genomics genetics

8/11/2019 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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genomics genetics

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