Genomes and genomics

Credits: Teaching resources from School of Forest Resources and

Environmental Science Michigan Tech University


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Origin of terms Genomes and
Genomics
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
New terms: Functional genomics,
transcriptomics, proteomics, metabolomics,
phenomics (Omics)
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What is the genome?
Entire genetic complement of an
organism
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How many types of genomes
are there in this world?
Prokaryotic genomes
Eukaryotic Genomes
Nuclear Genomes
Mitochondrial genomes
Choloroplast genomes

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Why should we study genomes?
Each and everyone is a unique creation!
Lifes little book of instructions
DNA blue print of life!
Human body has 10
13
cells and each cell
has 6 billion base pairs (A, C, G, T)
A hidden language/code determines which
proteins should be made and when
This language is common to all organisms

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Genome sequence can tell us
Everything about the organism's life
Its developmental program
Disease resistance or susceptibility
How do we struggle, survive and die?
Where are we going and where we came
from?
How similar are we to apes, trees, and
yeast?

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How will the study of Genomics
impact this century?
Biotechnology: more products
GMOs: More food-More problems?
Our society will not be the same!
Individualized medicine
Gene therapy
Disease free life?

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Now look at your neighbor
What do you see?
Someone is different than you!
Could be that your friend differs in his/her
sex, looks, nature, smartness, or simply
the way he/she dresses and talks
How much similarity you think you share
with your friend at the gene level?
99.9% so we could fix genes if we want
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Now look at your own hands and legs
Do they look similar? No!
But they contain the same DNA in each of
their cells
DNA makes RNA makes proteins
Different genes are expressed differently
in different cells, tissues and organs of an
organism
Having a gene does not mean it will be
expressed.
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Someone has a cancer gene!
It is a normal gene that got mutated or
changed and does not perform same job
But having a gene does not mean you will
get cancer
Because environment has a big role in
turning a gene on or off
Different genes and their products also
interact: microecosystem
Genes do not work alone (G+E)
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Genomics is the study of all
genes present in an organism
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Science of 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 Genomics
Human Genome Project
Goal: sequence 3 billion base pairs
High-quality sequence (<1 error per 10 K bases) ACGT
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
L
o
g

M
W

Distance
.
.
.
.
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Genomics relies on
high-throughput technologies
Automated sequencers
Fluorescent dyes
Robotics
Microarray spotters
Colony pickers
High-throughput genetics
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Sequencing genomes in
Months and Years
Sequencing genomes in
Minutes (14 min precisely)!!
Technology Revolution
Sequencing bysynthesis nanotechnologyapproach


From a Few Billion $ to $5000
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Industrial-scale Genomics Lab
2002 Paradigm Genetics, Inc. All rights reserve d. Used with permission.
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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
Amoeba dubia: 670 billion base pairs
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Lessons from sequencing
Variability of genome
structure: Non-
coding (junk?)
Duplication events
Transposons
Microsatellites
Repetitive DNAs
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 cells
differentiated state
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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
doesnt say how
the machine
works
Can use to get
global picture
e.g., RNA
expression
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Expression microarrays
Global expression
analysis
RNA levels of 30x10
3

genes 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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Regulatory network of sea urchin
development
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Future of sequencing
We have the genome! Whats next?
(post genome era)
Sequencing costs
Dropping each year
Could go down to
<$1,000/genome
Opens possibility of
sequencing genomes
of individuals:
23andMe
Greatly facilitates
comparative
genomics
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Comparative Genomics
What is conserved between species?
Genes for basic processes
Understand the uniqueness between
different species
Their adaptive traits
What makes closely related species
different?
Analyzing & comparing genetic material
from different species to study evolution,
gene function, and inherited disease
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What is compared?
Gene location
Gene structure
Exon number
Exon lengths
Intron lengths
Sequence similarity
Gene characteristics
Splice sites
Codon usage
Conserved synteny
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Figure 1 Regions of the human and mouse homologous genes: Coding exons
(white), noncoding exons (gray}, introns (dark gray), and intergenic regions
(black). Corresponding strong (white) and weak (gray) alignment regions of GLASS
are shown connected with arrows. Dark lines connecting the alignment regions
denote very weak or no alignment. The predicted coding regions of ROSETTA in
human, and the corresponding regins in mouse, are shown (white) between the
genes and the alignment regions.
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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 individuals
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
Remove
Toxic and
Nonresponders
Treat
Responders and Patients
Not 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)
Individuals 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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