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
• The term genome was used by German
botanist Hans Winker in 1920
• Collection of genes in haploid set of
• 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
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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!
• Life’s little book of instructions
• DNA blue print of life!
• Human body has 10
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
• How similar are we to apes, trees, and

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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
• Having a gene does not mean it will be
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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
– e.g., DNA sequencing, making libraries and
• High-throughput technology
– e.g., robotics for sequencing
• Computers are essential for processing and
analyzing the large quantities of data
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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
– Automated sequencing
• Decision to sequence other genomes:
yeast and bacteria
– Beginnings of comparative genomics

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Technical foundations of genomics
• Molecular biology:
• DNA sequencing
• Library construction
• PCR amplification
• Hybridization


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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 by‘synthesis nanotechnology’approach

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
• 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
• 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 cell’s
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
• 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 list in itself
doesn’t say how
the machine
• Can use to get
global picture
– e.g., RNA
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Expression microarrays
• Global expression
• RNA levels of 30x10

genes in the genome
analyzed in parallel
• Compare with
Northern blot
– Microarrays contain
more information by
many orders of
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Biological networks: Systems Biology
Food chain
Neuronal network
Transcriptional network
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Regulatory network of sea urchin
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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
• Opens possibility of
sequencing genomes
of individuals:
• Greatly facilitates
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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
• 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
• Grouping of gene
expression patterns
shows very clear
differences among the
• Used to tailor therapy
to individuals

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Pharmacogenomics: drug
therapies tailored to individuals
• Design therapies based on the individual’s
• Subtle, but important, differences in
– Cause differences in how one responds to
• Identify those who will suffer harmful side
effects from particular drugs

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Prescreening based on genomes
All patients with same diagnosis
Toxic and
Responders and Patients
Not Predisposed to Toxic
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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
– Potential
bioterrorism agents
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Ethical issues raised by genomics
(ELSI) (Ethical legal, societal
• Individual’s genome
holds key to disease
• 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
• Wanted to identify
susceptibility to carpal
tunnel syndrome
• Equal Employment
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
• Should we also
modify genes
responsible for traits
such as height or
• Should we allow the
cloning of human
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