Genomics. Genomics. Understanding the human genome. The human genome. Genomics = study of an organism s entire genome or entire DNA sequence
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1 Genomics Genomics Genomics = study of an organism s entire genome or entire DNA sequence billion bases % of DNA shared Humans % Chimpanzee % Mouse % Chicken 1.0 So what s a genome? The Human Genome Completed in 2004 Contains 3.2 billion base pairs But only 25,000 genes a surprise About the same as other organisms More than one million single nucleotide changes (SNPs) These small genetic differences between people will usher in a new era of personalized medicine evolution human genome [4 min] The human genome Genes only comprise <2% of the genome Genes contain the instructions for proteins The rest? Introns Regulatory sequences Repeated sequences and (controversially) "junk" DNA Understanding the human genome Functional genomics Understanding how the 25,000 genes work Understanding the function of intergenic regions
2 Junk DNA is vital after all Understanding the human genome Junk DNA parts of DNA that are not actual genes is active Contains 4 million gene switches Act like dimmer switches Control which genes are used in a cell and when Determine if a cell becomes a liver cell or a neuron Enormous implications for human health caused by tiny changes in hundreds of gene switches Comparative genomics Help understand how species have evolved Comparing human genomes identify base sequences that cause illness Help understand how genes are switched on and off Everyone s DNA is unique The DNA in our genomes can be used like a fingerprint But we all share 99.5% of our DNA How does this happen? Here s an example of a SNP Normal (HbA) Mutant (HbS) A change in a single nucleotide in the gene for the β subunit of hemoglobin (CTC to CAC) What are SNPs? What can we learn from SNPs? Analyze the DNA of people with and without a particular disease Tally the SNPs that are found in people with disease Use to identify SNPs that predispose individuals to that disease diabetes bipolar disorder coronary artery disease OMG guess what my genes say! Right now we understand very little of the meaning of those 3 billion bases About 20 potentially preventable health problems can be detected with gene testing e.g. BRCAI gene Coming soon inexpensive, widely available whole-genome sequencing
3 Personalized medicine Genetic engineering What is Genetic Engineering? Genetic engineering Moving genes from one organism to another Genes can be taken from one organism (plant, animal, virus, or bacteria) and transferred to another. Examples: Moving a human gene (e.g. the insulin gene) into bacteria Moving a bacterial gene (e.g. Bt toxin) into plants How is genetic engineering used? Medicine To develop drugs insulin, anticoagulants, human growth hormone, etc Use GE to obtain large amounts of rare proteins To make vaccines against viruses Agriculture Introduce pesticides or herbicideresistance into plants What was the First Commercial Use of Genetic Engineering? Producing human insulin in bacteria. In 1982, the FDA approved genetically engineered insulin for use by diabetics. Most of the insulin that s used to treat diabetics is now obtained from GE bacteria that contain the human insulin gene
4 Engineering bacteria to make human insulin insulin Isolate the gene for insulin and paste it into a plasmid Transfer the plasmid into bacteria Bacteria reproduce rapidly They become tiny insulin-producing factories Human insulin is isolated from the fermentation vat Making human insulin Humulin is produced in 4-story tall fermentation vats Plasmids are small rings of DNA found in bacteria they are separate from the much larger bacterial chromosome. Vaccinations save lives Contamination was a problem And it was the pig (not human) hormone Now GE bacteria produce large quantities of pure human insulin DNA technology is used to make vaccines Pig pancreases were once used as a source of insulin. What are plasmids? Vaccines protect the body against disease-causing organisms (usually a virus) Some vaccines are made of purified viral proteins. Injected into a person Immune response Person is protected from infection by that virus Vaccines work by boosting the immune system How viruses infect cells Virus binds to the plasma membrane The virus is taken into the cell where it starts an infection Viral RNA is integrated into the cell genome The infected cell manufactures new virus. The infected cell eventually ruptures and dies, releasing newly made virus Flu Attack! How A Virus Invades Your Body NPR 3:39
5 Have you been vaccinated for human papillomavirus (HPV)? HPV is passed by skin-to-skin contact The most common sexually transmitted virus in the US At least 70% of sexually active persons will be infected with genital HPV at some time in their lives. HPV infects both men and women. Over 99% of cervical cancer cases are linked to long-term HPV infections Genetically engineered food Genetically Engineered Crops Moving genes from one organism to another a plant in this case Example: Isolate the gene for Bt, a bacterial toxin that kills insect larvae (caterpillars), and move it into corn Bt Bt corn that makes its own pesticide Genetically Engineered Crops Bt corn produces a toxin that kills corn borer caterpillars It makes its own pesticide Most common traits introduced The most common types of genetic changes in GE crops Resistance to insects Bt crops Contain the Bt gene for a bacterial toxin that kills certain insects a natural pesticide Resistance to weed killers (herbicides) found in over 80% of GE crops planted worldwide
6 Top 3 GE crops in the US In 2008, 92% of the soybeans and 80% of the corn planted in the US had been genetically engineered Why genetic engineering is good for agriculture Introduce desirable traits Make crop easier to grow Resistant to herbicides Resistant to insects (Bt) Improve nutritional content more protein, vitamins Tolerate stress Drought-tolerance and salt-tolerance Golden rice Genetically modified to produce iron and betacarotene, a precursor of Vitamin A. Golden rice Developed in : nearing approval in several countries Took over 10 yrs to demonstrate that golden rice is safe for the environment and for consumption Same process for other GE crops Able to proceed more rapidly if variety has been bred traditionally Have you eaten a GE food? 80% of corn, 92% of soybeans grown in U.S. are GE crops. Almost all processed foods in U.S. contain genetically engineered ingredients Look for high fructose corn syrup in soda, cereal, chips, mayo, etc Concerns about GE crops are they Frankenfoods? Genetic engineering has been the cause of considerable controversy and protest Is eating GM food dangerous? does adding genes introduce novel proteins that maybe potentially harmful when consumed? could introduced proteins be allergens? Each crop is tested for safety 3 government agencies monitor GE foods
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