Quantifying Methylation of the C9orf72 Repeat Expansion
Author Information
Author(s): Udine Evan, Finch NiCole A., DeJesus-Hernandez Mariely, Jackson Jazmyne L., Baker Matthew C., Saravanaperumal Siva Arumugam, Wieben Eric, Ebbert Mark T.W., Shah Jaimin, Petrucelli Leonard, Rademakers Rosa, Oskarsson Björn
Primary Institution: Mayo Clinic
Hypothesis
Can targeted long-read sequencing quantify methylation levels of the C9orf72 repeat expansion?
Conclusion
The study demonstrates that the expanded C9orf72 repeat is more highly methylated than the wild-type allele and that methylation levels correlate with age and repeat length.
Supporting Evidence
- The expanded allele is more highly methylated than the wild-type allele.
- Increased methylation levels are observed in longer repeat expansions.
- Methylation levels correlate with age at collection and age at disease onset.
- Notable variability in total methylation levels was observed among individuals.
- The study utilized a targeted, amplification-free long-read sequencing method.
Takeaway
Researchers studied a gene that can cause diseases like ALS and found that its repeated section can be measured for a chemical change called methylation, which varies with age.
Methodology
Targeted, amplification-free long-read sequencing of DNA extracted from blood samples.
Potential Biases
Selection bias may have occurred due to the criteria used for participant selection.
Limitations
The study's sample size is modest, which may limit the generalizability of the findings.
Participant Demographics
The cohort included 15 ALS patients, 1 FTD patient, and 11 pre-symptomatic individuals, with a median age of 63 years.
Statistical Information
P-Value
2.76E-05
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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