14. Pseudogenes and clinical relevance

Question 1

What is a pseudogene?

Answer 1

DNA sequence that shows high degree of homology to functional gene

Contain multiple exons of the functional gene + variants the abolish function

Question 2

What are the two main classes of pseudogene?

Answer 2

1. Non-processed (duplicated)
2. Processed (retrotransposed)

Question 3

How do non-processed pseudogenes arise?

Answer 3

Arise from copy of gDNA (contain promoter, exons, introns) due to tandem duplication due to NAHR

Therefore often located close to functional counterparts

Question 4

How do processed pseudogenes arise?

Answer 4

Arise from copying of cDNA - contain exons only, lack promoter/regulator elements so not expressed

Question 5

Give two examples of how a pseudogene can interact with its active copy

Answer 5

1. Inactivation of PMS2 due to gene conversion to pseudogene
2. BRCA1 promoter deletion to to homologous recombination with pseudogene

Question 6

Given an example of how a pseudogene can act at the RNA level

Answer 6

PTENP1 mRNA binds to miRNA that would otherwise silence PTEN

Loss of PTENP1 in breast, colon, melanoma means that PTEN TSG is silenced by miRNA

Question 7

Give two examples of non-processed pseudogenes in disease

Answer 7

1. SMN1 & SMN2 - SMN2 retains partial functionality
2. CYP21A2 & CYP21AIP in CAH - recombination common, leads to dels/dups & gene conversions

Question 8

Give an example of a clinically-relevant processed pseudogene

Answer 8

UTP14c - retrotransposed copy of UTP14a

Nonsense variant seen in patients with infertility, causes spermatogenic arrest