Collaborator: University of California, Irvine
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HiFi long‑read WGS: sequencing performance of buccal and saliva samples and estimation of non‑human DNA contamination from unaligned HiFi reads
Presenting Author: Stuti Joshi, MS Take home points: gDNA isolation from buccal and saliva samples yielded suitable HMW DNA for HiFi LR-WGS. Variable contamination levels from the oral microbiome reduces mean sequencing depth. qPCR offers a means to make reliable pre-sequencing estimates of non-human content in buccal/saliva samples. Quantification of contamination prior to sequencing offers…
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Identification of de novo variants from parent-proband duos via long-read sequencing
Presenting Author: Leandros Boukas, MD, Children’s National; Boston Children’s Take home point: Being able to tell if a variant is de novo or inherited is critical for variant classification but is not possible unless you have both parents. We developed a tool using long-read sequencing leveraging phased haplotyping which allows determination of de novo status for…
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Long-read genome sequencing resolves genetic cases missed by short-read sequencing
Presenting Author: Greta Pitsava, MD Take home point: Long-read genome sequencing allows detection of variants not detectable by short read sequencing. We present several cases identified by the UCI-GREGoR program where the clinically relevant variant was found through long read sequencing after a negative short read test. This includes structural varaints, variants within hard to align low…
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The limits of Mendelian assumptions in genomic diagnostics: Evidence from longread whole genome sequencing and exome analysis
Presenting Author: Erica Smith, PhD Take home points: Some candidate findings identified on long read WGS do not follow the assumptions of Mendelian inheritance, being inherited from “healthy” parents or rather common in population databases. Similarly, in 16,500 consecutive previous diagnostic exome cases, there is also supporting evidence for incomplete penetrance and variable expressivity —…