T H G P: HE Uman Enome Roject
T H G P: HE Uman Enome Roject
T H G P: HE Uman Enome Roject
INTRODUCTION
Until the early 1970s, DNA was the most difficult cellular molecule for biochemists to analyze. DNA is now the easiest molecule to analyze we can now isolate a specific region of the genome, produce a virtually unlimited number of copies of it, and determine its nucleotide sequence overnight.
INTRODUCTION
At the height of the Human Genome Project, sequencing factories were generating DNA sequences at a rate of 1000 nucleotides per second 24/7. Technical breakthroughs that allowed the Human Genome Project to be completed have had an enormous impact on all of biology..
http://doegenomes.org
U.S. Department of Energy Genome Programs, Genomics and Its Impact on Science and Society, 2003
Unlike the human's seemingly random distribution of gene-rich areas, many other
organisms' genomes are more uniform, with genes evenly spaced throughout. Humans have on average three times as many kinds of proteins as the fly or worm because of mRNA transcript "alternative splicing" and chemical modifications to the proteins. This process can yield different protein products from the same gene.
Humans share most of the same protein families with worms, flies, and plants; but the
number of gene family members has expanded in humans, especially in proteins involved in development and immunity. Although humans appear to have stopped accumulating repeated DNA over 50 million years ago, there seems to be no such decline in rodents. This may account for some of the fundamental differences between hominids and rodents, although gene estimates are similar in these species. Scientists have proposed many theories to explain evolutionary contrasts between humans and other organisms, including those of life span, litter sizes, inbreeding, and genetic drift.
http://doegenomes.org
U.S. Department of Energy Genome Programs, Genomics and Its Impact on Science and Society, 2003
Scientists have identified about 3 million locations where single-base DNA differences
(SNPs) occur in humans. This information promises to revolutionize the processes of finding chromosomal locations for disease-associated sequences and tracing human history. The ratio of germline (sperm or egg cell) mutations is 2:1 in males vs females. Researchers point to several reasons for the higher mutation rate in the male germline, including the greater number of cell divisions required for sperm formation than for eggs.
http://doegenomes.org
U.S. Department of Energy Genome Programs, Genomics and Its Impact on Science and Society, 2003
to the discovery of whole new classes of proteins and genes, while revealing that many proteins have been much more highly conserved in evolution than had been suspected. Provided new tools for determining the functions of proteins and of individual domains within proteins, revealing a host of unexpected relationships between them.
100 million
97 million 137 million 12.1 million 4.6 million
25,000
19,000 13,000 6,000 3,200
9700
http://doegenomes.org
U.S. Department of Energy Genome Programs, Genomics and Its Impact on Science and Society, 2003
improve diagnosis of disease detect genetic predispositions to disease create drugs based on molecular information use gene therapy and control systems as drugs design custom drugs (pharmacogenomics) based on individual genetic profiles Microbial Genomics
rapidly detect and treat pathogens (disease-causing microbes) 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
U.S. Department of Energy Genome Programs, Genomics and Its Impact on Science and Society, 2003
evaluate the health risks faced by individuals who may be exposed to radiation (including low levels in industrial areas) and to cancercausing chemicals and toxins
Bio-archaeology, Anthropology, Evolution, and Human Migration study evolution through germline mutations in lineages study migration of different population groups based on maternal inheritance study mutations on the Y chromosome to trace lineage and migration of males compare breakpoints in the evolution of mutations with ages of populations and historical events
U.S. Department of Energy Genome Programs, Genomics and Its Impact on Science and Society, 2003
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 identify endangered and protected species as an aid to wildlife officials (could be used for prosecuting poachers) 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 authenticate consumables such as caviar and wine
http://doegenomes.org
U.S. Department of Energy Genome Programs, Genomics and Its Impact on Science and Society, 2003
http://doegenomes.org
U.S. Department of Energy Genome Programs, Genomics and Its Impact on Science and Society, 2003
Anticipated Benefits:
improved diagnosis of disease earlier detection of genetic predispositions to disease rational drug design gene therapy and control systems for drugs personalized, custom drugs
http://doegenomes.org
U.S. Department of Energy Genome Programs, Genomics and Its Impact on Science and Society, 2003
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 individuals 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.
http://doegenomes.org
U.S. Department of Energy Genome Programs, Genomics and Its Impact on Science and Society, 2003
ELSI ISSUES
Uncertainties associated with gene tests for susceptibilities and complex conditions (e.g., heart disease, diabetes, and Alzheimers disease).
http://doegenomes.org
U.S. Department of Energy Genome Programs, Genomics and Its Impact on Science and Society, 2003
Earned his Ph.D. in Physiology and Pharmacology from the University of California at San Diego and became a researcher at the National Institutes of Health. While serving first as a Section Chief and then as a Lab Chief in the National Institute of Neurological Disorders and Stroke, he developed expressed sequence tags or ESTs, a revolutionary new strategy for gene discovery. In 1992, he and his wife, Dr. Claire Fraser, founded The Institute for Genomic Research known as TIGR, where he served as President and Chief Scientific Officer until 1998. Dr. Venter and his team at TIGR decoded the genome of the bacterium Haemophilus influenzae, making it the first free-living organism to have its full DNA deciphered and to date have sequenced over 30 genomes. He now serves as Chairman of the Board of Trustees of TIGR.
In 1998, he founded Celera Genomics and announced that Celera would decode the human genome faster and more economically than the publicly funded consortium of scientists. That challenge is now credited with creating the climate of urgency that spurred competition and substantially accelerated the projects successful conclusion. At the White House press conference announcing the sequencing of the human genome, President Bill Clinton called it the most important, most wondrous map ever produced by mankind.
SEQUENCE GAPS
Brown. Genomes 2
Map of Chromosome 16
http://www.ornl.gov/sci/techresources/Human_Genome/education/images.shtml
by clone $0.30 per finished base $130 million per year for 7 years Total $900 million spent by end of 2003 Shotgun $0.01 per raw base $130 million for 3 years would provide 10 coverage/redundancy plus an additional $90 million for informatics
http://www-management.wharton.upenn.edu/pennings/coursedocuments/executive_education_courses/557/genome%20Paper%201.doc
http://www-management.wharton.upenn.edu/pennings/coursedocuments/executive_education_courses/557/genome%20Paper%201.doc
ALGORITHMS
Human Genome Project: GigAssembler Celera: Celera Assembler Euler Algorithm