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Publications of the Week

Assessment of the ExAC Data Set for the Presence of Individuals with Pathogenic Genotypes Implicated in Severe Mendelian Pediatric Disorders

By May 22, 2017May 29th, 2017No Comments

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 This week we profile a recent publication in Genetics in Medicine from the laboratory
of Dr. Wyeth Wasserman (second from right) at the BC Children’s Hospital Research Institute.

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

My laboratory is focused on the creation and application of computational software and methods for the analysis of human genome sequences.  In particular we increasingly focus on the analysis of non-coding genetic alterations that alter gene expression, and apply our methods to the identification of disease-causing variations for oediatric rare disease (for patients at BC Children’s Hospital and around the world).

What is the significance of the findings in this publication?

When you analyze the genome of a child with a rare disease you compare the observed DNA sequences with sequences that have been observed in healthy individuals (the background).  In this publication we demonstrate that many known disease causing variations are present in the leading global background database, and therefore researchers and clinicians need to be careful not to use the background database as an absolute filter.  Variations causing severe, rare disease will not be common in the database, but some healthy individuals might harbour them.  Based on our study, at least a portion of the individuals in the background database are likely to be mosaic for the variations – only a portion of the cells in their bodies have the alterations, so they remain healthy.

Briefly, what are the next steps for this research?

We will need to continue to develop background variation databases, increasing the number of individuals and making sure we provide background for under-represented populations (especially Indigenous peoples who are often absent).  In expanding these resources, we will need to mark the cases where disease-causing variations are observed, and provide guidance to clinicians and researchers about appropriate tolerances for such cases in evaluating new candidate disease variants.