ABSTRACT
BACKGROUND: Non-ketotic hyperglycinaemia (NKH) is an autosomal recessive inborn error of glycine metabolism characterized by accumulation of glycine in body fluids and various neurological symptoms. METHODS: This study describes the first screening of NKH in cataract captive-bred vervet monkeys (Chlorocebus aethiops). Glycine dehydrogenase (GLDC), aminomethyltransferase (AMT) and glycine cleavage system H protein (GCSH) were prioritized. RESULTS: Mutation analysis of the complete coding sequence of GLDC and AMT revealed six novel single-base substitutions, of which three were non-synonymous missense and three were silent nucleotide changes. CONCLUSION: Although deleterious effects of the three amino acid substitutions were not evaluated, one substitution of GLDC gene (S44R) could be disease-causing because of its drastic amino acid change, affecting amino acids conserved in different primate species. This study confirms the diagnosis of NKH for the first time in vervet monkeys with cataracts.
Subject(s)
Aminomethyltransferase/genetics , Cataract/veterinary , Chlorocebus aethiops , Glycine Decarboxylase Complex H-Protein/genetics , Glycine Dehydrogenase/genetics , Hyperglycinemia, Nonketotic/veterinary , Monkey Diseases/genetics , Point Mutation , Amino Acid Sequence , Aminomethyltransferase/chemistry , Aminomethyltransferase/metabolism , Animals , Cataract/genetics , Glycine Decarboxylase Complex H-Protein/chemistry , Glycine Decarboxylase Complex H-Protein/metabolism , Glycine Dehydrogenase/chemistry , Glycine Dehydrogenase/metabolism , Hyperglycinemia, Nonketotic/genetics , Mutation, MissenseABSTRACT
Niacin is the most effective drug available for raising levels of high-density lipoprotein (HDL) cholesterol. To evaluate its effects on plasma lipid concentrations, the authors administered a low dose of niacin to healthy, adult, female African green monkeys for 3 months. In the treated monkeys, low-density lipoprotein cholesterol concentrations decreased by 43% from baseline, whereas concentrations of HDL cholesterol and apolipoprotein A-I increased by 49% and 34%, respectively. The results suggest that in this primate model, a low dose of niacin can effectively increase concentrations of HDL cholesterol.
Subject(s)
Apolipoprotein A-I/blood , Chlorocebus aethiops , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Disease Models, Animal , Niacin/pharmacology , Analysis of Variance , Animals , Apolipoprotein A-I/drug effects , Body Weight , Cholesterol, HDL/drug effects , Cholesterol, LDL/drug effects , Female , Niacin/administration & dosage , Species SpecificityABSTRACT
BACKGROUND: Autism (MIM209850) is a neurodevelopmental disorder characterized by a triad of impairments, namely impairment in social interaction, impaired communication skills, and restrictive and repetitive behavior. A number of family and twin studies have demonstrated that genetic factors play a pivotal role in the etiology of autistic disorder. Various reports of reduced levels of reelin protein in the brain and plasma in autistic patients highlighted the role of the reelin gene (RELN) in autism. There is no such published study on the South African (SA) population. AIMS: The aim of the present study was to find the genetic association of intronic rs736707 and exonic rs362691 (single-nucleotide polymorphisms [SNPs] of the RELN gene) with autism in a SA population. METHODS: Genomic DNA was isolated from cheek cell swabs from autistic (136) as well as control (208) subjects. The TaqMan(®) Real-Time polymerase chain reaction and genotyping assay was utilized to determine the genotypes. RESULTS: A significant association of SNP rs736707, but not for SNP rs362691, with autism in the SA population is observed. CONCLUSION: There might be a possible role of RELN in autism, especially for SA populations. The present study represents the first report on genetic association studies on the RELN gene in the SA population.
Subject(s)
Autistic Disorder/genetics , Cell Adhesion Molecules, Neuronal/genetics , Extracellular Matrix Proteins/genetics , Genetic Predisposition to Disease , Nerve Tissue Proteins/genetics , Polymorphism, Single Nucleotide , Serine Endopeptidases/genetics , Adolescent , Child , Exons/genetics , Female , Gene Frequency , Genetic Association Studies , Genotype , Humans , Introns/genetics , Male , Real-Time Polymerase Chain Reaction , Reelin Protein , South AfricaABSTRACT
The serotonin transporter promoter length polymorphism (5-hydroxytryptamine transporter length polymorphism; 5-HTTLPR) has long been implicated in autism and other psychiatric disorders. The use of selective serotonin reuptake inhibitors (SSRIs) has a positive effect on treating some symptoms of autism. The effects of these drugs vary in individuals because of the presence of the S or L allele of 5-HTTLPR. Studies performed on various autistic populations have found different allele frequencies for the L and S alleles. Allele frequencies and genotypes of the South African autistic populations (African, mixed, and Caucasian) were compared with matching South African ethnic control populations. The *S/*S genotype was found to be highly significantly associated with all the South African autistic ethnic populations. In the South African African population the *S/*S genotype was present in 7 (33%) of the autistic individuals but in none of the control subjects, yielding infinitely large odds of developing autism. The odds of developing autism with the *S/*S genotype compared to the *L/*L genotype increased 10.15-fold in the South African mixed group and 2.74-fold in the South African Caucasian population. The allele frequency of the South African autistic population was also compared with studies of other autistic populations around the world, and highly significant differences were found with the Japanese, Korean, and Indian population groups. The difference was not significant for the French, German, Israeli, Portuguese, and American groups. This is the first South African study of autistic individuals of different ethnic backgrounds that shows significant differences in allele and genotype frequencies of 5-HTTLPR. The results of this study open new avenues for investigating the role of transmission of the L and S alleles in families with autism in South Africa.
Subject(s)
Autistic Disorder/genetics , Polymorphism, Genetic/genetics , Serotonin Plasma Membrane Transport Proteins/genetics , Alleles , Autistic Disorder/drug therapy , Autistic Disorder/epidemiology , Autistic Disorder/ethnology , Ethnicity , Gene Frequency , Genetics, Population , Genotype , Humans , Odds Ratio , Selective Serotonin Reuptake Inhibitors/therapeutic use , South Africa/epidemiologyABSTRACT
The serotonin transporter promoter length polymorphism (5-hydroxytryptamine transporter length polymorphism, 5-HTTLPR) in serotonin transporter gene has been implicated in numerous psychiatric disorders. Having a high affinity for the neurotransmitter serotonin (5-hydroxytryptamine, 5-HT), serotonin transporter controls the duration, availability and signaling capacity of 5-HT in the synapse. Association studies have focused extensively on this polymorphic region as the frequencies of long- and short-alleles of this gene differ greatly amongst populations and association studies have either reported conflicting results or nothing significant at all. In this study, the genotype and allele frequencies of 5-HTTLPR polymorphism were determined in the healthy South African (SA) individuals belonging to diverse ethnic backgrounds. Cheek cell samples were collected from the three major ethnic groups namely: Caucasians, Africans and coloreds/Mixed population. The DNA was extracted and genotyped for the 5-HTTLPR. Genotypes were compared amongst the three major ethnic groups from SA as well as to that of other studies around the world. This is the first study to report significant differences in the 5-HTTLPR genotype and allelic frequencies among various ethnic groups in SA. Future studies will target larger population groups and the estimation of frequency of these alleles in individuals with autism.
