Medical Genetics in Clinical Practise

Question 1

what does clinical assessment in a genetic clinic involve

Answer 1

• history
• pedigree
• Clinical examination: individual, family
• Genetic test: microarray, gene tests (mutation/single gene screen/gene panel)
• Synthesis

Question 2

who can do genetic counselling

Answer 2

• clinical geneticist
• genetic counsellor
• hospital doctor
• GP
• Nurse…

Question 3

what does sequencing automation allow

Answer 3

to sequence really large amounts of DNA

Question 4

Next-generation sequencing

Answer 4

• dec wet lab costs
• time taken to interpret sequence data dec
• interpretation of variants takes just as long and needs skilled scientist (reporting?)

Question 5

what does the presennce of the genetic clinic allow

Answer 5

targeted treatment for an individual based on their personal, family and genetic factors

Question 6

challenege of increasing testing

Answer 6

• varient interpretaion
• seperating pathogenic from benign variation
• sole cause rather than risk factor is current paradigm
• each genome had > half million variant

Question 7

breifly describe genome testing in the clinic

wtf is this bro?

Answer 7

• standard genetic testing: e.g. chromosome count etc. aimed at particular conditions considered likely
• 10,000 gennes implicated in rare disease

huge interpretation burden

Question 8

varients are only ____ some of the time

Answer 8

clinically-relevant

Question 9

how common are variants

Answer 9

~1 in 1000

Question 10

trio-based analysis

Answer 10

Trio analysis can be used to identify variants inherited from the parents causing recessive disease or dominant disease

Question 11

what does genome (and exome) trio-based analysis allow for

Answer 11

use to find the mutant gene out of millions of potential variants

Question 12

give all 5 variant classes and what each means

Answer 12

1. Clearly not pathogenic
2. unlikely to be pathogenic
3. unknown significance (VUS)
4. Likely to be pathogenic
5. Clearly pathogenic

Question 13

how do we decide the level of risk of a particular mutation

Answer 13

• publications
• locus specific variant registers (e.g. BRCA exchange)
• Population registers

Question 14

how do we decide the level of risk of missense variants

Answer 14

• publications
• locus specific variant registers
• Population registers
• alamut - in siilico analysis tools
• functional evidence

Question 15

challenges (with missense variants?)

Answer 15

• ethnicity
• duplicate entries
• phenotype availability
• commoner conditions harder

Question 16

pro/con of trio-based analysis

Answer 16

costs more in wet lab but reduces false calls

Question 17

what will happen as disease databases grow and compute power increases

Answer 17

analysis will become more automated

Question 18

what will be challenging in genetic counselling

Answer 18

briniging in variants of partial significance

Question 19

list some ethical challenges in genomic medicine

from google but in Lo

Answer 19

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.

Question 20

interpretation of genomic variation

from LO

Answer 20

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.

Question 21

role of clinical geneticist

Answer 21

medical doctor specialising in managing patients and families with or at risk of a genetic condition

Question 22

why would someone see a genetic counselor, medical geneticist, or other genetics professional

Answer 22

A personal or family history of a genetic condition, birth defect, chromosomal disorder, or hereditary cancer

Question 23

role of testing
for sporadic mutation in oncology

made ans up but in LO

Answer 23

check to see if cancer has developed in high-risk individuals (e.g. mammogram fro those with BRCA1/2 gene)