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Leprosy and the adaptation of human toll-like receptor 1
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نویسنده
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wong s.h. ,gochhait s. ,malhotra d. ,pettersson f.h. ,teo y.y. ,khor c.c. ,rautanen a. ,chapman s.j. ,mills t.c. ,srivastava a. ,rudko a. ,freidin m.b. ,puzyrev v.p. ,ali s. ,aggarwal s. ,chopra r. ,reddy b.s.n. ,garg v.k. ,roy s. ,meisner s. ,hazra s.k. ,saha b. ,floyd s. ,keating b.j. ,kim c. ,fairfax b.p. ,knight j.c. ,hill p.c. ,adegbola r.a. ,hakonarson h. ,fine p.e.m. ,pitchappan r.m. ,bamezai r.n.k. ,hill a.v.s. ,vannberg f.o.
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منبع
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plos pathogens - 2010 - دوره : 6 - شماره : 7 - صفحه:1 -9
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چکیده
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Leprosy is an infectious disease caused by the obligate intracellular pathogen mycobacterium leprae and remains endemic in many parts of the world. despite several major studies on susceptibility to leprosy,few genomic loci have been replicated independently. we have conducted an association analysis of more than 1,500 individuals from different case-control and family studies,and observed consistent associations between genetic variants in both tlr1 and the hla-drb1/dqa1 regions with susceptibility to leprosy (tlr1 i602s,case-control p = 5.7×10-8,or = 0.31,95% ci = 0.20-0.48,and hla-dqa1 rs1071630,case-control p = 4.9×10-14,or = 0.43,95% ci = 0.35-0.54). the effect sizes of these associations suggest that tlr1 and hla-drb1/dqa1 are major susceptibility genes in susceptibility to leprosy. further population differentiation analysis shows that the tlr1 locus is extremely differentiated. the protective dysfunctional 602s allele is rare in africa but expands to become the dominant allele among individuals of european descent. this supports the hypothesis that this locus may be under selection from mycobacteria or other pathogens that are recognized by tlr1 and its co-receptors. these observations provide insight into the long standing host-pathogen relationship between human and mycobacteria and highlight the key role of the tlr pathway in infectious diseases. © 2010 wong et al.
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آدرس
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wellcome trust centre for human genetics,university of oxford,oxford, United Kingdom, national centre of applied human genetics,school of life sciences,jawaharlal nehru university,new delhi, India, national centre of applied human genetics,school of life sciences,jawaharlal nehru university,new delhi, India, wellcome trust centre for human genetics,university of oxford,oxford, United Kingdom, wellcome trust centre for human genetics,university of oxford,oxford, United Kingdom, wellcome trust centre for human genetics,university of oxford,oxford,united kingdom,host susceptibility to infection program,singapore institute for clinical sciences,agency for science,technology and research, Singapore, wellcome trust centre for human genetics,university of oxford,oxford, United Kingdom, wellcome trust centre for human genetics,university of oxford,oxford, United Kingdom, wellcome trust centre for human genetics,university of oxford,oxford, United Kingdom, national centre of applied human genetics,school of life sciences,jawaharlal nehru university,new delhi, India, research institute of medical genetics,siberian branch of russian academy of medical sciences,tomsk, Russian Federation, wellcome trust centre for human genetics,university of oxford,oxford,united kingdom,research institute of medical genetics,siberian branch of russian academy of medical sciences,tomsk, Russian Federation, research institute of medical genetics,siberian branch of russian academy of medical sciences,tomsk, Russian Federation, national centre of applied human genetics,school of life sciences,jawaharlal nehru university,new delhi, India, national centre of applied human genetics,school of life sciences,jawaharlal nehru university,new delhi, India, national centre of applied human genetics,school of life sciences,jawaharlal nehru university,new delhi, India, department of dermatology and sexually transmitted diseases,maulana azad medical college,lok nayak jai prakash hospital,new delhi, India, department of dermatology and sexually transmitted diseases,maulana azad medical college,lok nayak jai prakash hospital,new delhi, India, wellcome trust centre for human genetics,university of oxford,oxford, United Kingdom, bath royal united hospital trust,combe park,bath, United Kingdom, calcutta school of tropical medicine,kolkata, India, calcutta school of tropical medicine,kolkata, India, infectious disease epidemiology unit,london school of hygiene and tropical medicine,london, United Kingdom, institute for translational medicine and therapeutics,school of medicine,university of pennsylvania,philadelphia,pa, United States, center for applied genomics,abramson research center,the children's hospital of philadelphia,philadelphia,pa, United States, wellcome trust centre for human genetics,university of oxford,oxford, United Kingdom, wellcome trust centre for human genetics,university of oxford,oxford, United Kingdom, mrc laboratories,fajara, Gambia, mrc laboratories,fajara, Gambia, center for applied genomics,abramson research center,the children's hospital of philadelphia,philadelphia,pa, United States, infectious disease epidemiology unit,london school of hygiene and tropical medicine,london, United Kingdom, centre for excellence in genomic sciences,madurai kamaraj university,madurai, India, national centre of applied human genetics,school of life sciences,jawaharlal nehru university,new delhi, India, wellcome trust centre for human genetics,university of oxford,oxford, United Kingdom, wellcome trust centre for human genetics,university of oxford,oxford, United Kingdom
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Authors
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