TRANSPOSONS, JUNK DNA

1. TRANSPOSONS

3. Mobilizing diversity: transposable
element
insertions in genetic variation and
disease
Presented By : Narmeen Arshad
FUUAST
MS 2014

4. Outline
• Introduction
• Mechanism of TE regulation in germ line
• Mechanism of TE regulation in Somatic cells
• TE & Cancers
• Identification techniques
• Conclusion

5. Transposable element
Junk DNA
Jumping Genes
Mobile Genetic
Elements
Transposons
 Selfish DNA

6. Transposable Elements
• A transposable element
is a DNA sequence that
can change its position
within the genome,
sometimes creating or
reversing mutations and
altering the
cell's genome size.
• Barbara McClintock's
discovery of
these jumping
genes earned her
a Nobel prize in 1983.

7. Characteristics of TE
• 45% of human chromosomal DNA is derived
fom TE.
• Contributes to genetic variation that leads to
spontaneous mutation & genetic
rearrangements.
• TE modify gene structure ---- hence alter gene
expression.
• Mobilization , reshuffling, rearrangement
occurs, that creates ---- “novel genes”.
• In Rare cases it causes mutations ---- disease.

8. Types of TE
• Reterotransposons ( Class I)
Copy & paste mechanism
• DNA transposons ( Class II)
Cut & paste mechanism

11. Imp. Characteristic of
Retrotransposons
• Of all mobile elements family , RT remain
actively mobile in human & primate genomes.
• Ongoing source of Genetic variation.
• By generating new transposons.

12. Effects of TE on host genome
• Little or no impact on gene function.
• Deleterious effect on host genome resulting in
disease.
• 65 diseases causing TE insertions have been
documented.

13. Mechanism of TE Regulation in Germ
Line
• Expansion occurs when TE is transmitted into
subsequent generations.
• Eg : DNA Methylation (There is also
considerable evidence suggesting that DNA
methylation suppresses proliferation of
transposable elements.)

14. Consequences of TE insertions in the
genome
• New insertions/passing through the germ line.
• Constitutional genetic diseases.
• Commonly involved TEs are ---- Alus, L1s,
SVA’s.

15. Eg of diseases caused by insertions:
• Alu & L1 -----induce coagulopathies by
disruption of coagulation factor VIII/IX
• Alu & SVA insertions causing -----
immunodeficiency.
• Line 1 insertion ---- results in muscular
dystrophies & cardiomyopathies.
• Intronic Alu insertion ---- disrupting function
of NF1 tumour suppressor causing
neurofibromatosis.

16. TE insertions in Somatic Cells
• Full length & processed L1 transcripts are
detected in human somatic tissues but in low
%.
• L1 somatic transposition have been
discovered in blastocysts from transgenic
mouse models expressing human L1 elements.
• This data suggests that L1 elements contribute
to somatic cells.

17. • Gage & Colleagues detected an increase in
copy # of L1 in some regions of adult human
brain.
• Brain samples contain approx. 80 additional
copies of L1 sequence per cell.
• Functional consequences are unknown.
• So the extent of genetic diversity due to TE
remains largely unexplored.

18. TE & Cancers
• A hall mark of cancer proliferation is
accumulation of somatic genetic changes.
• Eg : 1. Line1 reterotransposition ---- colon
cancer.
2. L1 insertions ---- Human lung tumors.
• Thus it is possible that tmors provide
environment where transposition events
occur.

20. Strategies for identifying TE insertions

21. TE & human genetic diversity
• Sequencing of human genome revealed that
single genome exhibits 0.1% variation.
• Bennet & colleagues tried to detect the
degree of genetic variation caused by TE.
• They analyzed data from 36 people of diverse
ancestry.
• They estimated human population have an
average of 2000 common TE polymorphism.

22. Conclusion :
• Computational analysis & experimental
validation suggests that roughly 700 novel
transposable element insertion events takes
place due to Alus, L1 & SVA in single diploid
genome.

23. Future approach
• TE plays role in structural variance ?
• Characterization of TE --- to study potential
functional consequences.
• Understanding of mechanism & regulation of
TE is not fully understood.

24. Reference paper

25. Thank you
QS …..?