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The brain lacks lymph vessels and must rely on other mechanisms for clearance of waste products, including amyloid [Formula: see text] that may form pathological aggregates if not effectively cleared. It has been proposed that flow of interstitial fluid through the brain's interstitial space provides a mechanism for waste clearance. Here we compute the permeability and simulate pressure-mediated bulk flow through 3D electron microscope (EM) reconstructions of interstitial space. The space was divided into sheets (i.e., space between two parallel membranes) and tunnels (where three or more membranes meet). Simulation results indicate that even for larger extracellular volume fractions than what is reported for sleep and for geometries with a high tunnel volume fraction, the permeability was too low to allow for any substantial bulk flow at physiological hydrostatic pressure gradients. For two different geometries with the same extracellular volume fraction the geometry with the most tunnel volume had [Formula: see text] higher permeability, but the bulk flow was still insignificant. These simulation results suggest that even large molecule solutes would be more easily cleared from the brain interstitium by diffusion than by bulk flow. Thus, diffusion within the interstitial space combined with advection along vessels is likely to substitute for the lymphatic drainage system in other organs.

We estimated additive genetic variation and heritability of survival after Gyrodactylus salaris infection from survival records in a pedigreed family material of wild Atlantic salmon (Salmo salar) in a controlled challenge test. We used a statistical model that distinguishes between survival time for the fish that died and the ability to survive the entire test as two separate traits. Eleven of the 49 full-sib families suffered 100% mortality, 15 families had between 10% and 25% survival, and the four least affected families had survival rates between 36% and 48%. Estimated heritability of survival on the liability scale was 0.32 ± 0.10. Time until death for fish that died during the test and the ability to survive the entire test were not expressions of the same genetic trait. Simply selecting survivors as parents for the next generation is expected to more than double the overall survival rate in only one generation, given similar exposure to the parasite. Improving the genetic capacity to survive the infection will probably not eradicate the parasite, but when used as a disease control measure, such improvement may contain the infection at a level where the parasite ceases to be a major problem. Resume: Nous estimons la variation genetique additive et l'heritabilite de la survie apres une infection a Gyrodactylus salaris a partir des donnees de survie dans un echantillon provenant d'une famille d'ascendance connue de saumons atlantiques (Salmo salar) sauvages dans un test controle d'exposition au parasite. Nous utilisons un modele statistique qui discrimine entre la duree de survie des poissons qui sont morts et la capacite de survivre a l'ensemble du test comme deux caracteristiques differentes. Onze des 49 familles de meme fratrie ont connu 100% de mortalite, 15 familles entre 10% et 25% de survie et les quatre familles les moins affectees ont eu des taux de survie variant de 36% a 48 %. L'heritabilite estimee de la survie sur une echelle de predisposition est de 0,32 ± 0,10. La duree de la survie jusqu'a la mort chez les poissons qui sont morts durant le test et la capacite de survivre a l'ensemble du test ne sont pas les expressions du meme trait genetique. Une simple selection des survivants comme parents de la generation suivante devrait vraisemblablement plus que doubler le taux global de survie dans une seule generation, lors d'expositions semblables au parasite. L'amelioration de la capacite genetique de survie a l'infection n'eradiquera probablement pas le parasite, mais une telle amelioration, utilisee comme mesure de controle de la maladie, peut maintenir l'infection a un niveau ou le parasite cesse d'etre un probleme serieux. [Traduit par la Redaction], Introduction Wild Atlantic salmon (Salmo salar) populations remain at historical low levels throughout the North Atlantic despite all of the measures that have been taken to arrest their continuous decline. [...]

The Pacific chinook salmon occurs as both white- and red-fleshed populations, with the flesh color type (red or white) seemingly under strong genetic influence. Previously published data on crosses between red- and white-fleshed individuals cannot be reconciled with a simple Mendelian two-locus, two-allele model, pointing to either a more complex inheritance pattern or the existence of gene interactions. Here we show that a standard single-locus, three-allele model can fully explain these data. Moreover, by implementing the single-locus model at the parameter level of a previously developed mathematical model describing carotenoid dynamics in salmon, we show that variation at a single gene involved in the muscle uptake of carotenoids is able to explain the available data. This illustrates how such a combined approach can generate biological understanding that would not be possible in a classical population genetic explanatory structure. An additional asset of this approach is that by allowing parameters to become phenotypes obeying a given genetic model, biological interpretations of mechanisms involved at a resolution level far beyond what is built into the original dynamic model are made possible. These insights can in turn be exploited in experimental studies as well as in construction of more detailed models.

Abstract: Pigmented flesh, a trait uniquely present in four of the 10 genera of salmonid fishes, is caused by the ubiquitous capacity of these genera for accumulating dietary carotenoids in [...]

Functional dependencies between genes are a defining characteristic of gene networks underlying quantitative traits. However, recent studies show that the proportion of the genetic variation that can be attributed to statistical epistasis varies from almost zero to very high. It is thus of fundamental as well as instrumental importance to better understand whether different functional dependency patterns among polymorphic genes give rise to distinct statistical interaction patterns or not. Here we address this issue by combining a quantitative genetic model approach with genotype-phenotype models capable of translating allelic variation and regulatory principles into phenotypic variation at the level of gene expression. We show that gene regulatory networks with and without feedback motifs can exhibit a wide range of possible statistical genetic architectures with regard to both type of effect explaining phenotypic variance and number of apparent loci underlying the observed phenotypic effect. Although all motifs are capable of harboring significant interactions, positive feedback gives rise to higher amounts and more types of statistical epistasis. The results also suggest that the inclusion of statistical interaction terms in genetic models will increase the chance to detect additional QTL as well as functional dependencies between genetic loci over a broad range of regulatory regimes. This article illustrates how statistical genetic methods can fruitfully be combined with nonlinear systems dynamics to elucidate biological issues beyond reach of each methodology in isolation.

Abstract Background The Atlantic salmon genome is in the process of returning to a diploid state after undergoing a whole genome duplication (WGD) event between 25 and100 million years ago. Existing data on the proportion of paralogous sequence variants (PSVs), multisite variants (MSVs) and other types of complex sequence variation suggest that the rediplodization phase is far from over. The aims of this study were to construct a high density linkage map for Atlantic salmon, to characterize the extent of rediploidization and to improve our understanding of genetic differences between sexes in this species. Results A linkage map for Atlantic salmon comprising 29 chromosomes and 5650 single nucleotide polymorphisms (SNPs) was constructed using genotyping data from 3297 fish belonging to 143 families. Of these, 2696 SNPs were generated from ESTs or other gene associated sequences. Homeologous chromosomal regions were identified through the mapping of duplicated SNPs and through the investigation of syntenic relationships between Atlantic salmon and the reference genome sequence of the threespine stickleback (Gasterosteus aculeatus). The sex-specific linkage maps spanned a total of 2402.3 cM in females and 1746.2 cM in males, highlighting a difference in sex specific recombination rate (1.38:1) which is much lower than previously reported in Atlantic salmon. The sexes, however, displayed striking differences in the distribution of recombination sites within linkage groups, with males showing recombination strongly localized to telomeres. Conclusion The map presented here represents a valuable resource for addressing important questions of interest to evolution (the process of re-diploidization), aquaculture and salmonid life history biology and not least as a resource to aid the assembly of the forthcoming Atlantic salmon reference genome sequence.

Abstract Background Red flesh colour is a unique trait found in some salmonid genera. Carotenoid pigments are not synthesized de novo in the fish, but are provided by dietary uptake. A better understanding of the molecular mechanisms underlying the cellular uptake and deposition of carotenoids could potentially be used to improve the low muscle deposition rate that is typically found in farmed Atlantic salmon. In addition, from an evolutionary point of view, the establishment and maintenance of this trait is still poorly understood. It has been demonstrated in several species that scavenger receptor class B, member 1 (SCARB1) is involved in intestinal absorption of carotenoids, which makes this gene a possible source of genetic variation in salmonid flesh pigmentation. Results In this study, a novel paralog of SCARB1 (SCARB1-2) was detected through screening for genetic variation in Atlantic salmon SCARB1. Full length SCARB1-2 encodes a protein with 89% identity to Atlantic salmon SCARB1, except for the C-terminal cytoplasmic tail that shows only 12% identity. The most prominent site of SCARB1 mRNA expression was in the mid gut, while a five-fold lower level was detected in Atlantic salmon skeletal muscle and liver. The SCARB1-2 mRNA was equally expressed in liver, muscle and mid gut, and at a lower level than SCARB1 mRNA. A total of seven different SCARB1-2 alleles comprising repetitive enhancer of zeste motifs (EZH2) were identified in the founding parents of a resource Atlantic salmon population. We mapped the SCARB1-2 paralog to a region on Atlantic salmon chromosome 1, containing a putative QTL for flesh colour. Addition of the SCARB1-2 marker increased the significance of this QTL, however the large confidence interval surrounding the QTL precludes confirmation of SCARB1-2 as a causative gene underlying variation in this trait. Conclusion We have characterised a novel paralog of SCARB1 (SCARB1-2), have mapped it to Atlantic salmon chromosome 1 and have described its expression in various tissues. Mapping with SCARB1-2 alleles added further evidence for a QTL affecting flesh colour on this chromosome, however further studies are needed to confirm a functional role for this gene in flesh colour pigmentation.