Opportunities of RNA-seq in Molecular Diagnosis of Primary Immunodeficiencies

Activity: Talk or presentation types › Oral presentation

Description

Primary immunodeficiencies (PIDs, also inborn errors of immunity) are a heterogeneous group of more than 400 genetic disorders characterised by a dysregulated immune response, resulting in infection susceptibility, as well as autoimmunity and increased malignancy risk. In most cases, PID is diagnosed late or goes completely undiagnosed. A precise molecular diagnosis would allow the confirmation of a clinical diagnosis and specify the sub-type of PID, enabling the patient to access more suitable treatment options, and family counselling. Currently, the standard molecular approach using exome and genome sequencing is only able to yield a diagnosis in up to 60% of cases, suggesting a need for improvement. RNA-seq has emerged as a complementary assay for rare disease profiling in the past 5 years, providing functional information support for prioritizing uncertain variants in the genome.. Bulk RNA-seq was performed on 54 individuals clinically diagnosed with PID (aged 0-69), as well as 5 control samples from individuals without immunodeficiency using KAPA RNA HyperPrep Kit with RiboErase (HMR) Globin (Roche) and paired-end sequencing with Illumina NovaSeq 6000. Expression and splicing outliers and mono-allelic expression were determined using DROP workflow.. Our analyses yielded aberrant expression in 37 out of 59 samples (on average, 3 per sample), splicing outliers in all samples (on average, 21 per sample) and mono-allelic expression in 29 samples (on average, 913 per sample, subsequently prioritized by additional variant filtering).. The observed transcriptome events reveal samples with previously known causal variants thus suggesting the utility of RNA-seq in supplementing exome/genome sequencing in diagnosing PID. Analysis is ongoing for further correlation with clinical and WGS findings.
Period29 Mar 2023
Event titleRSU International Research Conference 2023: Knowledge for Use in Practice
Event typeConference
OrganiserRīga Stradiņš University
LocationRiga, LatviaShow on map
Degree of RecognitionInternational

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