Genetic testing

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." It can provide information about a person's genes and chromosomes throughout life. Symptomatic diagnostic testing • Cell-free fetal DNA (cffDNA) testing a non-invasive (for the fetus) test. It is performed on a sample of venous blood from the mother and can provide information about the fetus early in pregnancy. it is the most sensitive and specific screening test for Down syndrome. • Newborn screening used just after birth to identify genetic disorders that can be treated early in life. A blood sample is collected with a heel prick from the newborn 24–48 hours after birth and sent to the lab for analysis. In the United States, newborn screening procedure varies state by state, but all states by law test for at least 21 disorders. If abnormal results are obtained, it does not necessarily mean the child has the disorder. Diagnostic tests must follow the initial screening to confirm the disease. 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 (PKU, a genetic disorder that causes intellectual disability if left untreated) and congenital hypothyroidism (a disorder of the thyroid gland). People with PKU do not have an enzyme needed to process the amino acid phenylalanine, which is responsible for normal growth in children and normal protein use throughout their lifetime. If there is a buildup of too much phenylalanine, brain tissue can be damaged, causing developmental delay. Newborn screening can detect the presence of PKU, allowing children to be placed on special diets to avoid the effects of the disorder. Despite the several implications of genetic testing in conditions such as epilepsy or neurodevelopmental disorders, many patients (especially adults) do not have access to these modern diagnostic approaches, showing a relevant diagnostic gap. • Carrier testing 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 performed on human embryos prior to the implantation as part of an in vitro fertilization procedure. Pre-implantation testing is used when individuals try to conceive a child through in vitro fertilization. Eggs from the woman and sperm from the man are removed and fertilized outside the body to create multiple embryos. The embryos are individually screened for abnormalities, and the ones without abnormalities are implanted in the uterus. • 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 ease a couple's uncertainty or help them decide whether to abort the pregnancy. It cannot identify all possible inherited disorders and birth defects, however. One method of performing a prenatal genetic test involves an amniocentesis, which removes a sample of fluid from the mother's amniotic sac 15 to 20 or more weeks into pregnancy. The fluid is then tested for chromosomal abnormalities such as Down syndrome (trisomy 21) and trisomy 18, which can result in neonatal or fetal death. Test results can be retrieved within 7–14 days after the test is done. This method is 99.4% accurate at detecting and diagnosing fetal chromosome abnormalities. There is a slight risk of miscarriage with this test, about 1:400. Another method of prenatal testing is chorionic villus sampling (CVS). Chorionic villi are projections from the placenta that carry the same genetic makeup as the baby. During this method of prenatal testing, a sample of chorionic villi is removed from the placenta to be tested. This test is performed 10–13 weeks into pregnancy, and the results are ready 7–14 days after the test is done. Another test using blood taken from the fetal umbilical cord is percutaneous umbilical cord blood sampling. • Predictive and presymptomatic testing 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 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. Hereditary breast cancer along with ovarian cancer syndrome are caused by gene alterations in the genes BRCA1 and BRCA2. Major cancer types related to mutations in these genes are female breast cancer, ovarian, prostate, pancreatic, and male breast cancer. Li-Fraumeni syndrome is caused by a gene alteration on the gene TP53. Cancer types associated with a mutation on this gene include breast cancer, soft tissue sarcoma, osteosarcoma (bone cancer), leukemia and brain tumors. In the Cowden syndrome there is a mutation on the PTEN gene, causing potential breast, thyroid or endometrial cancer. A sample of the cancer tissue can be sent in for genetic analysis by a specialized lab. After analysis, information retrieved can identify mutations in the tumor which can be used to determine the best treatment option. Non-diagnostic 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). • Paternity testing 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 used to determine ancestry or ethnic heritage for genetic genealogy. • Research testing includes finding unknown genes, learning how genes work and advancing 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. ==Medical procedure==

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. 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. ==Risks and limitations==

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". 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. 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. 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 cannot determine if a person will show symptoms of a disorder, how severe the symptoms will be, or whether the disorder will progress over time. "A number of scientists and scholars said companies might not be fully explaining the limitations of genetic testing, or what results actually mean." 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 understands and weighs these factors before making a decision. In 2013 the American College of Medical Genetics and Genomics (ACMG) recommended that certain genes always be included any time a genomic sequencing is done, and that labs should report the results. DNA studies have been criticised for a range of methodological problems and providing misleading interpretations on racial classifications. ==Direct-to-consumer genetic testing==

Direct-to-consumer (DTC) genetic testing (also called at-home 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 physicians, nurse practitioners, or genetic counselors acquire their patient's permission and then order the desired test, which may or may not be covered by health insurance. DTC genetic tests, however, allow consumers to bypass this process and purchase DNA tests themselves. DTC genetic testing can entail primarily genealogical/ancestry-related information, health and trait-related information, or both. Genetic testing has been taken on by private companies, such as 23andMe, Ancestry.com, and Family Tree DNA. These companies will send the consumer a kit at their home address, with which they will provide a saliva sample for their lab to analyze. The company will then send back the consumer's results in a few weeks, providing a breakdown of their ancestral heritage and possible health risks that accompany it. There are a variety of DTC genetic tests, ranging from tests for breast cancer alleles to mutations linked to cystic fibrosis. Possible benefits of DTC genetic testing are the accessibility of tests to consumers, promotion of proactive healthcare, and the privacy of genetic information. Possible additional risks of DTC genetic 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. In the United States, most DTC genetic test kits are not reviewed by the Food and Drug Administration (FDA), with the exception of a few tests offered by the company 23andMe. As of 2019, the tests that have received marketing authorization by the FDA include 23andMe's genetic health risk reports for select variants of BRCA1/BRCA2, pharmacogenetic reports that test for selected variants associated with metabolism of certain pharmaceutical compounds, a carrier screening test for Bloom syndrome, and genetic health risk reports for a handful of other medical conditions, such as celiac disease and late-onset Alzheimer's. DTC genetic 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." Apart from rare diseases that are directly caused by specific, single-gene mutation, diseases "have complicated, multiple genetic links that interact strongly with personal environment, lifestyle, and behavior." 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. 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. ==Governmental genetic testing==

In Estonia As part of its healthcare system, Estonia is offering all of its residents genome-wide genotyping. This will be translated into personalized reports for use in everyday medical practice via the national e-health portal. The aim is to minimise health problems by warning participants most at risk of conditions such as cardiovascular disease and diabetes. It is also hoped that participants who are given early warnings will adopt healthier lifestyles or take preventative drugs. == The Genographic Project ==

In 2005, National Geographic launched the "Genographic Project", which was a fifteen-year project that was discontinued in 2020. Over one million people participated in the DNA sampling from more than 140 countries, making the project the largest of its kind ever conducted. The project asked for DNA samples from indigenous people as well as the general public, which spurred political controversy among some indigenous groups, leading to the coining of the term "biocolonialism". ==Government regulation==

In the United States 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 person 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 genetic information when making hiring, firing, job placement, or promotion decisions. Although GINA protects against genetic discrimination, Section 210 of the law states that once the disease has manifested, employers can use the medical information and not be in violation of the law, even if the condition has a genetic basis. The legislation, the first of its kind in the United States, 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. 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. The Supreme Court also ruled that police were allowed to collect DNA from people arrested for serious offenses. In the European Union Effective as of May 25, 2018, companies that process genetic data must abide by the General Data Protection Regulation (GDPR). The GDPR is a set of rules/regulations that helps an individual take control of their data that is collected, used, and stored digitally or in a structured filing system on paper, and restricts a company's use of personal data. which mandates that health-related genetic tests can only be carried out under medical supervision to ensure the proper interpretation of results and informed decision-making. The law emphasizes genetic counseling and informed consent, protecting individuals from potential misuse or misunderstanding of their genetic data. In France The legal status of genetic testing in France is regulated under strict privacy and data protection laws, including the Bioethics Law. Direct-to-consumer (DTC) genetic tests, especially those for health-related purposes, are prohibited unless conducted with medical oversight to ensure informed consent and appropriate counseling. This is due to concerns about the potential misuse of genetic data and privacy violations. While health-related genetic testing is allowed within a medical context, tests for non-medical purposes, such as ancestry or personal traits, also face legal restrictions, particularly regarding consumer access. In Russia Russian law provides that the processing of special categories of personal data relating to race, nationality, political views, religious or philosophical beliefs, health status, intimate life is allowed if it is necessary in connection with the implementation of international agreements of the Russian Federation on readmission and is carried out in accordance with the legislation of the Russian Federation on citizenship of the Russian Federation. Information characterizing the physiological and biological characteristics of a person, based on which it is possible to establish his identity (biometric personal data), can be processed without the consent of the subject of personal data in connection with the implementation of international agreements of the Russian Federation on readmission, administration of justice and execution of judicial acts, compulsory state fingerprinting registration, as well as in cases stipulated by the legislation of the Russian Federation on defense, security, anti-terrorism, transport security, anti-corruption, operational investigative activities, public service, as well as in cases stipulated by the criminal-executive legislation of Russia, the legislation of Russia on the procedure for leaving the Russian Federation and entering the Russian Federation, citizenship of the Russian Federation and notaries. Within the framework of this program, it is also planned to include the peoples of neighboring countries, which are the main source of migration, into the genogeographic study on the basis of existing collections. In UAE By the end of 2021, the UAE Genome Project will be in full swing, as part of the National Innovation Strategy, establishing strategic partnerships with top medical research centers, and making sustainable investments in healthcare services. The project aims to prevent genetic diseases through the use of genetic sciences and innovative modern techniques related to profiling and genetic sequencing, in order to identify the genetic footprint and prevent the most prevalent diseases in the country, such as obesity, diabetes, hypertension, cancer, and asthma. It aims to achieve personalized treatment for each patient based on genetic factors. Additionally, a study by Khalifa University has identified, for the first time, four genetic markers associated with type 2 diabetes among UAE citizens. In Israel The Israeli Knesset passed the Genetic Information Law in 2000, becoming one of the first countries to establish a regulatory framework for the conducting of genetic testing and genetic counseling and for the handling and use identified genetic information. Under the law, genetic tests must be done in labs accredited by the Ministry of Health; however, genetic tests may be conducted outside Israel. The law also forbids discrimination for employment or insurance purposes based on genetic test results. Finally, the law takes a strict approach to genetic testing on minors, which is permitted only for the purpose of finding a genetic match with someone ill for the sake of medical treatment, or to see whether the minor carries a gene related to an illness that can be prevented or postponed. Under the Genetic Information Law as of 2019, commercial DNA tests are not permitted to be sold directly to the public, but can be obtained with a court order, due to data privacy, reliability, and misinterpretation concerns. ==Anthropological view==

Three to five percent of the funding available for the Human Genome Project was set aside to study the many social, ethical, and legal implications that will result from the better understanding of human heredity and the rapid expansion of genetic risk assessment by genetic testing which would be facilitated by this project. Genealogical DNA testing Genetic testing influences how we perceive identity, ancestry, and group membership. Genealogical DNA testing has been critiqued for its potential to affirm and normalise biological race science. Genetic ancestry tests—which use biological data to predict a person's genetic similarity to a variety of social groups—reify biological race by seemingly providing concrete biological explanations for racial group variety. Marketing for ancestry tests often supports this misconception that humans can be separated into biologically distinct groups. However, genetic ancestry testing also has the potential to complicate these same notions. Subjectivities, based on identification with a particular race, can be challenged when genetic testing reveals ancestry from another group. For instance, someone who identifies as white may have their subjective experiences challenged upon discovering shared ancestry with a marginalised group. This can force them to examine ideas of what it means for them to continue identifying as white. In Vitro Fertilisation Ethical implications surrounding genetic testing also arise with the use of In Vitro Fertilisation (IVF). Genetic testing is used in IVF to test embryos for potentially fatal diseases to determine the strongest candidates. With this they are also able to see the sex of these embryos, meaning people who undergo IVF are able to choose the sex of their future child. This gender selection of embryos is not aimed at assessing the viability of said embryo, rather a cultural act that has deep roots in most societies around the world. In patriarchal societies gender selection is used to facilitate son preference and the devaluing of daughters, reinforcing the existing hierarchies present in current society under the guise of choice. This practice is justified under the context of reproductive autonomy, it is clear that these so-called choices are culturally informed and shaped by society. This reinforces the stereotypes of each gender's roles within a family unit. It is argued that technologies, such as these, sort embryos for socially desirable traits and removes the natural randomness of sex determination with targeted intervention. Paternity testing While paternity testing has proven an important genetic test within the medical field, its place in shaping human experience cannot be overlooked. Paternity testing can provide answers to the fundamental individual need to know where one came from. However, the development of the technology has somewhat ridiculed the origins of 'father' being a provider of care, support, and inspiration regardless of bloodline. Paternity is not always defined by biology, 'father' or 'fathers' can be defined by their role as a provider of care and support to the offspring in contemporary society. With the increasing availability of tests, and the shifting recognition and meaning of paternity within the law, rates of paternity tests are increasing. Shifting legal practices, which are emphasising 'reproductive history' to declare paternity, to place more responsibility and rights upon the biological father. This discourse places the question of 'who is the father?' above the more significant question 'what is the father?'. The consideration of responsibilities that define fatherhood as 'lesser' is counterproductive to creating strong familial bonds, nor does it allow individuals to gain a deep sense of self through family. With the increasing demand for paternity testing, it is important for society to hold both meanings of fatherhood and the question of 'what' vs 'who' in equal importance. Paediatric genetic testing The American Academy of Pediatrics (AAP) and the American College of Medical Genetics (ACMG) have provided new guidelines for the ethical issue of pediatric 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. AAP and ACMG recommend holding off on genetic testing for late-onset conditions until adulthood, unless diagnosing genetic disorders during childhood can reduce morbidity or mortality (e.g., to start early intervention). Testing asymptomatic children who are at risk of childhood onset conditions can also be warranted. Both AAP and ACMG discourage the use of direct-to-consumer and home kit genetic tests because of concerns regarding the accuracy, interpretation and oversight of test content. Guidelines also state that parents or guardians should be encouraged to inform their child of the results from the genetic test if the minor is of appropriate age. For ethical and legal reasons, health care providers should be cautious in providing minors with predictive genetic testing without the involvement of parents or guardians. Within the guidelines set by AAP and ACMG, health care providers have an obligation to inform parents or guardians on the implication of test results. AAP and ACMG state that any type of predictive genetic testing should be offered with genetic counseling by clinical genetics, genetic counselors or health care providers. ==Costs and time==

From the date that a sample is taken, results may take weeks to months, depending upon the complexity and extent of the tests being performed. Results for prenatal testing are usually available more quickly because time is an important consideration in making decisions about a pregnancy. Prior to the testing, the doctor or genetic counselor who is requesting a particular test can provide specific information about the cost and time frame associated with that test. == See also ==