Sanele Khoza

Mendelian genetics contribute largely to the development of hypertension; therefore, the identification of genetic variants related to blood pressure (BP) regulation remains crucial and may reveal new therapeutic drug targets. The purpose of the present study was to screen the captive-bred Vervet colony for salt-sensitive sequence variants or single nucleotide polymorphisms (SNPs) in the selected Renin-Angiotensin-Aldosterone System (RAAS) genes associated with salt sensitivity. Blood samples were collected from 16 captive-bred Vervet monkeys for genotyping and gene expression analysis. The impact of the identified sequence variants was determined using online prediction tools. Sanger sequencing analysis revealed 21 sequence variants in AGT, CYP3A5, GRK4, and SCL4A5, of which 19 were novel and two were previously reported in humans. All novel variants were either predicted to be polymorphic, disease-causing, or possibly damaging by prediction tools. Furthermore, the mRNA expression for AGT was significantly higher in the normal BP group ( value = 0.02), and a similar trend was observed for CYP3A5 and GRK4, whereas SCL4A5 was higher in the hypertensive group. The identified salt-sensitive variants specifically in GRK4 may be suggestive to be the attributing factor of the elevated BP levels in these captive-bred Vervet monkeys. Therefore, RAAS variants could be considered as a biomarker to identify the potential risk of developing hypertension in both humans and nonhuman primates.

Background: Congenital cataract has been reported in a colony of captive‐bred vervet monkeys (Chlorocebus aethiops).Methods: Molecular tools such as genotyping and gene expression were used to identify mutations associated with congenital cataract in this vervet colony. Beaded filament structural protein 1 (BFSP1), beta‐crystallin B1 (CRYBB1), galactokinase1 (GALK1), and gap junction alpha‐8 protein (GJA8) were screened, sequenced, and analyzed for mutations in 24 vervet monkeys (control and cataract).Results: Five missense sequence variants were identified (V147E, A167P, L212F, N55K, and T247A), three of which were found to be potentially disease‐causing. Furthermore, downregulation was observed in BFSP1, CRYBB1, and GALK1 genes.Conclusion: This study reports two cases of incomplete penetrance and/or uniparental disomy (L212F and T247A) in BSFP1. Mutations in BSFP1 together with three mutations in GALK1 and GJA8 were predicted to be disease‐causing.

Background: Nonketotic hyperglycinemia (NKH) is a rare metabolic disorder that is characterized by high levels of glycine in plasma and cerebrospinal fluid in humans. In this study, total congenital cataract captive‐bred Vervet monkeys (Chlorocebus aethiops) that are hyperglycinemic were screened to identify mutations in Bola type 3 (BOLA3), glutaredoxin 5 (GLRX5), and lipoate synthase (LIAS) genes.Methods: Twenty‐four Vervet monkeys (12 hyperglycinemic and 12 healthy controls) were selected for mutation analysis using polymerase chain reaction (PCR), Sanger sequencing, and reverse transcriptase‐polymerase chain reaction (RT‐PCR).Results: Novel sequence variants were identified in BOLA3 (R23H and Q38R) and LIAS (R369I and A371A), and gene expression in the control group was significantly lower compared to the hyperglycinemic group (P < 0.05).Conclusion: The data obtained from this study will contribute to generation of new knowledge regarding the involvement of these genes in NKH development.