Proteomic analysis of muscle between hybrid abalone and parental lines Haliotis gigantea Reeve and Haliotis discus hannai Ino

To understand the potential molecular mechanism of heterosis, protein expression patterns were compared from hybrids of Haliotis gigantea (G) and Haliotis discus hannai (D) using two-dimensional gel electrophoresis (2-DE) and matrix-assisted laser desorption/ionization time-of-flight/time-of-flight analyses. Expression differences were observed in muscle samples from the four groups with 673±21.0 stained spots for H. discus hannai ♀ × H. discus hannai ♂ (DD), 692±25.6 for H. gigantea ♀ × H. gigantea ♂ (GG), 679±16.2 for H. discus hannai ♀ × H. gigantea ♂ (DG) (F₁ hybrid) and 700±19 for H. gigantea ♀ × H. discus hannai ♂ (GD) (F₁ hybrid). Different 2-DE image muscle protein spots had a mirrored relationship between purebreds and the F₁ hybrid, suggesting that all stained spots in F₁ hybrid muscle were on 2-DEs from parents. DD and DG clustered together first, and then clustered with GD, whereas the distance of DD and GG was maximal according to hierarchical cluster analysis. We identified 136 differentially expressed protein spots involved in major biological processes, including energy metabolism and stress response. Most energy metabolism proteins were additive, and stress-induced proteins displayed additivity or over-dominance. In these 136 identified protein spots, hybrid offspring with additivity or over-dominance accounted for 68.38%. Data show that a proteomic approach can provide functional prediction of abalone interspecific hybridization.     

Inheritance of Diapause in Crosses between the Northernmost and the Southernmost Strains of the Asian Corn Borer Ostrinia furnacalis

The northernmost Harbin strain (N strain) of the Asian corn borer, Ostrinia furnacalis enters facultative diapause as fully grown larvae in response to short daylengths; whereas the southernmost Ledong strain (S strain) exhibits almost no diapause under the same light conditions. In the present study, we examined the inheritance of diapause induction and termination by crossing the two strains under a range of environmental conditions. The N strain showed a typical long-day response with a critical daylength of approximately15.88 h at 22°C, 15.72 h at 25°C and 15.14 h at 28°C, whereas the S strain showed a weak photoperiodic response at 22°C. The F1 progeny also showed a long-day response at 22, 25 and 28°C. However, the critical daylengths in S ♀ × N ♂ crosses were significantly longer than those in N ♀ × S ♂ crosses, indicating a sex linkage in the inheritance of diapause induction, with the male parent having more influence on the following F1 progeny. The incidence of diapause in S ♀ × N ♂ crosses was the same as in the N strain under short daylengths of 11-13 h, indicating that diapause trait is completely dominant over the non-diapause trait. The critical daylength in backcross to N was significantly longer than it was in backcross to S, showing a grandfather gene effect. Whether the inheritance of diapause fits an additive hypothesis or not was dependent on the rearing photoperiod, and the capacity for diapause was transmitted genetically in the manner of incomplete dominance. The duration of diapause for the reciprocal crosses under different diapause-terminating conditions showed different patterns of inheritance. The results in this study reveal that genetic and genetic-environmental interactions are involved in diapause induction and termination in O. furnacalis.     

Gender-Mediated Differences in Vertical Transmission of a Nucleopolyhedrovirus

With the development of sensitive molecular techniques for detection of low levels of asymptomatic pathogens, it becoming clear that vertical transmission is a common feature of some insect pathogenic viruses, and likely to be essential to virus survival when opportunities for horizontal transmission are unfavorable. Vertical transmission of Spodoptera exigua multiple nucleopolyhedrovirus (SeMNPV) is common in natural populations of S. exigua. To assess whether gender affected transgenerational virus transmission, four mating group treatments were performed using healthy and sublethally infected insects: i) healthy males (H♂)×healthy females (H♀); ii) infected males (I♂)×healthy females (H♀); iii) healthy males (H♂)×infected females (I♀) and iv) infected males (I♂)×infected females (I♀). Experimental adults and their offspring were analyzed by qPCR to determine the prevalence of infection. Both males and females were able to transmit the infection to the next generation, although female-mediated transmission resulted in a higher prevalence of infected offspring. Male-mediated venereal transmission was half as efficient as maternally-mediated transmission. Egg surface decontamination studies indicated that the main route of transmission is likely transovarial rather than transovum. Both male and female offspring were infected by their parents in similar proportions. Incorporating vertically-transmitted genotypes into virus-based insecticides could provide moderate levels of transgenerational pest control, thereby extending the periods between bioinsecticide applications.     

Successful Wide Hybridization and Introgression Breeding in a Diverse Set of Common Peppers (Capsicum annuum) Using Different Cultivated Ají (C. baccatum) Accessions as Donor Parents

Capsicum baccatum, commonly known as ají, has been reported as a source of variation for many different traits to improve common pepper (C. annuum), one of the most important vegetables in the world. However, strong interspecific hybridization barriers exist between them. A comparative study of two wide hybridization approaches for introgressing C. baccatum genes into C. annuum was performed: i) genetic bridge (GB) using C. chinense and C. frutescens as bridge species; and, ii) direct cross between C. annuum and C. baccatum combined with in vitro embryo rescue (ER). A diverse and representative collection of 18 accessions from four cultivated species of Capsicum was used, including C. annuum (12), C. baccatum (3), C. chinense (2), and C. frutescens (1). More than 5000 crosses were made and over 1000 embryos were rescued in the present study. C. chinense performed as a good bridge species between C. annuum and C. baccatum, with the best results being obtained with the cross combination [C. baccatum (♀) × C. chinense (♂)] (♀) × C. annuum (♂), while C. frutescens gave poor results as bridge species due to strong prezygotic and postzygotic barriers. Virus-like-syndrome or dwarfism was observed in F₁ hybrids when both C. chinense and C. frutescens were used as female parents. Regarding the ER strategy, the best response was found in C. annuum (♀) × C. baccatum (♂) crosses. First backcrosses to C. annuum (BC₁s) were obtained according to the crossing scheme [C. annuum (♀) × C. baccatum (♂)] (♀) × C. annuum (♂) using ER. Advantages and disadvantages of each strategy are discussed in relation to their application to breeding programmes. These results provide breeders with useful practical information for the regular utilization of the C. baccatum gene pool in C. annuum breeding.     

Genome-wide association study identifies HLA-DP as a susceptibility gene for pediatric asthma in Asian populations

Asthma is a complex phenotype influenced by genetic and environmental factors. We conducted a genome-wide association study (GWAS) with 938 Japanese pediatric asthma patients and 2,376 controls. Single-nucleotide polymorphisms (SNPs) showing strong associations (P<1×10⁻⁸) in GWAS were further genotyped in an independent Japanese samples (818 cases and 1,032 controls) and in Korean samples (835 cases and 421 controls). SNP rs987870, located between HLA-DPA1 and HLA-DPB1, was consistently associated with pediatric asthma in 3 independent populations (P _combined = 2.3×10⁻¹⁰, odds ratio [OR] = 1.40). HLA-DP allele analysis showed that DPA1*0201 and DPB1*0901, which were in strong linkage disequilibrium, were strongly associated with pediatric asthma (DPA1*0201: P = 5.5×10⁻¹⁰, OR = 1.52, and DPB1*0901: P = 2.0×10⁻⁷, OR = 1.49). Our findings show that genetic variants in the HLA-DP locus are associated with the risk of pediatric asthma in Asian populations.     

High-density SNP mapping of the HLA region identifies multiple independent susceptibility loci associated with selective IgA deficiency

Selective IgA deficiency (IgAD; serum IgA<0.07 g/l) is the most common form of human primary immune deficiency, affecting approximately 1∶600 individuals in populations of Northern European ancestry. The polygenic nature of IgAD is underscored by the recent identification of several new risk genes in a genome-wide association study. Among the characterized susceptibility loci, the association with specific HLA haplotypes represents the major genetic risk factor for IgAD. Despite the robust association, the nature and location of the causal variants in the HLA region remains unknown. To better characterize the association signal in this region, we performed a high-density SNP mapping of the HLA locus and imputed the genotypes of common HLA-B, -DRB1, and -DQB1 alleles in a combined sample of 772 IgAD patients and 1,976 matched controls from 3 independent European populations. We confirmed the complex nature of the association with the HLA locus, which is the result of multiple effects spanning the entire HLA region. The primary association signal mapped to the HLA-DQB1*02 allele in the HLA Class II region (combined P = 7.69×10⁻⁵⁷; OR = 2.80) resulting from the combined independent effects of the HLA-B*0801-DRB1*0301-DQB1*02 and -DRB1*0701-DQB1*02 haplotypes, while additional secondary signals were associated with the DRB1*0102 (combined P = 5.86×10⁻¹⁷; OR = 4.28) and the DRB1*1501 (combined P = 2.24×10⁻³⁵; OR = 0.13) alleles. Despite the strong population-specific frequencies of HLA alleles, we found a remarkable conservation of these effects regardless of the ethnic background, which supports the use of large multi-ethnic populations to characterize shared genetic association signals in the HLA region. We also provide evidence for the location of association signals within the specific extended haplotypes, which will guide future sequencing studies aimed at characterizing the precise functional variants contributing to disease pathogenesis.     

GWAS identifies novel susceptibility loci on 6p21.32 and 21q21.3 for hepatocellular carcinoma in chronic hepatitis B virus carriers

Genome-wide association studies (GWAS) have recently identified KIF1B as susceptibility locus for hepatitis B virus (HBV)–related hepatocellular carcinoma (HCC). To further identify novel susceptibility loci associated with HBV–related HCC and replicate the previously reported association, we performed a large three-stage GWAS in the Han Chinese population. 523,663 autosomal SNPs in 1,538 HBV–positive HCC patients and 1,465 chronic HBV carriers were genotyped for the discovery stage. Top candidate SNPs were genotyped in the initial validation samples of 2,112 HBV–positive HCC cases and 2,208 HBV carriers and then in the second validation samples of 1,021 cases and 1,491 HBV carriers. We discovered two novel associations at rs9272105 (HLA-DQA1/DRB1) on 6p21.32 (OR = 1.30, P = 1.13×10⁻¹⁹) and rs455804 (GRIK1) on 21q21.3 (OR = 0.84, P = 1.86×10⁻⁸), which were further replicated in the fourth independent sample of 1,298 cases and 1,026 controls (rs9272105: OR = 1.25, P = 1.71×10⁻⁴; rs455804: OR = 0.84, P = 6.92×10⁻³). We also revealed the associations of HLA-DRB1*0405 and 0901*0602, which could partially account for the association at rs9272105. The association at rs455804 implicates GRIK1 as a novel susceptibility gene for HBV–related HCC, suggesting the involvement of glutamate signaling in the development of HBV–related HCC.     

HLA-DRB1-DQB1 haplotypes confer susceptibility and resistance to multiple sclerosis in Sardinia

Introduction

Genetic predisposition to multiple sclerosis (MS) in Sardinia (Italy) has been associated with five DRB1*-DQB1* haplotypes of the human leukocyte antigen (HLA). Given the complexity of these associations, an in-depth re-analysis was performed with the specific aims of confirming the haplotype associations; establishing the independence of the associated haplotypes; and assessing patients'' genotypic risk of developing MS.

Methods and Results

A transmission disequilibrium test (TDT) of the DRB1*-DQB1* haplotypes in 943 trio families, confirmed a higher than expected transmission rate (over-transmission) of the *13:03-*03:01 (OR = 2.9, P = 7.6×10⁻³), *04:05-*03:01 (OR = 2.4, P = 4.4×10⁻⁶) and *03:01-*02:01 (OR = 2.1, P = 1.0×10⁻¹⁵) haplotype. In contrast, the *16:01-*05:02 (OR = 0.5, P = 5.4×10⁻¹¹) and the *15:02-*06:01 (OR = 0.3, P = 1.5×10⁻³) haplotypes exhibited a lower than expected transmission rate (under-transmission). The independence of the transmission of each positively and negatively associated haplotype was confirmed relative to all positively associated haplotypes, and to the negatively associated *16:01-*05:02 haplotype. In patients, carriage of two predisposing haplotypes, or of protective haplotypes, respectively increased or decreased the patient''s risk of developing MS. The risk of MS followed a multiplicative model of genotypes, which was, in order of decreasing ORs: *04:05-*0301/*03:01-*02:01 (OR = 4.5); *03:01-*02:01/*03:01-*02:01 (OR = 4.1); and the *16:01-*05:02/*16:01-*0502 (OR = 0.2) genotypes. Analysis of DRB1 and DQB1 protein chain residues showed that the Val/Gly residue at position 86 of the DRB1 chain was the only difference between the protective *16:01- *15:02 alleles and the predisposing *15:01 one. Similarly, the Ala/Val residue at position 38 of the DQB1 chain differentiated the positively associated *06:02 allele and the negatively associated *05:02, *06:01 alleles.

Conclusions

These findings show that the association of specific, independent DRB1*-DQB1* haplotypes confers susceptibility or resistance to MS in the MS-prone Sardinian population. The data also supports a functional role for specific residues of the DRB1 and DQB1 proteins in predisposing patients to MS.     

Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals

Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10⁻⁸–1.2×10⁻⁴³). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3×10⁻⁴). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = 4.3×10⁻³, n = 22,044), increased triglycerides (p = 2.6×10⁻¹⁴, n = 93,440), increased waist-to-hip ratio (p = 1.8×10⁻⁵, n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4×10⁻³, n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p = 4.5×10⁻¹³, n = 96,748) and decreased BMI (p = 1.4×10⁻⁴, n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance.     

Beneficial effects of resistance exercise on glycemic control are not further improved by protein ingestion

Purpose

To investigate the mechanisms underpinning modifications in glucose homeostasis and insulin sensitivity 24 h after a bout of resistance exercise (RE) with or without protein ingestion.

Methods

Twenty-four healthy males were assigned to a control (CON; n = 8), exercise (EX; n = 8) or exercise plus protein condition (EX+PRO; n = 8). Muscle biopsy and blood samples were obtained at rest for all groups and immediately post-RE (75% 1RM, 8×10 repetitions of leg-press and extension exercise) for EX and EX+PRO only. At 24 h post-RE (or post-resting biopsy for CON), a further muscle biopsy was obtained. Participants then consumed an oral glucose load (OGTT) containing 2 g of [U-¹³C] glucose during an infusion of 6, 6-[²H₂] glucose. Blood samples were obtained every 10 min for 2 h to determine glucose kinetics. EX+PRO ingested an additional 25 g of intact whey protein with the OGTT. A final biopsy sample was obtained at the end of the OGTT.

Results

Fasted plasma glucose and insulin were similar for all groups and were not different immediately post- and 24 h post-RE. Following RE, muscle glycogen was 26±8 and 19±6% lower in EX and EX+PRO, respectively. During OGTT, plasma glucose AUC was lower for EX and EX+PRO (75.1±2.7 and 75.3±2.8 mmol·L⁻¹∶120 min, respectively) compared with CON (90.6±4.1 mmol·L⁻¹∶120 min). Plasma insulin response was 13±2 and 21±4% lower for EX and CON, respectively, compared with EX+PRO. Glucose disappearance from the circulation was ∼12% greater in EX and EX+PRO compared with CON. Basal 24 h post-RE and insulin-stimulated PAS-AS160/TBC1D4 phosphorylation was greater for EX and EX+PRO.

Conclusions

Prior RE improves glycemic control and insulin sensitivity through an increase in the rate at which glucose is disposed from the circulation. However, co-ingesting protein during a high-glucose load does not augment this response at 24 h post-exercise in healthy, insulin-sensitive individuals.     

Mitochondrial DNA haplogroup background affects LHON, but not suspected LHON, in Chinese patients

Recent studies have shown that mtDNA background could affect the clinical expression of Leber hereditary optic neuropathy (LHON). We analyzed the mitochondrial DNA (mtDNA) variation of 304 Chinese patients with m.11778G>A (sample #1) and of 843 suspected LHON patients who lack the three primary mutations (sample #2) to discern mtDNA haplogroup effect on disease onset. Haplogroup frequencies in the patient group was compared to frequencies in the general Han Chinese population (n = 1,689; sample #3). The overall matrilineal composition of the suspected LHON population resembles that of the general Han Chinese population, suggesting no association with mtDNA haplogroup. In contrast, analysis of these LHON patients confirms mtDNA haplogroup effect on LHON. Specifically, the LHON sample significantly differs from the general Han Chinese and suspected LHON populations by harboring an extremely lower frequency of haplogroup R9, in particular of its main sub-haplogroup F (#1 vs. #3, P-value = 1.46×10⁻¹⁷, OR = 0.051, 95% CI: 0.016–0.162; #1 vs. #2, P-value = 4.44×10⁻¹⁷, OR = 0.049, 95% CI: 0.015–0.154; in both cases, adjusted P-value <10⁻⁵) and higher frequencies of M7b (#1 vs. #3, adjusted P-value = 0.001 and #1 vs. #2, adjusted P-value = 0.004). Our result shows that mtDNA background affects LHON in Chinese patients with m.11778G>A but not suspected LHON. Haplogroup F has a protective effect against LHON, while M7b is a risk factor.     

A survey of linyphiid spiders from Xishuangbanna,Yunnan Province,China (Araneae,Linyphiidae)

Eight new genera and 30 new species are described: Cirrosus gen. n. (type species Cirrosus atrocaudatus sp. n. (♂♀)), Conglin gen. n. (type species Conglin personatus sp. n. (♀)), Curtimeticus gen. n. (type species Curtimeticus nebulosus sp. n. (♂)), Gladiata gen. n. (type species Gladiata fengli sp. n. (♂)), Glebala gen. n. (type species Glebala aspera sp. n. (♂)), Glomerosus gen. n. (type species Glomerosus lateralis sp. n. (♂)), Smerasia gen. n. (type species Smerasia obscurus sp. n. (♂♀)), Vittatus gen. n. (type species Vittatus fencha sp. n. (♂♀)); Batueta cuspidata sp. n. (♂♀), Capsulia laciniosa sp. n. (♂), Dactylopisthes separatus sp. n. (♀), Gongylidiellum bracteatum sp. n. (♀), Houshenzinus xiaolongha sp. n. (♂♀), Laogone bai sp. n. (♂), Laogone lunata sp. n. (♂♀), Maro bulbosus sp. n. (♀), Nasoonaria circinata sp. n. (♂♀), Neriene circifolia sp. n. (♂♀), Oedothorax biantu sp. n. (♀), Oilinyphia hengji sp. n. (♂♀), Paikiniana furcata sp. n. (♂♀), Parameioneta bishou sp. n. (♂♀), Parameioneta multifida sp. n. (♂♀), Parameioneta tricolorata sp. n. (♂♀), Tapinopa undata sp. n. (♂), Theoa bidentata sp. n. (♂♀), Theoa vesica sp. n. (♂♀), Vittatus bian sp. n. (♂♀), Vittatus latus sp. n. (♂♀), Vittatus pan sp. n. (♂♀). The male of Kaestneria bicultrata Chen & Yin, 2000 and the females of Asiagone perforata Tanasevitch, 2014 and Batueta similis Wunderlich & Song, 1995 are described for the first time; photos of Bathyphantes paracymbialis Tanasevitch, 2014 are provided.     

Four new spider species of the family Theridiosomatidae (Arachnida,Araneae) from caves in Laos

Four new species of the spider family Theridiosomatidae are described from caves in Laos: Alaria cavernicola sp. n. (♂♀), A. navicularis sp. n., (♂♀) A. bicornis sp. n. (♂♀), Chthonopes thakekensis sp. n. (♀). Diagnoses and illustrations for all new taxa are given. All holotypes are deposited in the Senckenberg Research Institute in Frankfurt am Main, Germany (SMF).     

A comprehensive evaluation of potential lung function associated genes in the SpiroMeta general population sample

Rationale

Lung function measures are heritable traits that predict population morbidity and mortality and are essential for the diagnosis of chronic obstructive pulmonary disease (COPD). Variations in many genes have been reported to affect these traits, but attempts at replication have provided conflicting results. Recently, we undertook a meta-analysis of Genome Wide Association Study (GWAS) results for lung function measures in 20,288 individuals from the general population (the SpiroMeta consortium).

Objectives

To comprehensively analyse previously reported genetic associations with lung function measures, and to investigate whether single nucleotide polymorphisms (SNPs) in these genomic regions are associated with lung function in a large population sample.

Methods

We analysed association for SNPs tagging 130 genes and 48 intergenic regions (+/−10 kb), after conducting a systematic review of the literature in the PubMed database for genetic association studies reporting lung function associations.

Results

The analysis included 16,936 genotyped and imputed SNPs. No loci showed overall significant association for FEV₁ or FEV₁/FVC traits using a carefully defined significance threshold of 1.3×10⁻⁵. The most significant loci associated with FEV₁ include SNPs tagging MACROD2 (P = 6.81×10⁻⁵), CNTN5 (P = 4.37×10⁻⁴), and TRPV4 (P = 1.58×10⁻³). Among ever-smokers, SERPINA1 showed the most significant association with FEV₁ (P = 8.41×10⁻⁵), followed by PDE4D (P = 1.22×10⁻⁴). The strongest association with FEV₁/FVC ratio was observed with ABCC1 (P = 4.38×10⁻⁴), and ESR1 (P = 5.42×10⁻⁴) among ever-smokers.

Conclusions

Polymorphisms spanning previously associated lung function genes did not show strong evidence for association with lung function measures in the SpiroMeta consortium population. Common SERPINA1 polymorphisms may affect FEV₁ among smokers in the general population.     

Mycobacterium tuberculosis complex mycobacteria as amoeba-resistant organisms

Background

Most environmental non-tuberculous mycobacteria have been demonstrated to invade amoebal trophozoites and cysts, but such relationships are largely unknown for members of the Mycobacterium tuberculosis complex. An environmental source has been proposed for the animal Mycobacterium bovis and the human Mycobacterium canettii.

Methodology/Principal Findings

Using optic and electron microscopy and co-culture methods, we observed that 89±0.6% of M. canettii, 12.4±0.3% of M. tuberculosis, 11.7±2% of M. bovis and 11.2±0.5% of Mycobacterium avium control organisms were phagocytized by Acanthamoeba polyphaga, a ratio significantly higher for M. canettii (P = 0.03), correlating with the significantly larger size of M. canetti organisms (P = 0.035). The percentage of intraamoebal mycobacteria surviving into cytoplasmic vacuoles was 32±2% for M. canettii, 26±1% for M. tuberculosis, 28±2% for M. bovis and 36±2% for M. avium (P = 0.57). M. tuberculosis, M. bovis and M. avium mycobacteria were further entrapped within the double wall of <1% amoebal cysts, but no M. canettii organisms were observed in amoebal cysts. The number of intracystic mycobacteria was significantly (P = 10⁻⁶) higher for M. avium than for the M. tuberculosis complex, and sub-culturing intracystic mycobacteria yielded significantly more (P = 0.02) M. avium organisms (34×10⁴ CFU/mL) than M. tuberculosis (42×10¹ CFU/mL) and M. bovis (35×10¹ CFU/mL) in the presence of a washing fluid free of mycobacteria. Mycobacteria survived in the cysts for up to 18 days and cysts protected M. tuberculosis organisms against mycobactericidal 5 mg/mL streptomycin and 2.5% glutaraldehyde.

Conclusions/Significance

These data indicate that M. tuberculosis complex organisms are amoeba-resistant organisms, as previously demonstrated for non-tuberculous, environmental mycobacteria. Intercystic survival of tuberculous mycobacteria, except for M. canettii, protect them against biocides and could play a role in their life cycle.     

Genome-wide scan identifies TNIP1, PSORS1C1, and RHOB as novel risk loci for systemic sclerosis

Systemic sclerosis (SSc) is an orphan, complex, inflammatory disease affecting the immune system and connective tissue. SSc stands out as a severely incapacitating and life-threatening inflammatory rheumatic disease, with a largely unknown pathogenesis. We have designed a two-stage genome-wide association study of SSc using case-control samples from France, Italy, Germany, and Northern Europe. The initial genome-wide scan was conducted in a French post quality-control sample of 564 cases and 1,776 controls, using almost 500 K SNPs. Two SNPs from the MHC region, together with the 6 loci outside MHC having at least one SNP with a P<10⁻⁵ were selected for follow-up analysis. These markers were genotyped in a post-QC replication sample of 1,682 SSc cases and 3,926 controls. The three top SNPs are in strong linkage disequilibrium and located on 6p21, in the HLA-DQB1 gene: rs9275224, P = 9.18×10⁻⁸, OR = 0.69, 95% CI [0.60–0.79]; rs6457617, P = 1.14×10⁻⁷ and rs9275245, P = 1.39×10⁻⁷. Within the MHC region, the next most associated SNP (rs3130573, P = 1.86×10⁻⁵, OR = 1.36 [1.18–1.56]) is located in the PSORS1C1 gene. Outside the MHC region, our GWAS analysis revealed 7 top SNPs (P<10⁻⁵) that spanned 6 independent genomic regions. Follow-up of the 17 top SNPs in an independent sample of 1,682 SSc and 3,926 controls showed associations at PSORS1C1 (overall P = 5.70×10⁻¹⁰, OR:1.25), TNIP1 (P = 4.68×10⁻⁹, OR:1.31), and RHOB loci (P = 3.17×10⁻⁶, OR:1.21). Because of its biological relevance, and previous reports of genetic association at this locus with connective tissue disorders, we investigated TNIP1 expression. A markedly reduced expression of the TNIP1 gene and also its protein product were observed both in lesional skin tissue and in cultured dermal fibroblasts from SSc patients. Furthermore, TNIP1 showed in vitro inhibitory effects on inflammatory cytokine-induced collagen production. The genetic signal of association with TNIP1 variants, together with tissular and cellular investigations, suggests that this pathway has a critical role in regulating autoimmunity and SSc pathogenesis.     

Taxonomic notes on the genus Eupoa ?abka, 1985 (Arachnida,Araneae, Salticidae)

The south-east Asian genus Eupoa is redescribed and diagnosed. Seven new species are diagnosed, described and illustrated: E. daklak sp. n. (♀) from Viet-Nam; E. lehtineni sp. n. (♂♀) from India, Thailand and Viet-Nam; E. lobli sp. n. (♂) from Malaysia; E. pappi sp. n. (♂) from Thailand; E. pulchella sp. n.(♂) from Thailand; E. schwendingeri sp. n. (♂♀) from Thailand; and E. thailandica sp. n. (♂♀) from Thailand. Eupoa prima Żabka, 1985 and E. yunnanensis Peng & Kim, 1997 are redescribed and illustrated on the basis of type and/or newly collected materials. The female of E. yunnanensis Peng & Kim, 1997 is found and described for the first time.