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Purpose The clinical diagnosis of pulmonary sarcoidosis is based on the presence of noncaseating granulomas in an appropriate clinical setting with either bilateral hilar adenopathy and/or parenchymal infiltrates. Lymphocytosis with an increased CD4/CD8 T cell ratio in bronchoalveolar lavage fluid is supportive. We evaluated the diagnostic accuracy of a predictive binary logistic regression model in sarcoidosis based on sex, age, and bronchoalveolar lavage fluid cell profile with and without the inclusion of HLA-DR.sup.+ CD8.sup.+ T cells and natural killer T-cell fractions. Methods A retrospective analysis of differential cell counts and lymphocyte phenotypes by flow cytometry in bronchoalveolar lavage was performed in 183 patients investigated for possible diffuse parenchymal lung disease. A logistic regression model with age, sex, lymphocyte fraction, eosinophils, and CD4/CD8 ratio in bronchoalveolar lavage fluid (basic model) was compared with a final model, which also included fractions of HLA-DR.sup.+ CD8.sup.+ T cells and natural killer T cells. Diagnostic accuracy of the two models was assessed by receiver operating characteristic (ROC) curves. Results The area under the ROC curve for the basic and final model was 0.898 [95 % confidence interval (CI) 0.852-0.945] and 0.937 (95 % CI 0.902-0.972), respectively, p = 0.008. Conclusions Assessment of HLA-DR.sup.+ CD8.sup.+ T cell and natural killer T-cell fractions may improve diagnostic accuracy and further strengthen the importance of bronchoalveolar lavage in the diagnostic workup of sarcoidosis. Electronic supplementary material The online version of this article (doi:10.1007/s00408-013-9527-8) contains supplementary material, which is available to authorized users., Author(s): A. Tøndell[sup.1] [sup.2] [sup.4] , A. D. Rø[sup.2] , A. Åsberg[sup.3] , M. Børset[sup.2] [sup.4] , T. Moen[sup.2] [sup.5] , M. Sue-Chu[sup.1] [sup.6] Author Affiliations: (1) Department of Thoracic [...]

Antinuclear antibodies (ANA) were demonstrated in 3 out of 10 Gordon setters with symmetrical lupoid onychodystrophy and in 5 out of 13 Gordon setters with black hair follicular dysplasia. Two dogs showed both symmetrical lupoid onychodystrophy and black hair follicular dysplasia, and one of these was ANA positive. The results suggest that symmetrical lupoid onychodystrophy and black hair follicular dysplasia in the Gordon setter might be autoimmune diseases that are pathogenetically related, which might indicate a common genetic predisposition.

Ion milling has been used to convert molecular beam epitaxy vacancy-doped Cd[sub x]Hg[sub 1-x]Te from p- to n-type. Electron beam induced current and remote electron beam induced current (REBIC) measurements have been performed to study the pn junction depth and lateral extension dependence on the milling time, milling current, and vacancy concentration. The conversion depth is linear with the milling time and current and inversely proportional to the vacancy concentration in layers thinner than 10 μm. This shows that filling of Hg vacancies in this region during conversion is limited by the rate of supply of extra Hg from the milling. The lateral extension also increases linearly with the milling time, the ratio of the lateral extension to the depth being ∼0.5. One can therefore use REBIC on the top surface to determine the junction depth, which greatly simplifies the measurement and does not destroy the diodes. © 2002 American Institute of Physics. [ABSTRACT FROM AUTHOR]

In this study, we describe the development and characterization of the first high-density single nucleotide polymorphism ( SNP) genotyping array for rainbow trout. The SNP array is publically available from a commercial vendor (Affymetrix). The SNP genotyping quality was high, and validation rate was close to 90%. This is comparable to other farm animals and is much higher than previous smaller scale SNP validation studies in rainbow trout. High quality and integrity of the genotypes are evident from sample reproducibility and from nearly 100% agreement in genotyping results from other methods. The array is very useful for rainbow trout aquaculture populations with more than 40 900 polymorphic markers per population. For wild populations that were confounded by a smaller sample size, the number of polymorphic markers was between 10 577 and 24 330. Comparison between genotypes from individual populations suggests good potential for identifying candidate markers for populations' traceability. Linkage analysis and mapping of the SNPs to the reference genome assembly provide strong evidence for a wide distribution throughout the genome with good representation in all 29 chromosomes. A total of 68% of the genome scaffolds and contigs were anchored through linkage analysis using the SNP array genotypes, including ~20% of the genome assembly that has not been previously anchored to chromosomes. [ABSTRACT FROM AUTHOR]

OBJECTIVE Continuous beta-cell rest with diazoxide preserves residual endogenous insulin production in type 1 diabetes. However, side effects have hampered therapeutic usefulness. In a double-blind study, we tested whether lower, intermittent dosing of diazoxide had beneficial effects on insulin production, metabolic control, and autoimmunity markers in the absence of side effects. RESEARCH DESIGN AND METHODS Forty-one newly diagnosed type 1 diabetic patients were randomized to 6 months of treatment with placebo or 100 mg diazoxide at bedtime. A1C, C-peptide (fasting and glucagon stimulated), and FoxP3(+) regulatory T-cells (Tregs) were measured. Patients were followed for 6 months after intervention. RESULTS Of six dropouts, three were due to perceived side effects; one subject in the diazoxide group experienced rash, another dizziness, and one in the placebo group sleep disturbance. Adverse effects in others were absent. Diazoxide treatment reduced A1C from 8.6% at baseline to 6.0% at 6 months and 6.5% at 12 months. Corresponding A1C value in the placebo arm were 8.3, 7.3, and 7.5% (P < 0.05 for stronger reduction in the diazoxide group). Fasting and stimulated C-peptide decreased during 12 months similarly in both arms (mean -0.30 and -0.18 nmol/l in the diazoxide arm and -0.08 and -0.09 nmol/l in the placebo arm). The proportion of Tregs was similar in both arms and remained stable during intervention but was significantly lower compared with nondiabetic subjects. CONCLUSIONS Six months of low-dose diazoxide was without side effects and did not measurably affect insulin production but was associated with improved metabolic control. [ABSTRACT FROM AUTHOR]

We report a case of aberrant expression of the T cell antigen CD8 in a patient with B cell chronic lymphocytic leukaemia (B-CLL). A 62-year-old Caucasian female with several enlarged lymph nodes and suspected to have B-CLL was referred to our laboratory for routine immunophenotyping. Peripheral blood cell count showed moderate leucocytosis without other abnormalities. The dual-colour flow cytometric analysis showed a typical B-CLL phenotype (CD45 +, CD19 +, κ +, λ -, CD20 +, CD23 +, IgM +, HLA-DR +, CD5/CD19 +, CD3 -). In addition, aberrant expression of the T cell marker CD8 was found, present on approximately 64% of the leukemic cells. This is a rare even, the significance and nature of this aberration has not yet been fully determined. In this case, our patient had a rapid response to treatment with a remarkable reduction in the number of leukemic cells only two weeks after beginning treatment. [ABSTRACT FROM AUTHOR]

In order to find potential correlations between HLA class II alleles and anti-SS-A,-SS-B, -Sm and anti-snRNP responses among Norwegian patients with systemic lupus erythematosus (SLE), HLA-DRB1, -DRB3*0101, -DQA1 and -DQB1 alleles were determined by DNA typing 50 patients and 108 controls. HLA distributions were analysed in the following autoantibody subgroups: anti-SS-A with -SS-B, anti-SS-A without -SS-B, anti-snRNP without -Sm, anti-SS-A without -snRNP and anti-snRNP without -SS-A. The autoantibodies were detected by EIA (enzyme immunuassay). Patients with anti-SS-A and -SS-B had significantly increased frequencies of DRB1*03, DRB3*0101, DQA1*0501, DQB1*0201 (in linkage disequilibrium) versus controls and versus patients without anti-SS-A and -SS-B. No differences in HLA distribution were found when the group with anti-SS-A alone was compared to the group with anti-SS-A and concomitant -SS-B. Comparing the groups with and without anti-SS-A and -SS-B, the highest RR were found for the alleles DRB1*03, DRB3*0101, DQB1*0501, DQB1*0201 (in linkage disequilibrium) with RR: 16.8, 5.0, 19.6, 10.3, respectively, P < 0.05). RR for DQw2/DQw6 heterozygotes was 3.5 (Ns.), and RR for cases having DQα molecules with glutamine in position 34 and DQβ molecules with leucine in position 26 on both chains was 6.3 (P < 0.05). No HLA associations were observed in the group with anti-snRNP without concomitant -Sm or without concomitant -SS-A. These results show that production of anti-SS-A and -SS-B is associated to the HLA alleles DRB1*03, DRB3*0101, DQA1*0501, DQB1*0201, and that this haplotype shows stronger correlation to these responses than DQw2/DQw6 heterozygosity or HLA molecules having glutamine in position 34 (DQα) and leucine in position 26 (DQβ). The failure to observe any correlation with DRB1*15,16 (DP,2) in the group with anti-SS-A alone may demonstrate ethnic differences concerning this response. The failure to identify any HLA associations for the anti-snRNP response may reflect the heterogeneity of the molecules that constitute this antigen. [ABSTRACT FROM AUTHOR]

Polyclonal activation of B-lymphocytes accompanies many retroviral infections. Friend derived murine immunosuppressive virus (Fd-MIV) is a non-defective murine retrovirus which was isolated from T-helper cells from mice infected with the acute transforming retrovirus Friend leukaemia complex (FLC). In contrast to FLC. Fd-MIV does not induce acute transformation of lymphoid and erythroid cells but causes immunosuppression and lymphadenopathy in adult NMRI mice. The effect of Fd-MIV infection on B-lymphocytes was studied. Fd-MIV infection led to a persistent hypergammaglobulinemy with a significant increase in the level of circulating IgG. IgM and immune complexes. In the spleen and lymph nodes. B-lymphocyte proliferation was found. Parallel to the development of hypergammaglobulinemy. autoantibodies to a variety of nuclear and other autoantigens was detected. In conclusion, the Fd-MIV infection leads to a B-lymphocyte dysfunction that has many parallels with AIDS. Furthermore, the Fd- MIV infection seems to represent an example of an autoimmune condition caused by an exogenous infectious agent. [ABSTRACT FROM AUTHOR]

Introduction: Mazes are linguistic disfluencies such as filled pauses, repetitions, or revisions of grammatical, phonological, or lexical aspects of words that do not contribute to the meaning of a sentence. Bilingual children are believed to increase the numbers of mazes in their native or heritage language, the minority language, as they become more proficient in the second language, the societal language. Mazes may increase over time in bilingual Spanish-speaking children as they become more proficient in English, the societal language in the United States. However, current studies have not been conducted longitudinally. Higher rates of mazes in the heritage language over time may be due to changes in language proficiency and differences in processing demands in the children as they use more complex language. Moreover, children with developmental language disorder (DLD) can also present higher rates of mazes than children with typical language. Heritage speakers, therefore, are at risk of being misdiagnosed with DLD due to high rates of mazes. Currently, we do not understand what the typical rates of mazes are as heritage speakers get older and become more proficient in the societal language. The current study examined the type and frequency of Spanish mazes longitudinally in a group of 22 Spanish heritage speakers with and without DLD and determined the changes over time., Methods: A total of 11 children with typical language development (TLD) and 11 with DLD participated in this 5-year longitudinal study. Using a wordless picture book, children completed a retelling task in Spanish during the spring of each academic year (PK to 3rd grade) as part of a 5-h testing battery. Narratives were transcribed and coded for types of mazes (filled pauses, repetitions, grammatical revisions, phonological revisions, and lexical revisions)., Results and Conclusion: The results of the study indicate that TLD children increased their overall percentage of mazed words and utterances. The opposite pattern was observed in the DLD group, which decreased their percentage of mazed words and utterances. In contrast, both groups demonstrated a decrease in repetitions in first grade and an increase in third grade. Additionally, the TLD and DLD children decreased in the percentage of fillers in first grade and then increased in the third grade. Results suggest that maze use is quite variable in heritage speakers and does not necessarily differentiate groups. Clinicians should not rely solely on mazes to determine ability status. In fact, high use of mazes can reflect typical language development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Martinez-Nieto, Moen, Pierce and Restrepo.)

Flavobacterium psychrophilum is the causative agent of bacterial cold-water disease (CWBD) and rainbow trout fry syndrome (RTFS), which affect salmonids. To better understand this pathogen and its interaction with the host during infection, including to support the development of resistant breeds and new vaccines and treatments, there is a pressing need for reliable and reproducible immersion challenge models that more closely mimic natural routes of infection. The aim of this present study was to evaluate a challenge model developed previously for rainbow trout for use in Atlantic salmon. First, preliminary challenges were conducted in Atlantic salmon (n = 120) and rainbow trout (n = 80) fry using two F. psychrophilum isolates collected from each fish species, respectively; fish had been pretreated with 200 mg/L hydrogen peroxide for 1 h. Thereafter, the main challenge was performed for just one F. psychrophilum isolate for each species (at 2 × 10 7  CFU/mL) but using larger cohorts (Atlantic salmon: n = 1187; rainbow trout: n = 2701). Survival in the main challenge was 81.2% in Atlantic salmon (21 days post-challenge) and 45.3% in rainbow trout (31 days post-challenge). Mortalities progressed similarly during the preliminary and main challenges for both species, demonstrating the reproducibility of this model. This is the first immersion challenge model of F. psychrophilum to be developed successfully for Atlantic salmon., (© 2022 The Authors. Journal of Fish Diseases published by John Wiley & Sons Ltd.)

Background: Streptococcosis is a major bacterial disease in Nile tilapia that is caused by Streptococcus agalactiae infection, and development of resistant strains of Nile tilapia represents a sustainable approach towards combating this disease. In this study, we performed a controlled disease trial on 120 full-sib families to (i) quantify and characterize the potential of genomic selection for survival to S. agalactiae infection in Nile tilapia, and (ii) identify the best genomic model and the optimal density of single nucleotide polymorphisms (SNPs) for this trait., Methods: In total, 40 fish per family (15 fish intraperitoneally injected and 25 fish as cohabitants) were used in the challenge test. Mortalities were recorded every 3 h for 35 days. After quality control, genotypes (50,690 SNPs) and phenotypes (0 for dead and 1 for alive) for 2472 cohabitant fish were available. Genetic parameters were obtained using various genomic selection models (genomic best linear unbiased prediction (GBLUP), BayesB, BayesC, BayesR and BayesS) and a traditional pedigree-based model (PBLUP). The pedigree-based analysis used a deep 17-generation pedigree. Prediction accuracy and bias were evaluated using five replicates of tenfold cross-validation. The genomic models were further analyzed using 10 subsets of SNPs at different densities to explore the effect of pruning and SNP density on predictive accuracy., Results: Moderate estimates of heritabilities ranging from 0.15 ± 0.03 to 0.26 ± 0.05 were obtained with the different models. Compared to a pedigree-based model, GBLUP (using all the SNPs) increased prediction accuracy by 15.4%. Furthermore, use of the most appropriate Bayesian genomic selection model and SNP density increased the prediction accuracy up to 71%. The 40 to 50 SNPs with non-zero effects were consistent for all BayesB, BayesC and BayesS models with respect to marker id and/or marker locations., Conclusions: These results demonstrate the potential of genomic selection for survival to S. agalactiae infection in Nile tilapia. Compared to the PBLUP and GBLUP models, Bayesian genomic models were found to boost the prediction accuracy significantly.

Background: One objective of this study was to identify putative quantitative trait loci (QTL) that affect indicator phenotypes for growth, nitrogen, and carbon metabolism in muscle, liver, and adipose tissue, and for feed efficiency. Another objective was to perform an RNAseq analysis (184 fish from all families), to identify genes that are associated with carbon and nitrogen metabolism in the liver. The material consisted of a family experiment that was performed in freshwater and included 2281 individuals from 23 full-sib families. During the 12-day feed conversion test, families were randomly allocated to family tanks (50 fish per tank and 2 tanks per family) and fed a fishmeal-based diet labeled with the stable isotopes 15 N and 13 C at inclusion levels of 2 and 1%, respectively., Results: Using a linear mixed-model algorithm, a QTL for pre-smolt growth was identified on chromosome 9 and a QTL for carbon metabolism in the liver was identified on chromosome 12 that was closely related to feed conversion ratio on a tank level. For the indicators of feed efficiency traits that were derived from the stable isotope ratios ( 15 N and 13 C) of muscle tissue and growth, no convincing QTL was detected, which suggests that these traits are polygenic. The transcriptomic analysis showed that high carbon and nitrogen metabolism was associated with individuals that convert protein from the feed more efficiently, primarily due to higher expression of the proteasome, lipid, and carbon metabolic pathways in liver. In addition, we identified seven transcription factors that were associated with carbon and nitrogen metabolism and located in the identified QTL regions., Conclusions: Analyses revealed one QTL associated with pre-smolt growth and one QTL for carbon metabolism in the liver. Both of these traits are associated with feed efficiency. However, more accurate mapping of the putative QTL will require a more diverse family material. In this experiment, fish that have a high carbon and nitrogen metabolism in the liver converted protein from the feed more efficiently, potentially because of a higher expression of the proteasome, lipid, and carbon metabolic pathways in liver. Within the QTL regions, we detected seven transcription factors that were associated with carbon and nitrogen metabolism.

Background: Understanding genetic architecture is essential for determining how traits will change in response to evolutionary processes such as selection, genetic drift and/or gene flow. In Atlantic salmon, age at maturity is an important life history trait that affects factors such as survival, reproductive success, and growth. Furthermore, age at maturity can seriously impact aquaculture production. Therefore, characterizing the genetic architecture that underlies variation in age at maturity is of key interest., Results: Here, we refine our understanding of the genetic architecture for age at maturity of male Atlantic salmon using a genome-wide association study of 11,166 males from a single aquaculture strain, using imputed genotypes at 512,397 single nucleotide polymorphisms (SNPs). All individuals were genotyped with a 50K SNP array and imputed to higher density using parents genotyped with a 930K SNP array and pedigree information. We found significant association signals on 28 of 29 chromosomes (P-values: 8.7 × 10 -133 -9.8 × 10 -8 ), including two very strong signals spanning the six6 and vgll3 gene regions on chromosomes 9 and 25, respectively. Furthermore, we identified 116 independent signals that tagged 120 candidate genes with varying effect sizes. Five of the candidate genes found here were previously associated with age at maturity in other vertebrates, including humans., Discussion: These results reveal a mixed architecture of large-effect loci and a polygenic component that consists of multiple smaller-effect loci, suggesting a more complex genetic architecture of Atlantic salmon age at maturity than previously thought. This more complex architecture will have implications for selection on this key trait in aquaculture and for management of wild salmon populations.

Red coloration of muscle tissue (flesh) is a unique trait in several salmonid genera, including Atlantic salmon. The color results from dietary carotenoids deposited in the flesh, whereas the color intensity is affected both by diet and genetic components. Herein we report on a genome-wide association study (GWAS) to identify genetic variation underlying this trait. Two SNPs on ssa26 showed strong associations to the flesh color in salmon. Two genes known to be involved in carotenoid metabolism were located in this QTL- region: beta-carotene oxygenase 1 (bco1) and beta-carotene oxygenase 1 like (bco1l). To determine whether flesh color variation is caused by one, or both, of these genes, functional studies were carried out including mRNA and protein expression in fish with red and pale flesh color. The catalytic abilities of these two genes were also tested with different carotenoids. Our results suggest bco1l to be the most likely gene to explain the flesh color variation observed in this population.

Males and females often differ in their fitness optima for shared traits that have a shared genetic basis, leading to sexual conflict. Morphologically differentiated sex chromosomes can resolve this conflict and protect sexually antagonistic variation, but they accumulate deleterious mutations. However, how sexual conflict is resolved in species that lack differentiated sex chromosomes is largely unknown. Here we present a chromosome-anchored genome assembly for rainbow trout (Oncorhynchus mykiss) and characterize a 55-Mb double-inversion supergene that mediates sex-specific migratory tendency through sex-dependent dominance reversal, an alternative mechanism for resolving sexual conflict. The double inversion contains key photosensory, circadian rhythm, adiposity and sex-related genes and displays a latitudinal frequency cline, indicating environmentally dependent selection. Our results show sex-dependent dominance reversal across a large autosomal supergene, a mechanism for sexual conflict resolution capable of protecting sexually antagonistic variation while avoiding the homozygous lethality and deleterious mutations associated with typical heteromorphic sex chromosomes.

Rationale and Objectives: Previous studies have demonstrated that quantitative relationships exist between stone fragility at lithotripsy and morphological features extracted from computed tomography (CT) scans. The goal of this study was to determine if variations in scanner model, patient size, radiation dose, or reconstruction parameters impact the accuracy of the prediction of renal stone fragility in an in vitro model., Materials and Methods: Sixty-seven kidney stones were scanned using routine single and dual energy stone protocols, mimicking average, and large patient habitus. Low dose scans were also performed. Each scan was reconstructed with routine protocol parameters, and with thinner (0.6 mm) or thicker (3 mm) images, two different reconstruction kernels, and iterative reconstruction at two strengths. Fragility of each stone was measured in a controlled ex vivo experiment. A single predictive model was developed from a reference CT protocol configuration and applied to data from each CT acquisition and reconstruction parameter tested to obtain estimated stone comminution times., Results: None of the investigated protocols showed a significant variation in the accuracy of stone fragility classification, except for the ones with the most aggressive iterative reconstruction and/or with thicker images. In these protocols, a number of stone fragility assessments changed from fragile to hard (or vice versa), compared to their ground truth measurement., Conclusion: Prediction accuracy of stone fragility models developed from CT data is robust to expected variations in CT stone protocols used for quantification tasks. This finding facilitates their future adoption to different clinical practices., (Copyright © 2018 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Single-nucleotide polymorphisms (SNPs) are highly abundant markers, which are broadly distributed in animal genomes. For rainbow trout ( Oncorhynchus mykiss ), SNP discovery has been previously done through sequencing of restriction-site associated DNA (RAD) libraries, reduced representation libraries (RRL) and RNA sequencing. Recently we have performed high coverage whole genome resequencing with 61 unrelated samples, representing a wide range of rainbow trout and steelhead populations, with 49 new samples added to 12 aquaculture samples from AquaGen (Norway) that we previously used for SNP discovery. Of the 49 new samples, 11 were double-haploid lines from Washington State University (WSU) and 38 represented wild and hatchery populations from a wide range of geographic distribution and with divergent migratory phenotypes. We then mapped the sequences to the new rainbow trout reference genome assembly (GCA&#95;002163495.1) which is based on the Swanson YY doubled haploid line. Variant calling was conducted with FreeBayes and SAMtools mpileup , followed by filtering of SNPs based on quality score, sequence complexity, read depth on the locus, and number of genotyped samples. Results from the two variant calling programs were compared and genotypes of the double haploid samples were used for detecting and filtering putative paralogous sequence variants (PSVs) and multi-sequence variants (MSVs). Overall, 30,302,087 SNPs were identified on the rainbow trout genome 29 chromosomes and 1,139,018 on unplaced scaffolds, with 4,042,723 SNPs having high minor allele frequency (MAF > 0.25). The average SNP density on the chromosomes was one SNP per 64 bp, or 15.6 SNPs per 1 kb. Results from the phylogenetic analysis that we conducted indicate that the SNP markers contain enough population-specific polymorphisms for recovering population relationships despite the small sample size used. Intra-Population polymorphism assessment revealed high level of polymorphism and heterozygosity within each population. We also provide functional annotation based on the genome position of each SNP and evaluate the use of clonal lines for filtering of PSVs and MSVs. These SNPs form a new database, which provides an important resource for a new high density SNP array design and for other SNP genotyping platforms used for genetic and genomics studies of this iconic salmonid fish species.

Iron loading in p.C282Y homozygous HFE hemochromatosis subjects is highly variable, and it is unclear what factors cause this variability. Finding such factors could aid in predicting which patients are at highest risk and require closest follow-up. The degree of iron loading has previously been associated with certain HLA-types and with abnormally low CD8 + cell counts in peripheral blood. In 183 Norwegian, p.C282Y homozygotes (104 men, 79 women) originally found through population screening we determined HLA type and measured total T-lymphocytes, CD4 + and CD8 + cells, and compared this with data on iron loading. In p.C282Y homozygous men, but not in homozygous women, we found that the presence of two HLA-A*03 alleles increased the iron load on average by approximately 2-fold compared to p.C282Y homozygous men carrying zero or one A*03 allele. On the other hand, the presence of two HLA-A*01 alleles, in male subjects, apparently reduced the iron loading. In p.C282Y homozygous individuals, the iron loading was increased if the CD8 + cell number was below the 25 percentile or if the CD4 + cell number was above the 75 percentile. This effect appeared to be additive to the effect of the number of HLA-A*03 alleles. Our data indicate that homozygosity for the HLA-A*03 allele significantly increases the risk of excessive iron loading in Norwegian p.C282Y homozygous male patients. In addition, low CD8 + cell number or high CD4 + cell number further increases the risk of excessive iron loading.

The infectious salmon anemia virus (ISAv) produces a systemic infection in salmonids, causing large losses in salmon production. However, little is known regarding the mechanisms exerting disease resistance. In this paper, we perform an RNA-seq analysis in Atlantic salmon challenged with ISAv (using individuals coming from families that were highly susceptible or highly resistant to ISAv infection). We evaluated the differential expression of both host and ISAv genes in a target organ for the virus, i.e. the spleen. The results showed differential expression of host genes related to response to stress, immune response and protein folding (genes such as; atf3, mhc, mx1-3, cd276, cd2, cocs1, c7, il10, il10rb, il13ra2, ubl-1, ifng, ifngr1, hivep2, sigle14 and sigle5). An increased protein processing activity was found in susceptible fish, which generates a subsequent unfolded protein response. We observed extreme differences in the expression of viral segments between susceptible and resistant groups, demonstrating the capacity of resistant fish to overcome the virus replication, generating a very low viral load. This phenomenon and survival of this higher resistant fish seem to be related to differences in immune and translational process, as well as to the increase of HIV-EP2 (hivep2) transcript in resistant fish, although the causal mechanism is yet to be discovered. This study provides valuable information about disease resistance mechanisms in Atlantic salmon from a host-pathogen interaction point of view., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Fillet yield (FY, %) is an economically-important trait in rainbow trout aquaculture that affects production efficiency. Despite that, FY has received little attention in breeding programs because it is difficult to measure on a large number of fish and cannot be directly measured on breeding candidates. The recent development of a high-density SNP array for rainbow trout has provided the needed tool for studying the underlying genetic architecture of this trait. A genome-wide association study (GWAS) was conducted for FY, body weight at 10 (BW10) and 13 (BW13) months post-hatching, head-off carcass weight (CAR), and fillet weight (FW) in a pedigreed rainbow trout population selectively bred for improved growth performance. The GWAS analysis was performed using the weighted single-step GBLUP method (wssGWAS). Phenotypic records of 1447 fish (1.5 kg at harvest) from 299 full-sib families in three successive generations, of which 875 fish from 196 full-sib families were genotyped, were used in the GWAS analysis. A total of 38,107 polymorphic SNPs were analyzed in a univariate model with hatch year and harvest group as fixed effects, harvest weight as a continuous covariate, and animal and common environment as random effects. A new linkage map was developed to create windows of 20 adjacent SNPs for use in the GWAS. The two windows with largest effect for FY and FW were located on chromosome Omy9 and explained only 1.0-1.5% of genetic variance, thus suggesting a polygenic architecture affected by multiple loci with small effects in this population. One window on Omy5 explained 1.4 and 1.0% of the genetic variance for BW10 and BW13, respectively. Three windows located on Omy27, Omy17, and Omy9 (same window detected for FY) explained 1.7, 1.7, and 1.0%, respectively, of genetic variance for CAR. Among the detected 100 SNPs, 55% were located directly in genes (intron and exons). Nucleotide sequences of intragenic SNPs were blasted to the Mus musculus genome to create a putative gene network. The network suggests that differences in the ability to maintain a proliferative and renewable population of myogenic precursor cells may affect variation in growth and fillet yield in rainbow trout.

The whole-genome duplication 80 million years ago of the common ancestor of salmonids (salmonid-specific fourth vertebrate whole-genome duplication, Ss4R) provides unique opportunities to learn about the evolutionary fate of a duplicated vertebrate genome in 70 extant lineages. Here we present a high-quality genome assembly for Atlantic salmon (Salmo salar), and show that large genomic reorganizations, coinciding with bursts of transposon-mediated repeat expansions, were crucial for the post-Ss4R rediploidization process. Comparisons of duplicate gene expression patterns across a wide range of tissues with orthologous genes from a pre-Ss4R outgroup unexpectedly demonstrate far more instances of neofunctionalization than subfunctionalization. Surprisingly, we find that genes that were retained as duplicates after the teleost-specific whole-genome duplication 320 million years ago were not more likely to be retained after the Ss4R, and that the duplicate retention was not influenced to a great extent by the nature of the predicted protein interactions of the gene products. Finally, we demonstrate that the Atlantic salmon assembly can serve as a reference sequence for the study of other salmonids for a range of purposes.