Chromosome 2p14 Is Linked to Susceptibility to Leprosy

BACKGROUND: A 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. METHODOLOGY: A 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 FINDINGS: Genome-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. CONCLUSION: A genome-wide linkage analysis has identified a new linkage locus on chromosome 2p14 for leprosy in Pedigrees from China

Clinical manifestations of the first patient when he suffered DDS syndrome.

<p>Generalized purpuric rash could be found on the face and trunk, and the lesions on the right leg were aggravated.</p

Clinical manifestations of the first patient when he was admitted in our clinics for the first time.

<p>Erythema and papules could be observed on the right leg with clear margin.</p

Clinical manifestations of the second patient when she was admitted for the first time.

<p>Intensive popular exanthematous rash was found on her trunk.</p

Depth-driven responses of microbial residual carbon to nitrogen addition approaches in a tropical forest: Canopy addition versus understory addition

Altres ajuts: the Fundación Ramón Areces grant CIVP20A6621.Canopies play an important role in nitrogen (N) redistribution in forest ecosystems, and ignoring the canopy's role might bias estimates of the ecological consequences of anthropogenic atmospheric N deposition. We investigated the effects of the approach of N addition (Canopy addition vs. Understory addition) and level of N addition (25 kg N ha−1yr−1 vs. 50 kg N ha−1yr−1) on microbial residual carbon (MRC) accumulation in topsoil and subsoil. We found that the response of MRC to both approach and level of N addition varied greatly with soil depth in a tropical forest over eight years of continuous N addition. Specifically, N addition enhanced the accumulation of fungal and total MRC and their contribution to soil organic C (SOC) pools in the topsoil, whereas it decreased the contribution of fungal and total MRC to SOC in the subsoil. The contrasting effects of N addition on MRC contribution at varying soil depths were associated with the distinct response of microbial residues production. Understory N addition showed overall greater effects on MRC accumulation than canopy N addition did. Our results suggest that the canopy plays an important role in buffering the impacts of anthropogenic atmospheric N deposition on soil C cycling in tropical forests. The depth-dependent response of microbial residues to N addition also highlights the urgent need for further studies of different response mechanisms at different soil depths

Genome‐wide meta‐analysis and fine‐mapping prioritize potential causal variants and genes related to leprosy

Abstract To date, genome‐wide association studies (GWASs) have discovered 35 susceptible loci of leprosy; however, the cumulative effects of these loci can only partially explain the overall risk of leprosy, and the causal variants and genes within these loci remain unknown. Here, we conducted out new GWASs in two independent cohorts of 5007 cases and 4579 controls and then a meta‐analysis in these newly generated and multiple previously published (2277 cases and 3159 controls) datasets were performed. Three novel and 15 previously reported risk loci were identified from these datasets, increasing the known leprosy risk loci of explained genetic heritability from 23.0 to 38.5%. A comprehensive fine‐mapping analysis was conducted, and 19 causal variants and 14 causal genes were identified. Specifically, manual checking of epigenomic information from the Epimap database revealed that the causal variants were mainly located within the immune‐relevant or immune‐specific regulatory elements. Furthermore, by using gene‐set, tissue, and cell‐type enrichment analyses, we highlighted the key roles of immune‐related tissues and cells and implicated the PD‐1 signaling pathways in the pathogenetic mechanism of leprosy. Collectively, our study identified candidate causal variants and elucidated the potential regulatory and coding mechanisms for genes associated with leprosy

Analysis of <i>POFUT1</i> Gene Mutation in a Chinese Family with Dowling-Degos Disease

<div><p>Dowling-Degos disease (DDD) is an autosomal dominant genodermatosis characterized by reticular pigmented anomaly mainly affecting flexures. Though <i>KRT5</i> has been identified to be the causal gene of DDD, the heterogeneity of this disease was displayed: for example, <i>POFUT1</i> and <i>POGLUT1</i> were recently identified and confirmed to be additional pathogenic genes of DDD. To identify other DDD causative genes, we performed genome-wide linkage and exome sequencing analyses in a multiplex Chinese DDD family, in which the <i>KRT5</i> mutation was absent. Only a novel 1-bp deletion (c.246+5delG) in <i>POFUT1</i> was found. No other novel mutation or this deletion was detected in <i>POFUT1</i> in a second DDD family and a sporadic DDD case by Sanger Sequencing. The result shows the genetic-heterogeneity and complexity of DDD and will contribute to the further understanding of DDD genotype/phenotype correlations and to the pathogenesis of this disease.</p></div