Human Chromosomes

by Miller, Orlando J.; Therman, Eeva

• ISBN13: 9780387950464
• ISBN10: 038795046X
• Edition: 4th
• Format: Paperback
• Copyright: 2000-11-01
• Publisher: Springer Nature

Summary

The fourth edition of this well-known text provides students, researchers and technicians in the area of medicine, genetics and cell biology with a concise, understandable introduction to the structure and behavior of human chromosomes. It covers both basic and up-to-date material on normal and defective chromosomes. This new edition is particularly strengthened by the complete revision of the material on the molecular genetics of chromosomes and chromosomal defects. The mapping and molecular analysis of chromosomes is one of the most exciting and active areas of modern biomedical research, and this book will be invaluable to scientists, students, technicians and physicians with an interest in the function and dysfunction of chromosomes. From the reviews of the third edition: "Each word "tells" in this concise gem of a human cytogenetics text...Superb organization makes this an excellent text...for any cytogenetics course." American Journal of Human Genetics"...the leading textbook in English on human cytogenetics." Cell

Table of Contents

Preface	v
Origins and Directions of Human Cytogenetics	1	(12)
Origins: Cytology, Genetics, and DNA Chemistry	2	(1)
The Midwives of Human Cytogenetics	3	(1)
The Birth of Clinical Cytogenetics	4	(2)
The Lyon Hypothesis	6	(1)
Adolescence: The Chromosome Banding Era	6	(1)
Somatic Cell Genetics and Chromosome Mapping	7	(1)
Maturity: The Molecular Era	8	(2)
References	10	(3)
The Mitotic Cell Cycle	13	(16)
The Cell Cycle: Interphase, Mitosis, and Cytokinesis	14	(2)
Cell Cycle Progression: Cyclins and Cyclin-Dependent Kinases	16	(3)
Cell Cycle Checkpoints	19	(1)
Prophase	20	(2)
Prometaphase, Centrosomes, and the Mitotic Spindle	22	(1)
Metaphase, Anaphase, and Telophase	22	(2)
Nondisjunction, Loss of Chromosomes, and Mosaicism	24	(1)
References	25	(4)
DNA Replication and Chromosome Reproduction	29	(16)
Replication Is Semiconservative	29	(2)
The Chemistry of Replication	31	(2)
Initiation at Many Sites: Origins of Replication	33	(2)
Replication Is Precisely Ordered: Replication Banding	35	(3)
The Control of DNA Replication	38	(2)
Replication of Chromosome Ends: Telomerase and Cell Aging	40	(1)
Postreplication Steps: DNA Methylation and Chromatin Assembly	41	(1)
References	42	(3)
General Features of Mitotic Chromosomes	45	(16)
Metaphase Chromosomes	45	(2)
The Chromosome Complement and Karyotype	47	(1)
DNA Content and DNA-Based Flow Cytometric Karyotypes	48	(1)
Centromeres and Kinetochores	49	(5)
Telomeres	54	(1)
Nucleolus Organizers and Ribosomal RNA Genes	55	(1)
Constitutive and Facultative Heterochromatin	56	(1)
References	56	(5)
The Chemistry and Packaging of Chromosomes	61	(18)
DNA Content and the Estimated Number of Base Pairs in the Genome	62	(1)
Histone Proteins and the Nucleosome	62	(1)
The Chromosome Scaffold and Chromatin Loops	63	(4)
Chromosome Domains in the Interphase Nucleus	67	(1)
The Nuclear Matrix: Replication and Transcription Complexes	68	(2)
Locus Control Regions and Functional Domains	70	(1)
Euchromatin and Heterochromatin: Regulation of Gene Function	71	(1)
Histone Modifications, DNA Methylation, and Chromosome Condensation	72	(2)
References	74	(5)
Chromosome Bands	79	(16)
Q-banding	80	(1)
C-banding	81	(2)
G-banding, R-banding, and T-banding	83	(1)
High-Resolution and Replication Banding	84	(1)
Banding with Other Fluorochromes and Nonfluorochromes	85	(2)
Antibody Banding	87	(1)
Nuclease Banding	88	(1)
In Situ Hybridization Banding	89	(1)
Nomenclature of Banded Chromosomes and Abnormal Karyotypes	89	(3)
References	92	(3)
Molecular Correlates of Chromosome Bands	95	(12)
GC- and AT-Rich Isochores	95	(3)
Unmethylated CpG Clusters and Housekeeping and Tissue-Specific Genes	98	(1)
Interspersed Repetitive DNA Sequences and Transposable Elements	99	(1)
Tandemly Repetitive Elements: Telomeres, Centromeres, and Satellite DNAs	100	(1)
Chromosomal Proteins and Chromatin Conformation	101	(2)
Functional Significance of Chromosome Bands	103	(1)
References	103	(4)
In Situ Hybridization	107	(18)
In Situ Hybridization of Repetitive and Unique DNA Sequences	108	(1)
Fluorescence In Situ Hybridization	109	(5)
Replication Timing by Fish	114	(1)
Cloned, PCR-Generated, and In Situ-Generated Probes	114	(2)
Chromosome-, Region-, and Band-Specific Painting Probes	116	(1)
Multicolor Fish, Spectral Karyotyping, and Bar Codes	117	(1)
High-Resolution (Interphase and Fiber) Fish	118	(3)
Comparative Genomic Hybridization	121	(1)
References	121	(4)
Main Features of Meiosis	125	(16)
Prophase I: Leptotene, Zygotene, Pachytene, Diplotene, and Diakinesis	127	(5)
Chiasmata and Genetic Recombination	132	(1)
Metaphase I, Anaphase I, Telophase I, Interkinesis, and Meiosis II	133	(1)
Female Meiosis: Dictyotene Arrest, Metaphase II Arrest, and Apoptosis	134	(1)
Male Meiosis	135	(1)
Segregation Distortion and Meiotic Drive	136	(1)
Meiotic Behavior of Three Homologoue Chromosomes	137	(1)
References	138	(3)
Details of Meiosis	141	(16)
The Switch from Mitosis to Meiosis	141	(1)
Pairing of Homologous Chromosomes	142	(1)
The Synaptonemal Complex and Recombination Nodules	142	(3)
Nonrandom Distribution of Meiotic Recombination Sites	145	(1)
Molecular Mechanisms of Meiotic Recombination	146	(3)
Meiotic DNA Damage Checkpoint	149	(2)
Absence of a Spindle' Assembly Checkpoint in Female Meiosis: Role in Nondisjunction?	151	(1)
References	151	(6)
Meiotic Abnormalities: Abnormal Numbers of Chromosomes	157	(18)
Incidence of Nondisjunction in Meiosis and Gametes	159	(2)
Incidence of Nondisjunction in Spontaneous Abortions, Stillborns, and Liveborns	161	(3)
Causes of Meiotic Nondisjunction	164	(1)
Maternal Age, Recombination, and Mechanisms of Nondisjunction	164	(4)
Parental Origin of Aneuploid Gametes	168	(1)
The Origin of Diploid Gametes and Polyploidy	169	(1)
Aneuploidy of Somatic (Mitotic) Origin: Mosaicism	170	(1)
References	171	(4)
Abnormal Phenotypes Due to Autosomal Aneuploidy or Polyploidy	175	(12)
Trisomy 21 and Down Syndrome	176	(2)
Trisomy 18 and Edwards Syndrome	178	(1)
Trisomy 13 and Patau Syndrome	178	(2)
Other Autosomal Aneuploidy Syndromes	180	(1)
Trisomy/Disomy Mosaicism	180	(1)
Triploidy and Tetraploidy	181	(1)
Spontaneous Abortions, Fetal Deaths, and Stillbirths	182	(1)
References	183	(4)
Chromosome Structural Aberrations	187	(20)
Chromosome and Chromatid Breaks and Rearrangements	189	(2)
Deletrons (Partial Monosomies), Including Ring Chromosomes	191	(2)
Duplications (Partial Trisomies)	193	(2)
Misdivision of the Centromere: Centric Fusion and Centric Fission	195	(1)
Pericentric and Paracentric Inversions	196	(1)
Reciprocal Translocations	197	(2)
Robertsonian Translocations (RTs)	199	(1)
Intrachromosomal and Interchromosomal Insertions	200	(1)
Complex and Multiple Rearrangements	201	(1)
References	202	(5)
The Causes of Structural Aberrations	207	(16)
Exogenous Causes of Structural Aberrations	210	(2)
Endogenous Causes of Structural Aberrations	212	(1)
Transposable Elements and Other Interspersed Repeats	213	(2)
Interspersed Repeats as Hotspots for Double-Strand Breaks and Rearrangements	215	(2)
References	217	(6)
Syndromes Due to Autosomal Deletions and Duplications	223	(16)
Cri du Chat (Cat Cry) and Wolf-Hirschhorn Syndromes	224	(3)
Ring Chromosome Phenotypes	227	(1)
The Critical Regions for Deletion (Segmental Aneusomy) Syndromes	228	(3)
Miller-Dieker Syndrome	231	(1)
Di George/Velocardiofacial/CATCH22 Syndromes	231	(1)
Critical Region for the Charcot-Marie-Tooth Type 1A Duplication Syndrome	232	(1)
Critical Region for Down Syndrome	232	(2)
References	234	(5)
Clinical Importance of Translocations, Inversions, and Insertions	239	(16)
Phenotypes of Balanced Translocation Heterozygotes (Carriers)	239	(1)
Aberrant Meiotic Segregation in Reciprocal Translocation Carriers	240	(3)
Aberrant Meiotic Segregation in Robertsonian Translocation Carriers	243	(2)
Phenotypes Associated with Unbalanced Duplication/Deficiency Karyotypes	245	(2)
Phenotypes of Inversion Heterozygotes (Carriers)	247	(1)
Aberrant Meiotic Segregation in Inversion and Insertion Carriers	247	(2)
Sperm Chromosomes in Meiotic Segregation Analysis	249	(2)
References	251	(4)
Sex Determination and the Y Chromosome	255	(12)
The Y Chromosome and Y Heterochromatin: The Y Body	255	(2)
The Two Pseudoautosomal Regions	257	(2)
Sex Determination: Rearrangements Localized the Male-Determining Gene to Yp	259	(1)
SRY, the Only Male-Determining Gene on the Y Chromosome	260	(1)
Autosomal Genes Involved in Male Sex Determination or Differentiation	261	(1)
Other Genes on the Y Chromosome	262	(1)
References	263	(4)
The X Chromosome, Dosage Compensation, and X Inactivation	267	(16)
The Single Active X (Lyon) Hypothesis	269	(2)
Skewed X Inactivation	271	(1)
The Critical Region for X Inactivation: X Inactivation Center and the XIST Gene	272	(2)
Reactivation of the X Chromosome	274	(1)
Regions That Escape X Inactivation: Functional Map of the X Chromosome	274	(2)
XiAutosome Translocations and Spreading of Inactivation (Position Effect)	276	(2)
References	278	(5)
Phenotypic Effects of Sex Chromosome Imbalance	283	(12)
Turner Syndrome	284	(1)
Is There a Critical Region for Turner Syndrome?	285	(2)
Polysomy X	287	(1)
Klinefelter Syndrome	288	(1)
Phenotypes Associated with Multiple Y Karyotypes	288	(1)
Deletions and Duplications of the X Chromosome: Risks Associated with Hemizygosity	289	(2)
XiAutosome and YiAutosome Translocations	291	(1)
References	291	(4)
Fragile Sites, Trinucleotide Repeat Expansion, and the Fragile X Syndrome	295	(14)
Common Fragile Sites: Methods of Induction	296	(3)
Heritable (Rare) Fragile Sites	299	(1)
FRAXA, the Fragile X Syndrome, and the FMR1 Gene	300	(1)
The Fragile X Phenotype Reflects the Number of CCG Repeats	301	(1)
Mechanism of Expansion of Trinucleotide and Other Repeats	301	(1)
Expansion of CCG Premutation Only in Maternal Meiosis	302	(1)
Mechanism of Inactivation of the FMR1 Gene	303	(1)
Other Trinucleotide Expansion Disorders	303	(2)
References	305	(4)
Euploid Chromosome Aberrations, Uniparental Disomy, and Genomic Imprinting	309	(14)
Uniparental Disomy	309	(1)
Confined Placental Mosaicism and the Origin of UPD	310	(1)
UPD Can Lead to Homozygosity of a Recessive Disease Gene	311	(1)
UPD Can Lead to Disease Due to a Novel Mechanism: Genomic Imprinting	311	(2)
Three Imprinting Disorders: Beckwith-Wiedemann, Prader-Willi, and Angelman Syndromes	313	(2)
Chimeras, Triploidy, and Tetraploidy	315	(2)
Ovarian Teratomas: Both Genomes Maternal in Origin	317	(1)
Hydatidiform Moles: Both Genomes Usually Paternal in Origin	318	(1)
References	319	(4)
Chromosome Changes in Cell Differntiation	323	(16)
Programmed DNA Loss	324	(1)
Facultative Heterochromatin: Chromatin Structure and Gene Expression	324	(1)
Nature and Mechanism of Genomic Imprinting	325	(2)
Tissue-Specific Differences in X Inactivation	327	(1)
Germline-Specific Gene Expression and Sex-Specific Imprinting	328	(1)
Embryonic Inactivation of All but One Centromere per Chromosome	329	(2)
Endoreduplication, Polyploidy, and Polyteny	331	(2)
Triradials, Multiradials, and ICF Syndrome, a Hypomethylation Disorder	333	(2)
References	335	(4)
Somatic Cell Hybridization in Cytogenetic Analysis	339	(14)
Cell Fusion	340	(1)
Complementation Analysis in Heterokaryons	340	(1)
Premature Chromosome Condensation and Allocycly	341	(2)
Somatic Cell Hybrids	343	(2)
Preferential Human Chromosome Loss from Rodent-Human Hybrids	345	(2)
Induced Chromosome Breakage: Radiation Hybrids	347	(1)
Microcell Hybrids	347	(1)
Chromosome and Gene Transfer: Transgenomes and Transgenes	348	(1)
References	349	(4)
Chromosome Instability Syndromes	353	(16)
Bloom Syndrome	354	(2)
Mitotic Recombination or Crossing Over	356	(1)
Fanconi Anemia	357	(2)
Ataxia Telangiectasia: A Cell Cycle Checkpoint Disorder	359	(1)
Related Disorders with Chromosome Instability	360	(3)
References	363	(6)
DNA and Gene Amplification	369	(16)
Double Minutes and Homogeneously Stained Regions	370	(1)
DMs and HSRs Are Expressions of Gene Amplification	370	(4)
Mechanisms of Gene Amplification	374	(5)
How Does Gene Amplification Lead to Cancer?	379	(1)
References	379	(6)
Genome Destabilization and Multistep Progression to Cancer	385	(20)
Immortality of Transformed and Malignant Cells	386	(1)
Genetic Basis of Cancer: Sequential Chromosome or Gene Mutations	387	(2)
Clonal Origin, Selection, and Multistep Tumor Progression	389	(2)
Spindle Aberrations and Instability of Chromosome Number	391	(3)
The Major Mechanism of Spindle Aberrations and Heteroploidy	394	(1)
Structural Chromosome Changes	394	(1)
DNA Damage Checkpoint and Structural Instability of Chromosomes	395	(2)
Other Causes of Structural Instability of Chromosomes	397	(1)
Environmental Causes of Cancer	398	(1)
References	399	(6)
Chromosomes and Cancer: Activation of Oncogenes	405	(10)
Mechanisms of Oncogene Action	406	(1)
Reciprocal Translocations and Oncogene Activation	407	(2)
How Do Translocations Activate Cellular Oncogenes?	409	(2)
Amplification and Oncogene Activation	411	(2)
Relaxation of Imprinting and Oncogene Activation	413	(1)
References	413	(2)
Chromosomes and Cancer: Inactivation of Tumor Suppressor Genes	415	(16)
Tumor/Nontumor Cell Hybrids: First Evidence for Tumor Suppressor Genes	415	(2)
Allele Loss and Loss of Heterozygosity	417	(1)
Retinoblastoma and the Two-Hit Model of Carcinogenesis	417	(1)
Mechanism of Tumor Suppression by a Functional RB1 Gene	418	(1)
The p53 Tumor Suppressor Gene, TP53	419	(1)
Other Genes That Affect the Cell Cycle	420	(1)
Imprinted Tumor Suppressor Genes	421	(2)
Genes That Suppress Oncogenes or Influence Transcription	423	(2)
Genes That Affect Cell Adhesion	425	(1)
Metastasis Suppressor Genes	426	(1)
References	426	(5)
Mapping Human Chromosomes	431	(16)
Genetic Linkage Maps	432	(3)
Mapping Disease Genes: Family Studies with Genetic Markers	435	(1)
Assignment of Genes to Chromosomes: Synteny Groups	435	(2)
Physical Maps	437	(3)
The Human Genome Project	440	(3)
References	443	(4)
Genome Plasticity and Chromosome Evolution	447	(16)
Genome Plasticity	448	(3)
Evolution of the Autosomes	451	(1)
Evolution of the X and Y Chromosomes: Dosage Compensation	452	(4)
Evolution of Telomeric and Centromeric Regions	456	(1)
References	457	(6)
The Future of Human Cytogenetics	463	(12)
Unsolved Problems	464	(1)
Genome Organization	465	(4)
Directions	469	(1)
New Technology	470	(2)
References	472	(3)
Index	475