Genetic testing, also known as DNA testing, is used to identify changes in DNA sequence or chromosome structure. Genetic testing can also include measuring the results of genetic changes, such as RNA analysis as an output of gene expression, or through biochemical analysis to measure specific protein output.[1] In a medical setting, genetic testing can be used to diagnose or rule out suspected genetic disorders, predict risks for specific conditions, or gain information that can be used to customize medical treatments based on an individual's genetic makeup.[1] Genetic testing can also be used to determine biological relatives, such as a child's biological parentage (genetic mother and father) through DNA paternity testing,[2] or be used to broadly predict an individual's ancestry.[3] Genetic testing of plants and animals can be used for similar reasons as in humans (e.g. to assess relatedness/ancestry or predict/diagnose genetic disorders),[4] to gain information used for selective breeding,[5] or for efforts to boost genetic diversity in endangered populations.[6]
The variety of genetic tests has expanded throughout the years. Early forms of genetic testing which began in the 1950s involved counting the number of chromosomes per cell. Deviations from the expected number of chromosomes (46 in humans) could lead to a diagnosis of certain genetic conditions such as trisomy 21 (Down syndrome) or monosomy X (Turner syndrome).[7] In the 1970s, a method to stain specific regions of chromosomes, called chromosome banding, was developed that allowed more detailed analysis of chromosome structure and diagnosis of genetic disorders that involved large structural rearrangements.[8] In addition to analyzing whole chromosomes (cytogenetics), genetic testing has expanded to include the fields of molecular genetics and genomics which can identify changes at the level of individual genes, parts of genes, or even single nucleotide "letters" of DNA sequence.[7] According to the National Institutes of Health, there are tests available for more than 2,000 genetic conditions,[9] and one study estimated that as of 2018 there were more than 68,000 genetic tests on the market.[10]
(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.[12] As of 2015 it is the most sensitive and specific screening test for Down syndrome.[13]
Cell-free fetal DNA
Newborn heel-prick blood sample collectionNewborn 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.[14] 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 mental illness if left untreated) and congenitalhypothyroidism (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.[14]
– 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. For example, people with a family history of polycystic kidney disease (PKD) who experience pain or tenderness in their abdomen, blood in their urine, frequent urination, pain in the sides, a urinary tract infection or kidney stones may decide to have their genes tested and the result could confirm the diagnosis of PKD.[15] Despite the several implications of genetic testing in conditions such as epilepsy or neurodevelopmental disorders, many patients (specially adults) do not have access to these modern diagnostic approaches, showing a relevant diagnostic gap.[16]
Diagnostic 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.
Carrier testing
– 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.[17]
Preimplantation genetic diagnosis
Small amounts of the chorionic villi are sampled during CVSPrenatal 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. 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 results are ready 7–14 days after the test was done.[18] 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 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 . For example, an individual with a mutation in BRCA1 has a 65% cumulative risk of breast cancer.[19] 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.[20] 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.[20] 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, help with making decisions about medical care and provide a better prognosis.
cancer
– determines the influence of genetic variation on drug response. When a person has a disease or health condition, pharmacogenomics can examine an individual's genetic makeup to determine what medicine and what dosage would be the safest and most beneficial to the patient. In the human population, there are approximately 11 million single nucleotide polymorphisms (SNPs) in people's genomes, making them the most common variations in the human genome. SNPs reveal information about an individual's response to certain drugs. This type of genetic testing can be used for cancer patients undergoing chemotherapy.[21] 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.[22]
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.[23] 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.[24]
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".[25] 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.[26] 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.[27] 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.[28] 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.[24]
Another limitation to genetic testing for a hereditary linked cancer, is the variants of unknown clinical significance. Because the human genome has over 22,000 genes, there are 3.5 million variants in the average person's genome. These variants of unknown clinical significance means there is a change in the DNA sequence, however the increase for cancer is unclear because it is unknown if the change affects the gene's function.[29]
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.[24]
Other risks include incidental findings—a discovery of some possible problem found while looking for something else.[30] In 2013 the American College of Medical Genetics and Genomics (ACMG) that certain genes always be included any time a genomic sequencing was done, and that labs should report the results.[31]
DNA studies have been criticised for a range of methodological problems and providing misleading, interpretations on racial classifications.[32][33][34][35][36]
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.[48]
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.[49]
Genetic testing has also 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, which is a breakdown of their ancestral heritage and possible health risks that accompany it.[50] Other companies, like National Geographic, have conducted public DNA surveys in an effort to better understand global ancestry and heritage. 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, which made the project the largest of its kind ever conducted.[51] 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".[52]
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.[53]
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.[54] The legislation, the first of its kind in the United States,[55] 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.[56][57] 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.[58] The Supreme Court also ruled that police were allowed to collect DNA from people arrested for serious offenses.[59]
Effective as of 25 May 2018, companies that process genetic data must abide by the General Data Protection Regulation (GDPR).[60][61] 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.[61] The regulation also applies to companies that offer products/services outside the EU.[61]
Russian law[62] 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, on the basis of 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.[63]
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.[64]
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.[65][66]
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.[67]
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.[75]
Biobank
DNA profiling
Designer baby
Genographic Project
Personalized medicine
Pre-implantation genetic diagnosis to avoid birth defects
