Application of Long-read Sequencing in Human Genetics

Recently, long-read sequencing with high accuracy has become a reality. Previous technologies allowed for the detection of particular classes of genetic variation and/or have focused on pre-defined regions of the genome. De novo assembly of an individual’s complete genome has also been difficult and time-intensive with the drastically shorter reads that have been the standard in our field. Long-read sequencing is a ground-breaking advance that enables us to perform analyses to assemble genomes within one day and to detect nearly all forms of variation in one single technology. In this talk, I will discuss the application of Pacific Biosciences (PacBio) HiFi long-read sequencing to human genetics. First, I will describe our analysis workflow for long-read sequencing that includes de novo assembly and mapping-based strategies to detect variation in a single individual. Second, I will detail the utility of public long-read sequencing data for filtering of variation detected within individuals. This approach helps narrow into relevant rare variation within an individual and is necessary for variation not detected by previous technologies. Third, I will discuss the benefit of long-read sequencing for phasing of variation regarding detection of compound heterozygous variants. Finally, I will show examples of our utilization of long-read sequencing to understand complex structural variation in individuals we have assessed in our lab. Overall, my talk will introduce the concept of long-read sequencing and its application in human genetics.

Learning Objectives:

1. Understand the concept of long-read sequencing

2. Learn applications of long-read sequencing to human genetics