Zandisiwe Emilia Magwebu
Medical Research Council, South Africa
Title: Identification of disease causing mutations in hyperglycinemic captive bred vervet monkeys (Chlorocebus aethiops)
Biography
Biography: Zandisiwe Emilia Magwebu
Abstract
High levels of glycine were observed in the plasma (457-795 µmol/L, normal <350 µmol/L) and CSF (7.5-12.7 µmol/L, normal range 3-8) of a small percentage (8%) of captive bred vervet monkeys characterized with total cataract formation at Primate Unit and Delft Animal Centre. Although cataracts have been documented for a variety of primate species, hyperglycinemia as well as this rare and unusual association of conditions have not been reported in the literature before and clearly need elucidation. The purpose of this study was to investigate the disease causing genes in hyperglycinemic vervet monkeys. Eight animals were selected based on their cataract and hyperglycinemic status. The monkeys were assigned into a control and spontaneous (cataract/ hyperglycinemic) group. Gene expression and genotyping experiments were conducted using RNA and DNA samples extracted from blood. Three genes that are associated with nonketotic hyperglycinemia were prioritized, namely: Glycine dehydrogenase (GLDC), aminomethyltransferase (AMT) and Solute Carrier Family 6, Member 9 (SLC6A9). Genotyping analysis of the complete coding sequence of GLDC, AMT and SLC6A9 revealed eight novel single base substitutions of which four were non-synonymous missense and four were silent nucleotide changes. For gene expression, AMT and SLC6A9 were down-regulated in hyperglycinemic monkeys. Therefore, it is possible that GLDC, AMT and SLC6A9 genes may be responsible for hyperglycinemia in captive bred vervet monkeys.