Genetic Testing (DNA Testing)
Genetic testing is called by many, the test of a Lifetime. In fact, this test allows the determination of the bloodlines and the genetic diagnosis of vulnerabilities in inherited diseases. In agriculture, a form of genetic testing known as “Progeny testing” which evaluate the quality in breeding stock, is currently used. I have witnessed it while living in Kansas. In population ecology, genetic testing on strength of population can be used. Never less, we can describe genetic testing as a medical test able to identify changes in chromosomes, proteins or genes, confirming or ruling out any suspected genetic condition or at least studying the possibilities on developing or transmitting a genetic condition. More than 1000 genetic tests are in use in our laboratories and many more are being developed. Only a handful are approved by the FDA (Food and Drug Administration). It is only in 2013 that the US Supreme court issued two rulings on Human Genetics (DNA).
Genetic testing is simply the analysis of chromosomes (DNA), proteins and certain metabolites to detect heritable disease related to mutations, genotypes or phenotypes. It can provide information about a person’s genes and chromosomes throughout life.
Several methods are used for genetic testing: Molecular Genetic, Chromosomal Genetic, Biochemical Genetic. Let us expand on them.
1- Molecular genetic test (Gene test) studying single genes or short lengths of DNA to identify variations or mutations that lead to a genetic disorder.
2- Chromosomal genetic test analyzing whole chromosomes or long lengths of DNA to see if there are genetic changes such as an extra copy at a chromosome that cause a condition.
3- Biochemical genetic tests studying the amount of activity level of proteins: abnormalities in either can indicate changes to the DNA that result in a genetic condition.
Genetic testing is voluntary. Testing has its benefits as well as its limitations and risks. The decision to submit self to testing is personal and complex. A Genecist or genetic counselor can certainly provide information about the pros and cons in having such test. They can discuss the social and emotional aspect of the test.
People have different reasons to be tested or not. It is also important to know if the disease being studied, can be treated or not. Often, there are no treatment, but the results can help deciding. Typically, in an unborn child, this is the best way in confirming the presence of a genetic disease. Embryos can be also screened as well as the person carrying the genes. When a physician is unable to diagnose a disease, Genetic testing becomes the best way to provide an answer or an explanation or often, a hope.
Many experts saw genetic testing / DNA sequencing as a curiosity rather than a medical necessity especially if it cost more than 8000 dollars to perform the studies. In 2001, the mopping of the human genome has given hope in the diagnosis and treatment of genetic disease, but we found out soon that it took. around six weeks to have results. Ernest Rady. A Canadian-American entrepreneur, donated 120 million of dollars to build The Rady Children Hospital for “Genomic Medicine”, in 2015. The studies were limited to critical pediatric patients in NICU and destined to improve their chances for survival. It allows also a compilation of data helping in the treatment of the sick babies.
A commercial software was developed to match symptoms reported by scientists dealing with mutations and fastest genetic diagnosis from mapping of the human genome were obtained at the institution. DNA decoding machine run 7 days a week and 23 hours a day to resolve problems. It takes an average of 96 hours from the time a blood sample enters the lab to the time specific sequences can be obtained. Mapping the genome become an easy process and once the DNA is decoded, the real challenge is to figure out what it means. Only a small percentage of genetic mutations is associated with diseases. A larger percentage is of unknown significance.
The genomic information generated will be soon available to physicians and patients. By example, a patient named Sebastina presented in her sequencing, a rare genetic defect called KCNQ2 which can contribute to “Ohtahara syndrome” associated with seizures depending on where and when the gene has mutated. The child may develop normally or can suffer of seizures disrupting the development of the brain leading to epilepsy, developmental delays, intellectual disability and Cerebral Palsy. Half of the patients does not survive past the age 2. The mutation in the case of Sebastina was found in the middle of the gene.
The genetic testing demonstrated that a pathway in the brain was affected, suggesting that a specific medication to control the seizures may be prescribed. Once the medication started, the brain scans improved, enhancing the chances to have a normal development. Sebastina was discharged from Rady’s children hospital, improved. Those are the changes that Dr Kingsmore and his team are trying to replicate at the genomic center.
Even if the DNA mapping does not lead to a specific diagnosis, it is valuable. The kids Holbrook in San Diego, Ca were studied after one of them was discovered to have an umbilical hernia and a heart condition both requiring surgical treatment. The father who works as a software developer decided to get genetic testing of the child to see if any genetic defect was associated with her condition and possibly could be passed to other children.
Many institutions like Cincinnati Children Medical Center are pushing the limits of genomic mapping to include the test in their regular medical workup. Some geneticists at the University of Kentucky and at the University of Michigan would love to see genomic sequencing used more often but in practice, the tests are too costly, and no insurer currently re-reimburses for expenses. Therefore, the Rady Genomic center is trying to prove the way genetic sequencing for sick babies will save money, sparing a lengthy hospitalization as well as providing a more specific therapy. It is estimated that more than a billion in NICU care nationwide can be saved in United States of America. They always go back to Sebastina ‘s case with her seizures and the way the sequencing mapping helped in stabilizing her symptoms.
At the Rady Genomic Center, all babies who have benefited from a DNA mapping are part of a research trial. Hundreds of newborns with unexplained illnesses have their symptoms resolved with life-changing treatments. The Food and Drug Administration and the NIH have supported the studies at Rady genomic Center in presenting a grant of 6 million de dollars to the institution.
We are looking for the day when Mapping the DNA of a sick baby will be as standard as ordering a blood test and one must remember that often these sick infants carry with them the answer to their own mystery illness. Genomic mapping can save life and must be part of every Children hospital armamentarium.
Clinicians have used genomic testing for many years as part of the standard care of patients with breast Cancer, Non-small cell lung carcinoma, ovarian and colorectal malignancies. As already proven in the Grady Genomic Center, now advanced genomic tumor assessment can also identify mutation in cancer cells. Advanced genomic testing is now offered through the Centers for Advanced Individual Medicine (CAIM) offering a state of art molecular science application. It is also an educational resource to keep oncologists up to date and to educate/treat patients. A simple biopsy of your tumor will allow cancer cells to be isolated and extracted. Then the DNA will be sequenced in the lab allowing to match previous sequences of genetic profile. If abnormalities are discovered, then they are compared to known mutations facilitating identical treatment used for these mutations. If there is a match, the oncologist will formulate a plan of treatment targeting each situation.
Many other types of testing are available:
1- Cell free fetal DNA performed on a sample of fetal blood or a venous blood from the mother able to be screened in early pregnancy. In 2015, it becomes the screening test for Down Syndrome.
2- Newborn screening through a blood sample collected with a heel prick from the newborn 24-48 hours after birth to test Phenylketonuria, mental illness, congenital hypothyroidism.
3- Diagnostic testing used for genetic or chromosomal conditions like in Polycystic Kidney Disease (PKD)
4- Carrier testing to identify people who carry one copy of a gene mutation like in Cystic Fibrosis
5- Pre-natal diagnosis: testing offered to couples with high chances in having a baby with genetic or chromosomal disorder
6- Predictive and pre-symptomatic testing used to detect gene mutations associated with disorders that appear after birth (BRCA1) with a 65% cumulative risk of breast Cancer. Hereditary breast cancer along with ovarian cancer syndrome caused by alterations of BRCA1 and BRCA2. The gene TP53 in the Li-Fraumeni Syndrome caused by a gene alteration. Malignancies associated of this gene are seen in breast cancer, soft tissue sarcoma, osteosarcoma, leukemia and brains tumors. In the Cowden syndrome a mutation of the PTEN gene causing breast, thyroid and endometrial cancers. Finally test for detecting Hemochromatosis have been developed.
7- Pharmacogenomic test: can check the genetic determination on a drug.
8- Non-diagnostic testing: DNA sequences to identify an individual for legal purposes. Paternity testing using special DNA markers. Israel utilize genetic markers to confirm the Jewish heritage of eligible migrants coming from the former Soviet Union (FSU) prior to become citizens under their Law of Return”.
The best DNA commercial tests kits, very popular on the market are: “MyHeritage” which advertises for searching lost relatives and can be done in 3 to 4 weeks with a specimen taken with a cheek swab. The “Ancestry” looks for family trees and can be done in 6 to 8 weeks taken from the saliva. The “GPS Origins” provides information about DNA migration routes in 4 to 6 weeks with specimen taken with a cheek swab.
The cost of genetic testing can vary from 100 dollars to more than 2000, depending on the complexity. Cost may also vary by state.
1- Genetic Home reference-NIH
2- “Regulation of Genetic Tests” NIH Research Institute USA Gov April 2015
3- Van Den Veyver. IB (Oct 2016) “Recent Advances in prenatal genetic screening and testing” Research 5, 2591
4- King, Elizabeth (2017) “Genetic Testing Challenge and changes in Testing for heredity cancer syndromes” Clinical Journal of Oncology Nursing 21 (5) 589-598
5- Genetic Testing” American Medical Association 2015-01-23
6- Holtzman NA, Murphy PD, Watson MS, Barr, PA (October 1997) “Predictive genetic testing from basic research to clinical practice” Science 278 (5338) 602-605.
7- Rochman, Bonnie (February 21, 2013) “New guidelines for Genetic Testing in children” Time
8- Genetic Tumor assessment. “Cancer Treatment Centers for America Rising Tide (18 November 2016)
9- Rady Children Hospital for Genomic Testing from 2015 to Present.
10- Audeh, MW (2006) “Letting the Genome out of the bottle” The New England Journal of Medicine 358 (20) 2184-5
11- McGonigle, Ian V “Genetic citizenship DNA Testing and Israeli Law of Return. Oxford Journals 21 May 2018
12- Ronald Bailey. “Ancestry con Hands over Client DNA, Test Results to Cops without warrant. “Reason.com