Introduction to Genomics 2nd Edition by Arthur Lesk ISBN 0198788668 9780198788664
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ISBN 10: 0198788668
ISBN 13: 9780198788664
Author: Arthur Lesk
Introduction to Genomics 2nd Edition Table of contents:
1 Introduction and Background
Learning goals
Genomics: the hub of biology
Phenotype = genotype + environment + life history + epigenetics
Varieties of genome organization
Chromosomes, organelles, and plasmids
Genes
The scope and applications of genome sequencing projects
Variations in genome sequences within species
Mutations and disease
Single-nucleotide polymorphisms
Haplotypes
A clinically important haplotype: the major histocompatibility complex
Populations
Species
The biosphere
Extinctions
The future?
Genome projects and our current library of genome information
High-throughput sequencing
De novo sequencing
Resequencing
Exome sequencing
What’s in a genome?
Some regions of the genome encode non-protein-coding RNA molecules
Some regions of the genome contain pseudogenes
Other regions contain binding sites for ligands responsible for regulation of transcription
Repetitive elements of unknown function account for surprisingly large fractions of our genomes
Dynamic components of genomes
Genomics and developmental biology
Genes and minds: neurogenomics
Genetics of behaviour
Proteomics
Protein evolution: divergence of sequences and structures within and among species
Mechanisms of protein evolution
Organization and regulation
Some mechanisms of regulation act at the level of transcription
Some mechanisms of regulation act at the level of translation
Some regulatory mechanisms affect protein activity
On the web: genome browsers
Genomics and computing
Archiving and analysis of genome sequences and related data
Databanks in molecular biology
Programming
Looking forward
Recommended reading
Exercises and problems
2 The Human Genome Project: Achievements and Applications
Learning goals
‘… the end of the beginning’
Human genome sequencing
What makes us human?
Comparative genomics
Genomics and language
The human genome and medicine
Prevention of disease
Detection and precise diagnosis
Genetic counselling—carrier status
Discovery and implementation of effective treatment
Tunable healthcare delivery: pharmacogenomics
‘Pop’ applications of genome sequencing
Genomics in personal identification
DNA ‘fingerprinting’
Personal identification by amplification of specific regions has superseded the RFLP approach
Mitochondrial DNA
Analysis of non-human DNA sequences
Parentage testing
Inference of physical features, and even family name
Ethical, legal, and social issues
Databases containing human DNA sequence information
Use of DNA sequencing in research on human subjects
Looking forward
Recommended reading
Exercises and problems
3 Mapping, Sequencing, Annotation, and Databases
Learning goals
Classical genetics as background
What is a gene?
Maps and tour guides
Genetic maps
Linkage
Linkage disequilibrium
Chromosome banding pattern maps
Restriction maps
Discovery of the structure of DNA
DNA sequencing
Frederick Sanger and the development of DNA sequencing
DNA sequencing by termination of chain replication
The Maxam–Gilbert chemical cleavage method
Automation of DNA sequencing
Organizing a large-scale sequencing project
Bring on the clones: hierarchical—or ‘BAC-to-BAC’—genome sequencing
Whole-genome shotgun sequencing
Next-generation sequencing
Roche 454 Life Sciences
Illumina
Ion Torrent/Personal Genome Machine (PGM)
PacBio
Oxford Nanopore
10X Genomics
The Bionano Irys system
Life in the fast lane
How much sequencing power is there in the world?
Databanks in molecular biology
Nucleic acid sequence databases
Protein sequence databases
Databases of genetic diseases—OMIM and OMIA
Databases of structures
Specialized or ‘boutique’ databases
Expression and proteomics databases
Databases of metabolic pathways
Bibliographic databases
Surveys of molecular biology databases and servers
Computer programming in genomics
Programming languages
How to compute effectively
Looking forward
Recommended reading
Exercises and problems
4. Evolution and Genomic Change
Learning goals
Evolution is exploration
Biological systematics
Biological nomenclature
Measurement of biological similarities and differences
Homologues and families
Pattern matching—the basic tool of bioinformatics
Sequence alignment
Defining the optimum alignment
Scoring schemes
Varieties and extensions
Approximate methods for quick screening of databases
Pattern matching in three-dimensional structures
Evolution of protein sequences, structures, and functions
Evolution of protein structure and function
Phylogeny
Calculation of phylogenetic trees
Short-circuiting evolution: genetic engineering
Looking forward
Recommended reading
Exercises and problems
5 Genomes of Prokaryotes and Viruses
Learning goals
Evolution and phylogenetic relationships in prokaryotes
Major types of prokaryotes
Do we know the root of the tree of life?
Genome organization in prokaryotes
Replication and transcription
Gene transfer
Archaea
The genome of Methanococcus jannaschii
Life at extreme temperatures
Comparative genomics of hyperthermophilic archaea: Thermococcus kodakarensis and pyrococci
Bacteria
Genomes of pathogenic bacteria
Genomics and the development of vaccines
Viruses
Nucleocytoplasmic large DNA viruses (or giant viruses)
Viral genomes
Recombinant viruses
Viruses and evolution
Influenza: a past and current threat
’Ome, ’ome, on the range: metagenomics, the genomes in a coherent environmental sample
Marine cyanobacteria—an in-depth study
Looking forward
Recommended reading
Exercises and problems
6 Genomes of Eukaryotes
Learning goals
The origin and evolution of eukaryotes
Evolution and phylogenetic relationships in eukaryotes
The yeast genome
The evolution of plants
The Arabidopsis thaliana genome
Genomes of animals
The genome of the sea squirt (Ciona intestinalis)
The genome of the pufferfish (Tetraodon nigroviridis)
The genome of the chicken (Gallus gallus domesticus)
The genome of the platypus (Ornithorhynchus anatinus)
The genome of the dog
Palaeosequencing—ancient DNA
Recovery of DNA from ancient samples
DNA from extinct birds
High-throughput sequencing of mammoth DNA
The phylogeny of elephants
Looking forward
Recommended reading
Exercises and problems
7 Comparative Genomics
Learning goals
Introduction
Unity and diversity of life
Taxonomy based on sequences
Sizes and organization of genomes
Genome sizes
Genome organization in eukaryotes
Photosynthetic sea slugs: endosymbiosis of chloroplasts
How genomes differ
Variation at the level of individual nucleotides
Duplications
Duplication of genes
Family expansion: G protein-coupled receptors
Comparisons at the chromosome level: synteny
What makes us human?
Comparative genomics
Genomes of chimpanzees and humans
Genomes of mice and rats
Model organisms for study of human diseases
The genome of Caenorhabditis elegans
The genome of Drosophila melanogaster
Homologous genes in humans, worms, and flies
Looking forward
Recommended reading
Exercises and problems
8 The Impact of Geno me Sequences on Human Health and Disease
Learning goals
Introduction
Some diseases are associated with mutations in specific genes
Haemoglobinopathies—molecular diseases caused by abnormal haemoglobins
Phenylketonuria
Alzheimer’s disease
Identification of genes associated with inherited diseases
Genome-wide association studies
GWAS of sickle-cell disease
GWAS of type 2 diabetes
GWAS of schizophrenia
The human microbiome
Treatment of abnormal microbiome composition
Cancer genomics
SNPs and cancer
Whole-genome sequencing association studies of breast cancer
Copy-number alterations in cancer
Chromosomal aberrations
Epigenetics and cancer
microRNAs and cancer
Immunotherapy for cancer
Looking forward
Recommended reading
Exercises and problems
9 Genomics and Anthropology: Human Evolution, Migration, and Domestication of Plants and Animals
Learning goals
Ancestry of Homo sapiens
The Neanderthal genome
The Denisovan genome
What do these data tell us?
What have Neanderthals and Denisovans done for us lately?
Ancient populations and migrations
Western civilization? ‘I think it would be a good idea’
Domestication of the dog
Domestication of the horse
Domestication of crops
Maize (Zea mays)
Rice (Oryza sativa)
Control of flowering time
History of rice domestication
Chocolate (Theobroma cacao)
The Theobroma cacao genome
Looking forward
Recommended reading
Exercises and problems
10 Transcriptomics
Learning goals
Introduction
Microarrays
Microarray data are semiquantitative
Applications of DNA microarrays
Analysis of microarray data
RNAseq
RNAseq versus microarrays
Expression patterns in different physiological states
Sleep in rats and fruit flies
Expression pattern changes in development
Variation of expression patterns during the life cycle of Drosophila melanogaster
Flower formation in roses
Expression patterns in learning and memory: long-term potentiation
Conserved clusters of co-expressing genes
Evolutionary changes in expression patterns
Applications of transcriptomics in medicine
Development of antibiotic resistance in bacteria
Childhood leukaemias
The Encyclopedia of DNA Elements (ENCODE)
Looking forward
Recommended reading
Exercises and problems
11 Proteomics
Learning goals
Introduction
Protein nature and types of proteins
Protein structure
The chemical structure of proteins
Conformation of the polypeptide chain
Protein folding patterns
Domains
Disorder in proteins
Post-translational modifications
Why is there a common genetic code with 20 canonical amino acids?
Separation and analysis of proteins
Polyacrylamide gel electrophoresis (PAGE)
Two-dimensional PAGE
Mass spectrometry
Identification of components of a complex mixture
Protein sequencing by mass spectrometry
Quantitative analysis of relative abundance
Measuring deuterium exchange in proteins
Experimental methods of protein structure determination
X-ray crystallography of proteins
Interpretation of the electron density: model building and improvement
How accurate are the structures?
NMR spectroscopy in structural biology
Protein structure determination by NMR
Low-temperature electron microscopy (cryoEM)
Classifications of protein structures
SCOP
SCOP2
Protein complexes and aggregates
Protein aggregation diseases
Properties of protein–protein complexes
Stoichiometry—what is the composition of the complex?
Affinity—how stable is the complex?
How are complexes organized in three dimensions?
Multisubunit proteins
Many proteins change conformation as part of the mechanism of their function
Conformational change during enzymatic catalysis
Motor proteins
Allosteric regulation of protein function
Allosteric changes in haemoglobin
Conformational states of serine protease inhibitors (serpins)
Protein structure prediction and modelling
Homology modelling
Secondary structure prediction
Prediction of novel folds: ROSETTA
Available protocols for protein structure prediction
Structural genomics
Directed evolution and protein design
Directed evolution of subtilisin E
Looking forward
Recommended reading
Exercises and problems
12 Metabolomics
Learning goals
Introduction
Classification and assignment of protein function
The Enzyme Commission
The Gene Ontology™ Consortium protein function classification
Comparison of EC and GO classifications
Metabolic networks
Databases of metabolic pathways
EcoCyc
The Kyoto Encyclopedia of Genes and Genomes
The Human Metabolome Database
Evolution and phylogeny of metabolic pathways
Alignment and comparison of metabolic pathways
Comparing linear metabolic pathways
Reconstruction of metabolic networks
Comparing non-linear metabolic pathways: the pentose phosphate pathway and the Calvin–Benson cycle
Metabolomics in ecology
Dynamic modelling of metabolic pathways
Looking forward
Recommended reading
Exercises and problems
13 Systems Biology
Learning goals
Introduction
Regulatory mechanisms
Two parallel networks: physical and logical
Networks and graphs
Robustness and redundancy
Connectivity in networks
Dynamics, stability, and robustness
Protein complexes and aggregates
Protein interaction networks
Protein–DNA interactions
DNA–protein complexes
Structural themes in protein–DNA binding and sequence recognition
Bacteriophage T7 DNA polymerase
Some protein–DNA complexes that regulate gene transcription
Regulatory networks
Structures of regulatory networks
Structural biology of regulatory networks
Gene regulation
The transcriptional regulatory network of Escherichia coli
The genetic switch of bacteriophage λ
Regulation of the lactose operon in Escherichia coli
The genetic regulatory network of Saccharomyces cerevisiae
Adaptability of the yeast regulatory network
Looking forward
Recommended reading
Exercises and problems
Epilogue
Glossary
Index
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