Identification of a haplotype block in the 5q31 cytokine gene cluster associated with the susceptibility to severe malaria
Izumi Naka,Nao Nishida,Jintana Patarapotikul,Pornlada Nuchnoi,Katsushi Tokunaga,Hathairad Hananantachai,Naoyuki Tsuchiya,Jun Ohashi +7 more
TLDR
A haplotype block in which a primary polymorphism associated with severe malaria is likely to be encoded was identified in Thai malaria patients.Abstract:
It has been previously demonstrated that a single nucleotide polymorphism (SNP) in the IL13 promoter region, IL13 -1055T>C (rs1800925), was associated with susceptibility to severe malaria in Thais. In the present study, fine association mapping for a cytokine gene cluster including IL4, IL5, and IL13 on chromosome 5q31 was conducted using the same malaria subjects to refine the region containing a primary variant or a haplotype susceptible to severe malaria. A total of 82 SNPs spanning 522 kb of the 5q31 region were analysed in 368 patients with Plasmodium falciparum malaria (203 mild malaria and 165 severe malaria patients). Only rs1881457 located in the promoter region of IL13, which is in linkage disequilibrium with rs1800925 (r2 = 0.73), showed a significant association with severe malaria after adjusting for multiple testing (P = 0.046 by permutation test). This SNP was in a haplotype block spanning 97 kb (from rs2069812 to rs2240032). The detected haplotype block contained the RAD50 gene and the promoter of IL13, but not the other genes. A haplotype block in which a primary polymorphism associated with severe malaria is likely to be encoded was identified in Thai malaria patients.read more
Citations
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Dissertation
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References
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Haploview: analysis and visualization of LD and haplotype maps
TL;DR: Haploview is a software package that provides computation of linkage disequilibrium statistics and population haplotype patterns from primary genotype data in a visually appealing and interactive interface.
Journal ArticleDOI
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Journal ArticleDOI
The Mre11 complex: at the crossroads of dna repair and checkpoint signalling.
TL;DR: The Mre 11 complex is a multisubunit nuclease that is composed of Mre11, Rad50 and Nbs1/Xrs2 and its functions in checkpoint signalling and DNA replication are uncovered.
Journal ArticleDOI
TNF concentration in fatal cerebral, non-fatal cerebral, and uncomplicated Plasmodium falciparum malaria.
Dominic P. Kwiatkowski,Adrian V. S. Hill,I. Sambou,P. Twumasi,J. Castracane,K. R. Manogue,Anthony Cerami,David Brewster,Brian Greenwood +8 more
TL;DR: It is concluded that increased TNF production is a normal host response to P falciparum infection, but that excessive levels of production may predispose to cerebral malaria and a fatal outcome.
Journal ArticleDOI
The cellular response to DNA double-strand breaks: defining the sensors and mediators.
TL;DR: This work discusses the possible role of the Mre11 complex as a primary damage sensor and the complex relationship between DNA damage sensors, transducers and mediators and proposed criteria for defining sensor proteins.