Boris KrivovyazJudyta JuranekA and P II TheHuman Genome Project The Human Genome Project- also known as HGP, was an international effort to discover the exactmakeup of the genetic material that controls the way human beings develop and grow.The project involved scientists from around the world, who worked together toachieve their aims. The project began in 1990 .The Human Genome Project (HGP)was one of the great accomplishments of exploration in history – an inwardjourney of discovery rather than an outward exploration of the planet or thecosmos; an international research effort to group and map all the genes -together known as the genome – of members of our species, Homo sapiens.
Concluded in April 2003, the HGP gave us the capability, for the first time, toread nature’s complete genetic blueprint for constructing a human being. TheHGP has declared that there are possibly about 20,500 human genes. Thecompleted human sequence can now identify their locations. This ultimate productof the HGP has given the world a resource of detailed information about thestructure, organization and function of the complete set of human genes.
Thisinformation can be thought of as the primitive set of inheritable”instructions” for the evolution and behavior of a human being. TheInternational Human Genome Sequencing Consortium issued he first draft of thehuman genome in the journal Nature in February 2001, with the sequence of theentire genome’s three billion base pairs some 90 percent complete. A startlingfinding of this first draft was that the number of human genes appeared to be extremelyfewer than previous estimates, which ranged from 50,000 genes to as many as140,000. The full sequence was completed and issued in April 2003. Francis Collins, the director of NHGRI,whoissued the majority of the genome in 2001, noted that the genome could be thought of interms of a book with multiple uses, he states that “It’s a history book -a narrative of the journey of our species through time. It’s a shop manual,with an incredibly detailed blueprint for building every human cell.
And it’s atransformative textbook of medicine, with insights that will give health careproviders immense new powers to treat, prevent and cure disease.” Themeans created through the HGP also move forward to inform efforts to constitutethe entire genomes of several other organisms used extensively in biologicalresearch, such as mice, fruit flies and flatworms. These efforts support eachother, because most organisms have many similar, or “homologous,”genes with similar functions. Thus, the identification of the sequence orfunction of a gene in a model organism, for example, the roundworm C. elegans,has the potential to explain a homologous gene in human beings, or in one ofthe other model organisms.
These determined objectives will continue to impose avariety of new technologies that have made it possible to relatively increase constructionof the first draft of the human genome and to continue to refine that draft. Therefore, advanced methods for widelydisseminating the information generated by the HGP to scientists, physiciansand others, is necessary to ensure the most rapid application of researchresults for the benefit of humanity. Biomedical technology and research are recipientsof the HGP.
However, the momentous implications for individuals and society forpossessing the detailed genetic information made possible by the HGP wererecognized from the outset. Another major component of the HGP – and an ongoingcomponent of NHGRI – is therefore devoted to the analysis of the ethical, legaland social implications (ELSI) of our newfound genetic knowledge, and thesubsequent development of policy options for public consideration.BackgroundTheHuman Genome Project (HGP), which functioned from 1990 to 2003, providedresearchers with basic information about the sequences of the three billionchemical base pairs (i.e., adenine [A], thymine, guanine, and cytosine thatmake up human genomic DNA (deoxyribonucleic acid). The Human Genome Project wasfurther intended to improve the technologies needed to interpret and analyzegenomic sequences, to identify all the genes encoded in human DNA, and toaddress the ethical, legal, and social implications that might arise fromdefining the entire human genomic sequence.Priorto the Human Genome Project, the base sequences of numerous human genes hadbeen determined through contributions made by many individual scientists.
However, the clear majority of the human genome remained uncharted, andresearchers, having recognized the requirement and value of having at hand thebasic information of the human genomic sequence, were beginning to search forways to uncover this information more quickly. Because the Human Genome Projectrequired billions of dollars that would inevitably be taken away fromtraditional biomedical research, many scientists, politicians, and ethicistsbecame involved in vigorous debates over the merits, risks, and comparativecosts of sequencing the entire human genome in one concerted undertaking.Despite the debate, the Human Genome Project was introduced in 1990 under theleadership of American geneticist Francis Collins, with funding from the U.S.Department of Energy and the National Institutes of Health (NIH). The effortwas soon united by scientists from around the world. Moreover, a sequence oftechnical developments in the sequencing process itself and in the computerhardware and software used to track and analyze the resulting data permitted fastgrowth of the project. Animatedstructure of a DNA molecule, showing the deoxyribose sugar molecules (green)and phosphate molecules (yellow crosses) that form the rudimentary external agendaof the DNA double helix.
Sets of nitrogenous bases (adenine bound to thymineand guanine bound to cytosine), which form bonds that look like the steps of aladder, join the external elements of the DNA molecule.Technologicaladvance, though, was only one of the services driving the pace of discovery ofthe Human Genome Project. In 1998 a remote-subdivision enterprise, CeleraGenomics, regulated by American biochemist and former NIH scientist J. CraigVenter, started to contend with and possibly challenge the openly sponsoredHuman Genome Project. At the core of the rivalry was the outlook of acquisitionof control over possible copyrights on the genome sequence, which was measureda pharmacological gem . Although the lawful and fiscal details remain uncertain,the competition between Celera and the NIH finished when they joined forces, thereforemoving conclusion of the rough draft sequence of the human genome.
Theconclusion of the rough draft was declared in June 2000 by Collins and Venter.For the following three years, the rough draft sequence was polished, prolonged,and further examined, and in April 2003, coinciding with the 50th anniversaryof the publication that described the double-helical structure of DNA, writtenby British biophysicist Francis Crick and American geneticist and biophysicistJames D. Watson, the Human Genome Project was declared complete.The ScienceToappreciate the greatness, encounter, and suggestions of the Human GenomeProject, it is significant initially to reflect the basis of science upon whichit was founded—the fields of standard, molecular, and human genetics.
Standardgenetics is considered to have begun in the mid-1800s with the work of Austrianbotanist, teacher, and Augustinian prelate Gregor Mendel, who demarcated thebasic laws of genetics in his studies of the garden pea (Pisum sativum). Mendelprospered in explaining that, for any given gene, offspring get from eachparent one form, or allele, of a gene. In addition, the allele that anoffspring gets from a parent for one gene is self-regulating of the alleleinherited from that parent for another gene. Mendel’s basic laws of genetics were prolongedupon in the early 20th century when molecular geneticists began directingresearch using model organisms such as Drosophila melanogaster (also called thevinegar fly or fruit fly) that provided a more inclusive assessment of thecomplexities of genetic transmission.
For example, molecular genetics studies verifiedthat two alleles can be codominant (characteristics of both alleles of a geneare expressed) and that not all traits are defined by single genes; in fact,many traits reflect the joint influences of numerous genes. The field ofmolecular genetics arose from the understanding that DNA and RNA (ribonucleicacid) create the genetic material in all living things. In physical terms, agene is a distinct stretch of nucleotides within a DNA molecule, with eachnucleotide comprising of an A, G, T, or C base unit. It is the precise sequenceof these bases that encodes the information contained in the gene and that isultimately translated into a final product, a molecule of protein or in somecases a molecule of RNA. The protein or RNA product may have a structural roleor a regulatory role, or it may help as an enzyme to promote the formation ormetabolism of other molecules, as well as carbohydrates and lipids. All thesemolecules work in concert to preserve the processes required for life.Moleculargenetics arose from the realization that DNA and RNA constitute the geneticmaterial of all living organisms.
(1) DNA, located in the cell nucleus, is madeup of nucleotides that contain the bases adenine (A), thymine (T), guanine (G),and cytosine (C). (2) RNA, which contains uracil (U) instead of thymine,transports the genetic code to protein-synthesizing sites in the cell. (3)Messenger RNA (mRNA) then carries the genetic information to ribosomes in thecell cytoplasm that translate the genetic information into molecules of protein.Studiesin molecular genetics led to studies in human genetics and the observation ofthe ways in which traits in humans are inherited. For instance, most behaviorsin humans and other species result from a blend of genetic and environmentalinfluences. In accumulation, some genes, such as those programmed at neighboringspots on a single chromosome, tend to be inherited together, rather thanindependently, whereas other genes, namely those encoded on the mitochondrialgenome, are inherited only from the mother, and yet other genes, encoded on theY chromosome, are passed only from fathers to sons. By means of data from theHuman Genome Project, scientists have projected that the human genome containsanywhere from 20,000 to 25,000 genes.
Developmentsin genetics and genomics continue to arise. Two significant developments compriseof the International HapMap Project and the beginning of large-scalecomparative genomics studies, both of which have been made possible by the accessibilityof records of genomic sequences of humans, as well as the accessibility ofrecords of genomic sequences of a multitude of other species.TheInternational HapMap Project is a joint effort between Japan, the UnitedKingdom, Canada, China, Nigeria, and the United States in which the goal is to recognizeand collect the genetic similarities and differences between peoplerepresenting four major human populations derived from the continents ofAfrica, Europe, and Asia. The documentation of genetic variations calledpolymorphisms that exist in DNA sequences among populations lets researchers definehaplotypes, indicators that distinguish specific regions of DNA in the humangenome. Association studies of the frequency of these haplotypes in control andpatient populaces can be used to help recognize possibly functional geneticdifferences that influence an individual toward disease or, alternatively, thatmay defend an individual from illness. Likewise, association studies of theinheritance of these haplotypes in families affected by a recognized genetictrait can also assist to locate the exact gene or genes that cause or alterthat trait.
Association and linkage studies have permitted the identificationof frequent disease genes and their modifiers.In distinctionto the International HapMap Project, which associates genomic sequences withinone species, comparative genomics is the study of similarities and differencesbetween different species. In recent years a overwhelming number of full oralmost full genome sequences from diverse species have been determined and droppedin public databases such as NIH’s Entrez Genome database.
By comparing thesesequences, often using a software device called BLAST (Basic Local AlignmentSearch Tool), researchers are able to identify degrees of similarity anddivergence between the genes and genomes of related or disparate species. Theresults of these studies have illuminated the evolution of species and ofgenomes. Such studies have also helped to draw attention to highly conservedregions of noncoding sequences of DNA that were originally thought to benonfunctional because they do not contain base sequences that are translatedinto protein.
However, some noncoding regions of DNA have been highly conservedand may play key roles in human evolution.The publicavailability of a complete human genome sequence represented a defining momentfor both the biomedical community and for society. In the years sincecompletion of the Human Genome Project, the human genome database, togetherwith other publicly available resources such as the HapMap database, has permittedthe identification of a diversity of genes that are associated with disease.This, in turn, has permitted more objective and accurate diagnoses, in somecases even before the onset of overt clinical symptoms.
Association and linkagestudies have identified additional genetic influences that modify thedevelopment or outcome for both rare and common diseases. The recognition that humangenomes may influence everything from disease risk to physiological response tomedications has led to the emergence of the concept of personalizedmedicine—the idea that knowledge of a patient’s entire genome sequence willgive health care providers the ability to deliver the most appropriate andeffective care for that patient. Indeed, continuing advances in DNA sequencingtechnology promise to lower the cost of sequencing an individual’s entiregenome to that of other, relatively inexpensive, diagnostic tests.The HumanGenome Project touches grounds past biomedical science in ways that are equallytangible and profound. For example, human genomic sequence information, examinedthrough a system called CODIS (Combined DNA Index System), has transformed thefield of forensics, allowing optimistic identification of individuals fromextremely tiny samples of biological substances, such as saliva on the seal ofan envelope, a few hairs, or a spot of dehydrated blood or semen. Indeed, encouragedby high rates of repetition (the tendency of a previously imprisoned criminalto return to previous illegal conduct regardless of sentence or incarceration),some governments have even introduced the rule of banking DNA samples from allconvicted criminals in order to shorten the identification of perpetrators offuture crimes.
While politically controversial, this policy has proved highlyeffective. By the same mark, guiltless men and women have been acquitted due toon DNA evidence, sometimes decades after wrongful convictions for crimes theydid not commit.ProportionalDNA sequence analyses of samples on behalf of distinct modern populations ofhumans have transformed the field of anthropology. For example, by followingDNA sequence variations present on mitochondrial DNA, which is maternallyinherited, and on the Y chromosome, which is paternally inherited, molecularanthropologists have confirmed Africa as the cradle of the modern humanspecies, Homo sapiens, and have identified the waves of human migration that emergedfrom Africa over the last 60,000 years to inhabit the other continents of theworld. Databases that map DNA sequence variations that are common in somepopulations but rare in others have enabled so-called molecular genealogists totrace the continent or even subcontinent of origin of given families orindividuals.
Perhaps more important than helping to trace the roots of humansand to see the differences between populations of humans, DNA sequenceinformation has allowed recognition of how closely related one population ofhumans is to another and how closely related humans are to the multitude ofother species that inhabit the Earth. 4Ways the Human Genome Project Changed Medicine 1) Therewere Personalized treatments with fewer side effectstreatment bytrial-and-error was forgotten. In some cases, doctors can modify the medicationsand doses by who you the person is , not just by what population they fit into. This is thanks to pharmacogenetics, which deals with how a person’s genes yourresponse to drugs. Pharmacogenetics can save people from hurtful side effectsand make the treatment faster and more effective. The field is still in its initialstages with much to learn.
2) Morefocus on personalized careTheHuman Genome Project covered all of our genes. But that big-picture approachhas paved the way for individual portraits of your health. For several types ofcancer and other conditions, doctors can predict your risk. Then they can helpyou do something about it. Genetics is one of many tools for personalized care,along with family history and others.3) Betterstudies, better scienceTheHuman Genome Project showed how much good a large-scale, multi-center approachcan do.
Many studies today build on that model, including President BarackObama’s brain-mapping initiative, announced in early April 2013. It’s aboutstrength in numbers: More scientists working together can ask more questionsand get more answers by studying more patients. 4) Datafor smarter decisionsTheresearchers in the Human Genome Project wanted to make data easier for doctorsto use. It was part of a push for better electronic medical records — to putmore information at your doctors’ fingertips and help them make smarterdecisions. The next step is to get all of these records to “talk” to each otherand become more universal. References:http://www.who.int/medicines/ebola-treatment/background_briefing_on_data_results_sharing_during_phes.pdf?ua=1https://report.nih.gov/NIHfactsheets/ViewFactSheet.aspx?csid=45