Human Genome ProjectGeorgia Stangeland, Melis Colak, Lisa Feng
History• 1990: with the joint cooperation of the United States Department of Energy and the National Institutes of Health, the Human Genome Project was initiated• 1998: Celera Corporation launched a parallel project to race against the public sector• 2000: a working draft of the human genome was completed• 2001: analyses of the working draft were published• 2003: the Human Genome Project was completed
Goals• Identify all the genes in human DNA• Determine the sequences of the nitrogenous base pairs that make up human DNA• Put information in databases for storage and reference• Discover more efﬁcient technologies for data analysis• Allow the private sector access to information and new technologies that arise from this project• Address the ethical, legal and social issues
Hierarchical Shotgun Method• Used by the publicly funded section of the HGP (the government)• How it is done: ✓ Genomic DNA cut into random fragments ✓ Inserted into BAC (bacterial artiﬁcial chromosome) vectors transform E. coli bacteria to be replicated ✓ Inserts isolated and mapped (Golden Tiling Path) ✓ Inserts fragmented and cloned in plasmids ✓ Sequences aligned so identical ones are overlapped http://www.bio.davidson.edu/courses/genomics/method/ shotgun.html
Whole Genome Shotgun Sequencing Method• Developed and used by the private section of the HGP (Celera)• How it is done: ✓ Random cutting into genomic DNA ✓ Fragments cloned in plasmids ✓ Obtained sequences are aligned and reassembled http://www.bio.davidson.edu/courses/genomics/method/ shotgun.html
Sanger Method• Invented by English biochemist Frederick Sanger• Earned him his second Nobel Prize in Chemistry in 1980 http://en.wikipedia.org/wiki/File:Frederick_Sanger2.jpg
• Also called the “dideoxy method” for its use of dideoxynucleotides• Also called the “chain termination method” due to the use of dideoxynucleotides that ceases the DNA chain elongation http://users.rcn.com/jkimball.ma.ultranet/ BiologyPages/D/DNAsequencing.html
Dideoxynucleotides• Lack the -OH chain at the 3’ end of DNA• Inhibits further elongation of DNA past the dideoxynucleotide due to the lack of the O atom• Dyed to be seen once ﬂuoresced using laser beams• Each nitrogenous bases ﬂuoresces different colours
How it is done• DNA template supplied with : ❖ deoxynucleotides (dATP, dTTP, dGTP, dCTP) ❖ dideoxynucleotides that have been dyed in different colours (ddATP, ddTTP, ddGTP, ddCTP) ❖ Taq DNA polymerase
Ethical, Legal, and Social Issues• Privacy and Conﬁdentiality of Genetic Information ✓ Who should have access to the information? ✓ Who owns and controls the genetic information? ✓ Should the genetic information have patents or copyrights attached to it?• Fairness in the use of Genetic Information ✓ How will this personal information be used? ✓ Should an individual be denied health insurance because of an increased risk of a disease found in their personal genome?• Psychological Impact, Stigmatism and Discrimination ✓ How does personal genetic information affect an individual and society’s perceptions of the individual? ✓ How does the genomic information affect members of minority communities?
Case StudyKyle is a gifted athlete who recently became aprofessional football player and signed a $50 millioncontract. During a routine physical checkup, Kyle wasgenetically tested, along with the rest of the team, forrisk of heart disease (a positive result would mean thatthe individual has a higher risk for the disease but itdoes not mean he or she will deﬁnitely become sick).Kyle’s test declared that he has a 25% chance ofdeveloping a speciﬁc heart disease. As a result, Kylewas released from his contract because the team did notwant to take any chances, even though Kyle was notsick and was not guaranteed to develop any heartdisease.
Beneﬁts• Molecular Medicine ✓ detect genetic predispositions to disease ✓ design pharmacogenomics (“custom drugs”) based on an individual’s genetic proﬁle• DNA Identiﬁcation ✓ identify potential suspects whose DNA may match evidence left at crime scenes ✓ exonerate persons wrongly accused of crimes ✓ identify crime and catastrophe victims ✓ establish paternity and other family relationships ✓ match organ donors with recipients in transplant programs
Relevance to Modern Day Science• Gene Testing Therapy• Pharmacogenomics• Gene Therapy
Gene Testing Therapy• A new form of testing for genetic disorders• Directly examines the DNA molecule itself• Uses: ✓ prenatal diagnostic testing ✓ newborn screening http://www.topnews.in/health/genetic-test-personalized-cancer- therapy-27653 ✓ forensic/identity testing
Pharmacogenomics• A branch of pharmacology• DNA may inﬂuence how a person receives a drug and its side effects• Customize treatments based on an individual’s genotype http://www.freewebs.com/pharmacogenomics/
Gene Therapy• direct alteration, insertion, or deletion of an individual’s DNA to treat diseases• corrects malfunctioning genes that are responsible for the development of diseases http://www.beltina.org/health-dictionary/gene-therapy- human-what-is-deﬁnition.html
ConclusionThe Human Genome Project hasenabled us to explore a new worldof self-identiﬁcation. It is extremelyhelpful when identifying criminalsor genetic diseases. It can be thebasis of technological and socialdevelopment in the near future. Andthus unlocks the door to newprospects.
Resourceshttp://www.councilforresponsiblegenetics.org/blog/post/Anniversary-of-the-Human-Genome-Project-Anything-to-Celebrate.aspxCook-Deegan R (1989). "The Alta Summit, December 1984". Genomics 5 (3): 661–3.doi:10.1016/0888-7543(89)90042-6Barnhart, Benjamin J. (1989). "DOE Human Genome Program". Human Genome Quarterlyhttp://genomics.energy.gov/http://www.ornl.gov/sci/techresources/Human_Genome/medicine/genetest.shtml http://www.topnews.in/health/genetic-test-personalized-cancer-therapy-27653 http://pharmaxchange.info/press/2011/01/gene-therapy-2/ http://www.freewebs.com/pharmacogenomics/ http://www.beltina.org/health-dictionary/gene-therapy-human-what-is-deﬁnition.html http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/D/DNAsequencing.html http://www.bio.davidson.edu/courses/genomics/method/shotgun.html http://home.comcast.net/~john.kimball1/BiologyPages/D/DNA_sequence.gif http://www.nature.com/scitable/topicpage/dna-sequencing-technologies-690http://www.dnalc.org/resources/animations/sangerseq.htmlhttp://www.woodrow.org/teachers/bi/1992/human_genome.htmlhttp://www.ornl.gov/sci/techresources/Human_Genome/publicat/primer/prim2.htmlhttp://www.genomenewsnetwork.org/articles/06_00/sequence_primer.shtml