bioinformatics workshop presentation
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Dr N A GanaiProfessor
Centre of Animal BiotechnologySKUAST-Kashmir
Contents Introduction to
Bioinformatics Complexity of life Size of genome Exponential growth in information
generation Why and how to handle this
information Definition of Bioinformatics?
Data bases Tools
Scope of Bioinformatics Anticipated benefits Ethical, Legal, and Social
Issues
Variation : Basis of evolution
What is Marker?
`̀
Marker is a piece of Marker is a piece of DNA molecule that is DNA molecule that is
associated with a associated with a certain trait of a certain trait of a
organismorganismMorphologicalMorphological
BiochemicalBiochemical
ChromosomalChromosomal
GeneticGeneticTypes of Types of MarkersMarkers
Animals are selected based on Animals are selected based on appearanceappearance
Eg. PIGMENTATIONEg. PIGMENTATION
Disadvantage: lack of polymorphismDisadvantage: lack of polymorphism
Animals are selected based on biochemical Animals are selected based on biochemical propertiesproperties
Eg. Hb, AMYLASE, BLOOD GROUPS ETC.Eg. Hb, AMYLASE, BLOOD GROUPS ETC.
Disadvantage:Disadvantage: Sex limitedSex limitedAge dependentAge dependentInfluenced by environmentInfluenced by environmentIt covers less than 10% of genomeIt covers less than 10% of genome
Animals are selected based on Animals are selected based on structural & numerical variationsstructural & numerical variations
Eg. Structural and Numerical VariationsEg. Structural and Numerical VariationsStructural- Structural- Deletions, Insertions etc.Deletions, Insertions etc.Numerical-Numerical- Trisomy, Monosomy, Nullysomy Trisomy, Monosomy, Nullysomy
Disadvantage: low polymorphismDisadvantage: low polymorphism
Molecular Marker
Revealing variation at a DNA level
Characteristics:Co-dominant expressionNondestructive assayComplete penetranceEarly onset of
phenotypic expression High polymorphism Random distribution
throughout the genome Assay can be automated
DNA isolated from any tissue eg. Blood, hair etc.
DNA isolated at any stage even during foetal life
DNA has longer shelf-life readily exchangeable b/w labs
Analysis of DNA carried out at early age/ even at the embryonic
Stage irrespective of sex.
Molecular Markers
Single locus markerSingle locus marker
Multi-locus markerMulti-locus marker
RFLP
Microsatellite
STS
DNA Fingerprinting
AFLP
RAPD
SNPs
DNA is not merely a molecule with a pattern; it is a code, a language, and an
information storage mechanism
Size of Human Genome Each cell carries: 3.2 billion base pairs
A code you need to write in 500 books, each book of 500 pages
Length of DNA in adult man: The total length of DNA present in one adult
human is calculated as: (length of 1 bp)(number of bp per cell)(number of cells in
the body)(0.34 × 10-9 m)(6 × 109)(1013)2.0 × 1013 meters
That is the equivalent of nearly 70 trips from the earth to the sun and back.
Human Genome Project• HGP: International research
effort• Began 1990, completed
2003
• Biggest ever project in life sciences
• 20 labs participated world around
• Next steps for ~30,000 genes– Function and regulation of all
genes– Significance of variations
between people– Cures, therapies, “genomic
healthcare”
Genomics
Transcriptomics
Proteomics Metabolomi
cs
Year Base Pairs Sequences1982 680,338 606
1983 2,274,029 2,427
1984 3,368,765 4,175
1985 5,204,420 5,700
1986 9,615,371 9,978
1987 15,514,776 14,584
1988 23,800,000 20,579
1989 34,762,585 28,791
1990 49,179,285 39,533
1991 71,947,426 55,627
1992 101,008,486 78,608
1993 157,152,442 143,492
1994 217,102,462 215,273
1995 384,939,485 555,694
1996 651,972,984 1,021,211
1997 1,160,300,687 1,765,847
1998 2,008,761,784 2,837,897
1999 3,841,163,011 4,864,570
2000 11,101,066,288 10,106,023
2001 15,849,921,438 14,976,310
2002 28,507,990,166 22,318,883
2003 36,553,368,485 30,968,418
2004 44,575,745,176 40,604,319
2005 56,037,734,462 52,016,762
2006 69,019,290,705 64,893,747
2007 83,874,179,730 80,388,382
2008 99,116,431,942 98,868,465
Av. Growth in data generation :
5400 times per year
Exponential Growth in Biological Databases:High throughput Technologies
PCR : by Kary Mullis 1983 - an employee of Cetus Corporation, a biotechnology firm in CaliforniaAwarded the Nobel Prize for the discovery of PCR in 1993
Microarray Technology
Real-Time PCR
DNA Chips
Sequencing
Sanger method : 1975Chain Termination Method
Maxam Gilbert : 1977Chemical Modification Method
Next Generation: 1994High Throughput Parallel sequencingEntire genome can be sequenced in a matter of weeks
History of DNA Sequencing
Avery: Proposes DNA as ‘Genetic Material’
Watson & Crick: Double Helix Structure of DNA
Holley: Sequences Yeast tRNAAla
1870
1953
1940
1965
1970
1977
1980
1990
2002
Miescher: Discovers DNA
Wu: Sequences Cohesive End DNA
Sanger: Dideoxy Chain TerminationGilbert: Chemical Degradation
Messing: M13 Cloning
Hood et al.: Partial Automation
• Cycle Sequencing • Improved Sequencing Enzymes• Improved Fluorescent Detection Schemes
1986
• Next Generation Sequencing•Improved enzymes and chemistry•Improved image processing
Adapted from Eric Green, NIH; Adapted from Messing & Llaca, PNAS (1998)
1
15
150
50,000
25,000
1,500
200,000
50,000,000
Efficiency(bp/person/year)
15,000
100,000,000,000 2008
The Genome Sequence is at hand…so?
“The good news is that we have the human genome. The bad news is it’s just a parts list”
What Next???
We need to know every part, its function and
application
What is Bioinformatics?
The newest, fastest growing specialty in the life sciences that integrates biotechnology and computer science.
Computers aid to collect, analyze, and interpret biological information at the molecular level.
Understand a living cell and how it functions at molecular level
Develop data basses and computational tools Databases to:
Store all the data (information) related to Genomics, Transcriptomics, preoteomics, Metabolomics
Tools to To mine (analyze) databases to generate knowledge
to better understand the living systems
Goal of Bioinformatics
Anticipated Benefits of Genome Research & Bioinformatics
Molecular Medicine : Gene Testing , Pharmacogenomics Gene Therapyimprove diagnosis of diseasedetect genetic predispositions to diseasecreate drugs based on molecular informationuse gene therapy and control systems as drugsdesign “custom drugs” (pharmacogenomics) based on individual genetic profiles
Huntigton disease (an inherited neurodegenerative disorder)
Symptoms:uncontrollable dance-like (choreatic) movements,mental disturbance,personality changes and intellectual impairment
repeats of the trinucleotide CAG,corresponding to polyglutamine blocks in the corresponding protein, huntingin
11-28 CAG repeats -->normal
29-34 CAG repeats---->likely to develop disease
35-41 CAG repeats develop mild symptoms
morethan 41 CAG repeats suffer full huntington disease
Diagnosis of disease and disease risk
Microbial Genomics rapidly detect and treat pathogens in clinical
practice develop new energy sources (biofuels) monitor environments to detect pollutants protect citizenry from biological and chemical
warfare clean up toxic waste safely and efficiently
DNA Identification (Forensics)identify potential suspects whose DNA may match evidence left at crime scenes
exonerate persons wrongly accused of crimes
establish paternity and other family relationships
identify endangered and protected species as an aid to wildlife officials (could be
detect bacteria and other organisms that may pollute air, water, soil, and food
match organ donors with recipients in transplant programs
determine pedigree for seed or livestock breeds
Benefits: …contined
Agriculture, Livestock Breeding, and Bioprocessing
grow disease-, insect-, and drought-resistant crops
breed healthier, more productive, disease-resistant farm animals
grow more nutritious produce
develop biopesticides
incorporate edible vaccines incorporated into food products
develop new environmental cleanup uses for plants like tobacco
Benefits …cont .
ELSI: Ethical, Legal, and Social Issues
• Privacy and confidentiality of genetic information.
• Fairness in the use of genetic information by insurers, employers, courts, schools, adoption agencies, and the military, among others.
• Psychological impact, stigmatization, and discrimination due to an individual’s genetic differences.
• Reproductive issues including adequate and informed consent and use of genetic information in reproductive decision making.
• Clinical issues including the education of doctors and other health-service providers, people identified with genetic conditions, and the general public about capabilities, limitations, and social risks; and implementation of standards and quality‑control measures.
Health and environmental issues concerning genetically modified foods (GM) and microbes.
Commercialization of products including property rights (patents, copyrights, and trade secrets) and accessibility of data and materials.
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