Microbial Functional Genomics, Genomic Technologies, And Their Applications
Chapter 1 Introduction What is genomics, and what are its applications?
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Transcript of Chapter 1 Introduction What is genomics, and what are its applications?
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Chapter 1
Introduction
What is genomics, and what are its applications?
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Contents
Why this format for a genomics “textbook”? What is genomics? Where did it come from? What are its major technologies? What are its applications? What are the ethical issues? Where is it going?
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Why this format for a genomics “textbook”?
A new format for a rapidly changing field Flexibility
Slides can be modified and rearranged Download updated material
URL: www.prenhall.com/benfey Modularity
Chapters are independent Print edition
Figures and text Space for notes
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Slide layout
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What is genomics?
A marriage of molecular biology, robotics, and computing
Tools and techniques of recombinant DNA technology e.g., DNA sequencing, making libraries and
PCRs High-throughput technology
e.g., robotics for sequencing Computers are essential for processing and
analyzing the large quantities of data generated
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Origin of terminology
The term genome was used by German botanist Hans Winker in 1920
Collection of genes in haploid set of chromosomes
Now it encompasses all DNA in a cell In 1986 mouse geneticist Thomas Roderick
used Genomics for “mapping, sequencing and characterizing genomes”
Functional genomics, transcriptomics, proteomics, metabolomics, phenomics (Omics)
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Origin of genomics
Human Genome Project Goal: sequence 3 billion base pairs High-quality sequence (<1 error per 10 K bases)
Immensity of task required new technologies Automated sequencing
Decision to sequence other genomes: yeast and bacteria Beginnings of comparative genomics
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Technical foundations of genomics
Molecular biology: recombinant-DNA technology
DNA sequencing Library construction PCR amplification Hybridization
techniques
Log
MW
Distance
. .. .
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Genomics relies onhigh-throughput technologies
Automated sequencers Robotics
Microarray spotters Colony pickers
High-throughput genetics
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Industrial-scale genomics laboratory
2002 Paradigm Genetics, Inc. All rights reserved. Used with permission.
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Bioinformatics: computational analysis of genomics data
Uses computational approaches to solve genomics problems Sequence analysis Gene prediction Modeling of biological
processes
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Genome sequencing
Analogy: Complete works of an author in partially
understood language
Two approaches Page by page All at once
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Page-by-page sequencing strategy
Sequence = determining the letters of each word on each piece of paper
Assembly = fitting the words back together in the correct order
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All-at-once sequencing strategy
Find small pieces of paper
Decipher the words on each fragment
Look for overlaps to assemble
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Genome size and gene number
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Lessons from sequencing
Variability of genome structure Duplication events Transposons Microsatellites
1 2 3 4 5
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Functional genomics
Once we know the sequence of genes, we want to know the function
The genome is the same in all cells of an individual, except for random mutations
However, in each cell, only a subset of the genes is expressed The portion of the genome that is used in each
cell correlates with the cell’s differentiated state
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Analogy for gene expression
Genome is a hard drive of a computer Contains all the
programs Gene expression
What’s loaded into RAM (short-term memory)
Subset of genome used in each cell
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Gene-by-gene approach to understand biological processes
• Analogous to understanding circuitry by following wires
• Choose one wire • Follow circuit to
transistor• Follow from transistor to
capacitor • Follow from capacitor to
power source• Do again
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Genomics provides a parts list
Provides list of all parts
Parts list in itself doesn’t say how the genome works
Can use to get global picture e.g., RNA
expression
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Genomics applications to biology
Cellular function Microarrays Proteomics Cellular networks
Evolutionary mechanisms Comparative genomics
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Expression microarrays
Global expression analysis
RNA levels of every gene in the genome analyzed in parallel
Compare with Northern blot Microarrays contain
more information by many orders of magnitude
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Biological networks: Systems Biology
Food chain
Neuronal network
Transcriptional network
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From parts to systems
Parts list + interactions = road map
Properties = traffic patterns
Want to understand properties Why certain traffic
patterns emerge Perturb system and see
how it responds Place traffic light at
intersection
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Regulatory network of sea urchin development
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Comparative genomics
Mechanisms of evolution What is conserved between species?
Genes for basic processes What makes closely related species
different? Their adaptive traits
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Conservation between species identifies important components
Compare parts lists Mantle clock Pocket watch Wristwatch
Identify essential elements of timekeeping Gears, hands, etc.
Superfluous parts Wristband
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Identifying adaptive traits
Compare parts lists Two watches from
same maker: one with date, other without
Reveals parts likely to function in date mechanism
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Humans and their ancestors
All great apes have high level of cognitive ability
But very different social behaviors
human
orangutangorilla
chimpanzee
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Applications of genomics to medicine
Genes for disease susceptibility Improved diagnosis Pharmacogenomics
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Improved disease diagnostics from genomics
Microarray analysis of gene expression from four different types of tumors
Grouping of gene expression patterns shows very clear differences among the tumors
Used to tailor therapy to individuals
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Pharmacogenomics: drug therapies tailored to individuals
Design therapies based on the individual’s genome
Subtle, but important, differences in genomes Cause differences in how one responds to drugs
Identify those who will suffer harmful side effects from particular drugs
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Prescreening based on genomes
All patients with same diagnosis
1 RemoveToxic and
Nonresponders
TreatResponders and PatientsNot Predisposed to Toxic
2
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Genomics applied to agriculture
Sequencing of crop-plant genomes
Gene discovery for useful traits
Genomewide regulatory networks to improve traits
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Farm-animal genomics
Genome sequencing of pigs, cows, sheep, and poultry
EST sequencing Agricultural pathogens
Potential bioterrorism agents
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Ethical issues raised by genomics(ELSI) (Ethical legal, societal
implications) Individual’s genome
holds key to disease susceptibility
Potential for misuse recognized by founders of Human Genome Project
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Genetic testing in the workplace
Major railroad company decided to perform DNA tests on employees
Wanted to identify susceptibility to carpal tunnel syndrome
Equal Employment Opportunity Commission filed suit to block action
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Genetic modification of humans
Once we know the genes responsible for particular diseases, should we “cure” the diseases?
Should we also modify genes responsible for traits such as height or beauty?
Should we allow the cloning of human beings?
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Future of sequencing We have the genome! What’s next?
(post genome era) Sequencing costs
Dropping each year Could go down to
$1,000/genome Opens possibility of
sequencing genomes of individuals
Greatly facilitates comparative genomics
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Future breakthroughs in technology
Sequencing By hybridization
Genetic analysis Rapid SNP detection
Proteomics Differential protein determination
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Summary I
Origins of genomics Molecular biology Robotics Computing
Genomics subdisciplines Genome sequencing Functional genomics Proteomics Bioinformatics
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Summary II
Applications Medicine Agriculture
Ethical issues Future developments