Presentation on theme: "10-18-08 Progress in Genomics in the last few Years & Future Prospects Genomics: The study of genes and their functions. Includes - understanding the structure."— Presentation transcript:
10-18-08 Progress in Genomics in the last few Years & Future Prospects Genomics: The study of genes and their functions. Includes - understanding the structure of the genomes - mapping genes and sequencing the DNA. Genomics examines the complex feedback mechanisms by which gene expression is controlled, and the interplay of genetic and environmental factors in disease.
Genomics subspecialties include: Functional genomics - Describes the way in which genes and their products, proteins, interact together in complex networks in living cells. If these interactions are abnormal, diseases can result. Structural genomics - the dissection of the architectural features of genes and chromosomes. Comparative genomics - the evolutionary relationships between the genes and proteins of different species. Epigenomics (epigenetics) - genetic effects not caused by changing DNA sequences (usually involving methylation) Pharmacogenomics - finding new biological targets and new ways to design drugs and vaccines.
Types of Mutations Point Mutations - One base added, deleted, or substituted for another
Other Types of Mutations Groups of bases, or whole genes may be added, deleted, inverted, or copied or moved to new locations
Other Types of Genetic Variation More Recently Discovered In Humans Methylation - attachment of CH 3 groups to DNA, which affects gene expression, and can be heritable. Identical twins may differ here Copy Number Variation (CNV) - People can have different numbers of copies of the same gene. The same person can have different numbers of copies in different tissues, or even different on the members of a pair of the same chromosomes. Thus there is more genetic variation among humans than recently thought. At a Webinar presentation this summer on CNV, the estimate of the average genetic difference between two random humans was upped from.1% to.5%
Most mutations lower survival probability, so they and their bearers were eliminated, at least until modern society. Harmless ones may spread within populations. This is called genetic drift. Rarely, mutations enhance their carrier’s survival chances within their environment, and become the norm in that group. The latter two types of mutations have produced the existing races and sub-races from groups isolated in different environs. Geneticists have been able to analyse these mutations in recent years to trace their migrations out of Africa and beyond in surprising detail.
Where and when groups of Homo sapiens migrated from Africa,evolving as they went.
Many religious fundamentalists deny evolution happened at all. The dysgenic leftist religion dogmatizes that evolution stopped acting on Homo sapiens when some of them left Africa about 50,000 years ago. In reality, evolution has continued to accelerate exponentially.
Some Discoveries So Far About Recent Human Evolution The FOXP2 gene, related to language ability, changed to its present form about 200,000 years ago, Before modern humans left Africa. About 37,000 years ago, a variant of a gene called microcephalin arose among people who had left Africa. This form of the gene causes the brain to grow larger. It spread rapidly among those who had left Africa, but is still much less common in sub-Saharan Africans. This change was soon followed by the flowering of the Aurignacian culture in Europe, best known for major improvements in the refinement of stone and bone tools, and the impressively sophisticated cave paintings in Spain and southern France.
A new allele of the gene ASPM arose 6,000 years ago. This may have helped helped enable development of writing and alphabets. It is now carried by 44% of Caucasians, is less common in East Asians, and rare to nonexistent in sub-Saharan Africans. The work of the Chinese-American geneticist Bruce Lahn, who discovered these last two variants has, tragically, apparently been stifled by dysgenicists. There are surely more such mutations left to be discovered. Since leaving Africa, people have become genetically less inclined to interpersonal violence and aggression. This was necessary for, and selected for, by the development of large permanent settlements, which were a prerequisite for civilization.
The Most Biologically Successful Human The typical male living in 1200 AD has 20 males today carrying his Y chromosome, because there are 20 times as many people now. Researchers have found one specific Y-chromosome carried by about 16 million men, mostly in Asia. They have determined it began proliferating about 1200 AD., and is almost surely that of Ghengis Khan. Ghengis had the most attractive women of each conquered area brought to him. He spent much of his time breeding when not conquering. His numerous sons generally did likewise.,
A Striking Example of Very Recent Human Evolution From about 800 - 1800 AD, the Jews of Europe, or Ashkenazim, were often restricted to jobs in finance, requiring high abstract intelligence. High quantitative reasoning ability was intensely selected for This likely selected for alleles which alter phospho-lipid and sphingo- lipid metabolism in the brain, because these can increase the number and strength of synaptic connections in heterozygous individuals. This led to a striking and persistent 12 -15 point higher average IQ Because of the nature of the IQ Bell Curve, the proportion of Jews rises exponentially at the higher end of the curve, where those are who produce the most critical advances in math & science, the basis for modern civilization.
Ashkenazim have won > 23% of Nobel prizes in science and medicine, tho only ~0.2% of the world’s population, despite discrimination, & persecution, and despite that being homozygous for some of the related genetic changes produces fatal neurological disorders, such as Tay-Sachs disease.
The Personal Genome Project The largest current coordinated project to get useful medical info from human genomics is run by Prof. George Church, head of computational genomics at Harvard Medical School The Goal is to sequence the exome (the 1% of the genome that actually codes for proteins) of 100,000 people. Volunteer participants agree to anonymous online publication of both their exome and much data on their phenome (the sum of an individual’s observable or measurable attributes, such as height, weight, medical history, et al.) All Researchers are free to try to find statistical correlations between the exome and phenomic traits.
Trends in Cost of Genomic Sequencing The current price/performance leader is probably the sequencer Church’s team developed. He says it is running at ~ 1/3 the cost of the Applied Biosystems machine, which recently claimed to have sequenced a human genome for $60,000 The rate of improvement in cost/genome is making Moore’s Law for cpu’s look like molasses flow in January. Several groups are racing for the $10 million Archon X Prize for Genomics, which is offered for the first team that can sequence 100 complete genomes in 10 days for < $10,000 each. A consensus of experts in the field think the cost / genome can be brought down to about $1,000 within 10 years, making it a routine part of preventive and diagnostic medical care for most people.
A startup called Pacific Biosciences vows to sequence a genome in 15 minutes for less than $1,000 by 2013,bringing genomics to the masses. They are backed by blue-chip venture capital firms including Mohr Davidow and Kleiner Perkins, Competitors Illumina ( ILMN ), Applied Biosystems ( ABI ), ILMN ABI and Helicos BioSciences ( HLCS ) have gone public. HLCS Complete Genomics and VisiGen Biotechnologies are still private. Analysts say this market could jump from its current $1.5 billion in revenues to tens of billions.
Some Personal Testing & Analysis Available as of Summer 2008 National Geographic Project: $99.95. Detects which branches of the Human diaspora your genes come from. DeCode & 23andMe : ~$1,000. Microarray tests for ~1 million known variants. Access to online database on medical risks & ancestry. Navigenics: $2,500. Microarray tests for ~1 million known variants. Includes personal counseling on medical risks. DNA Direct: $175 - $3,456. Various tests related to specific medical conditions. Knome: Full genome sequence. $350,000 (price expected to drop soon)
Potential Benefits of Genomics - Personalized preventive medicine and treatment based on individual risk profiles and prediction of likely drug effects. Example: The Hi-blood pressure drug Bildil was almost abandoned because it seemed not to help most people. Jay Cohn noticed it helps most people of African origin It probably enhances a protein, at a low level in Africans, that rids the body of excess salt. In the tropics, it is important to retain salt, but in America the same genetically lo level of that protein leads to chronic hi blood pressure and strokes, which are more prevalent among African Americans.
More Benefits - A vastly better understanding of human minds and their emotional defects in coping with the modern world. - A chance to reverse the current mass-psychotic dysgenics policies and trends in the West, currently retarding the advance of civilization. These started as a paranoid reaction to Germany and Japan’s errant eugenics policies. There won’t need to be any more racial conflict, because everyone can potentially share the best and most desirable genes available. These improvements will be resisted strongly, but will prevail because of the nearly universal human instinct to improve prospects for themselves and their children. It may be possible to genetically engineer organisms to economically produce renewable fuels and other chemicals, including drugs. -
Risks Congress recently passed a law intended to prevent discrimination based on genetic data. - From history, we can predict that most of the inevitable deluge of related government antics will be late, based on ignorance, fear of change, and biased to favor the richest and most fanatic lobbies involved. - Stifling bureaucracy, and Long and costly law suits. - As usual, the rich and powerful will get first access to expensive new treatments and enhancements. - Terrorists and governments will be more easily able to engineer deadly vectors of pandemics. Al Qaida has said it is Muslims’ duty to get such weapons and use them against non-muslims.
The American College of Medical Genetics www.acmg.net www.acmg.net is the main group trying to establish standards of accuracy, honesty, and public awareness of ethical implications. It is open to all genetics-related professionals. Genetics in Medicine, now published monthly, is the official journal of the ACMG. http://www.acmg.net//AM/Template.cfm?Section=Home3
Summary (1 of 2) Studies of ancient and modern DNA have given vastly more accurate details on the evolutionary relationships of most major known species We now know to where and when, within a few thousand years, our ancestors went after the one main group of 500-2,000 left Africa about 50,000 years ago We have only about 20-25 thousand genes, but their interrelated control mechanisms are much more complex than imagined until the last 5 years Price /performance of genetic sequencing is improving much faster than Moore’s Law. A full sequencing is likely to drop to ~$1,000 within 5-10 yrs.
Summary (2 of 2) Within a few years of we may be able to change our genomes & phenomes with major effects These changes can bring huge benefits to individuals and society, but also hold great risks. The most imaginative researchers are well aware of our ignorance of how all the aspects of genetics and the environment interact. Craig Venter pithily summed it up after he finished sequencing his genome: "We don't know sh*t about biology!".
Sources Molecular Biology of the Cell, 5th Ed., 2008 By Bruce Alberts, Alexander Johnson, Julian Lewis, Martin Raff, Keith Roberts, Peter Walter (the leading cell biology textbook for > 25 years) Before the Dawn: Recovering the Lost History of Our Ancestors by Nicolas Wade, 2007, The Penguin Press. 1 ET, Kodama G, Baldi P, Moyzis RK. 2006. Global landscape of recent inferred Darwinian selection for Homo sapiens Proc Nat Acad Sci USA 103:135-140. 2 History of Ashkenazi Intelligence By Gregory Cochran, Jason Hardy, Henry Harpending,Department of Anthropology, University of Utah, Salt Lake City, UT 84112 USA http://homepage.mac.com/harpend/.Public/AshkenaziIQ.jbiosocsci.pdf Paleoanthropology, Genetics, & Evolution Blog of John Hawks, Associate Professor of Anthropology, University of Wisconsin, Madison http://johnhawks.net/weblog/hawks/hawks.html
Genetic Early Adopters By Emily Singer, Technology Review, Sept. 8, 2008 file:///Users/Eric/Desktop/Genomics%20Ppt/The%20Genetic%20Early%20A dopters.webarchive Genomes ‘R’ Us by Michael Copeland, Fortune Magazine, Sept. 1, 2008, p. 46 Publications good for keeping up: Science, Nature, Technology Review, Scientific American, Science News Ray Kurzweil’s free e-newsletter http://www.kurzweilai.net/index.html?flash=1 iSteve.com - Genetics http://www.isteve.com/Articles_Genetics.htmhttp://www.isteve.com/Articles_Genetics.htm - Excellent journalist who refuses to obey P.C. censorship rules,