Chromosome 2p14 Is Linked to Susceptibility to Leprosy

Yang, Qing; Liu, Hong; Low, Hui-Qi; Wang, Haifeng; Yu, Yang; Fu, Xi’an; Yu, Gongqi; Chen, Mingfei; Yan, Xiaoxiao; Chen, Shumin; Huang, Wei; Liu, Jing; Zhang, Furen

doi:10.1371/journal.pone.0029747

Cited by 11 publications

(8 citation statements)

References 20 publications

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“…They suggested genomewide significant evidence for linkage on chromosome 2p14, and a suggestive evidence for linkage on chr.4q22 (rs1349350), chr.8q24 (rs1618523), and chr.16q24 (rs276990), as well as a moderate evidence for a linkage locus on chromosome 6q24–26 (rs6570858), overlapping a previously reported linkage region on chromosome 6q25-26 [112]. …”

Section: Genome-wide and Leprosysupporting

confidence: 51%

“…Recently, Yang et al [112] carried out a genome-wide single nucleotide polymorphism (SNP) based linkage analysis using 23 pedigrees, each with 3 to 7 family members affected by leprosy, in China [112]. They suggested genomewide significant evidence for linkage on chromosome 2p14, and a suggestive evidence for linkage on chr.4q22 (rs1349350), chr.8q24 (rs1618523), and chr.16q24 (rs276990), as well as a moderate evidence for a linkage locus on chromosome 6q24–26 (rs6570858), overlapping a previously reported linkage region on chromosome 6q25-26 [112].…”

Section: Genome-wide and Leprosymentioning

confidence: 99%

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Role ofHLA,KIR,MICA, and Cytokines Genes in Leprosy

Jarduli

Sell

Reis

et al. 2013

BioMed Research International

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Many genes including HLA, KIR, and MICA genes, as well as polymorphisms in cytokines have been investigated for their role in infectious disease. HLA alleles may influence not only susceptibility or resistance to leprosy, but also the course of the disease. Some combinations of HLA and KIR may result in negative as well as positive interactions between NK cells and infected host cells with M. leprae, resulting in activation or inhibition of NK cells and, consequently, in death of bacillus. In addition, studies have demonstrated the influence of MICA genes in the pathogenesis of leprosy. Specifically, they may play a role in the interaction between NK cells and infected cells. Finally, pro- and anti-inflammatory cytokines have been influencing the clinical course of leprosy. Data from a wide variety of sources support the existence of genetic factors influencing the leprosy pathogenesis. These sources include twin studies, segregation analyses, family-based linkage and association studies, candidate gene association studies, and, most recently, genome-wide association studies (GWAS). The purpose of this brief review was to highlight the importance of some immune response genes and their correlation with the clinical forms of leprosy, as well as their implications for disease resistance and susceptibility.

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Section: Genome-wide and Leprosysupporting

confidence: 51%

Section: Genome-wide and Leprosymentioning

confidence: 99%

Role ofHLA,KIR,MICA, and Cytokines Genes in Leprosy

Jarduli

Sell

Reis

et al. 2013

BioMed Research International

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“…LL: LOD score (D20S889) = 1.36, p = 0.006. TT: LOD score (D20S835) = 0.74, p = 0.033 Wallace et al ( 2004 ) 185 extended families from Malawi (83 nuclear families in the discovery phase) 21q22 LOD score = 1.4, p ≈ 0.001 Yang et al ( 2012 ) 23 Chinese families, including 82 affected individuals 2p14 HLOD = 3.51 (REC), LOD score = 1.48, p = 0.005 4q22 HLOD = 2.92 (DOM), LOD score = 1.21, p = 0.009 8q24 HLOD = 2.74 (REC), LOD score = 1.22, p = 0.009 16q24 HLOD = 1.93 (DOM), LOD score = 1.37, p = 0.006 6q24-q26 LOD score = 1.54, p = 0.004 DOM dominant model; HLOD heterogeneity logarithm of odds; LOD logarithm of the odds; LL lepromatous leprosy; MB multibacillary leprosy; MLB maximum likelihood binomial; PB paucibacillary leprosy; REC Recessive model; TT tuberculoid leprosy a Follow-up association analysis of candidate genes located in the regions linked to the disease are not included in this table b For studies in which the population sample consists of an extension of a previous published GWLS, only the new findings from the extended population analysis are shown c Peak/maximum LOD score is shown for each locus when available d In multi-stage studies, results shown are from the combined analysis with all families when available …”

Section: Leprosymentioning

confidence: 99%

“…Moreover, chromosomal region 21q22 was linked to leprosy polarization in families from Malawi (Wallace et al 2004 ). Finally, 2p14 was significantly linked to leprosy per se, while regions 4q22, 8q24 and 16q24 showed suggestive evidence for linkage in Chinese families (Yang et al 2012 ). Leprosy susceptibility genes underlying these linkage peaks are yet to be identified.…”

Section: Leprosymentioning

confidence: 99%

Human genetics of mycobacterial disease

2018

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Mycobacterial diseases are caused by members of the genus Mycobacterium, acid-fast bacteria characterized by the presence of mycolic acids within their cell walls. Claiming almost 2 million lives every year, tuberculosis (TB) is the most common mycobacterial disease and is caused by infection with M. tuberculosis and, in rare cases, by M. bovis or M. africanum. The second and third most common mycobacterial diseases are leprosy and buruli ulcer (BU), respectively. Both diseases affect the skin and can lead to permanent sequelae and deformities. Leprosy is caused by the uncultivable M. leprae while the etiological agent of BU is the environmental bacterium M. ulcerans. After exposure to these mycobacterial species, a majority of individuals will not progress to clinical disease and, among those who do, inter-individual variability in disease manifestation and outcome can be observed. Susceptibility to mycobacterial diseases carries a human genetic component and intense efforts have been applied over the past decades to decipher the exact nature of the genetic factors controlling disease susceptibility. While for BU this search was mostly conducted on the basis of candidate genes association studies, genome-wide approaches have been widely applied for TB and leprosy. In this review, we summarize some of the findings achieved by genome-wide linkage, association and transcriptome analyses in TB disease and leprosy and the recent genetic findings for BU susceptibility.

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“…A relatively small percentage of armadillos are resistant to M. leprae , and large sample sizes might be needed for conclusive genetic analysis. Genome-wide SNP linkage analysis and melting-curve-based assays have been used effectively to identify new SNPs in human studies (Misch et al, 2008; Yang et al, 2012), and the application of similar approaches might be possible with armadillos once the genome is fully annotated.…”

Section: Post-genomic Advancesmentioning

confidence: 99%

The armadillo: a model for neuropathy of leprosy and potentially other neurodegenerative diseases

Sharma

Lahiri

Scollard

et al. 2012

Disease Models &Amp; Mechanisms

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Leprosy (also known as Hansen’s disease) is an infectious peripheral neurological disorder caused by Mycobacterium leprae that even today leaves millions of individuals worldwide with life-long disabilities. The specific mechanisms by which this bacterium induces nerve injury remain largely unknown, mainly owing to ethical and practical limitations in obtaining affected human nerve samples. In addition to humans, nine-banded armadillos (Dasypus novemcinctus) are the only other natural host of M. leprae, and they develop a systemically disseminated disease with extensive neurological involvement. M. leprae is an obligate intracellular parasite that cannot be cultivated in vitro. Because of the heavy burdens of bacilli they harbor, nine-banded armadillos have become the organism of choice for propagating large quantities of M. leprae, and they are now advancing as models of leprosy pathogenesis and nerve damage. Although armadillos are exotic laboratory animals, the recently completed whole genome sequence for this animal is enabling researchers to undertake more sophisticated molecular studies and to develop armadillo-specific reagents. These advances will facilitate the use of armadillos in piloting new therapies and diagnostic regimens, and will provide new insights into the oldest known infectious neurodegenerative disorder.

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Chromosome 2p14 Is Linked to Susceptibility to Leprosy

Cited by 11 publications

References 20 publications

Role ofHLA,KIR,MICA, and Cytokines Genes in Leprosy

Role ofHLA,KIR,MICA, and Cytokines Genes in Leprosy

Human genetics of mycobacterial disease

The armadillo: a model for neuropathy of leprosy and potentially other neurodegenerative diseases

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