Chapter 16 Flashcards
Genetic tests
analysis of DNA, RNA, chromosomes, proteins, and protein metabolites co identify heritable variations in genes andlor chromosomes.
cell-free DNA (cf DNA),
-small pieces of non-genomic DNA circulating in the blood.
-can be collected from plasma or urine.
- To obtain cf DNA, whole blood is drawn into specialized tubes with a preservative to stabilize and separate the blood cells (preventing the release of genomic DNA) from the clear liquid with cyrokines, plasma, and the buffy coat (supernatant).
-The preservative prevents the release of genomic DNA from the white blood cells so that high- quality cf DNA can be isolated.
Diagnostic testing
Can Genetic Testing Tell Us Anything Besides Information About the Person Being Tested?
Yes-it provides information about other family members as well. For example, your patient’s parents may request genetic testing to confirm her diagnosis of CF If she tests positive, then both of her biologicalparents are almost certain to be CF carriers because it is an autosomal-recessive disease,and each of her current or future siblings has a 50% risk of being a carrier and a 25% risk of being affected. Testingonly one person in the family vvouldtell us something about the genetic risk of several family members.
Predictive testing
-for asymptomaric people who want information about their risk of developing a genetic disease in rhe future.
-Two types of predictive testing exist. A positive presymptomatic test indicates that rhe individual will develop rhe disease he or she was tested for at some point in the future (if he or she does not die from somerhing else first). (E.g., Huntington disease, HD)
-PredispositionaI testing is done when having a gene variant increases the likelihood that a person will develop a genetic disease, but that does nor mean that the person is certain to get it. Testing for rhe breast cancer risk alleles (mutations in BRCAI and BRCA2) is predispositional.
-These genes were formerly tested one at a time. Now that next-generation sequencing is available, multiple genes can be tested at the same time. Some laboratories can sequence as many as 80 genes at the same time.
Carrier testing
-done when persons have family members affected by a heritable disease, but they themselves are not affected.
-Carrier testing can also be done for persons who are at high risk of a genetic disease based on their ethniciry,
Table 16–2
Carrier Frequencies in Selected Genetic Condit ions
prenatal testing
-can be done to determine if the fetus carries a specific gene variant or a chromosomal disorder.
-Numerous kinds of prenatal genetic tests exist.
-These tests vary by when they can be done, the disorders tested for, and the invasiveness of the procedure.
-Chromosomal microarray analysis and next-generation sequencing have greatly improved the ability of prenatal tests to detect genetic disorders.
-Prenatal genetic tests can be either screening or diagnostic.
-Screening tests determine the likelihood that a fetus has a genetic disorder such as Down syndrome. During the first trimester (about the first 10-13 weeks of pregnancy), a pregnant woman’s blood is screened, and an ultrasound test is done. The ultrasound measures the thickness of an area toward the back of the ferus’s neck. This is called nuchal translucency (NT) screening.
-The availability of noninvasive prenatal screening (NIPS) using cell-free fetal DNA (eff DNA), as discussed earlier in this chapter, has greatly improved the accuracy of prenatal blood test results. These screening tests use the small amount of circulating DNA from the placenta (about 10% of maternal blood volume). This fetal DNA can be tested for disorders. including Down syndrome, trisomy 13, trisomy 18, and sex chromosome problems. cff DNA screening can be done beginning at 10 weeks, and it is particularly helpful for women who have an increased risk of carrying a baby with a chromosomal disorder.
-Second-trimester screening is usually done between 15 and 20 weeks. It typically includes the “quad” screen testing for aneuploidy. open neural rube defects, Down syndrome, and trisomy 18. (ACOG, 20 17b). Of course, it is important that parents understand that these tests are for screening only, and therefore accuracy is limited.
Preimplantation genetic diagnosis (PGD)
-process done in conjunction with in vitro fertilization.
-A group of embryos is tested prior to implantation when one or two cells are removed from the eight-cell blastocyst. -Cells from each embryo can be tested to find gene variants causing single-gene disorders or chromosomal problems, or to determine sex.
Newborn screening
-done to identify those infants at high risk of a variety of disorders for which immediate treatment or intervention is available.
-The tests are usually biochemical rather than gene based, but results can indicate the likelihood of a genetic disorder being present.
Table 16–4
Tvpes of GeneticTesting, Interpretation, and Follow-Up
laboratory-developed tests (LDTs),
which have been developed by a specific laboratory. Specimens tested using LOTs are typically shipped to the lab that developed the test for analysis.
quality of a genetic test is evaluated in three ways
We must know that a test is both accurate and reliable (analytical validity), we must be sure that the information provided from the test will be medically meaningful (clinical validity), and we must know that using this test will improve health care (clinical utility)
DNA sequencing
-refers to the analysis of the bases in a length of DNA.
- Laboratories most commonly look at the sequence of nucleorides in the regions that code for protein (exons) and the intron/exon boundaries, or splice sites. Now, the introns (non-protein-coding regions) and the regions between genes (intergenic regions) are sometimes being considered because they may contain sequence variations in regulatory sequences like promoters or silencers. DNA sequencing is the most accurate and most specific test used in identifying gene variants.
polymerase chain reaction (PCR)
-amplify (greatly increase the quantity of) tiny amounts of DNA for examination. Although the process is not complex, it does take some time.
-An elecrropherogram is a graphic illustration of the nucleotide sequence in a stretch of DNA amplified by PCR. Different colored spikes correspond to one of the four DNA bases (A is green, T is red, C is blue, and G is black). The lab technician can read the electropherogram and report any variations between the sequence found in the patient sample and the order that is reponed to be the common sequence (or wild type).
