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PfEMP1 are variant parasite antigens that are inserted on the surface of  Plasmodium falciparum  infected erythrocytes (IE). Through interactions with various host molecules, PfEMP1 mediate IE sequestration in tissues and play a key role in the pathology of severe malaria. PfEMP1 is encoded by a diverse multi-gene family called  var . Previous studies have shown that that expression of specific subsets of  var  genes are associated with low levels of host immunity and severe malaria. However, in most clinical studies to date, full-length  var  gene sequences were unavailable and various approaches have been used to make comparisons between  var  gene expression profiles in different parasite isolates using limited information. Several studies have relied on the classification of a 300 – 500 base-pair “DBLα tag” region in the DBLα domain located at the 5’ end of most  var  genes.   We assessed the relationship between various DBLα tag classification methods, and sequence features that are only fully assessable through full-length  var  gene sequences. We compared these different sequence features in full-length  var  gene from six fully sequenced laboratory isolates.   These comparisons show that despite a long history of recombination,    DBLα sequence tag classification can provide functional information on important features of full-length  var  genes. Notably, a specific subset of DBLα tags previously defined as “group A-like” is associated with CIDRα1 domains proposed to bind to endothelial protein C receptor.   This analysis helps to bring together different sources of data that have been used to assess var gene expression in clinical parasite isolates.

wellcome open research

A re-assessment of gene-tag classification approaches for describing var gene expression patterns during human Plasmodium falciparum malaria parasite infections