genomics genetics
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Genomes and genomics
Credits: Teaching resources from School of Forest Resources andEnvironmental Science Michigan Tech University
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Origin of terms Genomes andGenomics
The term genomewas used by Germanbotanist Hans Winker in 1920
Collection of genes in haploid set ofchromosomes
Now it encompasses all DNA in a cell In 1986 mouse geneticist Thomas Roderick
used Genomicsfor mapping, sequencingand 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 GenomesNuclear Genomes
Mitochondrial genomes
Choloroplast genomes
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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 Genomicsimpact 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 differentthan you!
Could be that your friend differs in his/hersex, looks, nature, smartness, or simplythe way he/she dresses and talks
How much similarity you think you sharewith 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 oftheir 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 orchanged 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 alsointeract: 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 DNAtechnology e.g., DNA sequencing, making libraries and
PCRs
High-throughput technology e.g., robotics for sequencing
Computers are essential for processing andanalyzing the large quantities of datagenerated
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Origin of Genomics
Human Genome Project Goal: sequence 3 billion base pairs
High-quality sequence (
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Technical foundations of genomics
Molecular biology:recombinant-DNA
technology
DNA sequencing
Library construction
PCR amplification
Hybridization
techniques
LogMW
Distance
. ..
.
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Genomics relies onhigh-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 RevolutionSequencing 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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Page-by-page sequencing strategy
Sequence =determining theletters of each
word on eachpiece of paper
Assembly = fitting
the words backtogether in thecorrect order
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All-at-once sequencing strategy
Find small piecesof paper
Decipher the
words on eachfragment
Look for overlaps
to assemble
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Genome size and gene number
Amoeba dubia: 670 billion base pairs 21SBL201 Lec 524-09-2014
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Lessons from sequencing
Variability of genomestructure: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, wewant 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 ineach cell correlates with the cellsdifferentiated state
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Gene-by-gene approach tounderstand biological processes Analogous tounderstanding 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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Expression microarrays
Global expressionanalysis
RNA levels of 30x103genes in the genome
analyzed in parallel
Compare withNorthern blot
Microarrays containmore information bymany orders ofmagnitude
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Biological networks: Systems Biology
Food chain
Neuronal network
Transcriptional network
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Regulatory network of sea urchindevelopment
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Future of sequencing
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Future of sequencingWe have the genome! Whats next?
(post genome era) Sequencing costs
Dropping each year
Could go down to
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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 GLASSare shown connected with arrows. Dark lines connecting the alignment regionsdenote very weak or no alignment. The predicted coding regions of ROSETTAinhuman, and the corresponding regins in mouse, are shown (white) between thegenes and the alignment regions.
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I d di di ti
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Improved disease diagnosticsfrom genomics
Microarray analysis ofgene expression fromfour different types oftumors
Grouping of geneexpression patternsshows very cleardifferences among thetumors
Used to tailor therapyto individuals
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Pharmacogenomics: drugtherapies tailored to individuals
Design therapies based on the individuals
genome
Subtle, but important, differences ingenomes
Cause differences in how one responds todrugs
Identify those who will suffer harmful sideeffects 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 foruseful traits
Genomewideregulatory networks toimprove traits
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Ethi l i i d b i
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Ethical issues raised by genomics(ELSI) (Ethical legal, societal
implications)
Individuals genome
holds key to disease
susceptibility
Potential for misuserecognized byfounders of HumanGenome Project
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Genetic testing in the workplace
Major railroadcompany decided toperform DNA tests onemployees
Wanted to identifysusceptibility to carpaltunnel syndrome
Equal EmploymentOpportunityCommission filed suitto block action
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Genetic modification of humans
Once we know thegenes responsible forparticular diseases,should we cure thediseases?
Should we alsomodify genesresponsible for traitssuch as height orbeauty?
Should we allow thecloning of humanbeings?
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