Coding vs Noncoding variation Flashcards Preview

GENE3340 MOLECULAR GENETICS > Coding vs Noncoding variation > Flashcards

Flashcards in Coding vs Noncoding variation Deck (13)
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1
Q

What are the 2 types of functional variants?

A
  1. Coding variant
    - amino acid variation
    - splice/reading frame variation
  2. Noncoding variant
    - transcriptional
    - post-transcriptional
    - non-coding RNA
    - epigenetic
2
Q

Most functional variation is?

A

Non-coding and regulatory

3
Q

What does DHS stand for?

A

DNASE I hypersensitive sites

4
Q

What is the workflow for variant functional identification?

A
  • fine mapping
  • in silico annotation
  • SNP function
  • target gene(s) identification
  • target gene(s) function
5
Q

What are the approaches to functional ID?

A
  • genetic linkage isn’t able to determine which SNPs are functionally important
  • genetic association better BUT LD limits functional ID
  • BIOINFORMATIC approaches good for coding SNPs
6
Q

What are the types of coding region variants?

A
  • frame-shift (indels)
  • base-substitutions:
    • synonymous: no AA change
    • non-synonymous: AA change
      • conservative = similar
      • semi conservation = +ve to -ve AA
      • radical - AA with different properties
7
Q

What are the bioinformatic approaches to predicting coding variant function?

A
  • Genomic evolutionary rate profiling (GERP)

- Polymorphism Phenotyping

8
Q

What is GERP?

A

Where orthologous nucleotide sequences are compared to determine evolutionary constraints to change in sequence. Identifies constrained elements by quantifying substitution deficits.

R = sum (expected - observed) where higher score = more significant

9
Q

What does deficits represent in GERP?

A

Deficits represent substitutions that would have occurred if the element was neutral DNA, but didn’t occur due to selective pressure

10
Q

What is PolyPhen?

A

Predicts impact of AA substitution on stability and function of a protein, using physical and comparative evolutionary comparisons. Estimates probability of variant being damaging to protein function.

11
Q

What are the prediction outcomes of PolyPhen?

A
  • Probably damaging, possibly damaging, benign or no prediction
12
Q

What is RegulomeDB?

A

Database which integrates functional data within ENCODE with genetic variation databases. Predicts whether variants are functional

13
Q

What are the prioritisation scores of RegulomeDB?

A

Category 1 = likely to affect binding and linked to expression of gene target

Category 2 = likely to affect binding

Category 3 = less likely to affect binding

Category 4 = minimal binding evidence