Question

What single technological contribution has impacted our understanding of the human genome? 4. Up to this point, how have researchers identified the genes most commonly associated with disease?

Answer 1

The Human Genome Project was a 15-year-long, publicly funded project initiated in 1990 with the objective of determining the DNA sequence of the entire euchromatic human genome within 15 years.The Human Genome Project originally aimed to map the nucleotides contained in a human haploid reference genome (more than three billion). The "genome" of any given individual is unique; mapping the "human genome" involved sequencing a small number of individuals and then assembling these together to get a complete sequence for each chromosome. Therefore, the finished human genome is a mosaic, not representing any one individual.The main goals of the Human Genome Project were first articulated in 1988 by a special committee of the U.S. National Academy of Sciences, and later adopted through a detailed series of five-year plans jointly written by the National Institutes of Health and the Department of Energy.Biological research has traditionally been a very individualistic enterprise, with researchers pursuing medical investigations more or less independently. The Human Genome Project (HGP) was declared complete in April 2003. An initial rough draft of the human genome was available in June 2000 and by February 2001 a working draft had been completed and published followed by the final sequencing mapping of the human genome on April 14, 2003. Although this was reported to cover 99% of the euchromatic human genome with 99.99% accuracy, a major quality assessment of the human genome sequence was published on May 27, 2004 indicating over 92% of sampling exceeded 99.99% accuracy which was within the intended goal. Further analyses and papers on the HGP continue to occur.The magnitude of both the technological challenge and the necessary financial investment prompted the Human Genome Project to assemble interdisciplinary teams, encompassing engineering and informatics as well as biology; automate procedures wherever possible; and concentrate research in major centers to maximize economies of scale.At this time, the principal goals laid out by the National Academy of Sciences have been achieved, including the essential completion of a high-quality version of the human sequence. Other goals included the creation of physical and genetic maps of the human genome, which were accomplished in the mid-1990s, as well as the mapping and sequencing of a set of five model organisms, including the mouse. All of these goals have been achieved within the time frame and budget first estimated by the NAS committee.the gene-containing portion of the genome is complete in nearly every functional way for the purposes of scientific research and is freely and publicly available. Even though the Human Genome Project is now completed, scientists will continue to develop and apply new technologies to the few remaining refractory problems. For its part, NHGRI will continue to support a wide range of research to develop new sequencing technologies, to interpret the human sequence and to use the newfound understanding of the human genome to improve human health.
On June 26, 2000, the International Human Genome Sequencing Consortium announced the production of a rough draft of the human genome sequence. In April, 2003, the International Human Genome Sequencing Consortium is announcing an essentially finished version of the human genome sequence. This version, which is available to the public, provides nearly all the information needed to do research using the whole genome.The difference between the draft and finished versions is defined by coverage, the number of gaps and the error rate. The draft sequence covered 90 percent of the genome at an error rate of one in 1,000 base pairs, but there were more than 150,000 gaps and only 28 percent of the genome had reached the finished standard. In the April 2003 version, there are less than 400 gaps and 99 percent of the genome is finished with an accuracy rate of less than one error every 10,000 base pairs. The differences between the two versions are significant for scientists using the sequence to conduct research. The work on interpretation and analysis of genome data is still in its initial stages. It is anticipated that detailed knowledge of the human genome will provide new avenues for advances in medicine and biotechnology. Clear practical results of the project emerged even before the work was finished. For example, a number of companies, such as Myriad Genetics, started offering easy ways to administer genetic tests that can show predisposition to a variety of illnesses, including breast cancer, hemostasis disorders, cystic fibrosis, liver diseases and many others. Also the etiolgies for cancers , Alzheimer's disease and other areas of clinical interest are considered likely to benefit from genome information and possibly may lead in the long term to significant advances in their management. The analysis of similarities between DNA sequences from different organisms is also opening new avenues in the study of evolution. In many cases, evolutionary questions can now be framed in terms of molecular biology; indeed, many major evolutionary milestones (the emergence of the ribosome and organelles, the development of embryos with body plans, the vertebrate immune system) can be related to the molecular level. Many questions about the similarities and differences between humans and our closest relatives (the primates, and indeed the other mammals) are expected to be illuminated by the data in this project.In addition to the human genome, the Human Genome Project sequenced the genomes of several other organisms, including brewers' yeast, the roundworm, and the fruit fly. In 2002, researchers announced that they had also completed a working draft of the mouse genome. By studying the similarities and differences between human genes and those of other organisms, researchers can discover the functions of particular genes and identify which genes are critical for life.
Human diseases are of two types "monogenic and polygenic". In monogenic diseases, only one gene is involved in etiology and follows the Mendelian pattern of inheritance. The phenotype of the monogenic disease may be complex. So many genes are measured by linkage analysis somewhere data are tranquil from affected families, the disease locus lies in the region of the genome, which is shared by all affected members of the family. Genetic research will lead to improved diagnosis and treatment of diseases. Researchers are creating new types of drugs based on what we know about genes. Because these newer drugs target certain sites in the body, they may have fewer side effects than many of today's medicines. Other new types of medicines will be tailored to an individual's unique genetic profile.On average, people probably carry from 5 to 10 genes with mutations in each of their cells. Problems happen when the particular gene is dominant or when a mutation is present in both copies of a recessive gene pair. Problems can also happen when several variant genes interact with each other — or with the environment — to increase susceptibility to diseases.If a person has a change in a dominant gene that is associated with a particular condition, he or she will usually have features of that condition. And, each of the person's children will have a 1 in 2 (50%) chance of inheriting the gene and developing the same features. Diseases and conditions caused by a dominant gene include achondroplasia (pronounced: ay-kon-druh-PLAY-zhuh, a form of dwarfism), Marfan syndrome (a connective tissue disorder), and Huntington disease (a degenerative disease of the nervous system).People who have a change in just one copy of a recessive gene are called "carriers." They don't usually have the disease because they have a normal gene copy of that pair that can do the job. When two carriers have a child together, however, the child has a 1 in 4 (25%) chance of getting a gene with a mutation from both parents, which would result in the child having the disease. Cystic fibrosis (a lung disease), sickle cell anemia(a blood disorder), and Tay-Sachs disease (which causes nervous system problems) are caused by recessive mutations from both parents coming together in a child.With recessive gene mutations on the X chromosome, usually only guys can develop the disease because they have only one X chromosome. Girls have two X chromosomes — since they have a back-up copy of another X chromosome, they don't always show features of X-linked conditions. These include the bleeding disorder hemophilia (pronounced: hee-muh-FIL-ee-uh) and color blindness.
Sometimes scientists alter genes on purpose. For many years, researchers have altered the genes in plants to produce other plants with special characteristics, such as an increased resistance to disease and pests or the ability to grow in difficult environments. We call this genetic engineering.Genome-wide linkage analysis and association studies are the two major ways to find out the genes responsible for complex disorders. Most of the genetic differences between individual people lie in single-nucleotide polymorphisms (SNPs). SNPs are natural variations in the four bases from which deoxyribonucleic acid (DNA) and gene are composed. It is mostly these differences that geneticist’s activity to trail chromosomes from parents to children, and in linkage analysis, to correlate the presence of certain chromosome sequences with the occurrence of disease . The linkage is a phenomenon of co-segregating loci, not alleles, within families. If two markers are close, there will not be much recombination between them and they will co-segregate. This principal to definition linkage in a pedigree-based analysis. Association studies at the population level are the next step to find the mapping.Association may result from the straight suggestion of the gene or linkage disequilibrium (LD) with the disease gene at the population level. Linkage always leads to an association but this is usually interfamilial with no association at the population level (linkage of genotype for a genetic marker to disease, may be unique to the particular family). In other words, linkage does not automatically mean a constant link with a specific allele. The allelic association may or may not be due to the linkage. Although recombination portion is what linkage studies depend on, LD is the foundation of association studies. The hypothesis is that the genetic marker studies are close enough to the actual disease gene and this will result in an allelic association at the population level.