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Publications of the Week

Multi-Platform Discovery of Haplotype-Resolved Structural Variation in Human Genomes

By April 16, 2019No Comments

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This week we profile a recent publication in Nature Communications involving the laboratory of
Dr. Peter Lansdorp at the Terry Fox Laboratory at BC Cancer.

Can you provide a brief overview of your lab’s current research focus?

My lab is exploring various applications of our single cell DNA template strand sequencing method (Strand-seq) as well as better ways to make Strand-seq libraries. In this latest Nature Communications paper we describe studies of human genome variation by the Human Genome Structural Variation Consortium (HGSV). This consortium aims to define a high-quality map of structural variation for humans and develop new methods to take advantage of the burgeoning array of genomics assays now available to define genomic structure, including long reads, chromatin confirmation assay, strand sequencing and synthetic read and read cloud technologies.

What is the significance of the findings in this publication?

This the most detailed study to date describing differences between human genomes. The findings are astounding: an average of 818,054 small insertions and deletions (genomic alterations that each affected less than 50 bases of DNA) and 27,622 SVs (genomic alterations that affected 50 bases or more of DNA) were identified per genome. Remarkably, an average of 156 polymorphic inversions were identified per genome using our Strand-seq method. Many of these previously unknown inversions intersect with genomic regions associated with genetic disease syndromes. Compared to the 5-6 million single nucleotides (SNP’s) that differ between people, these polymorphic inversions, with a total size of over 20 Mb, represent a rich source of currently unexplored genomic diversity.

What are the next steps for this research?

We are still working on improving our method. With that we will explore “missing heritability” in many disease. In collaboration with clinical researchers we hope to elucidate disease where a genetic component is suspected but so far undetected.

This research was funded by:

The work on inversions was mainly done by Ashley Sanders, a talented former graduate student in my lab, who is now a postdoc in the EMBL in Heidelberg. We generated the sequence data with funding from an Advanced Grant from the European Research Council.

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