L18 Functional Genomics

Question 1

what can synonymous variation affect

Answer 1

• Can change RNA stability, gene regulation (if variant lies within a Transcription Factor Binding Site), RNA splicing, speed of protein translation

Question 2

how can some variants alter rna processing

Answer 2

• Variants within introns can change splice sites crea-ng new isoforms, for example, excluding specific exons

Question 3

how to test significance of variants

Answer 3

1. human cells lines (primary/immortalised)

2. induced pluripotent stem cells

Question 4

primary vs immortalised cells

Answer 4

• Primary cells:
o Isolated from isssue
o Limited number of divisions, then apoptosis
• Immortalised cells:
o ‘transformed’- Derived from cancer OR
o Immortalised through natural selection, or overexpression of telomerase

Question 5

Pros and Cons of human cell lines

Answer 5

• PROS:
o human
o cheap to grow
o quick to do experiments

CONS:
o usually 2D culture = monolayer
o cannot mimic complex whole animal environment (non physiology level)
o Most = transformed (cancer) cells + may not be useful for studying other diseases occurring in differentiated cells

Question 6

what are Induced pluripotent stem cells (iPS)

Answer 6

• Made by ‘reversal’ of differentiation, sending cells back into a stem cell state

Question 7

2 Uses of iPS cells

Answer 7

1. affected cell= specific drug + treatment

2. repaired cells= transplant

Question 8

positives of • Micro-organisms and Invertebrate models

Answer 8

o inexpensive alternatives
o Have orthologous genes
o Easy gene manipulation
often shorter life cycles