Vahid Akbari is a Ph.D. student at BC Cancer in the Genome Sciences Centre in Canada. They presented at the Nanopore Community Meeting 2022 a session entitled “Simultaneous haplotyping and parent-of-origin assignment of homologous chromosomes without parental sequence data.” The approach they developed allows researchers to haplotype chromosomes and assign parent-of-origin without parent data. They noted that there are very few protocols to build homologs and assign paternal and maternal. The approach Akbari and team developed can tell which one is paternal and maternal. This is important because disease may be linked to an abnormal allele inherited from the father, for example. Another example Akbari noted was the use of this approach for BRCA1 mutations without sequencing an entire half of a family tree. The approach they developed uses Nanopore sequencing and Strand-seq developed by Peter Landsdorp lab. Akbari explained this is single-cell sequencing technology suitable for phasing. They first sequence the sample using Nanopore sequencing and then sequence with strand sequencing. The combined phasing of Nanopore + Strand-seq allows for adding methylation and imprinting information. In combination, this information can be used to assign parent-of-origin. The approach uses about 200 known imprinted regions. Akbari explained they tested the approach on the children from five benchmark trios (mother, father, child, B-lymphocyte cell line samples). They obtained ~99.7% accuracy for SNV and ~98.2% accuracy for indels. Akbari noted the limitations include difficulties with indels with Nanopore sequencing and one can’d to the X chromosome. their work was accepted to Cell Genomics. I had never considered the use of Nanopore sequencing for parent-of-origin assignments! It makes sense and is a beautifully simple, though technically challening, approach.
