PursueNatural has a goal to encourage you to be the master of your own genome – the biological inheritance from your parents. In a few years, it will become apparent that biological inheritance knowledge may be a life saver , and a gift equally valuable as financial inheritance. However, heredity is not destiny since genes alone do not define you. Harvard School of Public Health says that environmental factors (unknown), nutrition and physical activity offset the action of inherited obesity genes; however, the presence of the obesity genes in some people necessitate actions for prevention of obesity suchas higher levels of physical activity.
Just like you know how to regulate the temperature of your own home with the simple flip of a switch, in the same way you should want to know which “switch” controls the temperature of your body. How does your body regulate and differentiate between an infection and a very cold day? Today, we do not know the answer but the day is near when we will. At the very least, in the near future, we will be able to pinpoint a region in your genome which is different from that of your best friend, who could possibly tolerate a cold day far better than you and yet, succumb to an infection which you can fight off easily.
The ENCODE project studied 140 of the hundreds of cell types and identified many of the cell type specific control elements in the human body. The results of the ENCODE project (see below) best describe the regulation of the human genome.
“We were surprised that disease-linked genetic variants are not in protein-coding regions,” said Mike Pazin, Ph.D., an NHGRI program director working on ENCODE. “We expect to find that many genetic changes causing a disorder are within regulatory regions, or switches, that affect how much protein is produced or when the protein is produced, rather than affecting the structure of the protein itself. The medical condition will occur because the gene is aberrantly turned on or turned off or abnormal amounts of the protein are made. Far from being junk DNA, this regulatory DNA clearly makes important contributions to human health and disease.”
Let us begin the narration in the year 1953, when biologists, chemists and physicists became united in their excitement for the first time because James D. Watson and Francis Crick discovered the DNA-helix and shared the Nobel Prize nine years later with Maurice Wilkins, for solving one of mankind’s great riddles. The revolution in molecular genetics had begun.
The Discovery of the First Human Disease Gene
The first human disease gene was discovered in 1989 and announced with the publication of three historic papers on the process of discovery of the Cystic Fibrosis (CF) gene in the Journal Science, by three teams led by team leaders Dr. Lap Chi Tsui, who discovered that 70 percent of cystic fibrosis patients had three mutations in the CF gene; Dr Jack Riordan, who could detect the three mutations in diseased CF patient tissue; and Dr. Francis Collins who identified the CF gene segment on chromosome 7 and cloned the CF gene with the technique of chromosome walking and jumping. The latter technique of chromosome jumping was published a few years earlier in 1984 by Dr. Francis Collins under the direction of Dr. Sherman Weissman at Yale University. For the next nine years Dr. Francis Collins’s laboratory perfected the technique of identifying disease genes earning him the title of ‘gene hunter’. In 1993, looking for a successor after the resignation of Dr. James Watson, the National Human Genome Research Institute (NHGRI) of the NIH requested gene hunter, Dr. Francis Collins to lead them. For over a decade he led the institute to benefit science, medicine and humankind. He has been a proponent of personalized medicine and emphasized the importance of legal and ethical issues in genetics and genomics, particularly those concerned with privacy of genetic information, and discrimination in employment and insurance based on genetic information.
The First Sequence of the Human Genome
The age of biology probably began in 2001, when the International Human Genome Consortium published and reported the first initial analyses of the draft sequence of the human genome. A year earlier, in 2000, a completion of a working draft of the human genome sequence was announced amid much fanfare by President Bill Clinton with Dr. Francis Collins and Dr. Craig Venter. Since then, the international collaboration has been working to convert this draft into a complete genome sequence with high accuracy and nearly complete coverage. An update was published with 99% coverage and an error rate of 1 event per 100,000 bases in build 35 which has 2.85 billion nucleotides interrupted by only 341 gaps. This update publication serves as a firm foundation for biomedical research. Notably, the human genome seems to encode only 20,000 to 25,000 protein – coding genes. Many of the remaining gaps have duplications which will require new methods of study.
The First Supreme Court Decision on The Human Genome through a Controversial Gene patent
Dr. Francis Collins belongs to the group that believes in keeping the genome sequence free for all to access. Dr. Craig Venter belongs to the group that is a proponent of gene patents for commercial interests. Academic and commercial interests on genetic sequences clashed with the breast cancer gene patents owned by Myriad, over the cost of diagnosis of a breast cancer gene. The patents on the breast cancer genes used in diagnosis where owned by one company and this right was challenged all the way to the Supreme Court. In a unanimous 9-0 historic ruling, the Supreme Court announced the bar of human gene patenting and indicated that the naturally occuring genes of the Human Genome must remain free for all (Read the “Case summary and information” by the ACLU; read the New York Times article by Adam Liptak, “Justices, 9-0, bar patenting of Human Genes“). Ironically, the University of Washington’s geneticist, Dr. Marie-Claire King, who discovered the breast cancer gene is elated with the Supreme Court’s landmark ruling. Exclusive rights to genetic material have hampered research and the progress of science. While Dr King discovered the genes and the location of the genes, scientists at the University of Utah cloned the genes, patented them and marketed them. Dr. King can now market a better test that her team has developed, which had been prohibited by the patent. A 2013 film, “Decoding Annie Parker” dramatizes the story of the Breast cancer gene patent battle involving a single patient, Annie Parker, and discusses a little bit of the relevant science behind the patent.
The question remains how much exclusivity do you grant creatively to commercial entities to make it worth their while to invest in new discoveries. Is there a creative answer to encourage industry participation in the human genome era?
The ENCODE Project challenging the traditional view of how the Human Genome functions
Recently, there has been a very controversial sequel to the Human Genome Project announcement of the Draft sequence in 2000. The traditional view is that the human genome consists of a small number of genes and a vast expanse of junk-DNA with no function. Which means the junk-DNA is not biologically active. The ENCODE project was established by the NHGRI to identify all functional elements of the human genome. They published a set of papers in 2007 which challenged the traditional view of our genetic blueprint having discovered that genes do not function as independent entities. Rather, through a complex network, genes interact with DNA sequences that do not encode proteins; junk-DNA is involved in biologically active processes in a yet unknown manner. Read “New Findings Challenge Existing Views on the Human Genome“. This was the result of a pilot effort involving 35 groups in 80 world-wide organizations over 14 years to identify all functional elements in 1% of the Human Genome.
Dr. Francis Collins says this pilot project blazed the way to explore the functional landscape of the entire human genome. Several evolutionary biologists criticized the publication of the ENCODE data, being of the view that ENCODE was a group of computer biologists who did not understand the biology of the human genome. The protein coding segment of the human genome accounts for about 2% of the functional genome and evidenve exists for important functions in the rest of the genome. To access the human ENCODE data at UCSC click here.
On September 2012, an NHGRI funded study published a more dynamic view of how the Human Genome functions. Read “ENCODE data describes function of human genome“. Dr. Eric D. Green, the new Director of the NHGRI since 2009, is of the view that ENCODE has revealed that most of the human genome is involved in the complex choreography of converting genetic information into living cells and organisms (Read). The remarkable scale of this ENCODE project involved hundreds of researchers in USA, UK, Singapore, Japan and Spain with technologies standardized across the consortium. Some of the technologies only became available five years before this publication.
The ENCODE Consortium placed the resulting data sets as soon as they were verified for accuracy, prior to publication, in several databases that can be freely accessed by anyone on the Internet. These data sets can be accessed through the ENCODE project portal (www.encodeproject.org) as well as at the University of California, Santa Cruz genome browser, http://genome.ucsc.edu/ENCODE/, the National Center for Biotechnology Information, http://www.ncbi.nlm.nih.gov/geo/info/ENCODE.html and the European Bioinformatics Institute, http://useast.ensembl.org/Homo_sapiens/encode.html?redirect=mirror;source=www.ensembl.org.
The coordinated publication set includes one main integrative paper and five related papers in the journal Nature; 18 papers in Genome Research; and six papers in Genome Biology. The ENCODE data are so complex that the three journals have developed a pioneering way to present the information in an integrated form that they call threads.
Since the same topics were addressed in different ways in different papers, the new website, http://www.nature.com/encode, will allow anyone to follow a topic through all of the papers in the ENCODE publication set by clicking on the relevant thread at the Nature ENCODE explorer page. For example, thread number one compiles figures, tables, and text relevant to genetic variation and disease from several papers and displays them all on one page. ENCODE scientists believe this will illuminate many biological themes emerging from the analyses.
In addition to the threaded papers, six review articles are being published in the Journal of Biological Chemistry and two related papers in Science and one in Cell.
The ENCODE data are rapidly becoming a fundamental resource for researchers to help understand human biology and disease.
The NHGRI will invest in four more years to cover some more of the remaining part of the human genome.