This document discusses transposons, also known as transposable elements or jumping genes. Transposons are DNA sequences that can change their position within the genome, sometimes causing or reversing mutations. The document outlines the mechanisms by which transposable elements are regulated in germ cells and somatic cells, and how their insertions can contribute to genetic variation and disease. It also discusses how transposable element insertions have been linked to various genetic disorders and cancers. The conclusion estimates that around 700 novel transposable element insertion events occur in a single diploid human genome.

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
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