Lecture 1 Flashcards
(29 cards)
what does a predictive test provide?
provides evidence of the presence of a specific disease before the disease phenotype becomes evident in the patient
what can we gain from a predictive test?
if we have the genetic variant based on the genetic results we may suggest changes in treatment or in the lifestyle to avoid the occurrence of that specific phenotype
how can predictive testing be used? (ex of disease)
if we detect mutations on the factor V coagulation cascade (Leiden factor) knowing that an individual carrying the alteration is at a higher risk for thrombus compared to the general population we can treat accordingly → if a patient has this mutation and is pregnant, the gynecologist will be able to choose the best drug for that patient and will be much more careful when monitoring the patient throughout the pregnancy
what are the 5 potential goals of genetic testing?
- genetic diagnosis
- identification of the molecular basis underlying a phenotype
- classification of a disease
- prognosis
- monitoring
when genetic testing is performed, what is the driving force?
the clinical diagnosis → genetic testing is used as the confirmation of the clinical diagnosis
what do most research studies use to better investigate and understand the molecular basis for a disease?
the reference genome
if a diagnostic laboratory performs genetic testing using NGS and discovered a causative mutation, what occurs?
before reporting this mutation to the patient we must validate that mutation using first generation sequencing on the portion of the genome containing the mutation to make sure that the variant actually exists in the patient
what are the four inheritance models?
autosomal dominant, autosomal recessive, X-linked, and Y-linked
what is important to keep in mind in regards to inheritance models and genetic testing?
which type of inheritance pattern we have as well as that some disorders may have more than one
what is a Mendelian disorder?
when we have one gene that is causative / in which the presence of that variant is related with a pathological phenotype → presence of that variant is sufficient to have an altered phenotype
what is the classic example of a mendelian disorder?
cystic fibrosis: autosomal recessive - if I have a homozygous variant on the CFTR gene, the patient is affected
what are susceptibility genes?
means that we have variants of genes that may increase the risk of developing a disease, but having that variant is not sufficient to have the clinical phenotype
what are chromosomal alterations?
condition in which we don’t use the sequencing approach but we use for example cryogenic analysis (the analysis of the karyotype) in order to detect if there are numerical alterations, in case of syndromes that are diagnosed such as trisomy 21 → focused not on just the DNA sequence but the entire karyotype
what is carrier testing?
genetic testing on an individual that is not affected but we would like to know if that individual carries a mutation or variation
what are the four types of pre-natal testing?
- pre-implantation genetic diagnosis (PGD)
- cell-free fetal DNA testing
- chorionic villus sampling (CVS)
- amniocentesis
describe pre-implantation genetic diagnosis:
before implantation of the embryos, we can perform the genetic testing on the embryos to investigate if there are chromosomal aberrations or to look for a specific mutation that is transmitted in the family
what is chorionic villus sampling?
performed on the villocentesis and amniocentesis → quite invasive because they extract the fetus’ DNA for the analysis of the karyotype or for the analysis of specific familial mutations
describe the cell-free fetal DNA testing?
there is free-circulating fetal DNA found in maternal blood, so a peripheral blood sample can be taken from the mother for the analysis of fetal DNA
what is the downside to cell-free fetal DNA testing?
the accuracy of this approach is lower than the other two types of investigation - also, if variants are detected its necessary to confirm this alterations with the fold standard approach which is villocentesis or amniocentesis
what are the two types of post-natal testing?
carrier testing and whole genome sequencing
what is the advantage of NGS?
we can analyze the entire panel of associated genes at the same time, in the same analysis, or we can choose to focus on only the causative genes that are already associated with the clinical phenotype
what is an advantage to only selecting a few causative genes to sequence?
the quality of the sequencing is higher than whole exon sequencing because the sequence only has to focus on ten genes instead of 22,000 → the quality of the sequencing is fundamental for the quality of the diagnostic testing
what are the 6 components of a clinical molecular laboratory?
- skilled and trained staff
- dedicated instruments
- organization of spaces to avoid the possible contamination
- automation
- centralization
- high-throughput technologies
describe the organization of a clinical molecular laboratory in order to avoid contamination:
separate areas for the blood to be stored, the extraction of DNA, preparation for amplification, sequencing
