A replicative association study of Chromosome 6p21.3 with susceptibility to leprosy in an Indian population - 'a string hypothesis'
© Ali et al; licensee BioMed Central Ltd. 2010
Published: 11 October 2010
Leprosy is a chronic infectious disease, caused by Mycobacterium leprae, which affects mainly the skin and nerves of the host and results in characteristic deformity and disability. The role of host genetic factors in conferring susceptibility to this disease has long been a focus of research, with the discovery of many loci by segregation, twin and case-control studies [1, 2]. Here we propose how a perturbation involving a 'string' of DNA, co-evolved with a cluster of genes, provides a basis to the susceptibility to a this complex disease.
Materials and methods
We conducted a systematic three-stage, high resolution scan of the 6p21.3 chromosomal region of 177kb, within HLA class I and III region, with 111 SNPs genotyped using Sequenom Mass Array. We included a total of 2301 individuals, including patients and controls from the North Indian population and replicated our results in an East Indian population, from the geographically distinct state of Orissa.
Significant P-values for SNPs in 6p21.3 region
LTA 13kb upstream
HLA class II BTNL2-DRA
HLA class II BTNL2-DRA
In addition to discovering the function of the genes BAT1 and BTNL2, we also established the functional status of the SNPs through in-vitroreporter assays. Furthermore, our assessment of an interaction of multiple genes in unison within the 'string' provided us with a graded risk to leprosy, which is dependant on the combination of genotypes of the significantly associated functional SNPs. Our results provide the first demonstration of the genome combinations of the polar forms of leprosy and the role of independent SNPs/genes in reaction states of the leprosy.
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