Genetic testing – Wikipedia
Posted: November 1, 2016 at 11:47 pm
This article is about genetic tests for disease and ancestry or biological relationships. For use in forensics, see DNA profiling.
Genetic testing, also known as DNA testing, allows the the determination of bloodlines and the genetic diagnosis of vulnerabilities to inherited diseases. In agriculture, a form of genetic testing known as progeny testing can be used to evaluate the quality of breeding stock. In population ecology, genetic testing can be used to track genetic strengths and vulnerabilities of species populations.
In humans, genetic testing can be used to determine a child's parentage (genetic mother and father) or in general a person's ancestry or biological relationship between people. 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] The variety of genetic tests has expanded throughout the years. In the past, the main genetic tests searched for abnormal chromosome numbers and mutations that lead to rare, inherited disorders. Today, tests involve analyzing multiple genes to determine the risk of developing certain more common diseases such as heart disease and cancer.[2] 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.[3][4]
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.[5]
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."[6] It can provide information about a person's genes and chromosomes throughout life. Available types of testing include:
Non-diagnostic testing includes:
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[15]
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.[16] 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.[16][17] As of 2013 there are 9 genetic tests available.[18]
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
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.[19] 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 disorders, often using DNA sequencing. 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.
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 non-negligible 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".[20] 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.[21] 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.[22] 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 (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 their patient's permission and then order the desired test. DTC genetic tests, however, allow consumers to bypass this process and order DNA tests themselves.
There is a variety of DTC tests, ranging from tests 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, the potential misinterpretation of genetic information, issues related to testing minors, privacy of data, and downstream expenses for the public health care system.[23]
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.[24]
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 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 DTC 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.[25]
Ancestry.com, a company providing DTC DNA tests for genealogy purposes, has reportedly allowed the warrantless search of their database by police investigating a murder.[26] The warrantless search led to a search warrant to force the gathering of a DNA sample from a New Orleans filmmaker; however he turned out not to be a match for the suspected killer.[27]
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.[28]
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.[29] The legislation, the first of its kind in the U.S.,[30] 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.[31][32] 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.[33] The Supreme Court also ruled that police were allowed to collect DNA from people arrested for serious offenses.[34]
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.[35] 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 its 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 the 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.[35][36][37]
Israel uses DNA testing to determine if people are eligible for legal privileges given to specific ethnic groups. The policy where "many Jews from the Former Soviet Union (FSU) are asked to provide DNA confirmation of their Jewish heritage in order to immigrate as Jews and become citizens under Israel's Law of Return" has generated controversy. [38]
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