Human Genome Project

Human Genome Project 

In a simple word, Human Genome Project which began in 1990 is an international study of the entire human genetic material. It is design to map out all of the genes that make up human beings. All of the genes in a single organism are called the genome.

Human Genome Project and Pharmacy field are closely related :)

Methods:

Researchers have applied the findings from the human 
genome project in 3 major ways: 

• Determining the order, or "sequence," of all the bases in our genome's DNA.
• Mapping the locations of genes for major sections of all our chromosomes.
• Producing linkage maps, through which inherited traits (such as those for genetic disease) can be tracked over generations.

The genome was completed in 2003. Researchers are still studying it in order to improve the treatments, preventions strategies, and diagnostic techniques for genetic disorders, such as down syndrome and Hunting ton's disease.

Research (1990-Present)

• 1990: In 1990, the U.S. Department of Energy (DOE) and the National Institutes of Health (NIH) presented the Human Genome Project to Congress. The government approved the research project, and it is formally began.
• 1994: In 1994, a detailed human genome map was completed one year ahead of schedule. This map allowed researchers to see where genes are located in specific chromosomes.
• 1995: In 1995, a physical map of the human genome was completed. This map arranged large segments of DNA in order.
• 1996: In 1996, the genetic map of the mouse was completed. This was considered an important milestone because mice and humans share about 85% of their genes. This is why scientists often study human diseases and drugs in mice.
• 1998: In 1998, HGP researchers released a gene map that included 30,000 human genes that were believed to represent about one-third of all of the human genes.
• 1999: In 1999, HGP researchers finished the first completed sequence of a human chromosome 22. Researchers chose to sequence this chromosome because it is a relatively small chromosome, and detailed maps of the chromosome had already been developed. The genes were sequenced in both the long and short arm of the chromosome. The long arm contains at least 545 genes and is 33,400,000 base pairs in length.
• 2000: In 2000, researchers from Harvard Medical School used gene splicing techniques to produce fruit flies that exhibited symptoms of Parkinson's disease. Researchers inserted mutated genes that were suspected causes of Parkinson's disease. The scientists used fruit flies because they have a short life cycle, which makes it easy to quickly test theories about specific genes associated with Parkinson's disease and possible treatments.
• 2001: In 2001, the National Human Genome Research Institute (NHGRI), the DOE, and their partners in the International Human Genome Sequencing Consortium published the first draft of the human genome that was 90% complete in the journal Nature.
• 2002: In 2002, researchers used a family-based study to link bipolar disorder (BP) to a specific gene. The scientists analyzed blood samples from 283 families with histories of this psychological illness. The researchers concluded that genetics appears to play a role in the development of BP.
• 2003: In 2003, researchers from the Human Genome Project (HGP) completed the human genome and found that there are 30,000-40,000 genes in each human. This number surprised the research community, because it was initially estimated that a human had anywhere from 50,000 to 140,000 genes.
• Present: The completed human genome provides detailed information about the structure, organization, and function of human genes. This information is a basic set of instructions, or blueprint, for the development and function of a human being.
• The completion of the HGP has led researchers to study the genome of other organisms, including mice, fruit flies, and flatworms. Researchers believe that identifying genes in other organisms may help them understand human genes better.

The first clinical applications from the HGP will be in the area of diagnostics. With the exception of identical twins, no two human beings share the same genome. Yet, it is estimated that only 0.1% of the genome accounts for variability among humans.The final HGP sequence will serve as a model for comparison with individual genomes. As more genes become associated with a specific disease, the sequence, or partial sequence, from an individual will be compared with the model for purposes of diagnosis or even disease prevention. The role that multiple genes play in causing disease should be better understood with time. This could lead to a greater understanding of the etiology behind such genetically complex diseases as diabetes, heart disease, and schizophrenia.

Pharmacogenomics 

     A science that examines the inherited variations in genes that dictate drug response and explores the ways this variations can be used to predict whether a patient will have a good response to a drug, a bad response to a drug or no response at all.  

Pharmacogenetics 

    Refer to the study of inherited differences which causes variation in drug metabolism and response. 

Pharmacist may eventually used the patient's genetic profile to select the most appropriate medication for the treatment or prevention of the disease to which the patient is genetically predisposed. An individual genetics profile may also be used to choose a medication with minimal side effects by accounting for the genetic differences in the production of CYP450 enzymes.

The following examples demonstrate how knowledge of a patient's genetic profile may be used to provide a personalised medication or dose:

• Patients with a mutation in the gene coding for CYP2D6 will show little or no analgesic effect from codeine. Codeine is metabolized to its active metabolite, morphine, by CYP2D6.
• Patients suffering from Alzheimer's disease who have the E4 subtype of the gene coding for apo-lipoprotein E (apoE E4) are less likely to benefit from the drug tacrine. ApoE E4 affects cholinergic function in the brain.
• Trastuzumab, a monoclonal antibody, binds to a product of the HER2 gene to treat breast tumors that overexpress HER2. Tamoxifen, on the other hand, is not used in women whose tumor does not express the gene for the estrogen receptor.
• Cholesteryl ester transfer protein (CETP) functions in the metabolism of high-density lipoprotein (HDL). A genetic variant of the gene coding for CETP is correlated with higher CETP plasma levels and lower plasma levels of HDL. One study showed that pravastatin slowed the progression of coronary atherosclerosis in men who carried this genetic variant.
• Women who carry the blood-clotting variant factor V Leiden and were taking oral contraceptives were shown in one study to have a dramatically increased risk of developing cerebral-vein thrombosis.
• Many complications arising from cystic fibrosis (CF) can be traced to a mutation in the gene for cystic fibrosis transmembrane conductance regulator (CFTR) protein. Sodium phenylbutyrate, a medication approved for the regulation of ammonia levels in the blood, may be useful in the treatment of CF, as it also stimulates expression of the CFTR protein. An increase in the CFTR protein enhances the ability of chloride and water to enter and exit the cell, thus leading to a decrease in fluid buildup in the lungs.
• Glucose-6-phosphate dehydrogenase (G6PD) deficiency, the most common inherited enzymopathy, leads to hemolysis after ingestion of oxidant medications (antimalarials, sulfonamides, some analgesics and nitrofurans). Without G6PD, the red blood cells are not protected from oxidative damage and hemolytic anemia results.
• Patients taking desipramine or imipramine (metabolized to desipramine) may develop toxic plasma concentrations if there is a mutation in the gene coding for CYP2D6. CYP2D6 leads to the conversion of desipramine to an inactive metabolite.

          One area (among many) in which diagnostic and therapeutic advancements due to the HGP may improve therapy is cancer. Tumors are usually classified based on morphology, but two tumors that appear the same may not respond to the same treatment. If molecular differences between similar tumors could be classified, the choice of initial therapy could be improved. Once classifications are made concerning tumors that have distinctively different molecular profiles, relevant clinical data such as staging and grading could be integrated to assess therapeutic options as well as clinical outcomes. The HGP has the potential to alter the way cancer is classified and treated.

Implications:

• General: The completed human genome is similar to having an instructional map on how to make a human body. Researchers are now faced with the challenge of interpreting these so-called instructions in order to determine how genes work together in human health and disease. Scientists believe that genome-based research will lead to improved tools to diagnose, treat, and prevent inherited disorders, such as Huntington's disease.
• Human diseases: In 2005, the international HapMap Project was developed to use information from the Human Genome Project (HGP) to research genes involved in common human diseases. This initiative has led to the discovery of more than 1,800 genes that are associated with inherited disorders. Researchers from HapMap have found genetic factors that are related to conditions, such as obesity and age-related blindness.
• Today, as a result of the HGP, researchers are able to find a gene that is suspected of causing a specific disease in only a few days.
• Genetic testing: The results of the HGP have led to the development of more than 1,000 genetic tests for inherited human diseases and disorders. These tests allow patients to learn their risks of developing certain diseases. They are also used to diagnose inherited medical conditions.
• Biomedical products: The biomedical technology industry has also benefited from the completed human genome. Since the human genome was completed, many new technologies that use living cells and/or biological molecules have been designed. For instance, scientists are studying the safety and effectiveness of gene therapy, which involves inserting human genes into a patient as a possibly way to treat or prevent inherited disorders and some types of cancer. Currently, at least 350 biotechnology-based products are undergoing clinical trials. Patients should keep in mind that is usually takes more than 10 years for a company to perform the necessary studies in order to gain approval by the U.S. Food and Drug Administration (FDA).
• Stem cell research: The completion of the HGP has also led to stem cell research. Stem cells are unspecialized cells that can potentially develop into different types of specialized cells. These cells may help treat diseases that are currently incurable, such as Alzheimer's disease, Parkinson's disease, or multiple sclerosis (MS). There are three types of stem cells: adult stem cells, embryonic stem cells, and umbilical cord stem cells.
• Adult stem cells are present in many human body tissues and organs, including the brain, bone marrow, bloodstream, blood vessels, skeletal muscle, skin, and liver. These cells allow the person to repair damaged cells or produce new cells in a tissue or organ.
• Today, adult stem cells are commonly used in patients who need bone marrow transplants. Scientists have been studying these cells in laboratories to determine if adult stem cells can be manipulated to produce specific types of cells. If scientists can find ways to make the adult stem cells produce specialized cells, they may be able to treat diseases. For instance, these specialized cells might be able to replace insulin-producing cells in patients with diabetes or dopamine-producing cells in patients with Parkinson's disease.

Limitations:

• The results of the HGP have led to the development of more than 1,000 genetic tests for inherited human diseases and disorders. These tests are used to diagnose certain inherited medical conditions. They also allow patients to learn their risks of developing certain diseases. However, predictive genetic testing has sparked some debate because these tests only provide a probability for developing particular disorders. Even though many medical conditions have been linked to genetic causes, a person's biological makeup is not the only factor involved. Therefore, some people who carry a disease-associated mutation may never develop the disease. As a result, patients who test positive for a specific gene may become excessively worried about developing the disorder and experience a decreased quality of life.

• Similarly, it is commonly believed that an individual's genetic makeup is just one factor, among many others, that influence behaviour. An individual's environment, including social relationships and culture, has also been shown to influence behaviors. Therefore, if a person has just one gene associated with shyness, for instance, it does not necessarily mean that the person is going to be shy.