medical genetics in the clinic

Question 1

define pedigree

Answer 1

A pedigree is a diagram that depicts the biological relationships between an organism and its ancestors.
often it is used to look at the transmission of genetic disorders

Question 2

clinical assessment

Answer 2

history 
pedigree
clinical examination
genetic test 
synthesis 
genetic counselling

Question 3

what does clinical examination involve

Answer 3

individual and family

Question 4

genetic tests in clinical assessment

Answer 4

microarray - look at chromosome pattern for abnormalities

gene tests - mutations/single gene screen/gene panel

Question 5

next generation sequencing

Answer 5

wet lab costs fall 50%
more patients through at a time
look at more genes at a time
time taken to interpret sequence data reduced
BUT: interpretation of variants takes just as long and needs skilled scientists

Question 6

looking for somatic differences

Answer 6

looking for specific variants in cancer allows for targeted treatment

Question 7

challenge of increasing testing

Answer 7

variant interpretation
separating the pathogenicfrom the benign variation
sole cause rather than risk factor is current paradigm

Question 8

genome

Answer 8

~2% is coding
variants are very common - vary in scale; single base change, small insertions and deletions, large scale rearrangements
variants aren’t always clinically relevant

Question 9

variant classification

Answer 9

1. clearly not pathogenic
2. unlikely to be pathogenic
3. unknown significance
4. likely to be pathogenic
5. clearly pathogenic

Question 10

deciding on classification of variants

Answer 10

publications
locus specific variant registers
population registers

Question 11

missense variants

Answer 11

• alamut in silico analysis tools: working out which base changes and whether the location within the protein matters or not
• functional evidence

Question 12

challenges with variant classification

Answer 12

• ethnicity: African descent, number of variants is much greater due to fewer evolutionary bottlenecks
• duplicate entries
• phenotype availability
• commoner conditions are harder

Question 13

genomes and exomes

Answer 13

• trio based analysis costs more in the wet lab but reduces false calls - test both parents and the child
• as disease databases grow and computer power increases, analysis will become more automated
• bringing in variants of partial significance will be a challenge in genetic counselling