The work on interpretation 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, disorders of hemostasis, cystic fibrosis, liver diseases and many others. Also, the etiologies 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.
There are also many tangible benefits for biological scientists. For example, a researcher investigating a certain form of cancer may have narrowed down his search to a particular gene. By visiting the human genome database on the worldwide web, this researcher can examine what other scientists have written about this gene, including (potentially) the three-dimensional structure of its product, its function(s), its evolutionary relationships to other human genes, or to genes in mice or yeast or fruit flies, possible detrimental mutations, interactions with other genes, body tissues in which this gene is activated, diseases associated with this gene or other datatypes.Further, deeper understanding of the disease processes at the level of molecular biology may determine new therapeutic procedures. Given the established importance of DNA in molecular biology and its central role in determining the fundamental operation of cellular processes, it is likely that expanded knowledge in this area will facilitate medical advances in numerous areas of clinical interest that may not have been possible without them.The analysis of similarities between DNA sequences from different organisms is also opening new avenues in the study of the theory 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 from this project.
The Human Genome Diversity Project, spin-off research aimed at mapping the DNA that varies between human ethnic groups, which was rumored to have been halted, actually did continue and to date has yielded new conclusions. In the future, HGDP could possibly expose new data in disease surveillance, human development and anthropology. HGDP could unlock secrets behind and create new strategies for managing the vulnerability of ethnic groups to certain diseases (see race in biomedicine). It could also show how human populations have adapted to these vulnerabilities.
What's Turning Genomics Vision Into Reality
In "A Vision for the Future of Genomics Research," published in the April 24, 2003 issue of the journal Nature, the National Human Genome Research Institute (NHGRI) details a myriad of research opportunities in the genome era. This backgrounder describes a few of the more visible, large-scale opportunities.
The International HapMap Project
Launched in October 2002 by NHGRI and its partners, the International HapMap Project has enlisted a worldwide consortium of scientists with the goal of producing the "next-generation" map of the human genome to speed the discovery of genes related to common illnesses such as asthma, cancer, diabetes and heart disease.Expected to take three years to complete, the "HapMap" will chart genetic variation within the human genome at an unprecedented level of precision. By comparing genetic differences among individuals and identifying those specifically associated with a condition, consortium members believe they can create a tool to help researchers detect the genetic contributions to many diseases. Whereas the Human Genome Project provided the foundation on which researchers are making dramatic genetic discoveries, the HapMap will begin building the framework to make the results of genomic research applicable to individuals.
ENCyclopedia Of DNA Elements (ENCODE)
This NHGRI-led project is designed to develop efficient ways of identifying and precisely locating all of the protein-coding genes, non-protein-coding genes and other sequence-based, functional elements contained in the human DNA sequence. Creating this monumental reference work will help scientists mine and fully utilize the human sequence, gain a deeper understanding of human biology, predict potential disease risk, and develop new strategies for the prevention and treatment of disease.The ENCODE project will begin as a pilot, in which participating research teams will work cooperatively to develop efficient, high-throughput methods for rigorously and fully analyzing a defined set of target regions comprising approximately 1 percent of the human genome. Analysis of this first 30 megabases (Mb) of human genome sequence will allow the project participants to test and compare a variety of existing and new technologies to find the functional elements in human DNA.
Chemical Genomics
NHGRI is exploring the acquisition and/or creation of publicly available libraries of organic chemical compounds, also referred to as small molecules, for use by basic scientists in their efforts to chart biological pathways. Such compounds have a number of attractive features for genome analysis, including their wide structural diversity, which mirrors the diversity of the genome; their ability in many cases to enter cells readily; and the fact that they can often serve as starting points for drug development. The use of these chemical compounds to probe gene function will complement more conventional nucleic acid approaches.This initiative offers enormous potential. However, it is a fundamentally new approach to genomics, and largely new to basic biomedical research as a whole. As a result, substantial investments in physical and human capital will be needed. NHGRI is currently planning for these needs, which will include large libraries of chemical compounds (500,000 - 1,000,000 total); capacity for robotic-enabled, high-throughput screening; and medicinal chemistry to convert compounds identified through such screening into useful biological tools.
Genomes to Life
The Department of Energy's "Genomes to Life" program focuses on single-cell organisms, or microbes. The fundamental goal is to understand the intricate details of the life processes of microbes so well that computational models can be developed to accurately describe and predict their responses to changes in their environment."Genomes to Life" aims to understand the activities of single-cell organisms on three levels: the proteins and multi-molecular machines that perform most of the cell's work; the gene regulatory networks that control these processes; and microbial associations or communities in which groups of different microbes carry out fundamental functions in nature. Once researchers understand how life functions at the microbial level, they hope to use the capabilities of these organisms to help meet many of our national challenges in energy and the environment.
Structural Genomics Consortium
Structural genomics is the systematic, high-throughput generation of the three-dimensional structure of proteins. The ultimate goal for studying the structural genomics of any organism is the complete structural description of all proteins encoded by the genome of that organism. Such three-dimensional structures will be crucial for rational drug design, for diagnosis and treatment of disease, and for advancing our understanding of basic biology. A broad collection of structures will provide valuable biological information beyond that which can be obtained from individual structures.
Genetics of Disorders with Multifactorial Inheritance
The basis of many single-gene diseases has already been demonstrated at the protein and the DNA levels by the approaches of biochemical and molecular genetics. In addition, cytogenetics has revealed the chromosomal basis of a small but growing number of significant disorders. Among genetic phenotypes in general, however, single-gene or cytogenetic defects are greatly outnumbered by common disorders that appear to run in families but are neither single-gene nor chromosomal in origin. These disorders, which are still for the most part poorly understood genetically, are said to show multifactorial inheritance, indicating that they are caused by multiple factors, both genetic and, in many cases, environmental. Many congenital malformations show multifactorial inheritance. Other multifactorial disorders, in which the role of environment appears to be relatively large and the underlying etiology may be heterogeneous and complex, appear as common disorders of adult life.
Multifactorial inheritance is defined as inheritance by a combination of genetic factors and in some cases also nongenetic factors, each with only a relatively small effect. The term polygenic inheritance has a more restricted meaning, assuming inheritance hy a large number of genes with small, equal, additive effects, and in this formal sense it may not apply to any human disorder. Traits are sometimes loosely called polygenic when they are caused by multiple genes with no obvious environmental component, but in actual experience it is often hard to judge whether environment plays any causative role.
Multifactorial disorders recur within families, but they do not show any particular pedigree pattern in an individual family. Genetically, they have common characteristics that allow estimation of their multifactorial background and estimation of recurrence risks for an individual family may be larger or smaller than the average.
Consider the following genetic aspects of three different classes of multifactorial traits:
* Many normal characteristics have multifactorial inheritance and are characterized by continuous variation. For these characteristics, an "abnormal" phenotype is simply an extreme variant of the normal range; examples include many cases of nonspecific mental retardation and of unusually tall of short stature.
* A second group of multifactorial disorders is made up of common single congenital malformations, in which there appears to be underlying continuous variation in liability to a particular disorder, but there is no clinical effect until the patient's liability exceeds a "threshold" for the abnormal phenotype. These are usually known as multifactorial threshold traits.
* The third group comprises the common disorders of adult life that make up a large part of clinical medicine, such as coronary artery disease, diabetes mellitus, hypertension, obesity, and most forms of cancer, as well as common psychiatric illnesses, such as manic-depressive psychosis and schizophrenia. Environmental factors are considered to play a large part in these disorders, even though the role of genetics in their etiology is undeniable. In a sense, common disorders of adult life can also be considered threshold traits, but because of the complexity of the risk factors that can lead to them, they are regarded instead as a separate class.
Multifactorial inheritance is defined as inheritance by a combination of genetic factors and in some cases also nongenetic factors, each with only a relatively small effect. The term polygenic inheritance has a more restricted meaning, assuming inheritance hy a large number of genes with small, equal, additive effects, and in this formal sense it may not apply to any human disorder. Traits are sometimes loosely called polygenic when they are caused by multiple genes with no obvious environmental component, but in actual experience it is often hard to judge whether environment plays any causative role.
Multifactorial disorders recur within families, but they do not show any particular pedigree pattern in an individual family. Genetically, they have common characteristics that allow estimation of their multifactorial background and estimation of recurrence risks for an individual family may be larger or smaller than the average.
Consider the following genetic aspects of three different classes of multifactorial traits:
* Many normal characteristics have multifactorial inheritance and are characterized by continuous variation. For these characteristics, an "abnormal" phenotype is simply an extreme variant of the normal range; examples include many cases of nonspecific mental retardation and of unusually tall of short stature.
* A second group of multifactorial disorders is made up of common single congenital malformations, in which there appears to be underlying continuous variation in liability to a particular disorder, but there is no clinical effect until the patient's liability exceeds a "threshold" for the abnormal phenotype. These are usually known as multifactorial threshold traits.
* The third group comprises the common disorders of adult life that make up a large part of clinical medicine, such as coronary artery disease, diabetes mellitus, hypertension, obesity, and most forms of cancer, as well as common psychiatric illnesses, such as manic-depressive psychosis and schizophrenia. Environmental factors are considered to play a large part in these disorders, even though the role of genetics in their etiology is undeniable. In a sense, common disorders of adult life can also be considered threshold traits, but because of the complexity of the risk factors that can lead to them, they are regarded instead as a separate class.
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