Browsing by Author "Ramsay, Michele"
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- ItemASSAf consensus study on the ethical, legal and social implications of genetics and genomics in South Africa(Academy of Science of South Africa, 2018) Pepper, Michael S.; Dandara, Collet; De Vries, Jantina; Dhai, Amaboo; Labuschaigne, Melodie; Mnyongani, Freddy; Moodley, Keymanthri; Olckers, Antonel; Pope, Anne; Ramesar, Raj; Ramsay, Michele; Soodyall, Himla; Towers, WayneNo abstract available.
- ItemReduced DNA methylation at the PEG3 DMR and KvDMR1 loci in children exposed to alcohol in utero : a South African Fetal Alcohol Syndrome cohort study(Frontiers, 2015-03-10) Masemola, Matshane L.; Van der Merwe, Lize; Lombard, Zane; Viljoen, Denis; Ramsay, MicheleFetal alcohol syndrome (FAS) is a devastating developmental disorder resulting from alcohol exposure during fetal development. It is a considerable public health problem worldwide and is characterized by central nervous system abnormalities, dysmorphic facial features, and growth retardation. Imprinted genes are known to play an important role in growth and development and therefore four imprinting control regions (ICRs), H19 ICR, IG-DMR, KvDMR1 and PEG3 DMR were examined. It is proposed that DNA methylation changes may contribute to developmental abnormalities seen in FAS and which persist into adulthood. The participants included FAS children and controls from the Western and Northern Cape Provinces. DNA samples extracted from blood and buccal cells were bisulfite modified, the ICRs were amplified by PCR and pyrosequencing was used to derive a quantitative estimate of methylation at selected CpG dinucleotides: H19 ICR (six CpG sites; 50 controls and 73 cases); KvDMR1 (7, 55, and 86); IG-DMR (10, 56, and 84); and PEG3 DMR (7, 50, and 79). The most profound effects of alcohol exposure are on neuronal development. In this study we report on epigenetic effects observed in blood which may not directly reflect tissue-specific alterations in the developing brain. After adjusting for age and sex (known confounders for DNA methylation), there was a significant difference at KvDMR1 and PEG3 DMR, but not the H19 ICR, with only a small effect (0.84% lower in cases; p D 0.035) at IG-DMR. The two maternally imprinted loci, KvDMR1 and PEG3 DMR, showed lower average locus-wide methylation in the FAS cases (1.49%; p < 0.001 and 7.09%; p < 0.001, respectively). The largest effect was at the PEG3 DMR though the functional impact is uncertain. This study supports the role of epigenetic modulation as a mechanism for the teratogenic effects of alcohol by altering the methylation profiles of imprinted loci in a locus-specific manner.
- ItemWhole-genome sequencing for an enhanced understanding of genetic variation among South Africans(Nature Research (part of Springer Nature), 2017) Choudhury, Ananyo; Ramsay, Michele; Hazelhurst, Scott; Aron, Shaun; Bardien, Soraya; Botha, Gerrit; Chimusa, Emile R.; Christoffels, Alan; Gamieldien, Junaid; Sefid-Dashti, Mahjoubeh J.; Joubert, Fourie; Meintjes, Ayton; Mulder, Nicola; Ramesar, Raj; Rees, Jasper; Scholtz, Kathrine; Sengupta, Dhriti; Soodyall, Himla; Venter, Philip; Warnich, Louise; Pepper, Michael S.ENGLISH ABSTRACT: The Southern African Human Genome Programme is a national initiative that aspires to unlock the unique genetic character of southern African populations for a better understanding of human genetic diversity. In this pilot study the Southern African Human Genome Programme characterizes the genomes of 24 individuals (8 Coloured and 16 black southeastern Bantu-speakers) using deep whole-genome sequencing. A total of ~16 million unique variants are identified. Despite the shallow time depth since divergence between the two main southeastern Bantu-speaking groups (Nguni and Sotho-Tswana), principal component analysis and structure analysis reveal significant (p < 10−6) differentiation, and FST analysis identifies regions with high divergence. The Coloured individuals show evidence of varying proportions of admixture with Khoesan, Bantu-speakers, Europeans, and populations from the Indian sub-continent. Whole-genome sequencing data reveal extensive genomic diversity, increasing our understanding of the complex and region-specific history of African populations and highlighting its potential impact on biomedical research and genetic susceptibility to disease.