Genetic testing

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This article is about genetic tests for disease or ancestry. For use in forensics, see DNA profiling.

Genetic testing, also known as DNA testing, allows the genetic diagnosis of vulnerabilities to inherited diseases, and can also be used to determine a child's parentage (genetic mother and father) or in general a person's ancestry. In addition to studying chromosomes to the level of individual genes, genetic testing in a broader sense includes biochemical tests for the possible presence of genetic diseases, or mutant forms of genes associated with increased risk of developing genetic disorders. Genetic testing identifies changes in chromosomes, genes, or proteins.[1] Most of the time, testing is used to find changes that are associated with inherited disorders. The results of a genetic test can confirm or rule out a suspected genetic condition or help determine a person's chance of developing or passing on a genetic disorder. Several hundred genetic tests are currently in use, and more are being developed.[2][3]

Because genetic mutations can directly affect the structure of the proteins they code for, testing for specific genetic diseases can also be accomplished by looking at those proteins or their metabolites, or looking at stained or fluorescent chromosomes under a microscope.[4]

This article focuses on genetic testing for medical purposes. DNA sequencing, which actually produces a sequences of As, Cs, Gs, and Ts, is used in molecular biology, evolutionary biology, metagenomics, epidemiology, ecology, and microbiome research.

Types[edit]

Genetic testing is "the analysis of chromosomes (DNA), proteins, and certain metabolites in order to detect heritable disease-related genotypes, mutations, phenotypes, or karyotypes for clinical purposes."[5] It can provide information about a person's genes and chromosomes throughout life. Available types of testing include:

  • Newborn screening: Newborn screening is used just after birth to identify genetic disorders that can be treated early in life. The routine testing of infants for certain disorders is the most widespread use of genetic testing—millions of babies are tested each year in the United States. All states currently test infants for phenylketonuria (a genetic disorder that causes mental illness if left untreated) and congenital hypothyroidism (a disorder of the thyroid gland).
  • Diagnostic testing: Diagnostic testing is used to diagnose or rule out a specific genetic or chromosomal condition. In many cases, genetic testing is used to confirm a diagnosis when a particular condition is suspected based on physical mutations and symptoms. Diagnostic testing can be performed at any time during a person's life, but is not available for all genes or all genetic conditions. The results of a diagnostic test can influence a person's choices about health care and the management of the disease.
  • Carrier testing: Carrier testing is used to identify people who carry one copy of a gene mutation that, when present in two copies, causes a genetic disorder. This type of testing is offered to individuals who have a family history of a genetic disorder and to people in ethnic groups with an increased risk of specific genetic conditions. If both parents are tested, the test can provide information about a couple's risk of having a child with a genetic condition like cystic fibrosis.
  • Preimplantation genetic diagnosis: Genetic testing procedures that are performed on human embryos prior to the implantation as part of an in vitro fertilization procedure.
  • Prenatal diagnosis: Used to detect changes in a fetus's genes or chromosomes before birth. This type of testing is offered to couples with an increased risk of having a baby with a genetic or chromosomal disorder. In some cases, prenatal testing can lessen a couple's uncertainty or help them decide whether to abort the pregnancy. It cannot identify all possible inherited disorders and birth defects, however.
  • Predictive and presymptomatic testing: Predictive and presymptomatic types of testing are used to detect gene mutations associated with disorders that appear after birth, often later in life. These tests can be helpful to people who have a family member with a genetic disorder, but who have no features of the disorder themselves at the time of testing. Predictive testing can identify mutations that increase a person's chances of developing disorders with a genetic basis, such as certain types of cancer. For example, an individual with a mutation in BRCA1 has a 65% cumulative risk of breast cancer.[6] Presymptomatic testing can determine whether a person will develop a genetic disorder, such as hemochromatosis (an iron overload disorder), before any signs or symptoms appear. The results of predictive and presymptomatic testing can provide information about a person’s risk of developing a specific disorder and help with making decisions about medical care.
  • Pharmacogenomics: type of genetic testing that determines the influence of genetic variation on drug response.

Non-diagnostic testing includes:

  • Forensic testing: Forensic testing uses DNA sequences to identify an individual for legal purposes. Unlike the tests described above, forensic testing is not used to detect gene mutations associated with disease. This type of testing can identify crime or catastrophe victims, rule out or implicate a crime suspect, or establish biological relationships between people (for example, paternity).
  • Parental testing: This type of genetic test uses special DNA markers to identify the same or similar inheritance patterns between related individuals. Based on the fact that we all inherit half of our DNA from the father, and half from the mother, DNA scientists test individuals to find the match of DNA sequences at some highly differential markers to draw the conclusion of relatedness.
  • Genealogical DNA test: To determine ancestry or ethnic heritage for genetic genealogy
  • Research testing: Research testing includes finding unknown genes, learning how genes work and advancing our understanding of genetic conditions. The results of testing done as part of a research study are usually not available to patients or their healthcare providers.

Specific diseases[edit]

Many diseases have a genetic component with tests already available.

over-absorption of iron; accumulation of iron in vital organs (heart, liver, pancreas); organ damage; heart disease; cancer; liver disease; arthritis; diabetes; infertility; impotence[7]

Obstructive lung disease in adults; liver cirrhosis during childhood; when a newborn or infant has jaundice that lasts for an extended period of time (more than a week or two), an enlarged spleen, ascites (fluid accumulation in the abdominal cavity), pruritus (itching), and other signs of liver injury; persons under 40 years of age that develops wheezing, a chronic cough or bronchitis, is short of breath after exertion and/or shows other signs of emphysema (especially when the patient is not a smoker, has not been exposed to known lung irritants, and when the lung damage appears to be located low in the lungs); when you have a close relative with alpha-1 antitrypsin deficiency; when a patient has a decreased level of A1AT.

Elevation of both serum cholesterol and triglycerides; accelerated atherosclerosis, coronary heart disease; cutaneous xanthomas; peripheral vascular disease; diabetes mellitus, obesity or hypothyroidism

Muscle weakness (rapidly progressive); frequent falls; difficulty with motor skills (running, hopping, jumping); progressive difficulty walking (ability to walk may be lost by age 12); fatigue; intellectual retardation (possible); skeletal deformities; chest and back (scoliosis); muscle deformities (contractures of heels, legs; pseudohypertrophy of calf muscles)

Reduced synthesis of the hemoglobin-beta chain; microcytic hypochromic anemia

Venous thrombosis; certain arterial thrombotic conditions; patients with deep vein thrombosis, pulmonary embolism, cerebral vein thrombosis, and premature ischemic stroke and also of women with premature myocardial infarction; family history of early onset stroke, deep vein thrombosis, thromboembolism, pregnancy associated with thrombosis/embolism, hyperhomocystinemia, and multiple miscarriage. Individuals with the mutation are at increased risk of thrombosis in the setting of oral contraceptive use, trauma, and surgery.

Venous thrombosis; pulmonary embolism; transient ischemic attack or premature stroke; peripheral vascular disease, particularly lower extremity; occlusive disease; cerebral vein thrombosis; multiple spontaneous abortions; intrauterine fetal demise

Venous thrombosis; increased plasma homocysteine levels

Independent risk factor for coronary artery disease, ischemic stroke, venous thrombosis (including osteonecrosis)

Uncontrolled division of cancer cells

Inflammation confined to the colon; abdominal pain and bloody diarrhea; anal fistulae and peri-rectal abscesses can also occur

Large amount of abnormally thick mucus in the lungs and intestines; leads to congestioni, pneumonia, diarrhea and poor growth

Congenital loss of hearing; -prelingual, non-syndromic deafness

Tendon xanthomas; elevated LDL cholesterol; premature heart disease

Predisposition of acute myeloid leukemia; skeletal abnormalities; radial hypoplasia and vertebral defect and other physical abnormalities, bone marrow failure (pancytopenia), endocrine dysfunction, early onset osteopenia/osteoporosis and lipid abnormalities, spontaneous chromosomal breakage exacerbated by exposure to DNA cross-linking agents.

Mental retardation or learning disabilities of unknown etiology; autism or autistic-like characteristics; women with premature menopause. Subtle dysmorphism, log face with prominent mandible and large ears, macroorchidism in postpubertal males, behavioral abnormalities, due to lack of FMR1 in areas such as the cerebral cortex, amygdala, hippocampus and cerebellum

Characterized by slowly progressive ataxia; typically associated with depressed tendon reflexes, dysarthria, Babinski responses, and loss of position and vibration senses

over-absorption of iron; accumulation of iron in vital organs (heart, liver, pancreas); organ damage; heart disease; cancer; liver disease; arthritis; diabetes; infertility; impotence

Absence of ganglia in the gut

Progressive disorder of motor, cognitive, and psychiatric disturbances.

Hypolactasia; persistent diarrhea; abdominal cramps; bloating; nausea; flatus

MEN2A (which affects 60% to 90% of MEN2 families):Medullary thyroid carcinoma; Pheochromocytoma (tumor of the adrenal glands); Parathyroid adenomas (benign [noncancerous] tumors) or hyperplasia (increased size) of the parathyroid gland; MEN2B (which affects 5% of MEN2 families): Medullary thyroid carcinoma; Pheochromocytoma; Mucosal neuromas (benign tumors of nerve tissue on the tongue and lips); Digestive problems; Muscle, joint, and spinal problems; Typical facial features; Familial medullary thyroid carcinoma (FMTC) (which affects 5% to 35% of MEN2 families):Medullary thyroid carcinoma only

Affects skeletal and smooth muscle as well as the eye, heart, endocrine system, and central nervous system; clinical findings, which span a continuum from mild to severe, have been categorized into three somewhat overlapping phenotypes: mild, classic, and congenital.

Pseudocholinesterase (also called butyrylcholinesterase or "BCHE") hydrolyzes a number of choline-based compounds including cocaine, heroin, procaine, and succinylcholine, mivacurium, and other fast-acting muscle relaxants.[8] Mutations in the BCHE gene lead to deficiency in the amount or function of the protein, which in turn results in a delay in the metabolism of these compounds, which prolongs their effects. Succinylcholine is commonly used as an anaesthetic in surgical procedures, and a person with BCHE mutations may suffer prolonged paraylasis. Between 1 in 3200 and 1 in 5000 people carry BCHE mutations; they are most prevalent in Persian Jews and Alaska Natives.[8][9] As of 2013 there are 9 genetic tests available.[10]

Variable degrees of hemolysis and intermittent episodes of vascular occlusion resulting in tissue ischemia and acute and chronic organ dysfunction; complications include anemia, jaundice, predisposition to aplastic crisis, sepsis, cholelithiasis, and delayed growth. Diagnosis suspected in infants or young children with painful swelling of the hands and feet, pallor, jaundice, pneumococcal sepsis or meningitis, severe anemia with splenic enlargement, or acute chest syndrome.

Lipids accumulate in the brain; neurological dysfunction; progressive weakness and loss of motor skills; decreased social interaction, seizures, blindness, and total debilitation

Cutaneous photosensitivity; acute neurovisceral crises

Medical procedure[edit]

Genetic testing is often done as part of a genetic consultation and as of mid-2008 there were more than 1,200 clinically applicable genetic tests available.[11] Once a person decides to proceed with genetic testing, a medical geneticist, genetic counselor, primary care doctor, or specialist can order the test after obtaining informed consent.

Genetic tests are performed on a sample of blood, hair, skin, amniotic fluid (the fluid that surrounds a fetus during pregnancy), or other tissue. For example, a medical procedure called a buccal smear uses a small brush or cotton swab to collect a sample of cells from the inside surface of the cheek. Alternatively, a small amount of saline mouthwash may be swished in the mouth to collect the cells. The sample is sent to a laboratory where technicians look for specific changes in chromosomes, DNA, or proteins, depending on the suspected disorder. The laboratory reports the test results in writing to a person's doctor or genetic counselor.

Routine newborn screening tests are done on a small blood sample obtained by pricking the baby's heel with a lancet.

Risks and limitations[edit]

The physical risks associated with most genetic tests are very small, particularly for those tests that require only a blood sample or buccal smear (a procedure that samples cells from the inside surface of the cheek). The procedures used for prenatal testing carry a small but real risk of losing the pregnancy (miscarriage) because they require a sample of amniotic fluid or tissue from around the fetus.

Many of the risks associated with genetic testing involve the emotional, social, or financial consequences of the test results. People may feel angry, depressed, anxious, or guilty about their results. The potential negative impact of genetic testing has led to an increasing recognition of a "right not to know".[12] In some cases, genetic testing creates tension within a family because the results can reveal information about other family members in addition to the person who is tested. The possibility of genetic discrimination in employment or insurance is also a concern. Some individuals avoid genetic testing out of fear it will affect their ability to purchase insurance or find a job.[13] Health insurers do not currently require applicants for coverage to undergo genetic testing, and when insurers encounter genetic information, it is subject to the same confidentiality protections as any other sensitive health information.[14] In the United States, the use of genetic information is governed by the Genetic Information Nondiscrimination Act (GINA) (see discussion below in the section on government regulation).

Genetic testing can provide only limited information about an inherited condition. The test often can't determine if a person will show symptoms of a disorder, how severe the symptoms will be, or whether the disorder will progress over time. Another major limitation is the lack of treatment strategies for many genetic disorders once they are diagnosed.

A genetics professional can explain in detail the benefits, risks, and limitations of a particular test. It is important that any person who is considering genetic testing understand and weigh these factors before making a decision.

Direct-to-consumer genetic testing[edit]

Direct-to-consumer (DTC) genetic testing is a type of genetic test that is accessible directly to the consumer without having to go through a health care professional. Usually, to obtain a genetic test, health care professionals such as doctors acquire the permission of the patient and order the desired test. DTC genetic tests, however, allow consumers to bypass this process and order one themselves. There are a variety of DTC tests, ranging from testing for breast cancer alleles to mutations linked to cystic fibrosis. Benefits of DTC testing are the accessibility of tests to consumers, promotion of proactive healthcare and the privacy of genetic information. Possible additional risks of DTC testing are the lack of governmental regulation and the potential misinterpretation of genetic information, testing minors, privacy of data and downstream expenses for public health care system.[15]

Controversy[edit]

DTC genetic testing has been controversial due to outspoken opposition within the medical community. Critics of DTC testing argue against the risks involved, the unregulated advertising and marketing claims, and the overall lack of governmental oversight.[16]

DTC testing involves many of the same risks associated with any genetic test. One of the more obvious and dangerous of these is the possibility of severe misreading of test results. Without professional guidance, consumers can potentially misinterpret genetic information, causing them to be deluded about their personal health.

Some advertising for direct-to-consumer genetic testing has been criticized as conveying an exaggerated and inaccurate message about the connection between genetic information and disease risk, utilizing emotions as a selling factor. An advertisement for a BRCA-predictive genetic test for breast cancer stated: “There is no stronger antidote for fear than information.”[17]

Government regulation in the United States[edit]

Currently, the U.S. has no strong federal regulation moderating the DTC market. Though there are several hundred tests available, only a handful are approved by the Food and Drug Administration (FDA); these are sold as at-home test kits, and are therefore considered "medical devices" over which the FDA may assert jurisdiction. Other types of DTC tests require customers to mail in DNA samples for testing; it is difficult for the FDA to exercise jurisdiction over these types of tests, because the actual testing is completed in the laboratories of providers. As of 2007, the FDA had not yet officially substantiated with scientific evidence the claimed accuracy of the majority of direct-to-consumer genetic tests.[18]

With regard to genetic testing and information in general, legislation in the United States called the Genetic Information Nondiscrimination Act prohibits group health plans and health insurers from denying coverage to a healthy individual or charging that person higher premiums based solely on a genetic predisposition to developing a disease in the future. The legislation also bars employers from using individuals’ genetic information when making hiring, firing, job placement, or promotion decisions.[19] The legislation, the first of its kind in the U.S.,[20] was passed by the United States Senate on April 24, 2008, on a vote of 95-0, and was signed into law by President George W. Bush on May 21, 2008.[21][22] It went into effect on November 21, 2009.

In June 2013 the US Supreme Court issued two rulings on human genetics. The Court struck down patents on human genes, opening up competition in the field of genetic testing.[23] The Supreme Court also ruled that police were allowed to collect DNA from people arrested for serious offenses.[24]

In popular culture[edit]

Some possible future ethical problems of genetic testing were considered in the science fiction film Gattaca, the novel Next, and the science fiction anime series "Gundam Seed". Also some films which include the topic of genetic testing include The Island, Halloween: The Curse of Michael Myers, and the Resident Evil series.

Ethics[edit]

Pediatric genetic testing[edit]

The American Academy of Pediatrics (AAP) and the American College of Medical Genetics (ACMG) have provided new guidelines for the ethical issue of pediatrics genetic testing and screening of children in the United States. Their guidelines state that performing pediatric genetic testing should be in the best interest of the child. In hypothetical situations for adults getting genetically tested 84-98% expressing interest in getting genetically tested for cancer predisposition.[25] Though only half who are at risk of would get tested. AAP and ACMG recommend holding off on genetic testing for late-onset conditions until adulthood. Unless diagnosing genetic disorders during childhood and start early intervention can reduce morbidity or mortality. They also state that with parents or guardians permission testing for asymptomatic children who are at risk of childhood onset conditions are ideal reasons for pediatrics genetic testing. Testing for pharmacogenetics and newborn screening is found to be acceptable by AAP and ACMG guidelines. Histocompatibility testing guideline states that it’s permissible for children of all ages to have tissue compatibility testing for immediate family members but only after the psychosocial, emotional and physical implications has been explored. With a donor advocate or similar mechanism should be in place to protect the minors from coercion and to safeguard the interest of said minor. Both AAP and ACMG discourage the use of direct-to-consumer and home kit genetic because of the accuracy, interpretation and oversight of test content. Guidelines also state that if parents or guardians should be encouraged to inform their child of the results from the genetic test if minor is of appropriate age. If minor is of mature appropriate age and request results, the request should be honored. Though for ethical and legal reasons health care providers should be cautions in providing minors with predictive genetic testing without the involvement of parents or guardians. Within the guidelines AAP and ACMG state that health care provider have an obligation to inform parents or guardians on the implication of test results. To encourage patients and families to share information and even offer help in explain results to extend family or refer them to genetic counseling. AAP and ACMG state any type of predictive genetic testing for all types is best offer with genetic counseling being offer by Clinical genetics, genetic counselors or health care providers.[25][26][27]

See also[edit]

References[edit]

  1. ^ "What is genetic testing? - Genetics Home Reference". Ghr.nlm.nih.gov. 2011-05-30. Retrieved 2011-06-07. 
  2. ^ "Genetic Testing: MedlinePlus". Nlm.nih.gov. Retrieved 2011-06-07. 
  3. ^ "Definitions of Genetic Testing". Definitions of Genetic Testing (Jorge Sequeiros and Bárbara Guimarães). EuroGentest Network of Excellence Project. 2008-09-11. Retrieved 2008-08-10. [dead link]
  4. ^ Human Genome Project Information. Gene Testing
  5. ^ Holtzman NA, Murphy PD, Watson MS, Barr PA (October 1997). "Predictive genetic testing: from basic research to clinical practice". Science 278 (5338): 602–5. doi:10.1126/science.278.5338.602. PMID 9381169. 
  6. ^ Average risks of breast and ovarian cancer as...
  7. ^ a b c Health24 article on iron overload http://www.health24.com/medical/Condition_centres/777-792-1987-1992,53513.asp
  8. ^ a b National Library of Medicine, Genetics Home Reference. Pseudocholinesterase deficiency
  9. ^ Soliday, F. K.; Conley, Y. P.; Henker, R. (2010). "Pseudocholinesterase deficiency: A comprehensive review of genetic, acquired, and drug influences". AANA journal 78 (4): 313–320. PMID 20879632.  edit
  10. ^ National Library of Medicine, Genetic Testing Registry. Deficiency of butyrylcholine esterase
  11. ^ Allingham-Hawkins, Diane (2008-08-01). "Successful Genetic Tests Are Predicated on Clinical Utility". Genetic Engineering & Biotechnology News 28 (14) (Mary Ann Liebert). pp. 6, 9. ISSN 1935-472X. Retrieved 2008-09-23. 
  12. ^ Roberto Andorno, "The right not to know: an autonomy-based approach", Journal of Medical Ethics, 2004, 30(5): 435–439 [1]
  13. ^ Amy Harmon, "Insurance Fears Lead Many to Shun DNA Tests," The New York Times, February 24, 2008
  14. ^ "Genetic Information and Medical Expense Insurance", American Academy of Actuaries, June 2000
  15. ^ Borry, P., Cornel, M., HOWARD, H. (2011). Where are you going, where have you been. A recent history of the direct-to-consumer genetic testing market. Journal of Community Genetics.
  16. ^ Hunter et al., "Letting the Genome out of the Bottle" New England Journal of Medicine
  17. ^ Gollust et al., "Limitations of Direct-to-Consumer Advertising for Clinical Genetic Testing," JAMA.2002; 288: 1762-1767
  18. ^ Shawna Williams and Gail Javitt, "Direct-to-consumer genetic testing: empowering or endangering the public?," The Genetics and Public Policy Center, July 25, 2006 (updated 6/15/2007)
  19. ^ Statement of Administration policy, Executive Office of the President, Office of Management and Budget, 27 April 2007
  20. ^ Kennedy in support of genetic information nondiscrimination bill, Abril 24, 2008. Last access: 28/05/2008.
  21. ^ Keim, Brandon (May 21, 2008). "Genetic Discrimination by Insurers, Employers Becomes a Crime". Wired.com. Retrieved 2008-05-28. 
  22. ^ "Administration News | President Bush Signs Genetic Nondiscrimination Legislation Into Law," Kaiser Daily Health Policy Report, Kaiser Family Foundation, May 22, 2008
  23. ^ Liptak, Adam (June 13, 2013), "Justices, 9-0, Bar Patenting Human Genes", New York Times, retrieved June 30, 2013 
  24. ^ Liptak, Adam (June 3, 2013), "Justices Allow DNA Collection After an Arrest", New York Times, retrieved June 30, 2013 
  25. ^ a b Ross LF, Saal HM, David KL, Anderson RR, Pediatrics and the AA of, Genomics AC of MG and. 2013. Technical report: ethical and policy issues in genetic testing and screening of children. Genet Med [Internet] 15:234–245. Available from: http://www.nature.com/gim/journal/v15/n3/abs/gim2012176a.html
  26. ^ (Fallat et al. 2013)Fallat ME, Katz AL, Mercurio MR, Moon MR, Okun AL, Webb SA, Weise KL, Saul RA, Braddock SR, Chen E, et al. 2013. Ethical and Policy Issues in Genetic Testing and Screening of Children. Pediatrics [Internet] 131:620–622. Available from: http://pediatrics.aappublications.org/content/131/3/620
  27. ^ (@brochman) @brochman BR. New Guidelines for Genetic Testing in Children. Time [Internet]. Available from: http://healthland.time.com/2013/02/21/new-guidelines-for-genetic-testing-in-children/

Further reading[edit]

External links[edit]