26/1/20081 general introduction to the genome. 26/1/20082 an outlines molecular biology major events...

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General Introduction to the Genome

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An Outlines• Molecular Biology Major Events• DNA, RNA • Protein Synthesis(Transcription & Translation)• Genome Anatomy• Bioinformatics• Genomics Signal Processing

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• Molecular Biology Major Events• DNA, RNA • Protein Synthesis(Transcription & Translation)• Genome Anatomy• Bioinformatics• Genomics Signal Processing

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Molecular Biology Major Events

DNA Discovery

1865Mendel

Inheritance is controlled by unit factors

1881

Chromosomes are composed of DNA

1869Johann Friedrich

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Molecular Biology Major Events

1881

Chromosomes are composed of DNA

1911

Thomas Hunt

Genes on chromosomes are the discrete units of heredity

1941George Beadle

Identify that genes make proteins

Edward Tatum

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The Central Dogma1

2

3

TargetBookBook shelvesNucleus

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What is Life made of?

715

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Eukaryotes vs Prokaryotes

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DNA

DNA

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Prokaryotes EukaryotesSingle cell Single or multi cell

No nucleus Nucleus

No organelles Organelles

One piece of circular DNA Chromosomes

No mRNA post transcriptional modification

Exons/Introns splicing

915

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The Cell: Chemical Composition

–70% Water–7% Small molecules• Salts• Amino acids (Protein)• Nucleotides (DNA, RAN)

–23% macromolecules• Proteins• Polysaccharides• Lipids

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The Cell: The 3 Critical Molecules

DNA

Hold Genetic information Transfer Information

Synthesize Protein

PROTEIN

Form enzymesForm body’s components

RNA

m-RNA t-RNAr-RNA

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• Molecular Biology Major Events

• DNA, RNA • Protein Synthesis(Transcription & Translation)• Genome Anatomy• Bioinformatics• Genomics Signal Processing

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DNA: the Nucleotide

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Phosphate

Sugar

Nitrogenous base

A

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DNA: Nitrogenous base

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Purines Pyrimidines

A TG C

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DNA: Polymerization reaction

A T G C

5 P’ 3OH’

A T G C A T G C

5 3

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DNA: hydrogn bounds

A C G T A C G T

ACG

TACG

T

No of base pairs= Genome SizeHG= 3200 Mbp (Mb)

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AC

GT

AC

GTA

CG

TA

CG

T

Sugar- Phosphate Back bone

DNA: Watson - Crick Model 1951

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DNA: Watson - Crick Model

Sugar- Phosphate Back bone

No of base pairs= Genome SizeHG= 3200 Mbp (Mb)

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RNA versus DNA

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Phosphate

Sugar "Ribose”

Nitrogenous base

Phosphate

Sugar” deoxyRibose”

Nitrogenous base

G, A ,C,T G, A ,C,U

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Protein structure

• 1902 - Emil Hermann Fischer wins Nobel prize: showed amino acids are linked and form proteins

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A AFNG

GS T

SD

K

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Amino acid: Basic unit of proteinAmino acid: Basic unit of protein

COO-NH3+ C

R

HAn amino

acid

Different side chains, R, determine the properties of 20 amino acids.

Amino group Carboxylic acid group

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Protein structure

• Primary structure

• Secondary structure

• Super-secondary structure

• Tertiary structure

• Quaternary structure

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Protein Structure: Predication Problem

Protein sequence

Protein 3D structure

Protein Function

A FNG S T

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The Central Dogma:Genes is protein’s blueprint, Genes is protein’s blueprint,

Gene

GenomeDNA

Protein

Gene GeneGene

Gene

GeneGeneGeneGene

GeneGeneGeneGene

GeneGene

Protein Protein

ProteinProtein

Protein

ProteinProtein

Protein

Protein

Protein

Protein

ProteinProtein

Protein

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• Molecular Biology Major Events• DNA, RNA • Protein Synthesis(Transcription & Translation)• Genome Anatomy• Bioinformatics• Genomics Signal Processing

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Protein Synthesis: DNA, RNA, and the Flow of Information

TranslationTranscription

Replication

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Protein Synthesis: Gene Expression

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Gene 2

Gen

e 1

Pre-mRNA

mRNAGen

e 3

Transcription

1

2

3

Translation

Splicing

1

2

3

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Gene 2

Gen

e 1

Pre-mRNA

mRNAGen

e 3

Transcription

1

2

3

Translation

Alternative Splicing

1

3

2

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Gene 2

Gen

e 1

Pre-mRNA

mRNAGen

e 3

Transcription

1

2

3

Translation

m-RNA Editing

1

2

3

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Gene 2

Gen

e 1

Pre-mRNA

mRNAGen

e 31

2

3

Translation

AUGAUAACUAG

MS

AK

Start Codon

Stop Codon

CV

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Protein Synthesis: The Genetic Code

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Start

Stop

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Gene 1

R Ge

ne 1

1

2

3

1

2

3

Gene Regulation

Regulatory protein

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Gene Regulation

Regulatory protein Gene 1

Gene 1 Gene 2

Regulatory protein Gene 2

We have a little knowledge about regulatory mechanisms

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What a big Genome Size?

• The 12 font size enables approximately 60 nucleotides of DNA sequence to be written in a line 10 cm in length.

• Genome size = total number of nucleotide base pairs.– typically in millions of base pairs, or megabases

[abbreviated Mb or Mbp])

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• Molecular Biology Major Events• DNA, RNA • Protein Synthesis(Transcription & Translation)

• Genome Anatomy• Bioinformatics• Genomics Signal Processing

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the human genome sequence would stretch for 5000 km, the distance from Montreal to London, Los Angeles to Panama, Tokyo to Calcutta, Cape Town to Addis Ababa, or Auckland to Perth

The sequence would fill about 3000 books the size of book 600 pages size.

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Genome size of organism are different

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Genome size is not good indicator for genes number

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• Space is saved in the genomes of less complex organisms because the genes are more closely packed together.

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C-value paradox

• Correlation between the complexity of an organism and the size of its genome was looked on as a bit of a puzzle.

•

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Genome Anatomy

Gene 1

Gene 6Gene 5

Gene 4

Gene 2

Gene 3

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Human Genome Anatomy

Human genome Nuclear genome Mitochondrial genome

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Human Mitochondrial Genome Anatomy

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• it is much smaller than the nuclear genome(~17 kB), and it contains just 37 genes.

• 13 code proteins and 24 specify non-coding RNA.

• do not contain intron.• is typical of the

mitochondrial genomes of other animals

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Nuclear Human Genome Anatomy

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62%

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Nuclear Human Genome Anatomy: Protein Coding Genes

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Nuclear Human Genome Anatomy: Protein Coding Genes

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five exons, separated by four introns.

average exons= nine exons per gene

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Two gene segments (V28 and V29-1)

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Nuclear Human Genome Anatomy: pseudogene

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Non functional genes

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Nuclear Human Genome Anatomy: genome-wide repeat

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Nuclear Human Genome Anatomy: genome-wide repeat

•Tandemly repeated DNA•Minisatellite DNA•Microsatellite DNA

•Interspersed genome-wide repeats•SINE•LINES•LTR•DNA transposons

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Nuclear Human Genome Anatomy: genome-wide repeat Minisatellite DNA

• we are familiar with because of its association with structural features of chromosomes.

• Telomeric DNA, which in humans comprises hundreds of copies of the motif 5 -TTAGGG-3 .′ ′

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TTAGGGAATCCC

TTAGGGAATCCC

TTAGGGAATCCC

………………………..………………………..

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The content of the human nuclear genome: genome-wide repeat Microsatellite DNA

• microsatellites with a CA repeat, such as:

make up 0.25% of the genome, 8 Mb in all. • Single base-pair repeats such as:

make up another 0.15%.

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Nuclear Human Genome Anatomy: genome-wide repeat Interspersed repeat

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Gene Classification: Gene function

• This system has the advantage that the fairly broad functional categories used in can be further subdivided to produce a hierarchy of increasingly specific functional descriptions for smaller and smaller sets of genes.

• The weakness : functions have not yet been assigned to

many eukaryotic genes.

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Gene Classification: Gene function

• The gene catalog couldn’t tell us why we are human?

• it may still not be possible simply from genome comparisons with the chimpanzee genome to determine what makes us human

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Gene Classification: Gene function

• The major categories of protein coding genes represent the most studied areas of cell biology, which means that many of the relevant genes can be recognized because their protein products are known.

• Genes whose products have not yet been identified are more likely to be involved in the less well studied areas of cellular activity.

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Gene classification: Protein Domain

• A more powerful method is to base the classification not on the functions of genes but on the structures of the proteins that they specify.

• A protein molecule is constructed from a series of domains, each of which has a particular biochemical function.

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Gene classification: Protein Domain

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• Molecular Biology Major Events• DNA, RNA • Protein Synthesis(Transcription & Translation)• Genome Anatomy

• Bioinformatics• Genomics Signal Processing

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What is Bioinformatics?

• Integration of computational and biological methodsto convert biological information into general theories.

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aatgcatgcggctatgctaatgcatgcggctatgctaagctgggatccgatgacaatgcatgcggctatgctaatgcatgcggctatgcaagctgggatccgatgactatgctaagctgggatccgatgacaatgcatgcggctatgctaatgaatggtcttgggatttaccttggaatgctaagctgggatccgatgacaatgcatgcggctatgctaatgaatggtcttgggatttaccttggaatatgctaatgcatgcggctatgctaagctgggatccgatgacaatgcatgcggctatgctaatgcatgcggctatgcaagctgggatccgatgactatgctaagctgcggctatgctaatgcatgcggctatgctaagctgggatccgatgacaatgcatgcggctatgctaatgcatgcggctatgcaagctgggatcctgcggctatgctaatgaatggtcttgggatttaccttggaatgctaagctgggatccgatgacaatgcatgcggctatgctaatgaatggtcttgggatttaccttggaatatgctaatgcatgcggctatgctaagctgggaatgcatgcggctatgctaagctgggatccgatgacaatgcatgcggctatgctaatgcatgcggctatgcaagctgggatccgatgactatgctaagctgcggctatgctaatgcatgcggctatgctaagctcatgcggctatgctaagctgggaatgcatgcggctatgctaagctgggatccgatgacaatgcatgcggctatgctaatgcatgcggctatgcaagctgggatccgatgactatgctaagctgcggctatgctaatgcatgcggctatgctaagctcggctatgctaatgaatggtcttgggatttaccttggaatgctaagctgggatccgatgacaatgcatgcggctatgctaatgaatggtcttgggatttaccttggaatatgctaatgcatgcggctatgctaagctgggaatgcatgcggctatgctaagctgggatccgatgacaatgcatgcggctatgctaatgcatgcggctatgcaagctgggatccgatgactatgctaagctgcggctatgctaatgcatgcggctatgctaagctcatgcgg

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Bioinformatics

Statistics

BiologyComputer Science

Chemistry

Data structuresSoftware engineering

(C, C++,PERL)Cell structure

Genome, genesDNA, RNA

Protein structureMolecular bounds

Markof ModelNeural Network

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Bioinformatics Subareas

• The subareas within bioinformatics include Genomics and Proteomics.

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Genome comparisonevolutionary tree

Microarray AnalysisGene predicationGene classificationGene regulation

Protein 3D predicationProtein protein interactionProtein alignment

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• Molecular Biology Major Events• DNA, RNA • Protein Synthesis(Transcription & Translation)• Genome Anatomy• Bioinformatics

• Genomics Signal Processing

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What is GSP?

aatgcatgcggctatgctaatgcatgcggctatgctaagctgggatccgatgacaatgcatgcggctatgctaatgcatgcggctatgcaagctgggatccgatgactatgctaagctgggatccgatgacaatgcatgcggctatgctaatgaatggtcttgggatttaccttggaatgctaagctgggatccgatgacaatgcatgcggctatgctaatgaatggtcttgggatttaccttggaatatgctaatgcatgcggctatgctaagctgggatccgatgacaatgcatgcggctatgctaatgcatgcggctatgcaagctgggatccgatgactatgctaagctgcggctatgctaatgcatgcggctatgctaagctgggatccgatgacaatgcatgcggctatgctaatgcatgcggctatgcaagctgggatcctgcggctatgctaatgaatggtcttgggatttaccttggaatgctaagctgggatccgatgacaatgcatgcggctatgctaatgaatggtcttgggatttaccttggaatatgctaatgcatgcggctatgctaagctgggaatgcatgcggctatgctaagctgggatccgatgacaatgcatgcggctatgctaatgcatgcggctatgcaagctgggatccgatgactatgctaagctgcggctatgctaatgcatgcggctatgctaagctcatgcggctatgctaagctgg

Analysis Processing

Using Theory and Methods of Signal Processing

To gain global understanding of Genome.

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GSP Labs

• The Genomic Signal Processing Laboratory at

Texas A&M University.• The Computational Biology

Division of the Translational Genomics

Research Institute in Phoenix, Arizona.

Edward R. DoughertyTo model Genomic Regulatory Mechanisms for the purposes of diagnosis and therapy.

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GSP Labs

• Columbia's Genomic Information Systems Laboratory

at Columbia University

Dimitris Anastassiou

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GSP Labs

• DSP Group, Department of Electrical Engineering, California Institute of Technology

P. P. Vaidyanathan

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Mapping Character String to Numerical Sequences

AAAATTTTCCCGGGTAGCTTTCCCGGGT

0001110101010101111111111000

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Research Area of GSP

• Gene Predication• Genes Predication– Hidden Markov Models (HMM)– Fourier Transform– Wavelet Transform• Resonant Recognition Model (RRM)To identify the common hot spots of many protein

molecules using Fourier transform methods.•

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References

• http://biology.ucok.edu/bidlack/biology/notes.htm

• http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=genomes

• http://www.estrellamountain.edu/faculty/farabee/biobk/biobooktoc.html

• http://www.werathah.com/• http://lectures.molgen.mpg.de/

online_lectures.html

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References

• http://www.biology.lsu.edu/webfac/jmoroney/BIOL3090/

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THANKYOU FOR YOUR

ATTENATION