression -- 7.18 Translation -- 7.19 Nonsense-mediated decay -- 7.19.1 Suppression of nonsense mutations -- 7.20 Nonsense mutations and human disease -- 7.21 Approved RNA targeted therapeutics -- 7.22 Therapy with short inhibitory RNAs -- 7.23 MicroRNAs in therapeutic use -- 7.24 RNA sequencing in diagnosis of genetic diseases -- 7.25 Penetrance of mutations and modified penetrance -- 7.26 Variable penetrance of disease due to polymorphisms in regulatory factors -- 7.27 Penetrance in inherited eye diseases -- 7.28 Primary immunodeficiency and incomplete penetrance -- References -- 8 Standardized phenotype documentation, documentation of genotype phenotype correlations -- 8.1 Phenotype and clinical genetics -- 8.2 Congenital malformations and syndromes -- 8.2.1 Inborn errors of development -- 8.2.2 Twin studies and analysis of gene effects on phenotype -- 8.2.3 Accounting for phenotypic differences in individuals with the same genetic defect -- 8.3 Variable phenotypes associated with specific mitochondrial mutations -- 8.4 Variable genomic abnormalities in individuals with the same phenotype -- 8.5 Standardized phenotype documentation, documentation of genotype phenotype correlations databases -- 8.5.1 Clinical genetics and genomics databases -- 8.6 Phenome-wide association studies |
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8.7 Dysmorphology syndromes with overlapping features due to defect in gene products that function in a specific pathway -- 8.7.1 Gene products involved in the RAS/MAP signal transduction pathway and chromosomal map positions -- 8.8 Phenotypic defects due to defects in sonic hedgehog signaling pathway -- 8.9 Fibroblast growth factor signaling pathway -- 8.10 Fibroblast growth factor receptor defects -- 8.10.1 Mutations reported as pathogenic in achondroplasia multiple submitters -- 8.11 Transforming growth factor beta signaling pathway -- 8.11.1 Phenotypic features Loeys−Dietz syndromes -- 8.11.2 LDS type 4 TGFB2 mutations -- 8.11.3 LDS type 5 TGFB3 mutations -- 8.12 Marfan syndrome 15q21.1 FBN1 -- 8.12.1 FBN1 mutations in Marfan syndrome -- 8.13 FBN1 mutations, pathogenic, likely pathogenic, Marfan syndrome multiple submitters, without conflicts identified in Cl... -- 8.14 Connective tissue disorder Ehlers−Danlos syndrome disorders -- 8.14.1 COL3A, vascular EDS, pathogenic/likely pathogenic, mutations, multiple submitters, no conflicts -- 8.14.2 Classic type ̀ 9q34.3 COL5A AD collagen type V alpha 1 chain -- 8.14.3 Hypermobile Ehlers−Danlos syndrome -- 8.15 DNA methylation episignatures and phenotypic correlations -- References -- 9 Expansion of methods of gene editing therapy and analysis of safety and efficacy -- 9.1 Introduction -- 9.2 Therapies designed to block nucleotides or RNA derived from a specific gene -- 9.3 Oligonucleotide therapies -- 9.3.1 Steric block oligonucleotides -- 9.3.2 RNA inhibition in therapies -- 9.3.3 MicroRNAs as mRNA inhibitors -- 9.3.4 Long noncoding RNAs, small RNAs, endogenous antisense RNAs -- 9.4 Delivery challenges in oligonucleotide therapies -- 9.5 Splice mutations and diseases -- 9.6 Antisense therapies under investigation -- 9.7 Genomic data leading to therapeutics |
| Bibliography |
Includes bibliographical references and index |
| Notes |
Print version record |
| Subject |
Medical genetics.
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Genomics.
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Genetics, Medical
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Genomics
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Genomics
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Medical genetics
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| Form |
Electronic book
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| ISBN |
9780323915489 |
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0323915485 |
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