Genomics and Proteomics

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GENOMICS – PROTEOMICS and THE HUMAN GENOME PROJECT ALLAM KRISHNA VAMSHI, M.Pharmacy II sem, Dept. Of Pharmaceutics, Talla Padmavathi College Of Pharmacy.

OUTLINE…. : 

1. STRUCTURE OF DNA 2. NUCLEOTIDES 3. CODON 4. CHROMOSOME 5. GENE 6. GENOME 7. GENOMICS 8. PROTEOMICS 9. PROTEIN SYNTHESIS 10. BIO INFORMATICS 11. THE HUMAN GENOME PROJECT 12. PHARMACO GENOMICS 13.GENETIC VARIATIONS 14.POLYMORPHISMS 15.EFFECT OF POLYMORPHISM ON DRUG METABOLISM. 16.CONCLUSIONS 17. REFERENCES OUTLINE….

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Genetic Material of Cells….. It contains the Information needed to build the entire human body. Structure- DOUBLE HELIX. It is made up of repeating molecules called NUCLEOTIDES. Different arrangements of Nucleotides in a DNA provides the key to Diversity among living organisms…… DNA (Deoxyribo Nucleic Acid)

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DNA Nucleotide DNA Nucleotide

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Nitrogenous Bases PURINES 1. Adenine (A) 2. Guanine (G) PYRIMIDINES 3. Thymine (T) 4. Cytosine (C) Nitrogenous Bases

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* Three nucleotide sequence is called as a CODON.

What is a Chromosome?? : 

It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequence . Chromosomes vary widely between different organisms . What is a Chromosome??

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What is Gene ?? : 

Basic unit of Heriditary in living organism. It is a segment of DNA. Located at specific points of the Chromsome. Genes contains instructions for making PROTEINS. What is Gene ??

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What is Genome?? : 

It is the complete set of chromosomes of an organism. Every organism has a specific GENOME. i.e: The number of chromosomal pairs is specific for every organism. Human genome has 23pairs of chromosomes. What is Genome??

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A, T, G, C Codon Gene Chromosome Genome Abcdefg….xyz Word Sentence Chapter Book DNA is INFORMATION..

GENOMICS : 

GENOMICS Study of entire Genomes -- - Sequences - Gene organization & - Mutations at the DNA level.. Study of Information Flow within a cell & Functional Analysis.

Impact of GENOMICS on MEDICINE…. : 

Impact of GENOMICS on MEDICINE…. How to characterize new diseases? What new treatments can be discovered?? How do we treat individual patients???

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Main Applications : 

Structural genomics: Finding out the sequences of genomes. Functional genomics: probing the pattern of gene expression in a given cell type at a given time. Positional cloning: Finding genes involved in genetic traits, especially genetic diseases. Main Applications

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Physicians will use genetic information to diagnose and treat disease. Faster drug development research: (pharmacogenomics) Individualized drugs All Biologists/Doctors will use gene sequence information in their daily work.. Implications for BIOMEDICINE..

PROTEOMICS : 

It is the study of  “Proteome”. The word "proteome" is a blend of "protein" and "genome“. Large scale study of Proteins.. Particularly their structures and functions. PROTEOMICS

ABOUT PROTEINS… : 

Proteins are very important molecules & They are involved in virtually all cell functions. Each protein within the body has a specific function. Ex: 1. Antibodies - are specialized proteins involved in defending the body from antigens (foreign invaders). 2. Contractile Proteins - are responsible for movement. Examples include actin and myosin. 3. Enzymes - are proteins that facilitate biochemical reactions . lactase and pepsin 4. Hormonal Proteins - are messenger proteins which help to coordinate certain bodily activities 5. Structural Proteins - are fibrous and stringy and provide support. Examples include keratin, collagen, and elastin 6. Transport Proteins - are carrier proteins . . Hemoglobin transports oxygen through the blood ABOUT PROTEINS…

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DNA Transcription RNA Translation Protein Synthesis

Why Proteomics? : 

Whole Genome Sequence –complete, but it does not show how proteins function or biological processes occur. Post-translational modification –proteins sometimes chemically modified or regulated after synthesis. Protein – protein interactions. Proteins fold into specific 3-D structures which determine function. Gain insight into alternative splicing Aids in genome annotation. Why Proteomics?

Gene Splicing & Annotation : 

Gene splicing means cutting of gene in fragments and rejoining them according to the need. Annotation is the process by which the information about raw DNA sequences is added to the genome databases. Important aspect of annotation is identifying which parts of a genome are transcribed into mRNA. Obviously computer programs are essential to this process. Gene Splicing & Annotation

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Bio Informatics : 

Bio Informatics Bioinformatics is the application of computer technology and statistics to the management of biological information.

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Store/retrieve biological information (databases) Retrieve/compare gene sequences Predict function of unknown genes/proteins Search for previously known functions of a gene Compare data with other researchers Compile/distribute data for other researchers How do we use Bioinformatics?

Application Areas of Bioinformatics : 

Genomics Proteomics Pharmacogenomics Comparative Genomics Forensics Application Areas of Bioinformatics

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GENOMICS, PROTEOMICS & BIO INFORMATICS Find all the genes Translate genes to proteins“Compute” function by similarity search and comparison to known proteins “Compute” structure

Human Genome Project : 

U.S. govt. project coordinated by the Department of Energy and the National Institutes of Health, launched in 1986 by Charles DeLisi. Aims of the project: -To identify the approximate 1,00,000 genes in the human DNA. - Determine the sequences of the 3 billion bases that make up human DNA. - Store this information in databases. - Develop tools for data analysis. - Address the ethical, legal, and social issues that arise from genome research. Human Genome Project

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- Improvements in medicine. - Microbial genome research for fuel and environmental cleanup. - DNA forensics. - Improved agriculture. - Better understanding of evolution and human migration. - More accurate risk assessment. Benefits of Human Genome Project

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Improvements in medicine: improved diagnosis of disease. Microbial research: new energy sources, bio fuels. DNA forensics: identifying potential suspects at a crime scene. Agriculture: more nutritious produce. Evolution and human migration: study migration of different population groups based on female genetic inheritance. - Risk assessment: reduce the likelihood of heritable mutations. How is each area benefited specifically by the Human Genome Project?

PharmacoGenomics : 

It is the study of-- The inherited variations in genes that control the body’s response to drugs. The ways these variations can be used to predict whether a patient will have a good or bad response to a drug, or no response at all. PharmacoGenomics

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Adverse drug reactions account for over 2 million hospitalizations and 100,000 deaths annually in the U.S. Some promising medicines never come to market because they probably only work well on people with certain genotypes. Examples: Patients with different genetic variations may require different amounts of a drug to achieve the same effect (e.g. cytochrome p450s) Drugs may be toxic in patients of one genotype and helpful to patients of another. Importance

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The route to a new medicine ……………………..is a long one Idea Marketed Drug Years 11-15 Years Discovery Exploratory Development Full Development Phase I Phase II Phase III 0 15 5 10 Patent life 20 years Phase IV

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DISEASE GENETICS TARGET VARIABILITY SELECTING RESPONDERS PHARMACO- GENETICS Discovery Development Choosing the Best Targets Better Understanding of Our Targets Improving Early Decision Making Predicting Efficacy and Safety Applying PharmacoGenomics

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Genetic Variation : 

Mutations, Polymorphisms & SNPs Mutation A permanent, structural change in the DNA. Polymorphism A common (>1%) variation in the sequence of DNA among individuals. 1. Single Nucleotide Polymorphism (SNP) A common (>1%) single base variation in the DNA. or base substitution. 2. Deletions: A certain part is lost. ( abc----ac) 3. Insertions: A certain part is added. (ac--- abc) Genetic Variation

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ss Single Nucleotide Polymorphism (SNP) Single base variation in the DNA Thought to be a major cause of genetic diversities among different individuals in Drug response, Disease susceptibility...

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May result in a different amino acid or stop codon. May result in a change in protein function or quantity. May alter stability of mRNA. No consequence. Consequences of Polymorphisms

Effect of Polymorphism on Drug Metabolism : 

Ex: 1. CYP450 2D6 Levels.. 2. CYP450 2C19 Levels.. Effect of Polymorphism on Drug Metabolism

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CYP450 Content in Human Liver Low levels of P4502D6 & P4502C19

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CYP2D6 Minor P450 enzyme in human liver Metabolizes ~30% of drugs If low enzyme activity:  “Poor metabolizers” Higher risk of drug toxicity and drug interactions CYP450 2D6

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CYP2D6 Substrates Debrisoquine Amphetamine Dexfenfluramine Ouanoxan Ondansetron Antipsychotics Perphenazine Thioridazine Haloperidol Risperidone Minaprine Venlafaxine Beta Blockers Propafenone S-metoprolol Propranolol Timolol Alprenolol Bufuralol Carvedilol Antiarrhythmics Encainide Flecainide S-mexillitene Lidocaine Analgesics Dextromethorphan Codeine Tramadol Antidepressants Fluoxetine Fluvoxamine Paroxetine Amitriptylline Desipramine Clomipramine Imipramine

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CYP2D6 Poor Metabolizers Caucasians 5% -10% African-Americans 6% Africans 2% – 19% Japanese 0.5% Chinese 0.7% In poor metabolizers: - Higher risks for toxic reactions - Higher risks for drug interactions (e.g., codeine and propranolol)

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CYP2C19 Substrates Omperazole Lansoprazole Pantoprazole S-mephenytoin Hexobarbital R-mephobarbital Phenytoin Diazepam Citalopram Warfarin Proguanil Teniposide Nilutamide Indomethacin Moclobemide Propranolol (in part) Imipramine (in part) Clomipramine (in part) Amitryptylline (in part)

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CYP2C19 “Poor Metabolizers” Caucasians 2% - 3% Africans 3% - 5% Chinese ~14% Koreans ~14% Japanese ~20%

Here is my sequence… : 

Here is my sequence… CONCLUSION…

REFERENCES : 

http://www.informatik.uni-rostock.de/~us040/docs/genomics%20and%20proteomics%20I.pdf http://teaching.ust.hk/~bisc005/lecture%20notes/topic12/From%20human%20genomics%20to%20proteomics2.pdf. http://www.wepapers.com/Papers/74452/Introduction_to__Proteomics.ppt http://en.wikipedia.org/wiki/Bioinformatics http://www.google.co.in/images?hl=en&q=human+genome+project&um=1&ie=UTF&source=univ&ei=zi5YTIudLYWXrAfeg5SOBQ&sa=X&oi=image_result_group&ct=title&resnum=4&ved=0CEEQsAQwAw&biw=1024&bih=604 http://www.ornl.gov/sci/techresources/Human_Genome/home.shtml http://en.wikipedia.org/wiki/Polymorphism_%28biology%29 http://www.cs.mcgill.ca/~kaleigh/compbio/snp/snp_summary.pdf http://www.google.co.in/images?hl=en&q=dna+nucleotide&um=1&ie=UTF&source=univ&ei=ky9YTNa4PMivrAfhqbyOBQ&sa=X&oi=image_result_group&ct=title&resnum=1&ved=0CCgQsAQwAA&biw=1024&bih=604 http://www-personal.umich.edu/~grosania/lecture1.pdf REFERENCES

THANK U…. : 

THANK U….