Chromosome 2p14 is linked to susceptibility to leprosy.

Qing Yang,Shumin Chen,Haifeng Wang,Hong Liu,Jianjun Liu,Xi'An Fu,Xiaoxiao Yan,Furen Zhang,Wei Huang,Hui-Qi Low,Gongqi Yu,Yongxiang Yu,Mingfei Chen,Robert J Wilkinson

doi:10.1371/journal.pone.0029747

Abstract

BackgroundA genetic component to the etiology of leprosy is well recognized but the mechanism of inheritance and the genes involved are yet to be fully established.MethodologyA genome-wide single nucleotide polymorphism (SNP) based linkage analysis was carried out using 23 pedigrees, each with 3 to 7 family members affected by leprosy. Multipoint parametric and non-parametric linkage analyses were performed using MERLIN 1.1.1.Principal FindingsGenome-wide significant evidence for linkage was identified on chromosome 2p14 with a heterogeneity logarithm of odds (HLOD) score of 3.51 (rs1106577) under a recessive model of inheritance, while suggestive evidence was identified on chr.4q22 (HLOD 2.92, rs1349350, dominant model), chr. 8q24 (HLOD 2.74, rs1618523, recessive model) and chr.16q24 (HLOD 1.93, rs276990 dominant model). Our study also provided moderate evidence for a linkage locus on chromosome 6q24–26 by non-parametric linkage analysis (rs6570858, LOD 1.54, p = 0.004), overlapping a previously reported linkage region on chromosome 6q25–26.ConclusionA genome-wide linkage analysis has identified a new linkage locus on chromosome 2p14 for leprosy in Pedigrees from China.

Highlights

Leprosy is a chronic infectious disease caused by Mycobacterium leprae
We recently reported a genome wide association study (GWAS) of leprosy and identified significant associations between single nucleotide polymorphisms (SNPs) in the genes CCDC122, C13orf31, NOD2, TNFSF15, HLA-DR, and RIPK2 and a trend toward an association with a SNP in LRRK2
Suggestive evidence of susceptibility loci were found on chromosome 4q22 and 16q24 under a dominant model, chromosome 8q24 under a recessive model and chromosome 6q24–26 by non-parametric analysis

Summary

Introduction

Leprosy is a chronic infectious disease caused by Mycobacterium leprae. It affects the skin and peripheral nerves and can cause irreversible impairment of nerve function and consequent chronic disabilities [1]. Various genes (HLA-DR [7,8], PARK2/PACRG [9], LTA [10], TLRs [11,12], etc.) and genomic regions (10p13 [13], 6q25–26 [14], 6p21 [14], 17q11–q21 [15], 20p13 [16], etc.) of human genome have been associated with or linked to leprosy (or a particular clinical form of leprosy) by candidate gene association studies or genome-wide linkage analysis Few of these results have been replicated in different populations. We recently reported a genome wide association study (GWAS) of leprosy and identified significant associations between single nucleotide polymorphisms (SNPs) in the genes CCDC122, C13orf, NOD2, TNFSF15, HLA-DR, and RIPK2 and a trend toward an association with a SNP in LRRK2 Five of these genes encode proteins involved in the innate immune response [17]. We present a genome-wide SNP-based linkage analysis of 23 multiplex families, each with at least 3 patients with leprosy

Results

Discussion

Materials and Methods