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You are here Biopharmaceutical/ Genomic glossary Homepage/Search >Applications > Molecular Medicine >Genetic testing Genetic & genomic testing glossary & taxonomy
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Site Map analyte specific reagents: Drug approvals and clinical trials analytical sensitivity: The proportion of persons with a disease genotype who test positive. [Enhancing the oversight of genetic tests: Recommendations of the SACGT, Secretary's Advisory Committee on Genetic Testing, June 2000 http://www4.od.nih.gov/oba/sacgt/reports/oversight_report.pdf Related terms: clinical sensitivity and sensitivity. Labels, Signaling & Detection analytical specificity: The proportion of persons without a disease genotype who test negative. Enhancing the oversight of genetic tests: Recommendations of the SACGT, Secretary's Advisory Committee on Genetic Testing, June 200 http://www4.od.nih.gov/oba/sacgt/reports/oversight_report.pdf Related terms: clinical specificity and specificity Labels, Signaling & Detection But note that IUPAC (in a provisional recommendation) prefers the term "selectivity" instead of specificity, citing the many papers in which the two are used interchangeably. "This is very unfortunate as specificity is considered as an absolute term, and cannot be graded. [IUPAC Analytical Chemistry Division, Commission on General Aspects of Analytical Chemistry Provisional Recommendations "Selectivity in Analytical Chemistry. Recommendations for its use" Feb. 27, 2001] http://www.iupac.org/reports/provisional/abstract01/vessman_300901.html carrier testing: Performed to determine whether an individual carries one copy of an altered gene for a particular recessive disease. Enhancing the oversight of genetic tests: Recommendations of the SACGT, Secretary's Advisory Committee on Genetic Testing, June 2000 http://www4.od.nih.gov/oba/sacgt/reports/oversight_report.pdf The [American College of Medical Genetics'] [Sub]Committee [on cystic fibrosis [CF] carrier screening] recommends that CF carrier screening be offered to non- Jewish Caucasians and Ashkenazi Jews, and made available to other ethnic and racial groups who will be informed of their detectability through educational brochures, the informed consent process, and/ or other efficient methods. For example, Asian- Americans and Native- Americans without significant Caucasian admixture should be informed of the rarity of the disease and the very low yield of the test in their respective populations. Testing should be made available to African- Americans, recognizing that only about 50% of at- risk couples will be detected. An educational brochure and a consent form which recites this information as well as a sign- off for those choosing not to be tested after reading these materials is being prepared by the Working Group on Patient Education and Informed Consent. We recommend that preconception testing be encouraged whenever possible, although we recognize that for practical purposes, testing will often occur in the prenatal setting. [Wayne W. Grody et. al. "Laboratory Standards and Guidelines for Population- based Cystic Fibrosis Carrier Screening" Genetics in Medicine 3 (2): 149-154 March/ April 2001] http://www.faseb.org/genetics/acmg/pol-32.htm It will be interesting to see how many people opt for carrier testing, given this recent recommendation. Related terms: molecular genetic testing, preconception testing, prenatal diagnosis clinical sensitivity: The proportion of persons with a disease phenotype who test positive. Enhancing the oversight of genetic tests: Recommendations of the SACGT, Secretary's Advisory Committee on Genetic Testing, June 2000 http://www4.od.nih.gov/oba/sacgt/reports/oversight_report.pdf Related term: analytical sensitivity. clinical specificity: The proportion of persons without a disease phenotype who test negative. Enhancing the oversight of genetic tests: Recommendations of the SACGT, Secretary's Advisory Committee on Genetic Testing, June 2000 http://www4.od.nih.gov/oba/sacgt/reports/oversight_report.pdf Related term: analytical specificity "designer babies": Steven Pinker, Human Nature and Its Future, 2003 http://www.bioethics.gov/transcripts/march03/session3.html Not as inevitable as many people seem to think. ethics: Ethics familial cancer: Cancer genomics family history: Interpreting family histories can be complicated by many factors, including small families, incomplete or erroneous family histories and particularly by variable penetrance and the current lack of real understanding of the multiple genes involved in polygenic diseases. Family risk is often cited in terms of absolute number of affected relatives with a disease, when (particularly in larger families) the ratio of affected to non- affected relatives may be a more telling statistic. Interpreting statistics and risk factors are no easy tasks under any circumstances, much less one as potentially significant as genetic testing. Related term: sporadic cancer genetic counseling: A short-term educational counseling process for individuals and families who have a genetic disease or who are at risk for such a disease. Genetic counseling provides patients with information about their condition and helps them make informed decisions. [NHGRI] Related term: risk communication genetic discrimination: Cindy Pelligrini, legislative director for Rep. Louise Slaughter (New York) as part of a roundtable discussion on genetic discrimination said "It's Rep. Slaughter's view that all of us are ultimately uninsurable. The more that we learn about our genes, everyone has enough genetic flaws that we're anywhere from 5- 30 or 5- 50 depending who you are listening to, genetic flaws that predispose you to major, severe illnesses at some point in your lifetime. And so really what we are doing right now by allowing discrimination to happen is punishing the people with the bad luck to have the genes we have discovered first." [Dept. of Health and Human Services, National Committee on Vital and Health Statistics, Subcommittee on Privacy and Confidentiality, transcript, November 29, 2000] http://ncvhs.hhs.gov/001129tr2.htm Francis Collins, director of the National Institute for Human Genome Research, speaking at an American Association for the Advancement of Science event on the day Bill Clinton signed an executive order prohibiting federal government agencies from obtaining genetic information from employees or job applicants or from using genetic information in hiring and promotion decisions noted "But genetic information and genetic technology can be used in ways that are fundamentally unjust. Genetic information can be used as the basis for insidious discrimination. Already, with but a handful of genetic tests in common use, people have lost their jobs, lost their health insurance, and lost their economic well being because of the misuse of genetic information. It is estimated that all of us carry dozens of glitches in our DNA - so establishing principles of fair use of this information is important for all of us." [NHGRI in the news, "Dr. Francis Collins, Director of NHGRI, Applauds President Clinton's Action to Protect Federal Workers From Genetic Discrimination" Feb. 8, 2000] http://www.nhgri.nih.gov/NEWS/Executive_order/collins.html I'd
be very interested to hear of references in the scientific literature to back up
the quantitative estimates of individual genetic flaws. The only one I've
found is DL Halligan, PD Keightley, How many lethal alleles?
Trends in Genetics 19(2): 57- 59, Feb. 2003 Related terms: "good genes", "bad genes"; Ethics genetic enhancement: The use of genetic methodologies to improve functional capacities of an organism rather than to treat disease. MeSH, 2002 The subject of much discussion and concern over the ethics of, though new disease diagnoses, treatments (and concepts of "disease") are much closer than true genetic enhancements. The popular conception of selective breeding focuses on optimization of one or a very few traits (which produces tomatoes which ship well but have no taste, and purebred dogs with congenital hip dysplasia. Little attention has been paid to the tradeoffs (predictable and not) inevitable among polygenic traits. "Regression to the mean" also factors in. While two tall or two bright people tend to have children who are taller or brighter than average, they are NOT usually taller or brighter than the parents are. Only microbes with their greatly enhanced opportunities for evolving (with such short reproductive spans) seem to quickly get reliably bigger, better (in a sense) and stronger. Biological homeostasis is incredibly powerful. We may never be able to "enhance" complex traits such as intelligence or strength. But we need to learn how to talk about these issues -- preferably before actually being able to actually implement genetic enhancement. Beyond therapy: (enhancement), US President's Council on Bioethics http://www.bioethics.gov/topics/beyond_index.html
"Genetic enhancement: A conceptual and ethical challenge for gene therapy
regulation", Eric T. Juengst, Lahey Medica Related term: designer babies genetic privacy: Genetics Privacy and Legislation, HGMIS, DOE, US http://www.ornl.gov/TechResources/Human_Genome/elsi/legislat.html genetic screening: Testing a population group to identify a subset of individuals at high risk for having or transmitting a specific genetic disorder. [NHGRI] genetic susceptibility: Genetic susceptibility is a very broad term because not only does it describe genetic mutations that convey high levels of predisposition affecting a small proportion of the population, like BRCA1/2 mutations for breast cancer, but it also includes the huge number of unidentified genetic variations that are much more common in the population but convey lower levels of risk and often involve interaction with specific exposures in the environment. New tumors in cancer survivors, National Cancer Institute, Benchmarks 7 (1) : 2, 2007 http://www.cancer.gov/newscenter/benchmarks-vol7-issue1/page2 Broader term: susceptibility genetic testing: Until now, government sponsored committees convened to address ‘genetic testing’ have generally limited their definition and their reports to concerns regarding diseases caused by single gene mutations… Another class of ‘genetic tests’ is related to pharmacogenetics, including ... variants or other inherited polymorphic traits that are not diagnostic of disease ... Clear language and differentiation of respective ethical, legal and societal issues are required to prevent inaccurate vernacular usage creating a confused public perception. Allen Roses “Pharmacogenetics and the practice of medicine” Nature 405: 857-865 June 15 2000 Related terms: genetic
counseling, genetic discrimination, risk communication genetic test: An analysis performed on human DNA, RNA, genes and/or chromosomes to detect heritable or acquired genotypes, mutations, phenotypes, or karyotypes that cause or are likely to cause a specific disease or condition. A genetic test also is the analysis of human proteins and certain metabolites, which are predominantly used to detect heritable for acquired genotypes, mutations or phenotypes. The purposes of these genetic tests include predicting risks of disease, screening of newborns, directing clinical management, identifying carriers, and establishing prenatal or clinical diagnoses or prognoses in individuals, families or populations. Tests that are used primarily for other purposes, but that may contribute to diagnosing a genetic disease (e.g. blood smear, certain serum chemistries), would not be covered by this definition. Also excluded from the definition are tests conducted exclusively for forensic identify purposes. Enhancing the oversight of genetic tests: Recommendations of the SACGT, Secretary's Advisory Committee on Genetic Testing, June 2000 http://www4.od.nih.gov/oba/sacgt/reports/oversight_report.pdf Currently there is no
uniform or comprehensive system to assess the analytic and clinical validity of
tests before they are offered to patients, and there are no laboratory standards
that specifically address molecular genetic testing or require uniform
proficiency testing procedures for them. ... The Department of Health and Human
Services (HHS) agencies involved in current genetic testing oversight include:
The Centers for Medicare and Medicaid Services (CMS), the Food and Drug
Administration (FDA), the Centers for Disease Control (CDC), and the Office for
Human Research Protections. Currently, three statutory and regulatory
mechanisms, which all fall under the purview of agencies within HHS, govern
genetic tests: The Clinical Laboratory Improvement Amendments of 1988 (CLIA),
the Federal Food, Drug and Cosmetic Act and other regulations for protecting
human subjects of research. Who regulates genetic tests? Audrey Huang,
Shawna Williams, Genetics & Public Policy Center, 2007 http://www.dnapolicy.org/policy.issue.php?action=detail&issuebrief_id=10 genomic testing: Extensive media coverage of genomic discoveries has fueled the public appetite for personalized medicine and a rush to develop and market new genomic tests, often without the necessary intervening research. Public health sciences have an important role in evaluating the validity and utility of genomic tests, which include not only DNA-based tests for single gene variants, but complex genotypes, tests for acquired mutations, and measures of gene expression, from RNA microarrays to biochemical assays. Before a genomic test can be used for epidemiologic research or clinical practice, laboratory comparison with a gold standard must demonstrate analytic validity. Epidemiologic studies are needed to establish clinical validity (sensitivity, specificity, and predictive value). Research Priorities for Public Health Sciences in the Post- Genomic Era, Marta Gwinn and Muin J. Khoury, Centers for Disease Control, US Genetics in Medicine 4(6): 410- 411, 2002 http://www.cdc.gov/genomics/population/publications/priorities.htm germ cells: Reproductive cells in multicellular organisms. Unified Medical Language System, National Library of Medicine, US http://ghr.nlm.nih.gov/ghr/glossary/germcells germline mutation: A gene change in the body's reproductive cells (egg or sperm) that becomes incorporated into the DNA of every cell in the body of offspring; germline mutations are passed on from parents to offspring. Also called hereditary mutation. Cancernet (NCI) Dictionary of Cancer Terms, 2000 http://cancernet.nci.nih.gov/dictionary/dictionarya-g.html#g Current genetic tests focus on germline mutations. Related term: somatic cell "good genes", "bad genes": "There are no 'good' genes or 'bad' genes, there are merely networks that exist at various levels and at various connectivities, and at different states of sensitivity to perturbation," concluded Venter, Celera's president and chief scientific officer. "The notion that one gene equals one disease, or that one gene produces one key protein, is flying out the window." Science Hosts Press Event to Announce Sequencing of Human Genome, Science News Archives, 2001 http://www.aaas.org/news/releases/2001/human.shtml We now have glimpses of the concept that genes that confer advantages at one time in a person's life may have adverse effects as well. One of the best known examples is heterozygotes for sickle cell anemia being less susceptible to malaria (while homozygotes express the disease). Another possible example is APOE-4, associated with Alzheimer's disease, which may be correlated with a decreased risk of kidney damage following heart bypass surgery. Gene knockouts in model organisms have demonstrated that the absence of many genes may have no apparent effect upon phenotypes (though stress situations may reveal specific susceptibilities). Other single knockouts may have a catastrophic effect upon the organism, or be lethal so that the organism cannot develop at all. Human Genetics Commission: We are the UK Government's advisory body on new developments in human genetics and how they impact on individual lives. We give the Government advice on human genetics with a particular focus on the social, ethical and legal issues. Human Genetics Commission, UK http://www.hgc.gov.uk/Client/index.asp?ContentId=1 in vitro diagnostic multivariate index assays IVDMIAs: Draft Guidance for Industry, Clinical Laboratories and FDA Staff, In Vitro Diagnostic Multivariate Index Assays, CDRH, FDA, 2007 http://www.fda.gov/cdrh/oivd/guidance/1610.pdf molecular diagnostics: Traditionally, diagnostics has been quite distinct from therapeutic development. Molecular medicine is changing that paradigm, as molecular markers become increasingly important for understanding disease biology, selecting and validating targets, and assessing the efficacy and safety of compounds under development. Such molecular diagnostics have a much greater role, only one of which involves commercialization and use in patient care. CHI Molecular Diagnostics: Technological Advances fueling Market Expansion report, 2003 more in the Molecular Diagnostics & Medicine glossary molecular diagnostics - cancer: Cancer genomics glossary new-born screening: Performed in newborns in state public health programs to detect certain genetic diseases for which early diagnosis and treatment are available. Enhancing the oversight of genetic tests: Recommendations of the SACGT, Secretary's Advisory Committee on Genetic Testing, June 2000 http://www4.od.nih.gov/oba/sacgt/reports/oversight_report.pdf pharmacogenetic test: An assay intended to study interindividual variations in DNA sequence related to drug absorption and disposition (pharmacokinetics) or drug action (pharmacodynamics) including polymorphic variation in the genes that encode the functions of transporters, metabolizing enzymes, receptors, and other proteins. Guidance for Industry, Pharmacogenomic Data Submissions CDER, CBER, CDRH, FDA, March 2005 Non-binding recommendations. http://www.fda.gov/cber/gdlns/pharmdtasub.pdf Pharmacogenetic tests and genetic tests for inheritable markers: Guidance for Industry and FDA Staff, CDER, FDA, 2007 http://www.fda.gov/cdrh/oivd/guidance/1549.pdf Related term: protein biomarkers, proteomics biomarkers population genetics, population genomics: SNPs and other genetic variations post-genomic, post-Mendelian: Genomics preconception testing: See carrier testing, prenatal diagnosis predictive testing: Determines the probability that a healthy individual with or without a family history of a certain disease might develop that disease. Enhancing the oversight of genetic tests: Recommendations of the SACGT, Secretary's Advisory Committee on Genetic Testing, June 2000 http://www4.od.nih.gov/oba/sacgt/reports/oversight_report.pdf predisposition, genetic:
Increased susceptibility to a particular disease due to the
presence of one or more gene mutations, and/or a combination of alleles
(haplotype), not necessarily abnormal, that is associated with an increased risk
for the disease, and/or a family history that indicates an increased risk for
the disease. Definition from: GeneTests Related term: susceptibility. predisposition test: A test for a genetic predisposition (incompletely penetrant conditions). Not all people with a positive test result will manifest the disease during their lifetimes. Promoting Safe and Effective Genetic Testing in the United States: Final Report of the Task Force on Genetic Testing Editors: Neil A. Holtzman, Michael S. Watson, Sept. 1997 http://www.nhgri.nih.gov/ELSI/TFGT_final/ Related terms: predictive testing, predisposition, susceptibility preimplantation diagnosis: Used following in vitro fertilization to diagnose a genetic disease or condition in a preimplantation embryo. Enhancing the oversight of genetic tests: Recommendations of the SACGT, Secretary's Advisory Committee on Genetic Testing, June 2000 http://www4.od.nih.gov/oba/sacgt/reports/oversight_report.pdf Not a routine procedure, most often used when parents have previously had a child with a serious genetic illness. Genetic conditions can be diagnosed in embryos of only eight or even fewer cells, with one or more healthy embryos reimplanted.. prenatal diagnosis: Used to diagnose a genetic disease or condition in a developing fetus. Enhancing the oversight of genetic tests: Recommendations of the SACGT, Secretary's Advisory Committee on Genetic Testing, June 2000 http://www4.od.nih.gov/oba/sacgt/reports/oversight_report.pdf Related terms: carrier testing, molecular genetic screening presymptomatic test: Predictive testing of individuals with a family history. Historically, the term has been used when testing for diseases or conditions such as Huntington's disease where the likelihood of developing the condition (known as penetrance) is very high is people with a positive test result. Enhancing the oversight of genetic tests: Recommendations of the SACGT, Secretary's Advisory Committee on Genetic Testing, June 2000 http://www4.od.nih.gov/oba/sacgt/reports/oversight_report.pdf Current experience with genetic testing involves only a limited number of tests involving single genes. Our thinking about genetics is shaped by the Mendelian model of monogenic disorders with high penetrance (which tend to be relatively rare). How will we interpret -- and begin to make decisions about tests involving multiple genes (polygenic) disorders with varying penetrance. Will we become more aware of various tradeoffs, or continue to look for silver bullets to "cure" conditions (both acute and chronic)? Will the level of understanding of both biology and statistics be sufficient to allow informed public debate? Related terms: predisposition, susceptibility; Genomics pre-Mendelian risk communication: An educational process through which a genetic counselor attempts to interpret how a genetic condition is inherited and the chances that it might be passed on to children. [NHGRI] SACGT: Secretary's Advisory Committee on Genetic Testing. See under genetic testing. screening: Carrying out of a test or tests, examination(s) or procedure(s) in order to expose undetected abnormalities, unrecognized (incipient) diseases, or defects: examples are mass X-rays and cervical smears. [IUPAC Tox] Not the same as screening Drug discovery & development selectivity: See analytical specificity sensitivity (in analytical chemistry): Extent to which a small change in concentration of an analyte can cause a large change in the related measurement. (Gold, Loening, McNaught and Sehmi, 1987) [IUPAC Tox] sensitivity (of a screening test): Extent (usually expressed as a percentage) to which a method gives results that are free from false negatives; the fewer the false negatives, the greater the sensitivity. Quantitatively, sensitivity is the proportion of truly diseased persons in the screened population who are identified as diseased by the screening test (Galen and Gambino, 1975) Related Term specificity (of a screening test) [IUPAC Tox] Related terms: analytical sensitivity, clinical sensitivity sex selection: President's Council on Bioethics, http://www.bioethics.gov/topics/sex_index.html somatic cells: All body cells, except the reproductive cells. Somatic gene mutations (such as those caused by sun damage or radiation) are not inherited. Related terms: germline mutation, susceptibility. specificity: See analytical specificity, clinical specificity sporadic cancer: Cancer genomics susceptibility: This large diversity in responsiveness among individuals to environmental toxicants makes it difficult to determine actual risks, particularly at the low doses to which most people are exposed. Opportunities now exist for studies of genetic susceptibility for cancer and other diseases in which an environmental component can be presumed. Knowledge from such studies could, in the future, allow markers of genetic susceptibility to be incorporated into epidemiologic studies. This, in turn, would permit adjustment of interpretation of results to account for genetic susceptibility, thus greatly enhancing the sensitivity and power of these studies to detect environmental components of important diseases. Other projects being considered are a nutrition initiative to determine how nutritional status alters disease susceptibility, and development of transgenic mice that carry important environmental response gene. NIEHS Strategic Plan 2000 "Individual susceptibility", National Institute of Environmental Health Sciences, US, March 2000 http://www.niehs.nih.gov/external/plan2000/suscptblty.htm Susceptibility seems essentially synonymous with predisposition. Are there differences? Narrower term: genetic susceptibility Related terms: genetic screening, predisposition test, predictive test, risk communication; Pharmacogenomics glossary toxicogenomics uncertainty: Molecular Medicine Bibliography Other patient and disease related resources: Patient resources How to look for other unfamiliar terms IUPAC definitions are reprinted with the permission of the International Union of Pure and Applied Chemistry. |
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