Medical Genetics in Clinical Practise Flashcards
what does clinical assessment in a genetic clinic involve
- history
- pedigree
- Clinical examination: individual, family
- Genetic test: microarray, gene tests (mutation/single gene screen/gene panel)
- Synthesis
who can do genetic counselling
- clinical geneticist
- genetic counsellor
- hospital doctor
- GP
- Nurse…
what does sequencing automation allow
to sequence really large amounts of DNA
Next-generation sequencing
- dec wet lab costs
- time taken to interpret sequence data dec
- interpretation of variants takes just as long and needs skilled scientist (reporting?)
what does the presennce of the genetic clinic allow
targeted treatment for an individual based on their personal, family and genetic factors
challenege of increasing testing
- varient interpretaion
- seperating pathogenic from benign variation
- sole cause rather than risk factor is current paradigm
- each genome had > half million variant
breifly describe genome testing in the clinic
wtf is this bro?
- standard genetic testing: e.g. chromosome count etc. aimed at particular conditions considered likely
- 10,000 gennes implicated in rare disease
huge interpretation burden
varients are only ____ some of the time
clinically-relevant
how common are variants
~1 in 1000
trio-based analysis
Trio analysis can be used to identify variants inherited from the parents causing recessive disease or dominant disease
what does genome (and exome) trio-based analysis allow for
use to find the mutant gene out of millions of potential variants
give all 5 variant classes and what each means
- Clearly not pathogenic
- unlikely to be pathogenic
- unknown significance (VUS)
- Likely to be pathogenic
- Clearly pathogenic
how do we decide the level of risk of a particular mutation
- publications
- locus specific variant registers (e.g. BRCA exchange)
- Population registers
how do we decide the level of risk of missense variants
- publications
- locus specific variant registers
- Population registers
- alamut - in siilico analysis tools
- functional evidence
challenges (with missense variants?)
- ethnicity
- duplicate entries
- phenotype availability
- commoner conditions harder
pro/con of trio-based analysis
costs more in wet lab but reduces false calls
what will happen as disease databases grow and compute power increases
analysis will become more automated
what will be challenging in genetic counselling
briniging in variants of partial significance
list some ethical challenges in genomic medicine
from google but in Lo
Informed Decision Making.
Informed Consent and Genetic Testing.
Newborn Screening Genetic Testing.
Genetic and Genomic Research Testing.
Maintaining Privacy and Confidentiality of Genetic Information.
Preventing Genetic Discrimination.
Strengthening Genetic and Genomic Care Around the World.
interpretation of genomic variation
from LO
Variants are usually detected by reading the DNA code, a method called DNA sequencing. A proper report always contains the variant described on the DNA level. In addition, a report usually contains a description of the predicted consequence of the variant on the protein, rarely the consequence on RNA.
role of clinical geneticist
medical doctor specialising in managing patients and families with or at risk of a genetic condition
why would someone see a genetic counselor, medical geneticist, or other genetics professional
A personal or family history of a genetic condition, birth defect, chromosomal disorder, or hereditary cancer
role of testing
for sporadic mutation in oncology
made ans up but in LO
check to see if cancer has developed in high-risk individuals (e.g. mammogram fro those with BRCA1/2 gene)
