Computational analysis of candidate disease genes and variants for Salt-sensitive hypertension in indigenous Southern Africans
Article - Full Text
Supplemental File 1
Supplemental File 2
Supplemental File 3
Supplemental File 4
Supplemental File 5
Supplemental File 6
KAUST DepartmentComputational Bioscience Research Center (CBRC)
Applied Mathematics and Computational Science Program
Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division
Permanent link to this recordhttp://hdl.handle.net/10754/325286
MetadataShow full item record
AbstractMultiple factors underlie susceptibility to essential hypertension, including a significant genetic and ethnic component, and environmental effects. Blood pressure response of hypertensive individuals to salt is heterogeneous, but salt sensitivity appears more prevalent in people of indigenous African origin. The underlying genetics of salt-sensitive hypertension, however, are poorly understood. In this study, computational methods including text- and data-mining have been used to select and prioritize candidate aetiological genes for salt-sensitive hypertension. Additionally, we have compared allele frequencies and copy number variation for single nucleotide polymorphisms in candidate genes between indigenous Southern African and Caucasian populations, with the aim of identifying candidate genes with significant variability between the population groups: identifying genetic variability between population groups can exploit ethnic differences in disease prevalence to aid with prioritisation of good candidate genes. Our top-ranking candidate genes include parathyroid hormone precursor (PTH) and type-1angiotensin II receptor (AGTR1). We propose that the candidate genes identified in this study warrant further investigation as potential aetiological genes for salt-sensitive hypertension. © 2010 Tiffin et al.
CitationTiffin N, Meintjes A, Ramesar R, Bajic VB, Rayner B (2010) Computational Analysis of Candidate Disease Genes and Variants for Salt-Sensitive Hypertension in Indigenous Southern Africans. PLoS ONE 5: e12989. doi:10.1371/journal.pone.0012989.
PublisherPublic Library of Science (PLoS)
PubMed Central IDPMC2946338
- Patterns of genetic variation in the hypertension candidate gene GRK4: ethnic variation and haplotype structure.
- Authors: Lohmueller KE, Wong LJ, Mauney MM, Jiang L, Felder RA, Jose PA, Williams SM
- Issue date: 2006 Jan
- [A cross-racial analysis on the susceptible gene polymorphisms of salt-sensitive hypertension].
- Authors: Lu JP, Zhang L, Wang W
- Issue date: 2010 Oct
- Blood pressure variation in blacks: genetic factors.
- Authors: Grim CE, Robinson M
- Issue date: 1996 Mar
- Alpha1A-adrenergic receptor polymorphism: association with ethnicity but not essential hypertension.
- Authors: Xie HG, Kim RB, Stein CM, Gainer JV, Brown NJ, Wood AJ
- Issue date: 1999 Oct
- Hypertension, thermotolerance, and the "African gene": an hypothesis.
- Authors: Moskowitz DW
- Issue date: 1996 Jan
Showing items related by title, author, creator and subject.
Long- and short-term selective forces on malaria parasite genomesNygaard, Sanne; Braunstein, Alexander; Malsen, Gareth; Van Dongen, Stijn; Gardner, Paul P.; Krogh, Anders; Otto, Thomas D.; Pain, Arnab; Berriman, Matthew; McAuliffe, Jon; Dermitzakis, Emmanouil T.; Jeffares, Daniel C. (PLoS Genetics, Public Library of Science (PLoS), 2010-09-09) [Article]Plasmodium parasites, the causal agents of malaria, result in more than 1 million deaths annually. Plasmodium are unicellular eukaryotes with small ~23 Mb genomes encoding ~5200 protein-coding genes. The protein-coding genes comprise about half of these genomes. Although evolutionary processes have a significant impact on malaria control, the selective pressures within Plasmodium genomes are poorly understood, particularly in the non-protein-coding portion of the genome. We use evolutionary methods to describe selective processes in both the coding and non-coding regions of these genomes. Based on genome alignments of seven Plasmodium species, we show that protein-coding, intergenic and intronic regions are all subject to purifying selection and we identify 670 conserved non-genic elements. We then use genome-wide polymorphism data from P. falciparum to describe short-term selective processes in this species and identify some candidate genes for balancing (diversifying) selection. Our analyses suggest that there are many functional elements in the non-genic regions of these genomes and that adaptive evolution has occurred more frequently in the protein-coding regions of the genome. © 2010 Nygaard et al.
dPORE-miRNA: Polymorphic regulation of microRNA genesSchmeier, Sebastian; Schaefer, Ulf; MacPherson, Cameron R.; Bajic, Vladimir B. (PLoS ONE, Public Library of Science (PLoS), 2011-02-04) [Article]Background: MicroRNAs (miRNAs) are short non-coding RNA molecules that act as post-transcriptional regulators and affect the regulation of protein-coding genes. Mostly transcribed by PolII, miRNA genes are regulated at the transcriptional level similarly to protein-coding genes. In this study we focus on human miRNAs. These miRNAs are involved in a variety of pathways and can affect many diseases. Our interest is on possible deregulation of the transcription initiation of the miRNA encoding genes, which is facilitated by variations in the genomic sequence of transcriptional control regions (promoters). Methodology: Our aim is to provide an online resource to facilitate the investigation of the potential effects of single nucleotide polymorphisms (SNPs) on miRNA gene regulation. We analyzed SNPs overlapped with predicted transcription factor binding sites (TFBSs) in promoters of miRNA genes. We also accounted for the creation of novel TFBSs due to polymorphisms not present in the reference genome. The resulting changes in the original TFBSs and potential creation of new TFBSs were incorporated into the Dragon Database of Polymorphic Regulation of miRNA genes (dPORE-miRNA). Conclusions: The dPORE-miRNA database enables researchers to explore potential effects of SNPs on the regulation of miRNAs. dPORE-miRNA can be interrogated with regards to: a/miRNAs (their targets, or involvement in diseases, or biological pathways), b/SNPs, or c/transcription factors. dPORE-miRNA can be accessed at http://cbrc.kaust.edu.sa/dpore and http://apps.sanbi.ac.za/dpore/. Its use is free for academic and non-profit users. © 2011 Schmeier et al.
Conservative fragments in bacterial 16S rRNA genes and primer design for 16S ribosomal DNA amplicons in metagenomic studiesWang, Yong; Qian, Pei-Yuan (PLoS ONE, Public Library of Science (PLoS), 2009-10-09) [Article]Bacterial 16S ribosomal DNA (rDNA) amplicons have been widely used in the classification of uncultured bacteria inhabiting environmental niches. Primers targeting conservative regions of the rDNAs are used to generate amplicons of variant regions that are informative in taxonomic assignment. One problem is that the percentage coverage and application scope of the primers used in previous studies are largely unknown. In this study, conservative fragments of available rDNA sequences were first mined and then used to search for candidate primers within the fragments by measuring the coverage rate defined as the percentage of bacterial sequences containing the target. Thirty predicted primers with a high coverage rate (>90%) were identified, which were basically located in the same conservative regions as known primers in previous reports, whereas 30% of the known primers were associated with a coverage rate of <90%. The application scope of the primers was also examined by calculating the percentages of failed detections in bacterial phyla. Primers A519-539, E969- 983, E1063-1081, U515 and E517, are highly recommended because of their high coverage in almost all phyla. As expected, the three predominant phyla, Firmicutes, Gemmatimonadetes and Proteobacteria, are best covered by the predicted primers. The primers recommended in this report shall facilitate a comprehensive and reliable survey of bacterial diversity in metagenomic studies. © 2009 Wang, Qian.