Human genetics: problems and approaches
Gespeichert in:
| Hauptverfasser: | , |
|---|---|
| Format: | Buch |
| Sprache: | English |
| Veröffentlicht: |
Berlin [u.a.]
Springer
1997
|
| Ausgabe: | 3., completely rev. ed. |
| Schlagworte: | |
| Online-Zugang: | Inhaltsverzeichnis |
| Beschreibung: | 4. Aufl. u.d.T.: Vogel and Motulsky's Human genetics |
| Beschreibung: | XXXVI, 851 S. Ill., graph. Darst., Kt. |
| ISBN: | 3540602909 |
Internformat
MARC
| LEADER | 00000nam a2200000 c 4500 | ||
|---|---|---|---|
| 001 | BV010716774 | ||
| 003 | DE-604 | ||
| 005 | 20180122 | ||
| 007 | t | ||
| 008 | 960401s1997 gw abd| |||| 00||| eng d | ||
| 016 | 7 | |a 946121257 |2 DE-101 | |
| 020 | |a 3540602909 |9 3-540-60290-9 | ||
| 035 | |a (OCoLC)33897787 | ||
| 035 | |a (DE-599)BVBBV010716774 | ||
| 040 | |a DE-604 |b ger |e rakddb | ||
| 041 | 0 | |a eng | |
| 044 | |a gw |c DE | ||
| 049 | |a DE-355 |a DE-29 |a DE-29T |a DE-19 |a DE-20 |a DE-M49 |a DE-12 |a DE-M489 |a DE-188 |a DE-578 | ||
| 050 | 0 | |a QH431 | |
| 082 | 0 | |a 573.2/1 |2 20 | |
| 084 | |a WG 7000 |0 (DE-625)148612: |2 rvk | ||
| 084 | |a BIO 950f |2 stub | ||
| 084 | |a BIO 750f |2 stub | ||
| 100 | 1 | |a Vogel, Friedrich |d 1925-2006 |e Verfasser |0 (DE-588)120928892 |4 aut | |
| 245 | 1 | 0 | |a Human genetics |b problems and approaches |c F. Vogel ; A. G. Motulsky |
| 250 | |a 3., completely rev. ed. | ||
| 264 | 1 | |a Berlin [u.a.] |b Springer |c 1997 | |
| 300 | |a XXXVI, 851 S. |b Ill., graph. Darst., Kt. | ||
| 336 | |b txt |2 rdacontent | ||
| 337 | |b n |2 rdamedia | ||
| 338 | |b nc |2 rdacarrier | ||
| 500 | |a 4. Aufl. u.d.T.: Vogel and Motulsky's Human genetics | ||
| 650 | 7 | |a Antropogenetica |2 gtt | |
| 650 | 7 | |a Genetica |2 larpcal | |
| 650 | 4 | |a Genetik | |
| 650 | 4 | |a Genetik, tıbbi | |
| 650 | 4 | |a İnsan genetiği | |
| 650 | 4 | |a Genetics | |
| 650 | 4 | |a Genetics, Medical | |
| 650 | 4 | |a Human genetics | |
| 650 | 0 | 7 | |a Erbkrankheit |0 (DE-588)4015106-2 |2 gnd |9 rswk-swf |
| 650 | 0 | 7 | |a Humangenetik |0 (DE-588)4072653-8 |2 gnd |9 rswk-swf |
| 689 | 0 | 0 | |a Humangenetik |0 (DE-588)4072653-8 |D s |
| 689 | 0 | |5 DE-604 | |
| 689 | 1 | 0 | |a Erbkrankheit |0 (DE-588)4015106-2 |D s |
| 689 | 1 | |5 DE-604 | |
| 700 | 1 | |a Motulsky, Arno G. |d 1923-2018 |e Verfasser |0 (DE-588)172265177 |4 aut | |
| 856 | 4 | 2 | |m HBZ Datenaustausch |q application/pdf |u http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=007156252&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |3 Inhaltsverzeichnis |
| 999 | |a oai:aleph.bib-bvb.de:BVB01-007156252 | ||
Datensatz im Suchindex
| _version_ | 1804125197362528256 |
|---|---|
| adam_text | Contents Overview
1 History of Human Genetics 11
2 The Human Genome: Chromosomes 25
3 The Human Genome: Genes and DNA 83
4 Formal Genetics of Humans: Modes of Inheritance 129
5 Formal Genetics of Humans:
Linkage Analysis and Gene Clusters 163
6 Formal Genetics of Humans:
Multifactorial Inheritance and Common Diseases 195
7 Gene Action: Genetic Diseases 257
8 Gene Action: Developmental Genetics 361
9 Mutation: Spontaneous Mutation in Germ Cells 385
10 Mutation: Somatic Mutation, Cancer, and Aging 431
11 Mutation: Induction by Ionizing Radiation and Chemicals 457
12 Population Genetics: Description and Dynamics 495
13 Population Genetics: Consanguinity, Genetic Drift 549
14 Human Evolution 583
15 Behavioral Genetics: Research Strategies and Examples 623
16 Behavioral Genetics: Affective Disorders and Schizophrenia . . . 693
17 Behavioral Genetics: Differences Between Populations 705
18 Genetic Counseling and Prenatal Diagnosis 711
19 Genetic Manipulations and the Biological Future
of the Human Species 733
Contents
Introduction 1
1 History of Human Genetics 11
1.1 The Greeks 11
1.2 Scientists Before Mendel and Galton 12
1.3 Galton s Work 13
1.4 Mendel s Work 14
1.5 Application to Humans: Garrod s Inborn Errors of Metabolism .... 15
1.6 Visible Transmitters of Genetic Information:
Early Work on Chromosomes 16
1.7 Early Achievements in Human Genetics 17
1.7.1 ABO and Rh Blood Groups 17
1.7.2 Hardy Weinberg Law 17
1.7.3 Developments Between 1910 and 1930 17
1.8 Human Genetics, the Eugenics Movement, and Politics 17
1.8.1 United Kingdom and United States 17
1.8.2 Germany 18
1.8.3 Soviet Union 19
1.8.4 Human Behavior Genetics 19
1.9 Development of Medical Genetics (1950 the Present) 19
1.9.1 Genetic Epidemiology 19
1.9.2 Biochemical Methods 19
1.9.3 Genetic and Biochemical Individuality 20
1.9.4 Cytogenetics, Somatic Cell Genetics, Prenatal Diagnosis 20
1.9.5 DNA Technology in Medical Genetics 21
1.9.6 Unsolved Problems 21
Conclusions 21
References 22
XIV Contents
2 The Human Genome: Chromosomes 25
2.1 Human Cytogenetics: A Successful Late Arrival 25
2.1.1 History and Development of Human Cytogenetics 25
First Observations on Human Mitotic Chromosomes An Old Error
Is Corrected and a New Era Begins Solution of an Old Riddle:
Down Syndrome (Mongolism) Is Due to Trisomy 21 First Reports
on Trisomies and Monosomies of Sex Chromosomes Birth of Human
Cytogenetics 1956 1959: A Scientific Revolution Paradigm Group in Early
Human Cytogenetics Steps in the Development of Human Cytogenetics
Clinical Cytogenetics: The Most Popular Speciality of Human Genetics
2.1.2 Normal Human Karyotype in Mitosis and Meiosis 29
2.1.2.1 Mitosis 29
Cell Cycle Mitosis
2.1.2.2 Preparation and Staining of Mitotic Metaphase Chromosomes 30
Preparation Staining Banding Methods Available Methods Differences
Revealed by the Banding Methods Silver Staining ofNucleolus Organizer
Regions Chromosomes from Human Spermatozoa
2.1.2.3 Normal Human Karyotype in Mitotic Metaphase Chromosomes .... 31
Banding Techniques Individual Characterization of Human Chromosomes
Chromosome Heteromorphisms High Resolution Banding Electron Microscopic
Images of Human Chromosomes
2.1.2.4 Meiosis 37
Biological Function of Meiosis Meiotic Division I Meiotic Division II
Meiosis in the Human Male Meiosis in the Human Female Sex Difference
in Meiosis
2.2 Human Chromosome Pathology 44
2.2.1 Syndromes Due to Numeric Anomalies of Autosomes 44
Mechanisms Creating Anomalies in Chromosome Numbers Down
Syndrome Standard Karyotype in Down Syndrome Other Autosomal
Trisomies Triploidy Mosaics
2.2.2 Syndromes Due to Structural Anomalies of Autosomes 52
2.2.2.1 Karyotypes and Clinical Syndromes 52
First Observations of Down Syndrome Frequency of Translocation Down
Syndrome Gaps and Breaks Intrachromosomal Rearrangements
(Intrachanges) Interchromosomal Rearrangements (Interchanges) Description
of Human Karyotypes Chromosome Band Nomenclature Deletion Syndromes
Intrachanges: Paracentric and Pericentric Inversions Aneusomie de
Recombinaison Ring Chromosomes Fragments Isochromosomes
Interchanges: Centric Fusions (Robertsonian Translocations) Interchanges:
Reciprocal Translocations Phenotypes in Autosomal Chromosome Aberrations
2.2.2.2 Segregation and Prenatal Selection of Translocations:
Methodological Problems 64
Segregation of Translocations in the First Meiotic Division Expectations
for Unbalanced Zygotes Phenotypic Deviations in Balanced Translocation
Carriers Premature Sister Chromatid Separation (Heterochromatin Repulsion)
2.2.2.3 Small Deletions, Structural Rearrangements, and Monogenic
Disorders: Contiguous Gene Syndromes 67
Contents XV
2.2.3 Sex Chromosomes 69
2.2.3.1 First Observations 69
Nondisjunction of Sex Chromosomes and Sex Determination in Drosophila
XO Type in the Mouse First X Chromosomal Aneuploidies in Humans: XXY,
XO.XXX
2.2.3.2 X Chromosomal Aneuploidies in Humans: Current Knowledge 71
Difference Between X Chromosomal and Autosomal Aneuploidies
Clinical Classification ofX Chromosomal Aneuploidies; Mosaics Intersexes
2.2.3.3 Dosage Compensation for Mammalian X Chromosomes 72
Nature of the X Chromatin X Inactivation as the Mechanism of Gene Dosage
Compensation: Lyons Hypothesis Other Examples ofX Inactivation in
Humans Cells in Which the Second X Is Not Inactivated X Inactivation
and Abnormal X Chromosomes
2.2.4 Chromosome Aberrations and Spontaneous Miscarriage 76
Incidence of Prenatal Zygote Loss in Humans Incidence of Chromosome
Aberrations Types of Chromosome Aberrations in Aborted Fetuses
Phenotypes of Abortuses Some Conclusions
Conclusions 79
References 79
3 The Human Genome: Genes and DNA 83
3.1 Organization of Genetic Material in Human Chromosomes 83
3.1.1 Chromatin Structure 83
3.1.1.1 Single Copy and Repetitive DNA 83
Too Much DNA in a Human Genome? Repetitive DNA How Are Single
Copy and Repetitive DNA Located Relative to Each Other? Repetitive DNA
Sequences with Specific Functions Satellite DNA The Structure of Telomeres
3.1.1.2 Heterochromatin 85
Definitions and Properties Heteromorphisms: Function and Relationship
to Satellite DNA
3.1.1.3 The Nudeosome Structure of Chromatin 86
Chemical Composition of Chromatin Nucleosomes
3.1.1.4 Integration of the Chromatin Thread in Chromosome Structure .... 87
Interphase Mitotic and Meiotic Chromosomes
3.1.1.5 Integrated Model of Chromosome Structure 87
3.1.2 The Genetic Code 88
3.1.3 Fine Structure of Human Genes 88
3.1.3.1 Analysis of Human Genes 89
3.1.3.2 Restriction Endonucleases 89
Germinal Observations Principles of DNA Recombination Technology
Identification and Analysis of Genes: Southern Blotting Probes and Gene Libraries
3.1.3.3 Nucleic Acid Hybridization 92
Principle Gene Walking In Situ Hybridization with Radioactive Probes
Fluorescence In Situ Hybridization Comparative Genomic Hybridization
XVI Contents
3.1.3.4 Sequencing of DNA 97
Nucleotide Sequence and the Genetic Code
3.1.3.5 Polymerase Chain Reaction: A Method
that Has Revolutionized Molecular Biology 100
3.1.3.6 Analysis of the P Globin Gene 102
The Paradigmatic Role of the fi Globin Gene
3.1.3.7 Structure of the Factor VIII (Antihemophilic Factor) Gene 102
Antihemophilic Factor (Factor VIII) Research Strategy in Elucidating
the Factor VIII Gene Significance of These Studies An Exercise in
the Sociology of Science
3.1.3.8 The Gene of Huntington Disease (HD) 106
Analysis Prevalence and Mutation Rate Practical Questions Sociological
Observations Comparison of the Three Analyses
3.1.3.9 Positional Cloning 109
Chronic Granulomatous Disease A Classical Example of Positional Cloning:
The Cystic Fibrosis Gene
3.1.3.10 Gene Families 113
Examples of Gene Families Genes for Actin and Myosin A New Principle
in Genetic Analysis
3.1.3.11 Genetic Variability Outside Coding Genes 114
3.2 The Dynamic Genome 114
Movable Elements and Transposons Movable Elements in Bacteria
Transposable Elements in Eukaryotes Significance of Movable Elements
in Evolution? Movable Elements in the Human Genome? Gene Conversion
Does the Genome Fluctuate? How Constant Is the Genetic Information
and Its Transmission?
3.3 Attempts at Understanding Additional Aspects
of Chromatin Function 119
3.4 The Genome of Mitochondria 119
Structure and Function of Mitochondria The Genome of Mitochondria
DNA Polymorphism and the Question of Hereditary Diseases Due to
Mitochondrial Mutations
3.5 New Genetics and the Gene Concept 122
Intriguing Problems What Is a Gene? New Results on Structure
of Genes and Formal Genetics
Conclusions 123
References 124
4 Formal Genetics of Humans: Modes of Inheritance 129
4.1 Mendel s Modes of Inheritance and Their Application to Humans ... 129
4.1.1 Codominant Mode of Inheritance 130
4.1.2 Autosomal Dominant Mode of Inheritance 130 j
Late Manifestation, Incomplete Penetrance, and Variable Expressivity
Effect of Homozygosity on Manifestation of Abnormal Dominant Genes
Contents XVII
4.1.3 Autosomal Recessive Mode of Inheritance 134
Pseudodominance in Autosomal Recessive Inheritance
Compound Heterozygotes
4.1.4 X Linked Modes of Inheritance 137
X Linked Recessive Mode of Inheritance X Linked Dominant Mode
of Inheritance X Linked Dominant Inheritance with Lethality of the
Male Hemizygotes Genes on the Y Chromosome
4.1.5 Lethal Factors 140
Animal Models Lethals in Humans
4.1.6 Modifying Genes 141
Modifying Genes in the ABO Blood Group System Sex Limiting Modifying
Genes Modification by the Other Allele Modification by Variation in
Related Genes Modification by a DNA Polymorphism Within the Same Gene
4.1.7 Genomic Imprinting and Anticipation 142
4.1.8 Total Number of Conditions with Simple Modes
of Inheritance Known So Far in Humans 144
Difference in the Relative frequencies of Dominant and Recessive
Conditions in Humans and Animals?
4.1.9 Diseases Due to Mutations in the Mitochondrial Genome 145
Leber Optical Atrophy Deletions Diseases of Advanced Age
4.2 Hardy Weinberg Law and Its Applications 147
4.2.1 Formal Basis 147
Derivations from the Hardy Weinberg Law
4.2.2 Hardy Weinberg Expectations Establish the Genetic Basis
of ABO Blood Group Alleles 150
Multiple Allelisms Genetics of the ABO Blood Groups Meaning
of a Hardy Weinberg Equilibrium
4.2.3 Gene Frequencies 153
One Gene Pair: Only Two Phenotypes Known
4.3 Statistical Methods in Formal Genetics:
Analysis of Segregation Ratios 153
4.3.1 Segregation Ratios as Probabilities 153
4.3.2 Simple Probability Problems in Human Genetics 154
Independent Sampling and Prediction in Genetic Counseling
Differentiation Between Different Modes of Inheritance
4.3.3 Testing for Segregation Ratios Without Ascertainment Bias:
Codominant Inheritance 155
Dominance
4.3.4 Testing for Segregation Ratios: Rare Traits 155
Principal Biases Methods for Correcting Bias
4.3.5 Discrimination of Genetic Entities: Genetic Heterogeneity 157
Genetic Analysis of Muscular Dystrophy as an Example Multivariate Statistics
XVIII Contents 4.3.6 Conditions Without Simple Modes of Inheritance 158
Empirical Risk Figures Selecting and Examining Probands and Their
Families Statistical Evaluation, Age Correction Example Theoretical
Risk Figures Derived from Heritability Estimates?
Conclusions 160
References 160
5 Formal Genetics of Humans:
Linkage Analysis and Gene Clusters 163
5.1 Linkage: Localization of Genes on Chromosomes 163
5.1.1 Classic Approaches in Experimental Genetics:
Breeding Experiments and Giant Chromosomes 163
Linkage and Association
5.1.2 Linkage Analysis in Humans 164
Direct Observation of Pedigrees Statistical Analysis The Use oflod Scores
Recombination Probabilities and Map Distances The Sib Pair Method
Results for Autosomal Linkage, Sex Difference, and Parental Age Information
from Chromosome Morphology
5.1.3 Linkage Analysis in Humans:
Cell Hybridization and DNA Techniques 170
First Observations on Cell Fusion First Observation of Chromosome Loss in
Human Mouse Cell Hybrids and First Assignment of a Gene Locus Other
Sources of Information for Gene Localization DNA Polymorphisms and Gene
Assignment Gene Symbols To Be Used Present Status of Gene Localization
and Assignment to Autosomes Linkage ofX Linked Gene Loci Genetic and
Physical Map of the Homologous Segment ofX and Y Chromosomes The Y
Chromosome Linkage Analysis with Genetically Ill Defined, Quantitative
Traits? DNA Variants in Linkage Practical Application of Results from
Linkage Studies
5.2 Gene Loci Located Close to Each Other
and Having Related Functions 176
5.2.1 Some Phenomena Observed in Experimental Genetics 176
Closely Linked Loci May Show a Cis Trans Effect Explanation in Terms
of Molecular Biology A Number of Genes May Be Closely Linked
5.2.2 Some Observations in the Human Linkage Map 176
Types of Gene Clusters that Have Been Observed
Clusters Not Observed So Far
5.2.3 Why Do Gene Clusters Exist? 178
They Are Traces of Evolutionary History Duplication and Clustering
May Be Used for Improvement of Function
5.2.4 Blood Groups: Rh Complex (111700), Linkage Disequilibrium 178
History Fisher s Hypothesis of Two Closely Linked Loci Confirmation and
Tentative Interpretation of the Sequential Order Molecular Basis Linkage
Disequilibrium
5.2.5 Major Histocompatibility Complex 180
History Social Phenomenon: Formation of a Paradigm Group Main
Components of the MHC on Chromosome 6 Complement Components
Significance ofHLA in Transplantation Linkage Disequilibrium
The Normal Function of the System
5.2.6 Genes with Related Functions on the Human X Chromosome? 187 )
Contents XIX
5.2.7 Unequal Crossing Over 188
Discovery of Unequal Crossing Over Unequal Crossing Over
in Human Genetics First Event Consequences of Unequal
Crossing Over Intrachromosomal Unequal Crossing Over
Conclusions 191
References 191
6 Formal Genetics of Humans:
Multifactorial Inheritance and Common Diseases 195
6.1 Levels of Genetic Analysis 195
6.1.1 Findings at the Gene DNA Level 195
6.1.1.1 Analysis at the Gene Product Biochemical Level 195
6.1.1.2 Analysis at the Qualitative Phenotypic Level:
Simple Modes of Inheritance 196
Rare Conditions Qualitatively Different from the Normal
Frequent Variants; Bimodal Distribution
6.1.1.3 Genetic Analysis at the Quantitative Phenotypic Biometric Level . . . 200
Additive Model
6.1.1.4 Heritability Concept 205
6.1.1.5 An Example: Stature 207
6.1.1.6 Quantitative Genetics and the Paradigms of Mendel and Galton .... 208
Paradigms of Mendel and Galton: Explanatory Power
6.1.2 Multifactorial Inheritance in Combination with a Threshold Effect .. 210
6.1.2.1 Description of the Model 210
Animal Experiments
6.1.2.2 Simple Theoretical Model 212
6.1.2.3 How Should the Model Be Used for Analysis of Data? 212
Qualitative (or Semiquantitative) Criteria for Multifactorial Inheritance
Quantitative Criteria Comparison of Genetic Models
6.1.2.4 If the Statistical Analysis Gives No Clear Answer,
How Should We Decide? 215
6.1.2.5 Radiation Induced Dominant Skeleton Mutations in the Mouse:
Major Gene Mutations that Would Not Be Discovered in Humans . . . 216
6.1.2.6 Isolation of Specific Genetic Types with Simple Diallelic Modes
of Inheritance Using Additional, Phenotypic Criteria 216
6.1.2.7 How Can an Apparently Multifactorial Condition Be Analyzed
Further, When Special Types with Simple Modes of Inheritance
Cannot be Isolated? 217
A Complex Functional Defect is Caused by a Combination of Small
Aberrations A Multifactorial System Comprises a General Disposition
that May Lead to a Group of Related Diseases: Specific Dispositions
Influencing the Clinical Manifestation Pattern
XX Contents
6.2 Genetic Polymorphism and Disease 218
6.2.1 New Research Strategy 218
6.2.2 Disease Association of the Blood Groups 219
6.2.2.1 ABO Blood Groups 219
Wrong Hypothesis Leads to an Important Discovery Statistical Standard
Method A Flood of Investigations and Their Results Possible Biases
Failure to Find a Mechanism
6.2.2.2 The Kell System 222
Kell System Mutations, Acanthocytosis, and Chronic Granulomatous Disease
6.2.3 The HLA System and Disease 223
Probable Mechanisms of HLA Disease Associations Linkage and Association
6.2.4 aj Antitrypsin Polymorphism and Disease 226
a^Antitrypsin Polymorphism Association with Chronic Obstructive
Pulmonary Disease Significance of the New Research Strategy
Disease Associations of Other Polymorphisms
6.3 Nature Nurture Concept: Twin Method 228
6.3.1 Historical Remarks 228
6.3.2 Basic Concept 229
6.3.3 Biology of Twinning 229
Dizygotic Twins Monozygotic Twins Frequency of Twinning Factors
Influencing Frequency of Twin Births: Maternal Age and Birth Order Genetic
Factors Decrease in Twin Births in Industrialized Countries Frequencies
of Multiple Births of More than Two Children
6.3.4 Limitations of the Twin Method 232
Systematic Differences Between Twins and Nontwins
Peculiarities of the Twin Situation in Postnatal Life
6.3.5 Diagnosis of Zygosity 235
6.3.6 Application of the Twin Method to Alternatively
Distributed Characteristics 235
Case Reports Accumulated Case Reports Limited Representative
Sampling Unlimited Representative Sample
6.3.7 An Example: Leprosy in India 235
6.3.8 Twin Studies in Other Common Diseases 237
6.3.9 Twin Method in Investigating Continuously
Distributed Characteristics 238
Heritability Estimates from Twin Data
6.3.10 Meaning of Heritability Estimates: Evidence from Stature 238
Increase in Stature During the Past Century
Lesson to Be Learned from This Example
6.3.11 Twin Family Method 239
6.3.12 Co Twin Control Method 240
Contents XXI
6.4 Contribution of Human Genetics to Concepts and a Theory of Disease 240
6.4.1 General Principles 240
The Concepts of Disease and Diagnosis Diseases with Simple Causes
Genetics of Diabetes Mellitus Disease Concepts and Diagnosis Normal
Variation and Disease
6.4.2 Current Status of the Genetics of Common Diseases 244
6.4.2.1 Biological and Pathophysiological Approaches
to the Genetic Etiology of Common Diseases 245
Heterogeneity Analysis: Differentiation ofMonogenic Subtypes from the
Common Varieties Clinical Population Genetics Polymorphism and Disease
Heterozygotes for Rare Diseases May Be More Susceptible to a Functionally
Related Common Disease
6.4.2.2 Genetics of Coronary Heart Disease 246
Risk Factors Hyperlipidemias Familial Hypercholesterolemia Familial
Combined Hyperlipidemia Familial Hypertriglyceridemia Broad Beta
Disease of Type III Hyperlipoproteinemia (Remnant Removal Disease)
High Density Lipoprotein
6.4.2.3 Lipid Related Polymorphisms 248
Apolipoprotein E Polymorphism Lipoprotein (a) Polymorphism
6.4.2.4 Associations of Coronary Heart Disease with Genetic Markers 249
Protein Markers DNA Markers In Population Association Studies
Homocystein and Atherosclerosis Other Genetic Factors Implications
Conclusions 251
References 252
7 Gene Action: Genetic Diseases 257
7.1 Aspects of the Problem 257
Gene Action and Genetic Strategies Hereditary Diseases as Analytical
Tools for the Elucidation of Gene Action The Sequence of Problems To Be
Discussed
7.2 Genes and Enzymes 258
7.2.1 One Gene/One Enzyme Hypothesis 258
Early Forerunners Beadle s and Tatum s Simple Organism and Method of
Attack First Enzyme Defects in Humans Steps in Understanding Human
Enzyme Defects
7.2.2 Genes and Enzymes in Humans: Present State of Knowledge 261
Scope and Limitations of this Review
7.2.2.1 Discovery and Analysis of Enzyme Defects 261
Difference in Research Strategy Between Humans and Neurospora Clinical
Symptoms Leading to the Detection of Enzyme Defects Clinical Diagnosis
of Metabolic Defects Methods Used for Analysis of Enzyme Defects
Examination of Enzyme Defects in Human Fibroblast Cultures
7.2.2.2 Typical Group of Enzyme Defects: Erythrocyte Enzymes 263
Enzyme Defects in Glycolysis Nonspherocytic Hemolytic Anemias Enzyme
Defects in the Glycolytic Pathway Blood Is Readily Available for Examination
XXII Contents Analysis at the Enzyme Level Reveals Genetic Heterogeneity Residual Activity
Is Found Among Homozygotes In Almost All Enzyme Defects Clinical Findings
Caused by an Enzyme Defect Depend on the Normal Activity of This Enzyme in
a Variety of Different Tissues Pyruvate Kinase Deficiency Enzyme Activities
and Clinical Symptoms in Heterozygotes Aerobic Energy Production in the Red
Cell: Hexose Monophosphate Pathway Deficiency of Glucose 6 Phosphate
Dehydrogenase Difference Between the African and Mediterranean Variants
More Detailed Characterization of G6PD Variants G6PD Variants Observed
in Human Populations More Incisive Biochemical and Molecular Analysis
Clinical Significance Significance ofG6PD Variants for Understanding Human
Enzyme Deficiencies Phenocopy of a Genetic Enzyme Defect: Glutathione
Reductase Deficiency Other Enzyme Defects
7.2.2.3 Mucopolysaccharidoses 272
Deficiencies ofLysosomal Enzymes Mucopolysaccharidoses: Clinical
Picture Lysosome Storage and Urinary Excretion Biochemistry ofSulfated
Glycosaminoglycans Enzyme Deficiencies Consequences for Understanding
Genetic Heterogeneity Differential Diagnosis and Treatment of Mucopoly¬
saccharidoses Defect of a Recognition Marker for Lysosomal Hydrolases
Gaucher Disease (270800), a Glycolytic Storage Disease
7.2.2.4 Enzyme Defects Involving More than One Enzyme 279
Maple Syrup Urine Disease (Branched Chain Ketoaciduria) Other
Metabolic Defects Involving More Than One Enzyme A Fresh View
on the One Gene/One Enzyme (or One Gene/One Polypeptide) Hypothesis
7.2.2.5 Influence of Cofactors on Enzyme Activity 281
Enzyme Cofactors Folk Acid Dependency (229030, 249300, 229050):
Deficiencies in Transport and Coenzyme Formation Pyridoxine (Vitamin BJ,
Dependency
7.2.2.6 X Linked HPRT Deficiencies 282
Enzyme Defects as Tools for Some Basic Questions on Gene Action and
Mutation Lesch Nyhan Syndrome Molecular Heterogeneity Evidence
for X Inactivation Metabolic Cooperation Other Problems Examined
with HPRT Deficiency Immune Deficiency Diseases Associated
with Adenosine Deaminase and Nucleoside Phosphorylase Defects
7.2.2.7 Phenylketonuria: Paradigm for Successful Treatment
of a Metabolic Disease 285
Metabolic Oligophrenia Enzyme Defect in PKU Dietary
Treatment of PKU Genetic Heterogeneity of PKU
7.2.2.8 Heterozygote Detection 288
Heterozygote Detection for PKU and Hyperphenylalaninemia Health
Status of Heterozygotes Heterozygote Detection in General
Susceptibility to Common Diseases in Heterozygotes of Recessive Conditions
Heterozygote Testing in Hemophilia A and B and in Duchenne and Becker
Muscular Dystrophies Problems with Heterozygote Detection
7.2.2.9 Treatment of Inherited Metabolic Disease 292
General Principles Substitution (Protein or Enzyme) Therapy
Environmental Manipulation: Removal of a Metabolite Ahead of the Block
Environmental Manipulation: Substitution of a Metabolite Behind the Block
Elimination of the Metabolite Ahead of the Block and Substitution of the
Metabolite Behind the Block Treatment by Removing Secondary Effects
of the Metabolic Defect Dietary Treatment of Metabolic Diseases May Be Only
the Extreme of a More General Genetotrophic Principle
Contents XXIII
7.2.2.10 Enzyme Defects That Have Not Been Discovered 297
How Many Enzymes Are There and What Enzyme Defects Are Known?
What Enzyme Defects Are Not Known? Why Do We Know so Little About
Enzyme Defects of Central Building Functions?
7.2.2.11 Some General Conclusions Suggested by Analysis
of Human Enzyme Defects 298
Detection of Enzyme Defects Elucidation of Metabolic Pathways by Use
of Enzyme Defects Characteristics of Mutations Leading to Enzyme Defects
in Humans Mode of Inheritance and Heterozygotes
7.3 Human Hemoglobin 299
7.3.1 History of Hemoglobin Research 299
Sickle Cell Anemia: A Molecular Disease Single Amino Acid Substitution
7.3.2 Genetics of Hemoglobins 301
Hemoglobin Molecules Hemoglobin Genes Regulatory Elements
Downstream Sequences DNA Polymorphisms at the Globin Genes
Hemoglobin Variants Clinical Effects of Hemoglobin Variants Unstable
Hemoglobins Methemoglobinemia Due to HbM Erythrocytosis Due to
Hemoglobins with Abnormal Oxygen Affinity Sickle Cell Disorders
7.3.3 Other Types of Hemoglobin Mutations 310
Deletions Duplications
7.3.4 Thalassemias and Related Conditions 313
/? Thalassemia: Transcription or Promoter Mutations RNA Cleavage
and Polyadenylation Mutations Terminator (Nonsense) and Frameshift
Mutations RNA Processing Mutations Splice Mutations Deletion
Mutations at the Hb /S Globin Gene Cluster and Hereditary Persistence of Fetal
Hemoglobin Clinical Implications a Thalassemia: Deletion a Thalassemia
Hb a Nondeletion Thalassemia a Thalassemia and Mental Retardation
7.3.5 Population Genetics of Hemoglobin Genes (see also Sect. 12.2.1.6) .. 323
7.3.6 Screening and Prenatal Diagnosis of Hemoglobinopathies 324
Hemoglobin as a Model System
7.4 The Defense System 325
7.4.1 The Function of B Lymphocytes and the Formation of Antibodies .. 327
Myeloma Proteins as Research Tools Classes of Immunoglobulins
Constant and Variable Parts Common Origin of the Genes for All Chains
Genetic Determination of the Variable Chains Somatic Mutation or Selective
Activation of Genes? V Parts and the Specificity of Antibodies
7.4.2 T Cell Receptors and Their Genes 333
7.4.3 Genetic Diseases Due to Defects of Genes in the Defense System . . . 334
7.5 Pharmacogenetics and Ecogenetics 335
7.5.1 Pharmacogenetics 335
G6PD System Pseudocholinesterase (Butyrykholinesterase) Variation
Acetyltransferase Variation Debrisoquine Sparteine (CYP2D6) Polymorphism
Mephenytoin Polymorphism Other Monogenic Pharmacogenetic Traits
Multifactorial Pharmacogenetics Pharmacogenetic Variation at the Level
of the Target Organ
XXIV Contents 7.5.2 Ecogenetics 341
Carcinogens a^Antitrypsin Deficiency Paraoxonase Food
7.6 Mechanisms of Autosomal Dominance 345
7.6.1 Abnormal Subunit Aggregations 346
Dysfibrinogenemias
7.6.2 Disturbance of Multimeric Protein Function by Abnormal Subunits . 346
Hemoglobin Diseases
7.6.3 Abnormal Feedback Inhibition of Enzymes
and Structurally Abnormal Enzymes 347
Porphyria (176000): Decreased Enzyme Activity Increased Enzyme Activity
in Gout
7.6.4 Receptor Mutations 347
Receptors Familial Hypercholesterolemia
7.6.5 Membrane Defects 349
7.6.6 Deposition of Abnormal Fibrillar Proteins: Hereditary Amyloidoses . 349
Dominantly Inherited Alzheimer s Disease
7.6.7 Heritable Disorders of Connective Tissue 350
Myosin Genes and Dominant Hypertrophic Cardiomyopathy;
Disturbed Interaction of a Mutationally Altered Protein with Another Protein?
Prion Diseases
7.6.8 Dominantly Inherited Tumor Diseases 353
General Remarks
Conclusions 353
References 353
8 Gene Action: Developmental Genetics 361
8.1 Genetics of Embryonic Development 361
The Basic Problem of Developmental Genetics Gene Action in Eukaryotes,
Including Humans Function of Regulatory Mechanisms Alternative
Splicing Different Contribution of Maternal and Paternal Genotype to the
Child s Phenotype?
8.2 Genomic Imprinting 364
Prader Willi and Angelman Syndromes Transgene Expression
8.3 Transgenic Animals and Mouse Teratocarcinomas 367
8.3.1 Transgenic Animals and Related Methods 367
8.3.2 Mouse Teratocarcinomas as Research Tools
for Investigation of Early Development 368
8.4 Later Phases of Embryonic Development,
Phenocopies, Malformations 368
Indications for Interaction Between Genetic and Nongenetic Factors
in Malformation Production
Contents XXV
8.4.1 The Development of Structure 369
Syndromes Caused by Hox and Pax Genes in Humans
Timetable of Human Intrauterine Development
8.4.2 Birth Defects in Humans 370
8.4.3 Genotype Phenotype Relationships in Human
Chromosome Aberrations 374
Cellular Studies in Chromosome Aberrations Abnormal Phenotypes
Due to Chromosome Aberration and Gene Regulation
8.5 Sex Differentiation and Its Disturbances 376
Development of Sexual Dimorphism The Role of the SRYGene
Development of Secondary Sexual Characteristics Genetic
Control of Spermatogenesis: A Genetic Region on the Long Arm of the
Y Chromosome Testicular Feminization Syndrome Genetic Heterogeneity
Conclusions 380
References 380
9 Mutation: Spontaneous Mutation in Germ Cells 385
9.1 Reappraisal of Genetic Variants That May Occur by New Mutation . . 385
Genome Mutations Chromosome Mutations Gene Mutations
Cells in Which Mutations May Occur Mutation Rates
9.2 Genome and Chromosome Mutations in Humans 386
9.2.1 Mutation Rates 386
Methods Used Incidence and Mutation Rates: Genome Mutations
Incidence and Mutation Rates: Chromosome Mutations
9.2.2 Nondisjunction and the Age of the Mother 387
Statistical Evidence Higher Risk in Children of Very Young Mothers?
Age Specific Rates in Trisomies Maternal Age Effect in Other Trisomies
9.2.3 In Which Sex and at Which Meiotic Division
Does Nondisjunction Occur? 390
Evidence for the X Chromosome from X Linked Marker Studies
Direct Evidence from Chromosome Variants and DNA Polymorphisms
Use of Chromosomal Variants and DNA Markers
for Identification of Nondisjunction
9.2.4 Nondisjunction, Chromosome Variants, and Satellite Association . . . 392
Satellite Association Thyroid Disease and Antithyroid Antibodies
Do Thyroid Autoantibodies and Autoimmune Disease Also Enhance
the Risk for Other Aneuploidiesf
9.3 Gene Mutation: Analysis at the Phenotype Level 393
9.3.1 Methods for Estimating Mutation Rates 394
Direct Method Danforth s Formula Haldane s Indirect Method
for Mutation Rate Calculation Practical Problems in Applying
the Indirect Method Mutation Rates Cannot Be Estimated
for Autosomal Recessive Diseases
9.3.2 Results on Mutation Rates 398
Estimates Based on Population Surveys Achondroplasia Myotonic
dystrophy Retinoblastoma Acrocephalosyndactyly (Apert Syndrome)
Osteogenesis Imperfecta Tuberous Sclerosis Neurofibromatosis Marfan
XXVI Contents syndrome Polycystic disease of the kidneys X linked Recessive Conditions
Duchenne Type of Muscular Dystrophy Incontinentia Pigmenti Are These
Mutation Rates Representative of Comparable Mutations in the Human
Genome? Do These Mutation Rates Encompass the Total Mutability of the
Gene Loci Concerned? In What Context Should Human Mutation Rates
Involving Dominant or X Linked Phenotypes Be Investigated? Rates of
Mutation of Genes Not Leading to Hereditary Diseases
9.3.3 Mutation Rate and Age of the Father 402
One of Weinberg s Brilliant Ideas Watson Crick Model Stimulated
New Research on Paternal and Maternal Age Influences Cell Divisions
During Germ Cell Development in Both Human Sexes Early Development
Oogenesis Spermatogenesis Increase in Mutation Rate with Paternal Age
Other Dominant Mutations for Which a Paternal Age Effect Is Possible
Mutations Leading to Unstable Hemoglobins or Hemoglobin M and Paternal
Age Some Dominant Mutations Show Only a Small Paternal Age Effect
Another X Linked Disorder: Lesch Nyhan Syndrome
9.3.4 Possible Sex Difference in Mutation Rates 407
Sex Difference in the Mutation Rate for Hemophilia A Hemophilia B
Ornithine Transcarbamylase Deficiency Likely Higher Mutation Rate
in Male Germ Cells Causing the Lesch Nyhan Syndrome Fragile X Syndrome
No Sex Difference in Mutation Rates in Duchenne Muscular Dystrophy
Indirect Evidence for a Higher Mutation Rate in Male Germ Cells
Sex Difference in Mutation Rates of the Mouse Statistical Results and
Mutation Mechanisms
9.3.5 Germ Cell and Somatic Cell Mosaics for Dominant
or X Linked Mutations 410
Pedigree Observations Somatic Mosaicism Half Chromatid Mutations?
9.4 Gene Mutation: Analysis at the Molecular Level 411
9.4.1 Nucleotide and Codon Mutation Rates 411
First Examination of This Problem Estimate with More Direct Data
How Do Nucleotide Mutation Rates Compare with Estimates at the Phenotype
Level?
9.4.2 Various Molecular Types of Mutation 413
Single Base Pair Substitutions Transitions Are Especially Common
Mutation Mechanisms, Paternal Age Effect, and Sex Difference Deletions
Deletions and Sex Ratio of Mutation Rates Molecular Mechanisms of Deletions
Insertions, Duplications, and Inversions Mutations Leading to Hereditary
Diseases by DNA Triplet Expansion DNA Triplet Expansion Origin of the
Mutations Biological Function of Trinucleotide Repeats
9.4.3 Mutations in Micro organisms: Their Contribution
to Understanding of Human Mutation 423
Mutations as Errors of DNA Replication Mutator Genes Mutationlike
Events Due to Extranuclear Entities Such as Viruses and Transposons
9.5 Examination of Gene Mutations in Single Cells 424
First Attempt to Examine Mutations Occurring In Vitro
Examination of Mutant Cells In Vitro
Conclusions 426
References 426
10 Mutation: Somatic Mutation, Cancer, and Aging 431
10.1 Formation of Mosaics for Genome Mutations 431
Mechanism of Mosaic Formation in Early Cleavage
Contents XXVII
10.2 Hereditary Syndromes with Increased Chromosome Instability .... 431
Fanconi Anemia Bloom Syndrome Ataxia Telangiectasia
Chromosome Instability and Cancer
10.3 Molecular Mechanisms of Chromosomal Instability
and Tumor Formation Due to Somatic Mutation 434
10.3.1 Xeroderma Pigmentosum 434
Mechanisms ofDNA Repair Enzyme Defects in Xeroderma Pigmentosum
like Diseases Genetic Heterogeneity Malignant Neoplasias in Patients
with Xeroderma Pigmentosum Increased Cancer Risk in Heterozygotes
10.3.2 Molecular Mechanisms in Syndromes with Enhanced
Chromosome Instability 437
Chain of Events in the Formation of Malignant Neoplasias
by Somatic Mutation
10.4 Other Observations Suggesting Somatic Mutation
as a Mechanism in Carcinogenesis 439
History of the Somatic Mutation Hypothesis of Cancer Virus Etiology
Versus Somatic Mutation? Elucidation of the Origin of Malignant
Tumors as a Surplus Bonus of Genetic Theory
10.4.1 Neoplasias with Constant Chromosomal Aberrations 440
The Philadelphia Chromosome Chromosomal Patterns in Other Leukemias
10.4.2 Oncogenes 442
Basic Principles Cellular Transformation Oncogenes Involved
in Carcinogenesis Due to Chromosomal Rearrangements
10.4.3 Tumor Suppressor Genes 445
Retinoblastoma Mutations Necessary to Create a Malignant Cell Clone
Genetic Syndromes Associated with Tumors A Combination of Mutations
in Oncogenes and Tumor Suppressor Genes: Polyposis and Colon Cancer
10.4.4 A Genetic View of Human Cancer 451
10.5 Somatic Mutation and Aging 452
Aging and Death Studies on Biological Mechanisms of Aging in Single
Cells Molecular and Chromosomal Mechanisms
Conclusions 454
References 454
11 Mutation: Induction by Ionizing Radiation and Chemicals 457
Public Interest in Induced Mutation
11.1 Radiation Induced Mutation 457
11.1.1 Basic Facts and the Problems Posed by Them 457
Capacity of Energy Rich Radiation to Induce Mutation Some Technical
Remarks on Radiation Results and Concepts of Classic Radiation Genetics
Confirmation and Extension of These Results Influence of the Chemical
Environment, Especially the O2 Content of Irradiated Tissue Molecular Effects
of Radiation Basic Facts of Radiation Genetics Reconfirmed in Human
Lymphocyte Chromosomes
XXVIII Contents ^_^^
11.1.2 Problem of Estimating the Genetic Risk Due
to Radiation and Other Environmental Mutagens 461
Principles of Mutagenicity Testing In Vivo Test Systems for Mutagenic
Agents in Germ Cells of the Mouse Multiple Recessive Mutation Method
Test Systems for Somatic Mutations Methods from Molecular Genetics
11.1.3 Results of Radiation Mutagenicity Testing in Mammals 465
General Effects of Radiation on Mammalian Germ Cells Chromosome
Mutations in Male and Female Germ Cells of Mice Direct Evidence
of the Outcome of Induced Chromosome Aberrations Radiation Induced
Genome and Chromosome Mutations: Sensitivity of Certain Cell Stages
Radiation Induced Gene Mutation in the Male Germ Line Dose Rate Effect
Doubling Dose Population Experiments with Mice and Other Mammals
Conclusions from Mouse Radiation Genetics for Genetic Hazards to Humans
11.1.4 Human Population Exposure to Ionizing Radiation 469
Natural Background Radiation Additional Irradiation Due to Modern
Civilization
11.1.5 How Much of an Increase in the Spontaneous Mutation Rate
Must Be Anticipated? 471
How Many Additional Mutations Per Dose Are Induced? Phenotypic
Characteristics in Irradiated Human Populations Survivors of Atomic Bombs
in Hiroshima and Nagasaki Shift in Sex Ratio Due to X Linked Lethals?
Support for the Sex Ratio Shift by Studies After Exposure to X Rays
A Reassessment Using Additional Data and Methods The Chernobyl Accident
Irradiation of Parents for Medical Reasons and Trisomy 21 in Children
Higher Incidence of Structural Chromosome Anomalies and Down Syndrome
in Human Populations Exposed to High Background Radiation?
11.1.6 Evidence of Somatic Chromosome Mutations
After Exposure to Radiation 476
Medical Therapy Professional Exposure Atomic Bomb Survivors
Neoplastic Disease in Atomic Bomb Survivors
11.1.7 Projected Additional Mutations Per Dose 477
Autosomal Dominant and X Linked Recessive Diseases Autosomal Recessive
Diseases Chromosomal Diseases Congenital Anomalies and Multifactorial
Diseases How Many Naturally Occurring Spontaneous Mutations Are
Caused by Natural Background Radiation?
11.2 Chemically Induced Mutations 483
11.2.1 Extent of the Problem 483
History Mutagenic Compounds in the Human Environment Testing for
Mutagenesis by Chemical Compounds Has Now Become a Field of Toxicology
Ames Test as a Screening Test for Carcinogens?
11.2.2 How Widely Is the Human Population Exposed to the Agent? 486
An Important but Sometimes Neglected Question Population Exposure
to a Frequently Used Drug Population Exposure to Highly Mutagenic Drugs
Similar Studies Are Needed for Other Chemicals
11.2.3 How High an Increase in the Spontaneous Mutation Rate
Must Be Anticipated Due to Chemical Mutagens? 487
Chemically Induced Versus Radiation Induced Mutations Monitoring of
Human Populations for Increased Mutation Rates Present Social Attitudes
Toward Mutagenicity Testing Medical and Social Significance of Various
Types of Mutations
Conclusions 490
References 491
Contents XXIX
12 Population Genetics: Description and Dynamics 495
12.1 Population Description 496
12.1.1 Hardy Weinberg Law: Extended Consideration Gene Frequencies . . 496
Hardy Weinberg Law for Autosomal Genes Hardy Weinberg Law
for X Linked Genes Gene Frequencies
12.1.2 Genetic Polymorphisms 497
Definition and History Present Situation Biochemical Individuality
for Polymorphisms What Is the Proportion of Polymorphic Human Gene
Loci? Rare Variants Genetic Polymorphisms of Other (e.g., Structural)
Proteins DNA Polymorphisms Types ofDNA Polymorphism Applications
ofDNA Marker Studies Mitochondrial DNA Polymorphisms
12.1.3 Hereditary Diseases 504
Dominant and X Linked Recessive Diseases Autosomal Recessive Diseases
Phenylketonuria (2616000) and Hyperphenylalaninemia Other Conditions
High Frequencies of Recessive Diseases in Special Populations DNA Haplotypes
and Recessive Mutations Population Genetics of the PHA Gene Population
Genetics of the CFTR Gene
12.2 Systematic Changes in Gene Frequencies: Mutation and Selection . . . 508
12.2.1 Natural Selection 508
12.2.1.1 Mathematical Selection Models: Darwinian Fitness 508
Scope of Mathematical Models in Selection Theory and Their Limitations
Deterministic and Stochastic Models: Use of Computers How Should Models
Be Used in Practice? Concept of Darwinian Fitness
12.2.1.2 Selection Leading to Changes in Gene Frequencies
in One Direction 509
Symbols Used Elimination of Heterozygous Dominant Phenotypes
Partial Elimination of Autosomal Dominants Selection Relaxation
Selection Relaxation in Retinoblastoma Selection by Complete Elimination
of Homozygotes Partial Elimination of Homozygotes Gametic Selection
12.2.1.3 Selection Leading to a Genetic Equilibrium 514
Selection in Favor of Heterozygotes with Selective Disadvantage of Both
Homozygotes Heterozygote Advantage: Formal Consequences
12.2.1.4 Selection Leading to an Unstable Equilibrium 514
Selection Against Heterozygotes Pericentric Inversions Selection Against
Rh Heterozygotes ABO Blood Group System
12.2.1.5 Other Modes of Selection 517
Frequency Dependent Selection Frequency Dependent Selection in
Combination with Linkage Disequilibrium Density Dependent Selection
Kin Selection Selection for Continuously Distributed, Multifactorially
Determined Characters
12.2.1.6 Selection Due to Infectious Diseases 520
Selection Due to Infectious Diseases in Historical Populations History
of Some Infectious Diseases Distribution of Sickle Cell Gene and Other
Abnormal Hemoglobin Genes in the World Population Differential Mutation
Rates to HbS? Malaria Hypothesis Evidence for the Malaria Hypothesis
Some Other Aspects of the Malaria Hypothesis What Will Happen if the
Advantage of Heterozygotes Disappears? Population Genetics 0JG6PD Variants
and Falciparum Malaria In Vitro Studies of Malarial Growth in Red Cells
Ascertaining and Measuring of Selection in Humans
XXX Contents ________
12.2.1.7 Natural Selection and Population History:
HbE and 0 Thalassemia 528
Interaction of Two Abnormal Hemoglobin Genes in a Population
Distribution of HbE and Thalassemia HbE and Malaria Fitness of the
Genotypes Involving HbE and Thalassemia: Problem of a Genetic Equilibrium
Population Dynamics ofHbfiE and HbfiT Selection Relaxation Implications
of These Results for the Population History of Southeastern Asia Comparison
with HbfiS in Western Africa Hemoglobin /?£ in the Austroasiatic
(Mon Khmer) Language Group Some General Conclusions from the Studies
on HbE and Thalassemia Refinement of Analysis by Study ofDNA
Polymorphisms Studies on Sickle Cell Polymorphism in Africa: A Stochastic
Model for Replacement of One Allele by Another a+ Thalassemia and Malaria
in Melanesia
12.2.1.8 Selection in the ABO Blood Group System
and in Other Polymorphisms 533
ABO Blood Groups and Disease ABO Blood Groups and Infectious Disease
Distribution of ABO Alleles in the World Population Syphilis and Blood
Group 0 Cholera and Blood Group 0 Plague and Blood Group 0 Does
a Common Blood Group Antigen of the Microorganism Impair the Immune
Reaction of the Host? E. coli and Infectious Diarrheas ABO Blood Groups
and Smallpox Association Studies on Smallpox Patients Yield Contradictory
Results Blood Group A and Smallpox in the World Population Distribution
of ABO Blood Group Genes in the World Population and Selection by Infectious
Diseases Lesson of Studies on ABO Blood Group Selection for Research on
Natural Selection in Human Populations Genetic Susceptibilities and
Infectious Diseases Natural Selection by Infectious Agents Is Likely for the
MHC Polymorphism Does Genetic Liability to Atopic Diseases Lead to an
Increased Resistance to Helminth Infestation? Interaction Between the
Human Host and Infective Agents
Conclusions 545
References 545
13 Population Genetics: Consanguinity, Genetic Drift 549
13.1 Deviations from Random Mating 549
13.1.1 Consanguineous Matings 549
13.1.1.1 Inbreeding Coefficient 549
All Human Beings Are Relatives Degrees of Relationship Normally Consid¬
ered Two Useful Measures: Coefficient of Kinship and Inbreeding Coefficient
Coefficient of Inbreeding and the Hardy Weinberg Law Calculation of the
Inbreeding Coefficient F Examples Inbreeding Coefficient of a Population
13.1.1.2 Inbreeding and Inherited Disease 552
Frequency of Children with Recessive and Multifactorial Diseases in
Consanguineous Matings Compared with Nonconsanguineous Matings
Inbreeding Coefficient F in Various Population Groups Decline in
Consanguinity in Industrial Countries Social and Psychological Influences
on the Frequency of Consanguineous Marriages Influence of the Decline
of Consanguinity on the Incidence of Recessive Diseases
13.1.2 Concept of Genetic Load 559
13.1.2.1 Theory 559
Estimation of the Overall Number of Recessive Genes in the Human
Population Intuitive Background: Our Load of Mutations Effect of Variation
on Fitness Definition of the Genetic Load An Example Estimate
Contents XXXI
of the Expressed Genetic Damage Estimate of the Overall Mutation Rate
of Detrimental Mutations Impact of the Genetic Load Concept on Human
Population Genetics Discussions and Controversies Concerning the Load
Concept
13.1.2.2 Practical Applications of the Theory 562
Attempts to Assess the Genetic Load by Consanguinity Studies Recessive
Diseases and Congenital Malformations in the Offspring of Consanguineous
Marriages Other Parameters Showing an Inbreeding Effect: Cognitive
Abilities Overall Estimate ofZygote Loss Due to Parental Consanguinity
13.1.2.3 Critical Evaluation 565
Theoretical Interpretation Medical Evidence
13.1.2.4 More Direct Approaches for Calculating the Number
of Deleterious Recessive Genes Per Individual 566
Studies on Children from Incestuous Matings Consanguinity in Parents
of Severely Mentally Retarded Children Alternative Approach for
Calculating the Average Number of Deleterious Recessive Genes in Humans
Consanguinity Effects and the Level of Genetic Analysis Effect of
Long Standing Inbreeding
13.2 Differentiation Between Population Subgroups 569
13.2.1 Genetic Distance 569
Real Mating Structure of Human Populations Population History or Selection?
Methods for Determining Genetic Distances
13.2.2 Gene Flow 570
Effects of Migration on Gene Frequencies Migration and Selection
Measuring the Admixture of Genes to a Population Subgroup Rationale for
Measuring the Admixture of Genes to a Population Subgroup Estimates of the
Admixture of Genes from Whites to African Americans Evidence of Selection
13.3 Chance Fluctuations of Gene Frequencies 571
13.3.1 Genetic Drift 571
Deterministic and Stochastic Models Island Model A More General Case
Decay of Variability
13.3.2 Genetic Drift in Co operation with Mutation and Selection 573
Mutation Fate of a New Mutation Selection Mutation and Selection
Together Rare Inherited Diseases in Human Isolates Example: Mai de Meleda
Other Examples Rare Flora in Rare Soil : Hereditary Diseases in Finland
Population History of Finland Recessive Disorders in Finland Conclusions from
the Experience in Finland for Research in Population Genetics of Rare Disorders
Conclusions 580
References 580
14 Human Evolution 583
14.1 Paleoanthropological Evidence 583
Population Genetics Helps To Understand Evolution
Evidence from Paleoanthropology
14.2 Genetic Mechanisms of Evolution of the Human Species 583
14.2.1 Chromosome Evolution and Speciation 585
Chromosome Number of Humans and Closely Related Nonhuman Primates
Comparison of Chromosome Structure with Banding Methods Example
XXXII Contents Comparison of Overall Karyotypes of the Five Species Presence and Absence
of Certain Segments Chromosome Rearrangements in Evolution and
in the Current Population Selective Advantage of High Rate of Spontaneous
Miscarriage in Humans? Homologies of Chromosomes and Chromosomal
Segments Between Humans and Other, More Remotely Related Species
How Can a Chromosome Rearrangement Become Fixed in a Population?
Development of Chromosome Bands Direct DNA Studies in Human and
Animal Fossils
14.2.2 Comparison of Satellite DNA in Higher Primates 593
Human Satellite DNA Comparison with Chromosome Evolution
14.2.3 Protein Evolution 594
Protein Sequences Phylogenetic Tree for Hemoglobin Genes Rates
of Evolution for Different Proteins Gene Duplications Evolution of Genes
for Protein Domains Advantageous or Neutral Mutations? Arguments
Against General Applicability of the Neutral Hypothesis Genetic Sufficiency
Limitations of Present Knowledge of Natural Selection and Neutral Substitutions
in the Evolution of Proteins Evolutionary Clock and Mutation Special
Problems Posed by Highly Variable DNA Polymorphisms Evolution by
Reshuffling ofExons Comparison of the Protein Data with Data from
Chromosome Evolution and Satellite DNA
14.2.4 DNA Polymorphisms and Evolution 602
A Phylogenic Tree of Mitochondrial DNA
14.2.5 Behavior 604
Man the Toolmaker Social Structure of Early Prehuman and Human
Groups Precursors of Language and Cultural Tradition in Apes and
Monkeys Behavioral Characteristics of Humans in Common with Other
Species Human Sodobiology Similarities and Differences Between Humans
and Animals: The Problem of Emergence
14.2.6 Investigation of Current Primitive Populations 608
Problems for Which Primitive Populations Could Provide Evidence
Populations in Which These Problems Have Been Studied Size of Population
Groups and Isolation Population Control Natural Selection Due to
Differential Fertility Balance by Disease Can These Observations on a Few
Indian Tribes Be Generalized? Relaxation of Selection
14.3 Genetics of Group Differences Within the Human Species 610
14.3.1 Races 610
Race Classification Genetic Differences Between Races How Did the
Genetic Race Differences Evolve? Genetic Differences That Can Be Explained
by Specific Selective Mechanisms: Skin Pigmentation and Ultraviolet Light
Frequency of the Fy~ Allele in Blacks Lactose Restriction and Persistence
Lactose Restriction and Malabsorption What Is Normal? What Is Abnormal?
Natural Selection Vitamin D and GC Serum Groups Possible Selective
Mechanisms for Other Racial Characteristics
14.3.2 Future of Human Races: Racial Crossing 617
Will Races Disappear? Interracial Crosses in Hawaii Scope of the Study
and Data Results and Interpretation Questions Not Answered by the
Hawaii Study
Conclusions 618
References 618
Contents XXXIII
15 Behavioral Genetics: Research Strategies and Examples 623
Scope and Conceptual Difficulties of Human Behavior Genetics Practical
Difficulties and Possible Resolution Importance of the Field Paradigms
of Mendel and Galton in Behavioral Genetics
15.1 Animal Models 624
15.1.1 Research in Insects 624
Dialects in the Language of Bees Genetic Dissection of Behavior
in Drosophila Mouse Mutants Affecting Embryonic Development of the
Brain What Can We Learn from Drosophila Experiments for a Genetic
Analysis of Human Behavior?
15.1.2 Behavioral Genetic Experiments in the Mouse 626
An Example of a Single Gene Abnormality: The Obese Mouse. Inferences to
Human Obesity Genetic Differences in Alcohol Uptake Learning Ability
Simple Mode of Inheritance for Conditioned Avoidance Learning Heredity
and Environment in Maze Learning Psychosexual Behavior Must Also be
Learned Attempts at Elucidating the Biological Mechanisms of Behavior
Differences Possible Significance of Experiments with Mice and Other
Mammals for Behavioral Genetic Analysis in Humans
15.2 Behavioral Genetics in Humans 631
Normal and Abnormal Behavior Observation and Measurement of Human
Behavior
15.2.1 Investigations with Classical Phenomenological Methods 632
15.2.1.1 Reappraisal of Classical Methods 632
Family Investigations Twin Method MZ Twins Reared Apart: Studies
on Adopted and Foster Children
15.2.1.2 Mental Retardation and Deficiency 633
Definition Incidence of Mental Subnormality Two Biological Groups
X Linked Mental Retardation (XLMR) X Linked Behavioral Disturbance
Rett Syndrome Mild or High Grade Mental Retardation Empirical Risk
Figures Twin Studies
15.2.1.3 Intelligence and Performance in the Normal and Superior Ranges . . 638
Superior Achievement Variability in the Normal Range: Nature
of Intelligence Intelligence and Intelligence Testing Growing Unease over
Intelligence Testing Among Psychologists New Approaches for a Better
Understanding of Human Intelligence Family and Twin Studies for Assessing
the Genetic Contribution to Normal Variability of Intelligence Success in
Schools Intelligence Tests in Families and Twins Heritability Estimates
Twin Study on Swedish Conscripts Twin Performance on IQ Test Is Lower
Than That of Singletons MZ Twins Reared Apart Overall Results of
Studies on MZ Pairs Reared Apart Studies on Adopted and Foster Children
Some Environmental Influences on Intelligence What Does the Available
Evidence Show Regarding Genetic Variability of Intelligence in the Normal
Range? Paradigm Clash also in Psychology Research on IQ and Politics
15.2.1.4 Special Cognitive Abilities and Personality 647
Special Cognitive Abilities Intelligence Is Not Everything Twin Data for
Temperament, Sensory and Motor Functions, and Personality Longitudinal
Study of Twins Possible Consequences for Educational Policy
15.2.1.5 Behavior and the Genetics of Human Sensation 650
Genetics of Scent Differences ( Olfactogenetics ) Visual Perception Genetics
of Color Vision The Rods: Hereditary Diseases Due to Genetically Abnormal
Rhodopsin Genetic Heterogeneity Why Does Autosomal Dominant
Retinitis Pigmentosa Occur? Tasting: the Role ofGustducin
XXXIV Contents 15.2.1.6 Abnormal and Socially Deviant Behavior 656
Criminality Homosexuality Neuroses Eating Disorders: Anorexia
Nervosa and Bulimia Gilles de la Tourette Syndrome
15.2.2 Chromosome Aberrations and Psychological Abnormalities 659
Human Chromosome Aberrations and Behavior: Possibilities and Limitations
15.2.2.1 Autosomal Aberrations 659
Down Syndrome Social Problems
15.2.2.2 Aberrations of the X Chromosome 660
Klinefelter Syndrome Klinefelter Variants Therapy and Prevention
Turner Syndrome Intelligence Defect in Turner Syndrome
Triple X Syndrome
15.2.2.3 XYY Syndrome 662
Somatic Symptoms Higher Prevalence Among Criminals Intellectual
Dysfunction or Simply Stature? Studies on Unbiased Samples Results
of the Study Social and Therapeutic Consequences What Can We Learn
from the XYY Story About the Attitude of Scientists in the Face of a Problem
of Great Public Concern? Chromosome Aberrations and Behavior: Some
General Conclusions Brain Morphology in Chromosomal Aberrations
A Common Morphological Substrate in Various Types of Mental Retardation?
15.2.3 Suggested Novel Approaches to Human Behavior Genetics 667
15.2.3.1 Genetic Variability That Could Influence Human Behavior 667
General Metabolism Variability of Hormones Genetic Variability
Within the Brain
15.2.3.2 Genetic Variability Outside the Brain That Influences
Human Behavior 670
Enzyme Defects Leading to Mental Deficiency Self Mutilating Behavior in the
Lesch Nyhan Syndrome: Uric Acid Hetewzygotes of Recessive Disorders
15.2.3.3 Hormone Action 672
How Do Hormones Act? Tomboyism in Girls Prenatally Exposed to
Masculinizing Compounds Testicular Feminization Homosexuality and
Hormones
15.2.3.4 Brain Physiology: Genetics of the EEG 674
Human EEG Twin Studies Family Studies Sex Difference in EEG Patterns
How Is the EEG Produced in the Brain? Influences of Inherited EEG Variations
on Personality Association Between a Waves and Spatial Ability Averaged
Evoked EEG Potentials
15.2.3.5 Genetic Aspects of Alcoholism 677
Animal Models Studies with Classic Methods: Family, Twin, and Adoption
Studies Psychiatric Symptoms Preceding Alcoholism Genetic Variability of
Alcohol Metabolism Reaction of the Brain to Alcohol as Measured by the
EEG Can Our Knowledge of Neurophysiological Mechanisms of the EEG
Explain the Differential Reaction to Alcohol?
15.2.3.6 Brain Physiology: Genetic Variability Affecting Neurotransmitters . . 681
Analysis at the Biochemical Level Is Needed: The Synopsis Chemical Types
of Neurotransmitters Catecholamines Animal Experiments on Genetic
Variability in Catecholamine Metabolism Psychotropic Drugs Possible
Genetic Variability at the Level of Receptors: Isoreceptors
Conclusions 683
References 684
Contents XXXV
16 Behavioral Genetics: Affective Disorders and Schizophrenia ... 693
16.1 Affective Disorders 693
Genetic Investigations in Affective Disorders and Schizophrenia Twin and
Family Studies of Affective Disorders Bipolar and Unipolar Types: Empirical
Risk Figures Simple Modes of Inheritance: Problems with Linkage Studies
Schizoaffective Disorder
16.2 Schizophrenia 697
Diagnosis and Epidemiology Twin and Family Studies in Schizophrenia
Empirical Risk Figures Adoption Studies in Schizophrenia Biological
Hypotheses in Schizophrenia Schizophrenia in the Light of Human
Genetics Research Strategies for Further Elucidation of the Genetic Basis of
Schizophrenia Critical Assessment of the Attempts to Relate Behavioral
Variability to Biochemical Differences in Brain Function
Conclusions 703
References 703
17 Behavioral Genetics: Differences Between Populations 705
Differences in IQ and Achievement Between Ethnic Groups Group Differences
in Behavioral Traits? Intelligence and Achievement of Ashkenazi Jews
Difference in Mean IQ Between Ethnic Groups in the United States,
Especially Between African Americans and Whites Explanation: Genetic or
Socioeconomic? Is All Research That Has Been Done in This Field Scientifically
and Socially Worthless? If Genetic Group Differences Did Indeed Exist,
Would They Suggest Any Consequences in Social Policy? Intermarriage
Conclusions 710
References 710
18 Genetic Counseling and Prenatal Diagnosis. Human Genome
Project 711
18.1 Genetic Counseling 711
Diagnosis Recurrence Risks Molecular Diagnosis Communication
Consanguinity Heterozygote Detection Reproductive Options and
Alternatives Detection of Genetic Diseases in Relatives Directive vs
Nondirective Genetic Counseling Assessment of Genetic Counseling and
Psychosocial Aspects
18.2 Prenatal Diagnosis 718
Amniocentesis Chorionic Villus Sampling Ultrasonography Fetoscopy
Maternal Blood Sampling Indications for Prenatal Diagnosis
18.3 Genetic Screening 724
Phenylketonuria Screening: Prevention of Mental Retardation Screening
Mothers at Risk for Chromosomal Malformations Screening for
Autosomal Recessive Traits Screening for Neural Tube Defects Extensive
Future Screening of All Newborns for Many Polymorphisms?
18.4 Human Genome Project 727
A Large Scale Science Project Advantages The First Initiative Methods
Research Organizations Human Diversity Project Ethical, Legal, and
Social Aspects
Conclusions 730
References 731
XXXVI Contents ____ , 19 Genetic Manipulations and the Biological Future
of the Human Species 733
19.1 Genetic Manipulation 733
Conservative Approach: Germinal Choice and Artificial Insemination Are
Large Scale Attempts at Breeding Human Beings by Such Methods Inevitable?
Molecular Biology and Speculations on Genetic Manipulation Induction of
Specific Mutations Gene Transfer and Expression in Eukaryotes Safety
19.2 Human Gene Therapy 736
Somatic Gene Therapy Germinal Gene Therapy Approaches to Gene Therapy
Vectors Indications for Gene Therapy: Monogenic Diseases Indications
for Gene Therapy: Other Diseases Impact Public Reaction to New
Achievements and Prospects of Molecular Biology Further Speculations on
Gene Manipulation The Need for a Dialogue on Ethical Issues
19.3 Biological Future of Mankind 741
Human Evolution Is Not Finished Major Forces Determining Evolution
Genetic Drift Mutation Trends in Spontaneous Mutation Rates: Chromosome
Mutations Gene Mutations Ionizing Radiation and Chemical Mutagens
Selection: Dominant and X Linked Diseases Natural Selection: Recessive
Diseases Gradual Loss of Functions That Are Now Being Maintained by
Multifactorial Genetic Systems Increase in the Number of Intellectual
Subnormals? A Favorable Selective Trend: Abandoning of Genetic Adaptations
with Otherwise Unfavorable Effects The Human Species in the Future
Conclusions 747
References 747
Appendix 1 Methods for Estimating Gene Frequencies 749
Appendix 2 Testing and Estimating Segregation Ratios; Correction of
Ascertainment Biases in Rare Diseases; Multifactorial and Mixed
Models; Related Statistical Problems 751
Appendix 3 Data Bases and Expert Systems 757
Appendix 4 Diagnosis of Zygosity 761
Appendix 5 Heritability Estimates from Twin Data 769
Appendix 6 Genetic Counseling 775
Appendix 7 Linkage Calculations: Programs and Examples 783
Appendix 8 Standardized Nomenclature for Human Genes 793
Further Reading 797
!ndex 807
|
| any_adam_object | 1 |
| author | Vogel, Friedrich 1925-2006 Motulsky, Arno G. 1923-2018 |
| author_GND | (DE-588)120928892 (DE-588)172265177 |
| author_facet | Vogel, Friedrich 1925-2006 Motulsky, Arno G. 1923-2018 |
| author_role | aut aut |
| author_sort | Vogel, Friedrich 1925-2006 |
| author_variant | f v fv a g m ag agm |
| building | Verbundindex |
| bvnumber | BV010716774 |
| callnumber-first | Q - Science |
| callnumber-label | QH431 |
| callnumber-raw | QH431 |
| callnumber-search | QH431 |
| callnumber-sort | QH 3431 |
| callnumber-subject | QH - Natural History and Biology |
| classification_rvk | WG 7000 |
| classification_tum | BIO 950f BIO 750f |
| ctrlnum | (OCoLC)33897787 (DE-599)BVBBV010716774 |
| dewey-full | 573.2/1 |
| dewey-hundreds | 500 - Natural sciences and mathematics |
| dewey-ones | 573 - Specific physiological systems in animals |
| dewey-raw | 573.2/1 |
| dewey-search | 573.2/1 |
| dewey-sort | 3573.2 11 |
| dewey-tens | 570 - Biology |
| discipline | Biologie |
| edition | 3., completely rev. ed. |
| format | Book |
| fullrecord | <?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>02007nam a2200553 c 4500</leader><controlfield tag="001">BV010716774</controlfield><controlfield tag="003">DE-604</controlfield><controlfield tag="005">20180122 </controlfield><controlfield tag="007">t</controlfield><controlfield tag="008">960401s1997 gw abd| |||| 00||| eng d</controlfield><datafield tag="016" ind1="7" ind2=" "><subfield code="a">946121257</subfield><subfield code="2">DE-101</subfield></datafield><datafield tag="020" ind1=" " ind2=" "><subfield code="a">3540602909</subfield><subfield code="9">3-540-60290-9</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(OCoLC)33897787</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)BVBBV010716774</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-604</subfield><subfield code="b">ger</subfield><subfield code="e">rakddb</subfield></datafield><datafield tag="041" ind1="0" ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="044" ind1=" " ind2=" "><subfield code="a">gw</subfield><subfield code="c">DE</subfield></datafield><datafield tag="049" ind1=" " ind2=" "><subfield code="a">DE-355</subfield><subfield code="a">DE-29</subfield><subfield code="a">DE-29T</subfield><subfield code="a">DE-19</subfield><subfield code="a">DE-20</subfield><subfield code="a">DE-M49</subfield><subfield code="a">DE-12</subfield><subfield code="a">DE-M489</subfield><subfield code="a">DE-188</subfield><subfield code="a">DE-578</subfield></datafield><datafield tag="050" ind1=" " ind2="0"><subfield code="a">QH431</subfield></datafield><datafield tag="082" ind1="0" ind2=" "><subfield code="a">573.2/1</subfield><subfield code="2">20</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">WG 7000</subfield><subfield code="0">(DE-625)148612:</subfield><subfield code="2">rvk</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">BIO 950f</subfield><subfield code="2">stub</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">BIO 750f</subfield><subfield code="2">stub</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Vogel, Friedrich</subfield><subfield code="d">1925-2006</subfield><subfield code="e">Verfasser</subfield><subfield code="0">(DE-588)120928892</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Human genetics</subfield><subfield code="b">problems and approaches</subfield><subfield code="c">F. Vogel ; A. G. Motulsky</subfield></datafield><datafield tag="250" ind1=" " ind2=" "><subfield code="a">3., completely rev. ed.</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="a">Berlin [u.a.]</subfield><subfield code="b">Springer</subfield><subfield code="c">1997</subfield></datafield><datafield tag="300" ind1=" " ind2=" "><subfield code="a">XXXVI, 851 S.</subfield><subfield code="b">Ill., graph. Darst., Kt.</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="b">n</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="b">nc</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="500" ind1=" " ind2=" "><subfield code="a">4. Aufl. u.d.T.: Vogel and Motulsky's Human genetics</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">Antropogenetica</subfield><subfield code="2">gtt</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">Genetica</subfield><subfield code="2">larpcal</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Genetik</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Genetik, tıbbi</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">İnsan genetiği</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Genetics</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Genetics, Medical</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Human genetics</subfield></datafield><datafield tag="650" ind1="0" ind2="7"><subfield code="a">Erbkrankheit</subfield><subfield code="0">(DE-588)4015106-2</subfield><subfield code="2">gnd</subfield><subfield code="9">rswk-swf</subfield></datafield><datafield tag="650" ind1="0" ind2="7"><subfield code="a">Humangenetik</subfield><subfield code="0">(DE-588)4072653-8</subfield><subfield code="2">gnd</subfield><subfield code="9">rswk-swf</subfield></datafield><datafield tag="689" ind1="0" ind2="0"><subfield code="a">Humangenetik</subfield><subfield code="0">(DE-588)4072653-8</subfield><subfield code="D">s</subfield></datafield><datafield tag="689" ind1="0" ind2=" "><subfield code="5">DE-604</subfield></datafield><datafield tag="689" ind1="1" ind2="0"><subfield code="a">Erbkrankheit</subfield><subfield code="0">(DE-588)4015106-2</subfield><subfield code="D">s</subfield></datafield><datafield tag="689" ind1="1" ind2=" "><subfield code="5">DE-604</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Motulsky, Arno G.</subfield><subfield code="d">1923-2018</subfield><subfield code="e">Verfasser</subfield><subfield code="0">(DE-588)172265177</subfield><subfield code="4">aut</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="m">HBZ Datenaustausch</subfield><subfield code="q">application/pdf</subfield><subfield code="u">http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=007156252&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA</subfield><subfield code="3">Inhaltsverzeichnis</subfield></datafield><datafield tag="999" ind1=" " ind2=" "><subfield code="a">oai:aleph.bib-bvb.de:BVB01-007156252</subfield></datafield></record></collection> |
| id | DE-604.BV010716774 |
| illustrated | Illustrated |
| indexdate | 2024-07-09T17:57:44Z |
| institution | BVB |
| isbn | 3540602909 |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-007156252 |
| oclc_num | 33897787 |
| open_access_boolean | |
| owner | DE-355 DE-BY-UBR DE-29 DE-29T DE-19 DE-BY-UBM DE-20 DE-M49 DE-BY-TUM DE-12 DE-M489 DE-188 DE-578 |
| owner_facet | DE-355 DE-BY-UBR DE-29 DE-29T DE-19 DE-BY-UBM DE-20 DE-M49 DE-BY-TUM DE-12 DE-M489 DE-188 DE-578 |
| physical | XXXVI, 851 S. Ill., graph. Darst., Kt. |
| publishDate | 1997 |
| publishDateSearch | 1997 |
| publishDateSort | 1997 |
| publisher | Springer |
| record_format | marc |
| spelling | Vogel, Friedrich 1925-2006 Verfasser (DE-588)120928892 aut Human genetics problems and approaches F. Vogel ; A. G. Motulsky 3., completely rev. ed. Berlin [u.a.] Springer 1997 XXXVI, 851 S. Ill., graph. Darst., Kt. txt rdacontent n rdamedia nc rdacarrier 4. Aufl. u.d.T.: Vogel and Motulsky's Human genetics Antropogenetica gtt Genetica larpcal Genetik Genetik, tıbbi İnsan genetiği Genetics Genetics, Medical Human genetics Erbkrankheit (DE-588)4015106-2 gnd rswk-swf Humangenetik (DE-588)4072653-8 gnd rswk-swf Humangenetik (DE-588)4072653-8 s DE-604 Erbkrankheit (DE-588)4015106-2 s Motulsky, Arno G. 1923-2018 Verfasser (DE-588)172265177 aut HBZ Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=007156252&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Vogel, Friedrich 1925-2006 Motulsky, Arno G. 1923-2018 Human genetics problems and approaches Antropogenetica gtt Genetica larpcal Genetik Genetik, tıbbi İnsan genetiği Genetics Genetics, Medical Human genetics Erbkrankheit (DE-588)4015106-2 gnd Humangenetik (DE-588)4072653-8 gnd |
| subject_GND | (DE-588)4015106-2 (DE-588)4072653-8 |
| title | Human genetics problems and approaches |
| title_auth | Human genetics problems and approaches |
| title_exact_search | Human genetics problems and approaches |
| title_full | Human genetics problems and approaches F. Vogel ; A. G. Motulsky |
| title_fullStr | Human genetics problems and approaches F. Vogel ; A. G. Motulsky |
| title_full_unstemmed | Human genetics problems and approaches F. Vogel ; A. G. Motulsky |
| title_short | Human genetics |
| title_sort | human genetics problems and approaches |
| title_sub | problems and approaches |
| topic | Antropogenetica gtt Genetica larpcal Genetik Genetik, tıbbi İnsan genetiği Genetics Genetics, Medical Human genetics Erbkrankheit (DE-588)4015106-2 gnd Humangenetik (DE-588)4072653-8 gnd |
| topic_facet | Antropogenetica Genetica Genetik Genetik, tıbbi İnsan genetiği Genetics Genetics, Medical Human genetics Erbkrankheit Humangenetik |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=007156252&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT vogelfriedrich humangeneticsproblemsandapproaches AT motulskyarnog humangeneticsproblemsandapproaches |