Genetic Testing Flashcards
genetic tests can be used to determine
the genetic cause of a disease
confirm a suspected diagnosis
predict future illness
detect when an individual might pass a genetic mutation to his or her children
screen newborns, fetuses or embryos used in in vitro fertilization for genetic defects.
informed consent
the process of educating a person about the test and obtaining permision to carry out testing.
informed consent can only be given by adults who are
competent to make medical decisions for themselves.
diagnostic testing is used to
diagnose, rule out or rule in a specific genetic disease.
diagnostic testing is used to confirm a diagnosis when
a particular condition is suspected based on symptoms and/or family history.
types of diagnostic tests
chromosome analysis
biochemical diagnostics
DNA diagnostics
exome sequencing
chromosome analyses - karyotype procedure
blood sample is culture and treated with a mitosis blocker. It is centrifuged and placed on a microscope glass slide and the chromosomes are stained and look at under a microscope.
biochemical diagnostic testing involves
the measurement of enzymes/metabolites to determine if they are abnormal in some way.
They may be done from blood, urine, spinal fluid or other tissue samples, depending on the disease.
DNA testing
identification of specific disease causing mutation
identification of causative gene/mutation in undiagnosed mendelian diseases
techniques
DNA testing: identification of specific disease causing mutation
confirm clinical or biochemical diagnosis
identify carriers, especially for X linked traits.
accurate prenatal diagnosis.
single gene test
minimal locus heterogeneity
distinctive clinical findings clearly point to a specific gene
Limitations of NGS sequencing technology to detect trinucleotide repeat disorders and disorders with epigenetic abnormalities.
gene panel
heterogeneity
disorders with overlapping phenotype - differential diagnosis
disorders share one manifestation but may have completely different overall presentation.
Diseases assoicated with genes from a common pathway structure.
principal indications for prenatal diagnosis
maternal age >35 years
previous child with chromosome or biochemical abnormality.
presence of structural chromosome abnormality in oen of the parents.
family history of a genetic disease that may be diagnosed or ruled out by biochemical or DNA analysis.
parents diagnosed as carriers of a recessive disease after a population screening test.
methods of prenatal diagnosis
invasive testing:
chorionic villus sampling (10 - 11 weeks after LMP)
amniocentesis (15 - 17 weeks after LMP)
noninvasive testing
maternal serum alpha fetoprotein
1st and 2nd trimester maternal serum screening
fetal DNA in maternal blood.
cells obtained by either CVS or anmno can be analyzed directly or cultured for
chromosome analysis
measure substrate level/enzyme activity
source of DNA for mutation detection
detection of genomic disorders
submicroscopic chromosomal deletions/deuplications
fetal DNA in maternal blood
now mainly trisomies
several commercial methods in development
non-invasive 20 - 30 mL of mother’s blood.
microdeletion FISH panel: combined frequency
1 in 430 to 1000
array comparative genomic hybridization (aCGH)
detects submicroscopic gain gain or loss of genetic material
CNVs may be pathogenic, benign or of unknown significance.
widely used in postnatal diagnosis of MR/multiple congential anomalies when chromosomes have been normal.
aCGH general screening
1 in 250 positive
cfDNA comes from apoptotic cells derived from
maternal circulation (adipocytes, white blood cells) fetal (placental cells (trophoblasts) in the maternal circulation)
commercial noninvasive prenatal testing - trisomies tested
13, 18, 21
natera’s panorama - genetic testing method
single nucleotide polymorphism
verinata’s verifi - genetic testing method
massively parallel sequencing
sequenom’s materniT21 plus - genetic testing method
massively prallel sequencing
ariosa’s harmony - genetic testing method
chromosome selective sequencing
present use of noninvasive prenatal testing
trisomies 13, 18, 21
sex chromosome abnormalities
future uses of noninvasive prenatal testing
single gene defects small microdeletion/duplication CNVs methylation patterns (epigenetics)
NIPT is not a
diagnostic test for fetal aneuploidy, and therefore a positive NIPT result requires an invasive test to confirm the findings.
Some therefore consider there to be insufficient evidence to support the use of NIPT for screening in the general population.
preimplantation genetic diagnosis
refers to genetic profiling of embryos prior to implantation.
5 main groups of patients that might utilize preimplantation genetic diagnosis (PGD)
pateints that are having IVF with advanced maternal age
patients of any aged with repeated IVF failure (3 more more failed attempts)
to screen or inherited genetic diseaes
patients that are carriers of chromosomal translocations.
patients that have had recurrent miscarriages.
A recent study found that babies born after PGD testing had
no increased risk of congenital malformation and no adverse effect on growth.
presymptomatic testing
applies to disorders with virtually complete penetrance
positive DNA test indicates patient is affected and will eventually develop disease symptoms.
predispositional testing
applies to disease with reduced penetrance
positive DNA test confers increased risk of disease but that doesn’t predict that patient will manifest the disease.
predictive testing has significant psychosocial risks
genetic counseling and psychosocial support required.
risk of insurance or employment discrimination
presymptomatic testing - definitition
testing to determine if a patient will develop a childhood or adult-onset disorder.
It may be offered to individuals who have a family history of a specific genetic disease.
diseases tested with predispositional testing
genetic disease with reduced penetrance (presence of a mutatnt gene confers increased risk of eventual disease, but does not predict that any particular patient will get the disase)
predispositional testing is available for
BRCA1 and 2 genes in breast/ovarian canver
carrier testing is used to
identify people who carry one copy of a gene mutation which causes autosomal recessive disorders.
carrier testing is offered to
individuals who have a family history of an AR genetivc disorder
people in certain ethnic groups with an increased risk of specific genetic conditions.
direct to consumer genetic testing
direct to consumer genetic testing refers to genetic tests that are marketed direclty to consumers. It provides access to a peron’s genetic information without necessarily involing a doctor or insurance company in the process.
most famous direct to consumer company
23 and me
it was stopped from interpreting data since they were not clearly explaining results.
There are more than __ genetic tests for over 4,000 diseases and conditions in the national instituate of health’s genetic testing registry.
There are more than 14,000 genetic tests for over 4000 diseases and conditions in the national institute of health’s genetic testing registry.
