Technology Seminar (10 Aug 2015)



Technology Seminar

Reveal the Complexity of the Human Genome
with Long Read Sequencing


Dr Meredith Ashby
Senior Scientist, Pacific Biosciences

10 August 2015 (Mon)
10:00 am – 12:00 noon

Seminar Room 1B, G/F
The Hong Kong Jockey Club Building for Interdisciplinary Research
5 Sassoon Road, Pokfulam, Hong Kong

10:00 - 10:40 am Session I: Putting the ‘W’ Back in Whole Genome Assembly

The advent of low cost genome sequencing has enabled many successful studies showing causal links between genetic variation and human disease. However, the majority of the uncovered associations involve single nucleotide variants (SNVs) and small insertion and deletion (indel) events, due to the inherent limitations of relying on short reads for variant detection. With non-SNV DNA variation accounting for 74% of all variant bases in the human genome, it is unsurprising that there continue to be missing links in our understanding of how disease phenotypes relate to underlying genotypes.

To overcome the challenge of hidden heritability, genetic disease researchers need comprehensive views of all the variation in human genomes. The recent de novo assembly of a range of human genomes with PacBio sequencing illustrates how bias-free, single molecule long reads can reveal previously hidden structural variants and provide direct variant phasing information across multi-gene regions. In addition, a population specific, gold standard reference assembly dramatically improves the mappability of resequencing data and enables short read detection of population specific common structural variants, giving access to novel variant types and regions of the human genome that were previously opaque, and enabling new insights into the genetic basis of heritable disease.

10:40 - 11:00 am Break

11:00 - 11:30 am Session II: Resolving Complex Regions with Targeted Sequencing

For some research questions, a targeted sequencing approach is both more practical and economical, focusing data collection on critical genomic regions or transcripts while increasing the depth of sequencing or number of samples. The pairing of long reads with either PCR amplification or capture methods enables a range of applications that are challenging or impossible with short reads. Homopolymeric stretches, repetitive elements, or short tandem repeats (STRs) within genes can thwart short-read approaches. Similarly, haplotype reconstruction from short reads relies on imputation, which is not always reliable, particularly when structural variants or de novo mutations are a factor.

Targeted sequencing leveraging PacBio’s single molecule, long read technology has been used to obtain continuous sequence information through previously intractable complex regions linked to human disease including repetitive elements in MUC5AC, STRs in Fragile X, complex rearrangements in Potocki-Lupski Syndrome, and rare SNPs BCR-ABL drug resistance. Long read sequencing data has a critical role to play in elucidating the full scope of genomic complexity that impacts human health.

About the Speaker:

Dr Meredith Ashby Dr Meredith Ashby is a Senior Scientist at Pacific Biosciences. She completed her PhD at CalTech working on mapping gene regulatory networks in sea urchin development just as the sea urchin genome was being sequenced. Inspired by the impact of genome sequencing on her research, she joined PacBio after a brief postdoc at UCSF. She has been with the company since 2009, and has worked in R&D on both sequencing and bioinformatics application development. She is now focused on developing tools and applications applying PacBio long read sequencing to solve unmet needs in human genome sequencing.



Co-organized with Gene Company  Gene Company Logo
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