Browsing by Subject "Permutation"

Now showing 1 - 3 of 3
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    Open Access
    Integrative analysis of mRNA expression and half-life data reveals trans-acting genetic variants associated with increased expression of stable transcripts
    (Public Library of Science, 2013) Nguyen, Thong T; Seoighe, Cathal
    Genetic variation in gene expression makes an important contribution to phenotypic variation and susceptibility to disease. Recently, a subset of cis -acting expression quantitative loci (eQTLs) has been found to result from polymorphisms that affect RNA stability. Here we carried out a search for trans -acting variants that influence RNA stability. We first demonstrate that differences in the activity of trans -acting factors that stabilize RNA can be detected by comparing the expression levels of long-lived (stable) and short-lived (unstable) transcripts in high-throughput gene expression experiments. Using gene expression microarray data generated from eight HapMap3 populations, we calculated the relative expression ranks of long-lived transcripts versus short-lived transcripts in each sample. Treating this as a quantitative trait, we applied genome-wide association and identified a single nucleotide polymorphism (SNP), rs6137010, on chromosome 20p13 with which it is strongly associated in two Asian populations ( p =  4×10 −10 in CHB - Han Chinese from Beijing; p  = 1×10 −4 in JPT - Japanese from Tokyo). This SNP is a cis -eQTL for SNRPB in CHB and JPT but not in the other six HapMap3 populations. SNRPB is a core component of the spliceosome, and has previously been shown to affect the expression of many RNA processing factors. We propose that a cis -eQTL of SNRPB may be directly responsible for inter-individual variation in relative expression of long-lived versus short-lived transcript in Asian populations. In support of this hypothesis, knockdown of SNRPB results in a significant reduction in the relative expression of long-lived versus short-lived transcripts. Samples with higher relative expression of long-lived transcripts also had higher relative expression of coding compared to non-coding RNA and of RNA from housekeeping compared to non-housekeeping genes, due to the lower decay rates of coding RNAs, particularly those that perform housekeeping functions, compared to non-coding RNAs.
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    Open Access
    Optimising regionalisation techniques: identifying centres of endemism in the extraordinarily endemic-rich Cape Floristic Region
    (Public Library of Science, 2015) Bradshaw, Peter L; Colville, Jonathan F; Linder, H Peter
    We used a very large dataset (>40% of all species) from the endemic-rich Cape Floristic Region (CFR) to explore the impact of different weighting techniques, coefficients to calculate similarity among the cells, and clustering approaches on biogeographical regionalisation. The results were used to revise the biogeographical subdivision of the CFR. We show that weighted data (down-weighting widespread species), similarity calculated using Kulczinsky's second measure, and clustering using UPGMA resulted in the optimal classification. This maximized the number of endemic species, the number of centres recognized, and operational geographic units assigned to centres of endemism (CoEs). We developed a dendrogram branch order cut-off (BOC) method to locate the optimal cut-off points on the dendrogram to define candidate clusters. Kulczinsky's second measure dendrograms were combined using consensus, identifying areas of conflict which could be due to biotic element overlap or transitional areas. Post-clustering GIS manipulation substantially enhanced the endemic composition and geographic size of candidate CoEs. Although there was broad spatial congruence with previous phytogeographic studies, our techniques allowed for the recovery of additional phytogeographic detail not previously described for the CFR.
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    Open Access
    A panel of ancestry informative markers for the complex five-way admixed South African Coloured population
    (Public Library of Science, 2013) Daya, Michelle; Merwe, Lize van der; Galal, Ushma; Möller, Marlo; Salie, Muneeb; Chimusa, Emile R; Galanter, Joshua M; Helden, Paul D van; Henn, Brenna M; Gignoux, Chris R
    Admixture is a well known confounder in genetic association studies. If genome-wide data is not available, as would be the case for candidate gene studies, ancestry informative markers (AIMs) are required in order to adjust for admixture. The predominant population group in the Western Cape, South Africa, is the admixed group known as the South African Coloured (SAC). A small set of AIMs that is optimized to distinguish between the five source populations of this population (African San, African non-San, European, South Asian, and East Asian) will enable researchers to cost-effectively reduce false-positive findings resulting from ignoring admixture in genetic association studies of the population. Using genome-wide data to find SNPs with large allele frequency differences between the source populations of the SAC, as quantified by Rosenberg et. al's -statistic, we developed a panel of AIMs by experimenting with various selection strategies. Subsets of different sizes were evaluated by measuring the correlation between ancestry proportions estimated by each AIM subset with ancestry proportions estimated using genome-wide data. We show that a panel of 96 AIMs can be used to assess ancestry proportions and to adjust for the confounding effect of the complex five-way admixture that occurred in the South African Coloured population.