An Introduction to Human Molecular Genetics: Mechanisms of Inherited Diseases

by Jack J. Pasternak (Univ. of Waterloo, Ontario, Canada)

• ISBN13: 9781891786037
• ISBN10: 1891786032
• Format: Hardcover
• Copyright: 1999-01-01
• Publisher: Wiley-Liss

Summary

This text is targeted at upper-level undergraduate students, graduate students, and medical students. It is also an excellent reference for researchers and physicians who need a clinically relevant reference for the molecular genetics of inherited human diseases.

Author Biography

Jack J. Pasternak, Ph.D. is Professor of Biology at the University of Waterloo, Ontario, Canada.

Table of Contents

Preface	xv
PART I Fundamentals of Genetics	1	(80)
Understanding Human Disease	3	(18)
Human Genetic Disease	4	(3)
Human Genetics from 1900 to 1957	7	(8)
Eugenics: Genetics Misinterpreted	11	(2)
The Molecularization of Genetics	13	(2)
Genes and Phenotypes	15	(2)
from the human genetics files OMIM: An Important Online Source of Information about Human Genetic Disorders	15	(2)
key terms	17	(1)
summary	17	(1)
references	18	(1)
review questions	19	(2)
The Genetic System: Chromosomes	21	(20)
Human Chromosomes	22	(5)
Maintaining the Chromosome Number	22	(1)
Cell Division Cycle: The Mitotic Process	22	(3)
The Meiotic Process	25	(2)
Characterizing Human Chromosomes	27	(4)
Chromosome Abnormalities	31	(7)
Whole Chromosome Changes: Aneuploidy	31	(1)
Chromosome Structural Changes	32	(2)
from the human genetics files Discovering the Phases of the Cell Cycle	34	(4)
key terms	38	(1)
summary	38	(1)
references	39	(1)
review questions	40	(1)
The Genetic System: Mendel's Laws of Inheritance and Genetic Linkage	41	(40)
Dominance, Recessiveness, and Segregation	42	(3)
Independent Assortment	45	(3)
Genetic Linkage	48	(4)
Constructing Genetic Maps	52	(4)
Three-Point Cross	53	(3)
Chi-Square Distribution: Testing for Significance	56	(3)
Multiple Alleles	59	(1)
Human Genetics	60	(10)
Autosomal Dominant Inheritance	62	(1)
Autosomal Recessive Inheritance	62	(3)
X-Linked Inheritance	65	(1)
Using Pedigrees to Study Human Genetic Disorders	66	(4)
Detection and Estimation of Genetic Linkage in Humans	70	(1)
from the human genetics files Genetic Counseling	70	(1)
The Logarithm of the Likelihood Ratio Method of Linkage Analysis: LOD Score	71	(5)
Allele-Sharing Tests for Detecting Linkage	76	(1)
key terms	77	(1)
summary	78	(1)
references	79	(1)
review questions	79	(2)
PART II Principles of Human Molecular Genetics	81	(146)
The Molecular Biology of the Gene	83	(34)
Properties of Genetic Material	83	(1)
Structure of DNA	84	(3)
DNA Replication	87	(2)
Decoding Genetic Information: RNA and Protein	89	(4)
Translation	93	(5)
Regulation of mRNA Transcription	98	(3)
Nucleotide Sequence Alteration: Mutation	101	(3)
from the human genetics files Hemoglobinopathies and Thalassemias: An Abundance of Mutations	102	(2)
Mutations of Structural Genes	104	(5)
Nomenclature for Mutations	109	(2)
Dominant Mutations and Genetic Disorders	111	(2)
key terms	113	(1)
summary	113	(1)
references	114	(1)
review questions	115	(2)
Recombinant DNA Technology	117	(42)
Restriction Endonucleases	118	(4)
Cloning Vectors	122	(5)
Plasmid Cloning Vector pUC19	124	(3)
Screening DNA Constructs by DNA Hybridization	127	(3)
In situ Hybridization	130	(1)
Chemical Synthesis of DNA	131	(2)
Sequencing DNA	133	(4)
Polymerase Chain Reaction	137	(4)
Human-Rodent Somatic Cell Hybrids	141	(3)
Human DNA Libraries	144	(11)
Genomic Libraries	144	(3)
Chromosome DNA Libraries	147	(1)
Chromosome DNA Libraries from a Human Genome YAC Library	147	(2)
Chromosome Libraries from Flow-Sorted Chromosomes and Monochromosomal Hybrid Cell Lines	149	(1)
from the human genetics files Multicolor Karyotyping: Coloring Chromosomes	150	(3)
Region-Specific Chromosome Libraries	153	(1)
Constructing a cDNA Library	153	(2)
key terms	155	(1)
summary	155	(2)
references	157	(1)
review questions	158	(1)
Genetic and Physical Mapping of the Human Genome	159	(46)
Genetic Mapping of Human Chromosomes	160	(15)
Genetic Polymorphism	160	(1)
Restriction Fragment Length Polymorphism	160	(4)
Short Tandem Repeat Polymorphism	164	(2)
Mapping of a Genetic Disease Locus to a Chromosome Location	166	(4)
Multilocus Mapping of Human Chromosomes	170	(4)
Inserting a Disease Gene into a Linkage Map	174	(1)
Homozygosity Mapping	175	(2)
Linkage Disequilibrium Mapping	177	(4)
Radiation Hybrid Mapping	181	(4)
Physical Mapping of the Human Genome	185	(10)
Assembling Contigs from YAC, BAC, and PAC Libraries	185	(6)
Assembling Contigs from Cosmid, P1, and Lambda Libraries	191	(3)
from the human genetics files Single-Nucleotide Polymorphisms: The Next Generation of Genetic Markers	194	(1)
Transcriptional Mapping	195	(1)
Integration of Cytogenetic, Genetic, and Physical Maps	196	(1)
The Human Genome Project	197	(3)
Ethical, Legal, and Social Implications	198	(2)
key terms	200	(1)
summary	200	(1)
references	201	(2)
review questions	203	(2)
Discovering Human Disease Genes	205	(22)
Detection of Mutations in Human Genes	206	(11)
Single-Strand Conformational Analysis	206	(1)
Denaturing Gradient Gel Electrophoresis	207	(3)
Heteroduplex Analysis	210	(2)
Chemical Mismatch Cleavage	212	(2)
Direct DNA Sequencing	214	(1)
from the human genetics files Genomic Analyses Using DNA Microarrays	214	(1)
Protein Truncation Test	215	(2)
Cloning Human Disease Genes	217	(8)
Functional Gene Cloning	217	(1)
Candidate Gene Cloning	218	(1)
Positional Gene Cloning	219	(5)
Positional-Candidate Gene Cloning	224	(1)
key terms	225	(1)
summary	225	(1)
references	226	(1)
review questions	226	(1)
PART III Molecular Genetics of Diseases and Disorders	227	(224)
Molecular Genetics of Muscle Disorders	229	(28)
Structure of Skeletal Muscle	230	(2)
Dystrophin and Associated Muscle Proteins	232	(1)
Cardiac and Smooth Muscle	233	(1)
Studying Inherited Muscle Disorders	233	(1)
Duchenne Muscular Dystrophy	234	(6)
Discovering the DMD Gene	235	(4)
Dystrophin and Mutations of the DMD Gene	239	(1)
Limb-Girdle Muscular Dystrophy	240	(1)
Congenital Muscular Dystrophy	241	(2)
Dilated Cardiomyopathy	243	(2)
Hypertrophic Cardiomyopathy	245	(2)
Facioscapulohumeral Muscular Dystrophy	247	(1)
Emery-Dreifuss Muscular Dystrophy	248	(1)
Myotubular Myopathy	249	(3)
from the human genetics files Detecting Gene Mutations	250	(2)
Nemaline Myopathy	252	(1)
key terms	252	(1)
summary	253	(1)
references	254	(2)
review questions	256	(1)
Molecular Genetics of Neurological Disorders	257	(50)
Neurons	258	(2)
Nonneuronal Cells of the Nervous System	260	(1)
Resting Membrane Potential	260	(1)
Initiation, Propagation, and Synaptic Transmission of a Nerve Impulse	261	(3)
Parts of the Brain	264	(3)
Alzheimer Disease	267	(9)
Biochemistry of Senile Plaques and Neurofibrillary Tangles	268	(3)
Genetics of Alzheimer Disease	271	(1)
Mutations of the Amyloid Precursor Protein Gene	271	(2)
Mutations in the Presenilin Genes	273	(1)
Genetic Risk Factors for Alzheimer Disease	274	(2)
Huntington Disease and Other Trinucleotide Repeat Expansion Diseases	276	(8)
Amyotrophic Lateral Sclerosis	284	(2)
Charcot-Marie-Tooth Disease	286	(4)
from the human genetics files Genetically Engineered Animal Models for Studying Inherited Human Disorders	288	(2)
Inherited Prion Diseases	290	(3)
Schizophrenia	293	(6)
Genetic Analysis of Schizophrenia and Other Complex Traits	295	(2)
Possible Genes and Chromosome Loci for Schizophrenia	297	(2)
Bipolar Affective Disorder	299	(1)
Alcoholism	300	(1)
key terms	301	(1)
summary	302	(2)
references	304	(2)
review questions	306	(1)
Molecular Genetics of the Eye	307	(38)
Human Visual System	308	(5)
Structure of the Eye	308	(3)
Phototransduction: Conversion of Radiant Energy into Nerve Impulses	311	(2)
Studying the Molecular Basis of Inherited Disorders of the Human Eye	313	(1)
Genetic Disorders of the Human Eye	313	(18)
Corneal Dystrophies	313	(1)
from the human genetics files Searching for the Genetic Basis of Myopia	314	(1)
Glaucoma	315	(3)
Aniridia	318	(2)
Cataracts	320	(4)
Retinitis Pigmentosa	324	(5)
Congenital Stationary Night Blindness	329	(1)
Choroideremia	330	(1)
Color-Vision Defects	331	(6)
Isolation of Human Rhodopsin and Color Opsin Genes	332	(1)
Molecular Genetics of Red and Green Color-Vision Defects	333	(3)
Blue Cone Monochromacy	336	(1)
Blue Color--Vision Defect	337	(1)
Rod Monochromacy	337	(1)
key terms	337	(1)
summary	338	(1)
references	339	(4)
review questions	343	(2)
Molecular Genetics of Mitochondrial Disorders	345	(20)
Mitochondria and Oxidative Phosphorylation	345	(4)
Mitochondrial Genetics	349	(3)
from the human genetics files Revelations from the Grave: Using Mitochondrial DNA Analysis to Resolve Historical Mysteries	350	(2)
Mitochondrial Disorders	352	(5)
Myoclonus Epilepsy and Ragged-Red Fibers (MERRF)	352	(1)
Mitochondrial Encephalomyopathy with Lactic Acidosis and Stroke-like Episodes (MELAS)	353	(2)
Leber Hereditary Optic Neuropathy (LHON)	355	(1)
Neuropathy, Ataxia, and Retinitis Pigmentosa (NARP)	356	(1)
Kearns-Sayre Syndrome (KSS)	356	(1)
Nuclear-Encoded Mitochondrial Disorders	357	(4)
Mitochondrial Protein Importation Defects	357	(1)
Substrate Transport Defects	358	(1)
Substrate Utilization Defects	358	(1)
Iron Transport Defect	359	(1)
Electron Transport Chain Defect	359	(1)
Mitochondrial DNA Defects	360	(1)
key terms	361	(1)
summary	361	(1)
References	362	(1)
review questions	363	(2)
Molecular Genetics of Cancer Syndromes	365	(52)
Cell Proliferation and Cancer	366	(16)
Signal Transduction Pathway for Cell Proliferation	367	(4)
Regulation of the Cell Division Cycle	371	(3)
Apoptosis: Programmed Cell Death	374	(1)
Tumor Metastasis	374	(2)
Oncogenes	376	(4)
Alteration of Oncogenes in Cancer Cells	380	(1)
Tumor Suppressor Genes	380	(2)
Neurofibromatoses	382	(3)
Neurofibromatosis Type 1	382	(2)
Neurofibromatosis Type 2	384	(1)
Breast Cancer	385	(2)
Von Hippel-Lindau Syndrome	387	(3)
Retinoblastoma	390	(2)
from the human genetics files Philadelphia Chromosome, Two-Hit Hypothesis, and Comparative Genomic Hybridization	390	(2)
Wilms Tumor	392	(1)
Multiple Endocrine Neoplasia Type 1	393	(1)
Multiple Endocrine Neoplasia Type 2	393	(3)
Li-Fraumeni Syndrome	396	(2)
Colorectal Cancer	398	(7)
Familial Adenomatous Polyposis	399	(2)
Hereditary Nonpolyposis Colorectal Cancer	401	(4)
Ataxia-Telangiectasia	405	(1)
Bloom Syndrome	406	(3)
Fanconi Anemia	409	(2)
Xeroderma Pigmentosum	411	(1)
key terms	412	(1)
summary	413	(1)
references	413	(3)
review questions	416	(1)
Human Gene Therapy	417	(34)
Ex Vivo Gene Therapy	421	(5)
In Vivo Gene Therapy	426	(1)
Viral Gene Delivery Systems	426	(7)
Retrovirus Vector System	426	(1)
Adenovirus Vector System	427	(2)
Adeno-Associated Virus Vector System	429	(1)
Herpes Simplex Virus Vector System	430	(3)
Nonviral Gene Delivery Systems	433	(4)
from the human genetics files Some of the Social Implications of Human Gene Therapy	436	(1)
Prodrug-Activation Therapy	437	(2)
Nucleic Acid Therapeutic Agents	439	(8)
In Vivo Antisense RNA	441	(1)
Antisense Oligonucleotides	441	(2)
Nucleic Acid Pharmaceuticals	443	(1)
Ribozymes	444	(1)
Oligonucleotide Correction of Genetic Conditions	445	(2)
key terms	447	(1)
summary	447	(1)
references	448	(2)
review questions	450	(1)
Glossary	451	(32)
Index	483