Crumbling Genome: The Impact of Deleterious Mutations on Humans

A thought–provoking exploration of deleterious mutations in the human genome and their effects on human health and wellbeing Despite all of the elaborate mechanisms that a cell employs to handle its DNA with the utmost care, a newborn human carries about 100 new mutations, originated in their parents, about 10 of which are deleterious. A mutation replacing just one of the more than three billion nucleotides in the human genome may lead to synthesis of a dysfunctional protein, and this can be inconsistent with life or cause a tragic disease. Several percent of even young people suffer from diseases that are caused, exclusively or primarily, by pre ]existing and new mutations in their genomes, including both a wide variety of genetically simple Mendelian diseases and diverse complex diseases such as birth anomalies, diabetes, and schizophrenia. Milder, but still substantial, negative effects of mutations are even more pervasive. As of now, we possess no means of reducing the rate at which mutations appear spontaneously. However, the recent flood of genomic data made possible by next–generation methods of DNA sequencing, enabled scientists to explore the impacts of deleterious mutations on humans with previously unattainable precision and begin to develop approaches to managing them. Written by a leading researcher in the field of evolutionary genetics, Crumbling Genome reviews the current state of knowledge about deleterious mutations and their effects on humans for those in the biological sciences and medicine, as well as for readers with only a general scientific literacy and an interest in human genetics. Provides an extensive introduction to the fundamentals of evolutionary genetics with an emphasis on mutation and selection Discusses the effects of pre–existing and new mutations on human genotypes and phenotypes Provides a comprehensive review of the current state of knowledge in the field and considers crucial unsolved problems Explores key ethical, scientific, and social issues likely to become relevant in the near future as the modification of human germline genotypes becomes technically feasible Crumbling Genome is must–reading for students and professionals in human genetics, genomics, bioinformatics, evolutionary biology, and biological anthropology. It is certain to have great appeal among all those with an interest in the links between genetics and evolution and how they are likely to influence the future of human health, medicine, and society. INDICE: 1 Genotypes and Phenotypes 11.1 DNA is a Text 11.2 Genomes Small and Large 61.3 Genes and Intergenic Regions 71.4 Cells, Mitosis, and Meiosis 141.5 From Genotype to Phenotype 17Further Reading 212 Mendelian Inheritance and Population Genetics 232.1 Inheritance is Discrete 232.2 Populations are Genetically Variable 272.3 Loci and Genes 332.4 Effects of Alleles on Phenotypes 372.5 Mendelian Traits and Diseases 43Further Reading 463 Complex Traits and Their Inheritance 493.1 Complex Inheritance of Phenotypes 493.2 Properties of a Complex Trait 523.3 Complex Traits in Populations 553.4 Effects of Heredity and Environment on Complex Traits 603.5 Polymorphic Loci Behind Complex Variation 64Further Reading 684 Unavoidable Mutation 714.1 Phenomenon of Mutation 714.2 Kinds of Mutations 734.3 Spontaneous Mutation 754.4 Evolution of Mutation Rates 774.5 Artificial Mutagenesis and Antimutagenesis 79Further Reading 815 Struggle for Fidelity 835.1 Fidelity of DNA Replication 835.2 Cleaning Up After the Replisome 885.3 Dealing with DNA Damages 915.4 Harms of Broken Maintenance 965.5 Mechanisms of Mutation 100Further Reading 1046 Mutation Rates 1076.1 Measuring Mutation Rates 1076.2 Data on Mutation Rates 1096.3 Guilty Older Men 1126.4 Rates of Phenotypically Drastic Mutations 1146.5 Mild Mutations and Mutational Pressures 118Further Reading 1217 Natural Selection 1237.1 Vulnerable Adaptations and Their Evolutionary Origin 1237.2 Two Basic Characteristics of Selection 1277.3 Measuring Natural Selection 1297.4 Selection at a Polymorphic Locus 1327.5 Selection on a Quantitative Trait 135Further Reading 1388 Functioning DNA and Junk DNA 1418.1 Selective Neutrality and Random Drift 1418.2 Effective Population Size 1448.3 Junk DNA Provides the Simplest Evidence for Evolution 1448.4 Finding Functioning Genome Segments 1458.5 The Genomic Rate of Deleterious Mutations 147Further Reading 1489 It Takes All the Running You Can Do 1499.1 Middle Class Neighborhood for Drosophila 1499.2 Selection Against Deleterious Alleles 1539.3 Mutation Selection Equilibrium 1559.4 Inbreeding Depression 1589.5 Dangerous Slightly Deleterious Alleles 160Further Reading 16210 Phenomenon of Imperfection 16510.1 Phenotypic and Genotypic Imperfection 16510.2 Five Evolutionary Causes of Imperfection 16810.3 Weakly Perfect Human Genotypes and Phenotypes 17110.4 Native, Novel, and Optimal Environments 17310.5 Factors, Exacerbating Mutation Imperfection 175Further Reading 17611 Our Imperfect Fitness 17711.1 Properties of an Allele 17711.2 Human Derived Alleles 18011.3 Average Imperfection of a Genotype 18611.4 Variation Among Genotypes 19011.5 Selection in Modern Human Populations 192Further Reading 19712 Our Imperfect Wellness 19912.1 Qualitative Characteristics of Wellness 19912.2 Quantitative Traits 20612.3 Contributions of Heredity and Environment 20812.4 Wellness ]impairing Alleles 21112.5 Genetic Architecture of Wellness 215Further Reading 21713 Mutational Pressure on Our Species 21913.1 Mutational Pressure on Diseases 21913.2 Mutational Pressure on Quantitative Traits 22513.3 Possible Increase of the Mutational Pressure 22613.4 De Novo Mutations and Human Wellness 22813.5 Optimistic and Pessimistic Scenarios 230Further Reading 23114 Ethical Issues 23314.1 Lessons from History 23314.2 Modern Practices 23714.3 Humanist Ethics and the Main Concern 24114.4 The Main Concern and Ethical Dilemmas 24414.5 Role of Scientists 247Further Reading 25015 What to Do? 25315.1 Conditionally Beneficial or Unconditionally Deleterious? 25315.2 Mutationless Utopia: What Could It Be? 25715.3 Mutationless Utopia: Is It Ever Going to Happen? 26115.4 What Can I Do Without Germline Genotype Modification? 26515.5 Prognosis 268Further Reading 269Index

• ISBN: 978-1-118-95211-5
• Editorial: Wiley–Blackwell
• Encuadernacion: Rústica
• Páginas: 296
• Fecha Publicación: 04/07/2017
• Nº Volúmenes: 1
• Idioma: Inglés