Genetic analysis of length-dependent GAA/TTC and TTTCA/TGAAA repeat-induced GCR formation

Malikova, Suzanne (2023) Genetic analysis of length-dependent GAA/TTC and TTTCA/TGAAA repeat-induced GCR formation. Bachelor's Research Project (period 2b), Biology.

Preview	Text bBIO_2023_MalikovaS.pdf.pdf Download (1MB) | Preview
	Text toestemming.pdf Restricted to Registered users only Download (128kB)

Abstract

Currently, 13 short tandem repeat sequences are known to be involved in over 50 neurodegenerative human diseases. GAA repeat expansions in the FXN gene are the cause of Friedreich’s ataxia, and Benign adult familial myoclonic epilepsy is associated with extending TTTCA repeats. In this pilot, we study these two repeats and their complementary sequences of several lengths, and how they affect repeat-induced fragility. By means of a GCR assay and high-throughput robotic replica-pinning, we can determine the frequency of Gross Chromosomal Rearrangement in repeat-containing yeast strains. Here, we demonstrate a GAA/TTC repeat-induced length-dependent increase in GCR formation. Moreover, we show that GCR formation is orientation-dependent, as strains with complementary repeat sequences result in varying GCR frequencies. None of the strains reached the desired GCR frequency of 30-50%, but strains containing TTC160 and GAA95 can be used to identify genes that suppress GCRs. However, to identify genes that promote GAA/TTC repeat fragility, and genes that are involved in TTTCA/TGAAA repeat fragility in general, strains with longer repeat lengths should be tested to reach higher GCR frequencies to be useful in the genome-wide screen.

Item Type:	Thesis (Bachelor's Research Project (period 2b))
Supervisor name:	Novarina, D.
Degree programme:	Biology
Thesis type:	Bachelor's Research Project (period 2b)
Language:	English
Date Deposited:	07 Jun 2023 14:34
Last Modified:	07 Jun 2023 14:34
URI:	https://fse.studenttheses.ub.rug.nl/id/eprint/29977

Actions (login required)

View Item