Event Title

Computational Approaches to Detection of Mosaic Variants in Patients with Epilepsy

Advisor(s)

Dr. Gemma L. Carvill, PhD; Northwestern University, Feinberg, School of Medicine

Discipline

Medical and Health Sciences

Start Date

21-4-2021 10:45 AM

End Date

21-4-2021 11:05 AM

Abstract

Approximately 70-80% of epilepsy cases are likely caused by genetic variants. Somatic variants are mutations with low allele fractions that occur in only a portion of a patient’s cells, often because of somatic mosaicism. Given these variants’ low read counts in sequenced DNA, they are frequently missed. In our project, we compared the sensitivity of variant callers, MuTect and Mosaic Forecast. We also used MELT to detect mobile element insertions. We built multiple-sample pipelines and applied them to the whole exome and/or genome sequencing data of a cohort of epilepsy patients collected for a national and international collaboration. Candidate somatic variants detected using these methods were then validated with PCR amplification and Sanger Sequencing or targeted NGS of the patients’ DNA samples. In our initial analysis of the cohort, MuTect identified a candidate somatic variant in the gene GLUL (p.M1V).

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Apr 21st, 10:45 AM Apr 21st, 11:05 AM

Computational Approaches to Detection of Mosaic Variants in Patients with Epilepsy

Approximately 70-80% of epilepsy cases are likely caused by genetic variants. Somatic variants are mutations with low allele fractions that occur in only a portion of a patient’s cells, often because of somatic mosaicism. Given these variants’ low read counts in sequenced DNA, they are frequently missed. In our project, we compared the sensitivity of variant callers, MuTect and Mosaic Forecast. We also used MELT to detect mobile element insertions. We built multiple-sample pipelines and applied them to the whole exome and/or genome sequencing data of a cohort of epilepsy patients collected for a national and international collaboration. Candidate somatic variants detected using these methods were then validated with PCR amplification and Sanger Sequencing or targeted NGS of the patients’ DNA samples. In our initial analysis of the cohort, MuTect identified a candidate somatic variant in the gene GLUL (p.M1V).