human genome project by varaprasad

all about hgp by varaprasad

1. VAAGESWARI INSTITUTE OF PHARMACEUTICAL SCIENCES KARIMNAGAR FOR PARTIAL FULLFILMENT OF JNTU ACADEMICS SEMINAR THE HUMAN GENOME PROJECT (HGP) PRESENTED BY PADALA VARAPRASAD HT NO:15EC1R0030 Under The Guidance Of Mrs. P.MAMATHA MSc , Mphil Department of microbiology and biotechnology

2. REASONS I choose this topic because of 3 reasons The human genome project has been an amazing adventure into ourselves, to understand our own DNA book It is the world’s biggest collaborative biological project hundreds of scientist worked for more than 20 research centers in 6 countries ( united states, united kingdom, germany , canada , japan , china ) for 13 years to unlock the secret of life or more clearly to crack the code of DNA The international effort to sequence the 3 billion DNA letters is considered by many to be one of the most ambitious scientific undertaking of all time 2

3. INTRODUCTION GENE is sequence of DNA or RNA that code for a molecule that has a function GENOME is the complete set of chromosomal and extra-chromosomal genes present in an organism INTODUCTION TO HUMAN GENOME PROJECT The human genome project (HGP) was an international scientific research project The idea was picked up by the US government Two major funding agencies , the US Department of Energy and National Institute of Health with international partners in a quest to sequence all 3 billion base pairs BINFORMATICS is another branch which simultaneously developed in order to store and analyze information of HGP the ethical legal and social implications (ELSI) was established in 1989 3

4. Timelines/milestones 1985 - Robert Sinsheimer at UCSC proposed the idea of sequencing the human genome. 1986 - the U.S. Dept of Energy and the National Institute of Health came forward to fund the Human Genome Project. 1990 – HGP was officially launched with James Watson as its Project Director. the 1st gene to be mapped was BRCA1, which is the gene for breast cancer. 1994 – HGP’s Human genetic mapping goal was achieved. 2003 - finished version of human genome sequence was completed. HGP ended with all the goals achieved. 4

5. Pioneers of Human Genome Project Robert Sinsheimer proposed the idea of sequencing the human genome in the year 1985. Charles DeLisi and David Smith proposed the budget for Human Genome Project. James Watson headed the NIH Genome Program. Francis Collins succeeded James Watson in 1993 as the overall Project Head and the Director of the NIH . Jim Kent , developed a software , GigAsseblemr , that allowed the publicly funded Human Genome Project to assemble and publish the human genome sequence 5

6. Goals Of Human Genome Project To identify the all genes in human DNA To develop a genome linkage map and physical map of human genome To know the functions of genes To determine the sequence of 3 billion base pairs that make up human DNA Store this information in public database 6

7. Strategies/technical aspects of HGP GENE MAPING : the graphical representation of arrangement of genes or DNA sequences in a chromosome It is two types Physical mapping A physical map is an ordered set of DNA fragments expressed in physical units ( basepairs ) Physical mapping uses molecular biology techniques to examine DNA molecules directly in order to construct maps showing the positions of genes. Genetic Maps A genetic map is based on the frequencies of recombination between adjacent genes during crossover of homologous chromosomes Genetic markers are invaluable for genome mapping A genetic marker is a gene or DNA sequence with a known location on a chromosome that can be used to identify individuals or species. An example of a marker includes restriction fragment length polymorphisms (RFLP). 7

8. DNA Sequencing Sequencing means determining the exact order of the base pairs. method used by the HGP to produce the finished version of the human genetic code is map based or BAC based sequencing DNA Sequencing methods 1. Maxam -Gilbert chemical cleavage method 2. Sanger chain-termination method 3. shotgun method 8

9. SANGER’S METHOD • Developed by Frederick Sanger and colleagues in 1977 He used a third form of ribose in which the hydroxyl group is missing from both the 2’ and the 3’ carbons that is dideoxyribose whenever a dideoxynucleotide was incorporated into a polynucleotide, the chain would irreversibly stop, or terminate that’s why it is also called as chain termination method 9

10. ddNTPs lack the 3’ OH group to which the next dNTP of the growing DNA chain is added. Without the 3’ OH, no more nucleotides can be added, and DNA polymerase falls off. The resulting newly synthesized DNA chains will be a mixture of lengths, depending on how long the chain was when a ddNTP was randomly incorporated. 10

11. Shotgun Sequencing Shotgun sequencing, also known as shotgun cloning, is a method used for sequencing long DNA strands or the whole genome. In shotgun sequencing, DNA is broken up randomly into numerous small segments and overlapping regions are identified between all the individual sequences that are generated. Multiple overlapping reads for the target DNA are obtained by performing several rounds of this fragmentation and sequencing. Computer programs then use the overlapping ends of different reads to assemble them into a continuous sequence. The shotgun approach was first used successfully with the bacterium Haemophilus influenzae . Craig Venter used this method to map the Human genome project in 2001. 11

12. Genome Annotation The process of identifying the locations of genes and the coding regions in a genome to determine what those genes do Finding and attaching the structural elements and its related function to each genome locations Structural annotation: gene structure prediction Identifying elements( Introns / exons,CDS,stop,start ) in the genome Functional annotation: gene function prediction Attaching biological information to these elements eg : for which protein exon will code for 12

13. A vector is a DNA molecule that has the ability to replicate in an appropriate host cell, and into which the DNA insert is integrated for cloning Two of the most popular vector: 1.Yeast artificial chromosomes (YACs): are genetically engineered chromosomes derived from the DNA of the yeast, Saccharomyces cerevisiae , 2.Bacterial artificial chromosomes (BACs): A bacterial artificial chromosome (BAC) is an engineered DNA molecule, used to clone DNA segment in bacterial cells ( E. coli). Vectors For Human Genome Project 13

14. Salient Feature Of HGP (Outcomes) Human genome contains 3164.7m (3.1b ) base pairs Average gene contents of 3000 bases largest human gene- dystrophin (2.4m bases) Total number of genes 30,000 Repeated sequences make large portions Less than 2% genome codes for proteins 1.4 million locations have SNP’s 14

15. Applications Helps in identifying disease causing gene. design “custom drugs” ( pharmacogenomics ) based on individual genetic profiles. Improve gene theraphies Benefitted the advancement of forensic science Disadvantages: 15 years $3billions 15

16. Conclusion The human genome has been a long process worked on by many research scientist at many different locations. The project ended costing about $2.7billion Now that all 30,000 or so genes that make up the human genome have been deciphered, pharmaceutical industries are emerging to capitalize the custom based drug treatment. Understanding human genetic variation promises to have a great impact on our ability to uncover the cause of individual variation in response to therapeutics. The study of association between genetics and drug response is called pharmacogenomics . The potential implication of genomics and pharmacogenomics in clinical research and clinical medicine is that disease could be treated according to the interindividual differences in drug disposition and effects, thereby enhancing the drug discovery and providing a stronger scientific basis of each patient's genetic constitution 16

17. References Ananthanarayan and Paniker (2009)Text book of microbiology,8 th edition,page no:63,68,483,487 Dr R Vasanthakumari (2013)Textbook Of Microbiology,2nd Edition,page no:242 Roger Y. Stanier , John L Ingraham , Mark L Wheelis , Rage R Painter(1992)General Microbiology,5 th edition,page no:321-323 https://www.genome.gov/12011238/an-overview-of-the-human-genome-project/ 17

18. THANK YOU 18