Asian Science Citation Index is committed to provide an authoritative, trusted and significant information by the coverage of the most important and influential journals to meet the needs of the global scientific community.  
ASCI Database
308-Lasani Town,
Sargodha Road,
Faisalabad, Pakistan
Fax: +92-41-8815544
Contact Via Web
Suggest a Journal
Articles by A. E Fry
Total Records ( 2 ) for A. E Fry
  Y. Y Teo , A. E Fry , K Bhattacharya , K. S Small , D. P Kwiatkowski and T. G. Clark

Current genome-wide surveys of common diseases and complex traits fundamentally aim to detect indirect associations where the single nucleotide polymorphisms (SNPs) carrying the association signals are not biologically active but are in linkage disequilibrium (LD) with some unknown functional polymorphisms. Reproducing any novel discoveries from these genome-wide scans in independent studies is now a prerequisite for the putative findings to be accepted. Significant differences in patterns of LD between populations can affect the portability of phenotypic associations when the replication effort or meta-analyses are attempted in populations that are distinct from the original population in which the genome-wide study is performed. Here, we introduce a novel method for genome-wide analyses of LD variations between populations that allow the identification of candidate regions with different patterns of LD. The evidence of LD variation provided by the introduced method correlated with the degree of differences in the frequencies of the most common haplotype across the populations. Identified regions also resulted in greater variation in the success of replication attempts compared with random regions in the genome. A separate permutation strategy introduced for assessing LD variation in the absence of genome-wide data also correctly identified the expected variation in LD patterns in two well-established regions undergoing strong population-specific evolutionary pressure. Importantly, this method addresses whether a failure to reproduce a disease association in a disparate population is due to underlying differences in LD structure with an unknown functional polymorphism, which is vital in the current climate of replicating and fine-mapping established findings from genome-wide association studies.

  A. E Fry , A Ghansa , K. S Small , A Palma , S Auburn , M Diakite , A Green , S Campino , Y. Y Teo , T. G Clark , A. E Jeffreys , J Wilson , M Jallow , F Sisay Joof , M Pinder , M. J Griffiths , N Peshu , T. N Williams , C. R Newton , K Marsh , M. E Molyneux , T. E Taylor , K. A Koram , A. R Oduro , W. O Rogers , K. A Rockett , P. C Sabeti and D. P. Kwiatkowski

The prevalence of CD36 deficiency in East Asian and African populations suggests that the causal variants are under selection by severe malaria. Previous analysis of data from the International HapMap Project indicated that a CD36 haplotype bearing a nonsense mutation (T1264G; rs3211938) had undergone recent positive selection in the Yoruba of Nigeria. To investigate the global distribution of this putative selection event, we genotyped T1264G in 3420 individuals from 66 populations. We confirmed the high frequency of 1264G in the Yoruba (26%). However, the 1264G allele is less common in other African populations and absent from all non-African populations without recent African admixture. Using long-range linkage disequilibrium, we studied two West African groups in depth. Evidence for recent positive selection at the locus was demonstrable in the Yoruba, although not in Gambians. We screened 70 variants from across CD36 for an association with severe malaria phenotypes, employing a case–control study of 1350 subjects and a family study of 1288 parent–offspring trios. No marker was significantly associated with severe malaria. We focused on T1264G, genotyping 10 922 samples from four African populations. The nonsense allele was not associated with severe malaria (pooled allelic odds ratio 1.0; 95% confidence interval 0.89–1.12; P = 0.98). These results suggest a range of possible explanations including the existence of alternative selection pressures on CD36, co-evolution between host and parasite or confounding caused by allelic heterogeneity of CD36 deficiency.

Copyright   |   Desclaimer   |    Privacy Policy   |   Browsers   |   Accessibility