The genetic basis of salinity tolerance traits in Arctic charr (Salvelinus alpinus)

<p>Abstract</p> <p>Background</p> <p>The capacity to maintain internal ion homeostasis amidst changing conditions is particularly important for teleost fishes whose reproductive cycle is dependent upon movement from freshwater to seawater. Although the physiology of seawater osmoregulation in mitochondria-rich cells of fish gill epithelium is well understood, less is known about the underlying causes of inter- and intraspecific variation in salinity tolerance. We used a genome-scan approach in Arctic charr (<it>Salvelinus alpinus</it>) to map quantitative trait loci (QTL) correlated with variation in four salinity tolerance performance traits and six body size traits. Comparative genomics approaches allowed us to infer whether allelic variation at candidate gene loci (e.g., <it>ATP1α1b, NKCC1, CFTR</it>, and <it>cldn10e</it>) could have underlain observed variation.</p> <p>Results</p> <p>Combined parental analyses yielded genome-wide significant QTL on linkage groups 8, 14 and 20 for salinity tolerance performance traits, and on 1, 19, 20 and 28 for body size traits. Several QTL exhibited chromosome-wide significance. Among the salinity tolerance performance QTL, trait co-localizations occurred on chromosomes 1, 4, 7, 18 and 20, while the greatest experimental variation was explained by QTL on chromosomes 20 (19.9%), 19 (14.2%), 4 (14.1%) and 12 (13.1%). Several QTL localized to linkage groups exhibiting homeologous affinities, and multiple QTL mapped to regions homologous with the positions of candidate gene loci in other teleosts. There was no gene × environment interaction among body size QTL and ambient salinity.</p> <p>Conclusions</p> <p>Variation in salinity tolerance capacity can be mapped to a subset of Arctic charr genomic regions that significantly influence performance in a seawater environment. The detection of QTL on linkage group 12 was consistent with the hypothesis that variation in salinity tolerance may be affected by allelic variation at the <it>ATP1α1b </it>locus. <it>IGF2 </it>may also affect salinity tolerance capacity as suggested by a genome-wide QTL on linkage group 19. The detection of salinity tolerance QTL in homeologous regions suggests that candidate loci duplicated from the salmonid-specific whole-genome duplication may have retained their function on both sets of homeologous chromosomes. Homologous affinities suggest that loci affecting salinity tolerance in Arctic charr may coincide with QTL for smoltification and salinity tolerance traits in rainbow trout. The effects of body size QTL appear to be independent of changes in ambient salinity.</p

Growth-related quantitative trait loci in domestic and wild rainbow trout (Oncorhynchus mykiss)

Background: Somatic growth is a complex process that involves the action and interaction of genes and environment. A number of quantitative trait loci (QTL) previously identified for body weight and condition factor in rainbow trout (Oncorhynchus mykiss), and two other salmonid species, were used to further investigate the genetic architecture of growth-influencing genes in this species. Relationships among previously mapped candidate genes for growth and their co-localization to identified QTL regions are reported. Furthermore, using a comparative genomic analysis of syntenic rainbow trout linkage group clusters to their homologous regions within model teleost species such as zebrafish, stickleback and medaka, inferences were made regarding additional possible candidate genes underlying identified QTL regions.Results: Body weight (BW) QTL were detected on the majority of rainbow trout linkage groups across 10 parents from 3 strains. However, only 10 linkage groups (i.e., RT-3, -6, -8, -9, -10, -12, -13, -22, -24, -27) possessed QTL regions with chromosome-wide or genome-wide effects across multiple parents. Fewer QTL for condition factor (K) were identified and only six instances of co-localization across families were detected (i.e. RT-9, -15, -16, -23, -27, -31 and RT-2/9 homeologs). Of note, both BW and K QTL co-localize on RT-9 and RT-27. The incidence of epistatic interaction across genomic regions within different female backgrounds was also examined, and although evidence for interaction effects within certain QTL regions were evident, these interactions were few in number and statistically weak. Of interest, however, was the fact that these predominantly occurred within K QTL regions. Currently mapped growth candidate genes are largely congruent with the identified QTL regions. More QTL were detected in male, compared to female parents, with the greatest number evident in an F 1male parent derived from an intercross between domesticated and wild strain of rainbow trout which differed strongly in growth rate.Conclusions: Strain background influences the degree to which QTL effects are evident for growth-related genes. The process of domestication (which primarily selects faster growing fish) may largely reduce the genetic influences on growth-specific phenotypic variation. Although heritabilities have been reported to be relatively high for both BW and K growth traits, the genetic architecture of K phenotypic variation appears less defined (i.e., fewer major contributing QTL regions were identified compared with BW QTL regions)

Distribution of ancestral proto-Actinopterygian chromosome arms within the genomes of 4R-derivative salmonid fishes (Rainbow trout and Atlantic salmon)

Comparative genomic studies suggest that the modern day assemblage of ray-finned fishes have descended from an ancestral grouping of fishes that possessed 12-13 linkage groups. All jawed vertebrates are postulated to have experienced two whole genome duplications (WGD) in their ancestry (2R duplication). Salmonids have experienced one additional WGD (4R duplication event) compared to most extant teleosts which underwent a further 3R WGD compared to other vertebrates. We describe the organization of the 4R chromosomal segments of the proto-rayfinned fish karyotype in Atlantic salmon and rainbow trout based upon their comparative syntenies with two model species of 3R ray-finned fishes. Results: Evidence is presented for the retention of large whole-arm affinities between the ancestral linkage groups of the ray-finned fishes, and the 50 homeologous chromosomal segments in Atlantic salmon and rainbow trout. In the comparisons between the two salmonid species, there is also evidence for the retention of large whole-arm homeologous affinities that are associated with the retention of duplicated markers. Five of the 7 pairs of chromosomal arm regions expressing the highest level of duplicate gene expression in rainbow trout share homologous synteny to the 5 pairs of homeologs with the greatest duplicate gene expression in Atlantic salmon. These regions are derived from proto-Actinopterygian linkage groups B, C, E, J and K. Conclusion: Two chromosome arms in Danio rerio and Oryzias latipes (descendants of the 3R duplication) can, in most instances be related to at least 4 whole or partial chromosomal arms in the salmonid species. Multiple arm assignments in the two salmonid species do not clearly support a 13 proto-linkage group model, and suggest that a 12 proto-linkage group arrangement (i.e., a separate single chromosome duplication and ancestral fusion/fissions/recombination within the putative G/H/I groupings) may have occurred in the more basal soft-rayed fishes. We also found evidence supporting the model that ancestral linkage group M underwent a single chromosome duplication following the 3R duplication. In the salmonids, the M ancestral linkage groups are localized to 5 whole arm, and 3 partial arm regions (i.e., 6 whole arm regions expected). Thus, 3 distinct ancestral linkage groups are postulated to have existed in the G/H and M lineage chromosomes in the ancestor of the salmonids

Prevalence of sleep disordered breathing in a population of Canadian grainworkers

OBJECTIVES: To determine the prevalence of sleep disordered breathing (SDB) in a Canadian population of industrial workers (grainworkers). To determine the clinical features that are predictive of SDB and the validity of self-reported snoring. DESIGN: Cross-sectional, interviewer-administered questionnaire with selective recruitment of subjects for home sleep monitoring. SETTING: Community setting, Vancouver, British Columbia. PARTICIPANTS: All male grainworkers at grain elevators in Vancouver were approached for completion of a questionnaire. Eighty-three per cent of 524 subjects completed the questionnaire and were divided by presumed risk for SDB into four groups. All subjects in the highest risk group (group 1-frequent snoring and witnessed apneas) and a random sample of 40 subjects in the other three groups (group 2 -frequent snoring without witnessed apneas; group 3 -infrequent snoring rare; group 4 -nonsnoring) were approached for home sleep monitoring and 42% consented. INTERVENTIONS: Interviewer-administered questionnaire and home sleep monitoring. RESULTS: The overall prevalence of SDB in this relatively overweight group was estimated to be 25%, with a stepwise increase from group 4 to group 1 (7%, 29%, 40%, 60%). Presence of snoring and witnessed apneas, a greater body-mass index and a larger neck circumference were associated with SDB. Self-reported snoring was not found to be predictive. CONCLUSIONS: This first study of the prevalence of SDB in Canada suggests that SDB is at least as prevalent in Canada as in other industrialized nations and may actually be more common than previously thought. Further studies are required to determine the morbidity, mortality and economic loss associated with SDB in industrial workers. Key Words: Home monitoring, Obstructive sleep apnea, Screening, Self-reported snoring, Sleep disordered breathing Prévalence des troubles respiratoires du sommeil dans une population de travailleurs du grain OBJECTIFS : Déterminer la prévalence des troubles respiratoires du sommeil dans une population canadienne de travailleurs de l&apos;industrie du grain. Déterminer les caractéristiques cliniques prédictives des troubles respiratoires du sommeil et la validité du ronflement signalé par les sujets eux-mêmes. MODÈLE : Questionnaire transversal rempli par un intervieweur et recrutement sélectif de sujets pour mener des études du sommeil à domicile. CONTEXTE : Dans la communauté de Vancouver en Colombie-Britannique. PARTICIPANTS : On a demandé à tous les sujets de sexe masculin travaillant dans les silos à grains de répondre à un questionnaire. Quatre-vingt-trois pour cent des 524 sujets ont complété le questionnaire ; ils étaient divisés en quatre groupes selon le risque présumé de troubles respiratoires du sommeil. On a demandé à tous les sujets du groupe à risque le plus élevé (groupe 1 -ronflement fréquent et apnées observées) et un échantillon aléatoire de 40 sujets dans les trois autres groupes (groupe 2 -ronflement fréquent sans apnées observées ; groupe 3 -rare ronflement occasionnel ; groupe 4 -aucun ronflement) de subir des études de sommeil à domicile. Quarante-deux pour cent des sujets ont consenti à subir de telles études. INTERVENTIONS : Questionnaire rempli par un intervieweur et études du sommeil à domicile. RÉSULTATS : La prévalence globale des troubles respiratoires du sommeil dans cette population relativement obèse a été estimée à 25 %, avec une augmentation par paliers du groupe 4 jusqu&apos;au groupe 1 (7 %, 29 %, 40 %, 60 %). Le ronflement et les apnées observées, un index de masse corporelle plus élevé et un tour du cou plus grand étaient associés à des troubles respiratoires du sommeil. voir page suivante S leep disordered breathing (SDB), including obstructive sleep apnea and obstructive sleep hypopnea, is associated with significant mortality (1,2) and morbidity (3). SDB is most common in middle-aged men, but its true prevalence in this group is still being determined. While early studies estimated the prevalence of SDB to be 0.9% and 1.3%, (4,5) more recent studies from the United States and Australia (6-8) have reported prevalence rates of SDB in middle-aged men to be in the range of 10% to 15%. To date there have been no published studies of the prevalence of SDB in Canada. The main objective of this study was to obtain an estimate of the prevalence of SDB in industrial workers, using a population of men working at grain elevators in Vancouver, British Columbia as a model. To achieve this objective we studied subjects with all levels of risk for SDB. A secondary objective was to determine which clinical features and anthropometric data were predictive of SDB. We also examined the relationship between self-reported snoring and recorded snoring. PATIENTS AND METHODS Subjects: The target population was men working in grain terminals. The sample frame, for the purpose of this study, consisted of men working at the grain terminals in the Vancouver area. Questionnaire administration: Subjects completed a questionnaire administered by trained interviewers that included questions concerning demographic data, sleep disturbance (snoring, witnessed apneas, daytime sleepiness), smoking history and included the American Thoracic Society Respiratory Disease Questionnaire (9). All subjects had their height, weight, blood pressure and neck circumference measured. The subjects were divided into four groups based on the reported presence of snoring and witnessed apneas: group 1, frequent snoring and witnessed apneas; group 2, frequent snoring without witnessed apneas; group 3, infrequent snoring or rare; group 4, nonsnoring. All subjects in group 1 and a random sample of 40 subjects in groups 2 to 4 were approached about overnight home sleep monitoring. Subjects who consented formed the sample population for determining SDB prevalence. Home sleep monitoring: Home sleep was monitored using the Mesam 4 (Madaus Medizin Elektronik, Freiburg, Germany) (10). The Mesam 4 is a four-channel digital recording device. The Mesam system has been validated in two previous studies (10,11). A polysomnographic technologist, trained in the use of the Mesam 4, set up the device at the subject&apos;s home on the study night and retrieved it the next morning. Heart rate was monitored through a single-lead electrocardiogram (modified V2) and R-R intervals were measured in milliseconds. Snoring sounds were monitored through an electric subminiature microphone, type MCE 2,000 (frequency range, 30 to 20,000 cycles/s ± 2dB, sensitivity 0.6 mV/microbar at 1000 cycles/s ± 4 dB; Conrad Electronics, Hirschau, Germany), taped above the larynx. Arterial oxygen saturation was measured continuously with a finger probe. The body position sensor, a flat cylinder 18 mm high with a diameter of 50 mm, was placed on the lower part of the sternum. Automated scoring software is available with the Mesam that provides a respiratory disturbance index. However, previous research has shown that hand scoring provides results that are more closely related to the results of simultaneous polysomnography than the automated analysis results (11). The Mesam recordings were therefore hand scored in 5 min epochs. This was done independently and in a blinded fashion by two physicians trained in SDB and familiar with the Mesam 4. Interobserver variability was determined using the Kappa statistic (12). Snoring was scored as absent, present during less than 50% of the recording, or present during 50% or more of the recording. A respiratory event was scored if at least two of the following three parameters were present: pauses in snoring of at least 10 s; heart rate deceleration and acceleration of at least 10 beats/min; and an associated arterial oxygen desaturation of at least 2%. If recurrent episodes were present during the majority of a 5 min epoch, the epoch was defined as positive for SDB. The subjects&apos; records were then classified based on the following criteria: normalevents less than 10% of the recording; possible SDB -events 10% to 30% of the recording; definite SDB -events greater than 30% of the recording. The Mesam 4 does not record sleep; therefore, the total study time is not equivalent to a total sleep time. Using a total study time rather than a total sleep time tends to underestimate the degree of SDB. This approach was adopted to avoid concerns that the prevalence of SDB would be overestimated in this population. Calculation of prevalence: The prevalence of both suspected and definite SDB was calculated but the conservative latter definition was used for the primary analysis. The prevalence of SDB was calculated in each sample group by the equation: Prevalence = (number of subjects with definite SDB × 100%)/ total number of subjects To estimate the overall prevalence of definite SDB in the entire group of grainworkers the prevalence obtained from each sample groups was projected to their respective total groups. Overall prevalence = [(sample group 1)(number of subjects in total group 1) + (sample group 2)(number of subjects in total group 2) + (sample group 3)(number of subjects in total group 3) + (sample group 4)(number of subjects in total group 4)] × 100%/total number of grainworkers Can Respir J Vol 5 No 3 May/June 1998 185 Prevalence of SDB in grainworkers Le ronflement signalé par les sujets eux-mêmes ne représentait pas un facteur prédictif. CONCLUSIONS : Cette première étude sur la prévalence des troubles respiratoires du sommeil au Canada permet de croire qu&apos;ils sont aussi fréquents dans ce pays que dans les autres pays industrialisés mais aussi que leur incidence serait en fait plus importante que celle présumée antérieurement. D&apos;autres études sont nécessaires pour déterminer la morbidité, la mortalité et la perte économique associées aux troubles respiratoires du sommeil chez les travailleurs industriels. where sample group refers to the prevalance of SDB in the sample group specificed. Before this calculation, subjects approached for home sleep monitoring who did not participate (refused or could not be contacted) were compared with their respective total groups in terms of age, body mass index (BMI) and neck circumference. If no significant difference was found between the sample group and total group, then the previously described formula was used to calculate prevalence. If a significant difference was found between a sample group and either those who did not participate or the group as a whole then the above formula was modified such that the respective group prevalence was multiplied by only the number of subjects in the sample group and not by the entire total group. Statistics: One-way ANOVA was used to to compare the anthropometric data and a c 2 test was used to compare the questionnaire data (categorical) among the four total groups and among the three home sleep monitoring derived diagnostic groups (normal, possible SDB, definite SDB). The sample groups and the total groups were compared by an unpaired Student&apos;s t test. Prevalence was calculated as described above, and the interobserver variability was calculated using the Kappa statistic (a Kappa score greater than 0.7 is indicative of minimal interobserver variability). RESULTS Questionnaire data: Four hundred and thirty-seven men of the 524 men approached completed the questionnaire and had a limited physical examination (83% response rate). Nineteen (4.3%) admitted to snoring often and had a history of witnessed apneas (group 1), 98 (22.3%) snored often without witnessed apneas (group 2), 185 (42.3%) snored sometimes or rarely (group 3) and 135 (31.1%) were nonsnorers (group 4). These groups differed significantly in the distribution of neck circumference (P&lt;0.0001), BMI (P&lt;0.0001) and age (P&lt;0.05) ( The distribution of diagnoses from home sleep monitoring differed among the four groups By projecting the prevalence of definite SDB found in the four sample groups to their respective total group the overall prevalence of SDB was estimated to be 25% in this group of grainworkers: In group 1 the prevalence of the sample group was multiplied by the number of subjects in the sample group rather than the total group. There was a significant difference in BMI between those studied (heavier) and those who were not studied (P&lt;0.02, Table 2), although those who were studied were similar to the total group. There were no significant differences between those subjects studied and those that did not participate in sample groups 2 to 4 (P&gt;0.05, Figure 1) Prevalence of definite sleep disordered breathing in the sample groups and the total population There were no differences among the total groups and their respective sample groups in age, BMI or neck circumference. The two physicians scoring the Mesam studies agreed on categorization of the studies 85% of the time. In the studies in which there was not complete agreement, the two physicians were never more than one category removed. The interobserver variability, as calculated by the Kappa statistic, was 0.7. Factors associated with SDB: Among grainworkers who underwent home sleep monitoring, the presence of snoring (P&lt;0.005) and witnessed apneas (P&lt;0.04), a greater BMI (P&lt;0.040) and a larger neck circumference (P&lt;0.02) were found to be predictive of definite SDB. However, the presence of daytime sleepiness, history of hypertension (patient reported) and smoking history were not associated with the presence of SDB. There was no difference in measured blood pressure between the patients with and those without SDB. The relatively small sample size in each group may limit the power to detect true differences among the groups. Validity of self-reported snoring: Fifty-eight subjects underwent home sleep monitoring. Fourteen of these subjects denied snoring but home sleep monitoring revealed that five did not snore, five snored for less than 50% of the night and four snored for more than 50% of the night DISCUSSION In this first study of the prevalence of SDB in Canada, we found that 25% of a population of male grainworkers had SDB. The known risk factors of male sex and higher than average BMI in the study population are probably responsible for a higher prevalence of SDB than previously reported. A history of snoring and witnessed apneas as well as greater BMI and larger neck circumference were found to be useful predictors of SDB, a finding consistent with previous studies (6,13-15). Smoking was more common in subjects who re- ported snoring (with or without witnessed apneas) but we did not find a previously reported association between smoking history and SDB (7). Furthermore, self-reported snoring was not found to be a reliable guide to the presence of recorded snoring. A number of factors could have contributed to our finding of a greater prevalence of SDB in our study than that reported by others. Certain assumptions were made in previous prevalence studies, the most common of which is that self-reported snoring and daytime sleepiness were reliable symptoms of SDB The recognition of obstructive breathing associated with neurological arousal without accompanying arterial oxygen desaturation has expanded the definition of SDB. It is now apparent that there is a continuum of SDB associated with progressively more clinical consequences, from chronic snoring to obstructive sleep hypopnea to severe obstructive sleep apnea. The diagnostic threshold to define SDB within this continuum directly affects the measured prevalence. For example, the initial study by Lavie (4) used a diagnostic threshold of an apnea index greater than 10/h; however, if one uses an apnea index more than five/h the prevalence moves from 1% to nearly 16% in a group of male industrial workers. The use of home oximetry to define cases of SDB, a less sensitive monitoring system than conventional overnight, in-hospital polysomnography, has also contributed to the underestimation of prevalence rates. Stradling and Crosby (17) studied 893 men with overnight oximetry and found that 45 (5%) had more than five desaturations of 4% per hour. Thirty-one of these men had overnight polysomnography, and three had severe, nonpositional SDB (0.3%) and 18 had mild to moderate, positional apnea (2.4%). Men with clinically significant SDB with apneas and hypopneas without associated desaturations of 4% would have been missed using this methodology. More recent studies conducted in the United States and Australia using expanded definitions of SDB have found prevalence rates similar to our study (10% to 20%). In a recent study from the United States, 40% of middle-aged men and 30% of middle-aged women were found to be habitual snorers (6). Significant SDB was defined as the presence of an apnea-hypopnea index (AHI) greater than five/h (from polysomnography) and symptoms of excessive daytime sleepiness. About 4% of middle-aged men and 2% of middle-aged women met these criteria. When they defined SDB based only on AHI, 24% of middle-aged men had an AHI greater than five/h, 15% had an AHI greater than 10 per hour, and 9% had an AHI greater than 15/h. These prevalence rates are similar to those found in our study. Bearpark and colleagues Obesity is a significant risk factor for SDB. We examined a relatively healthy, nonhypertensive population of middleaged, working men who had a higher average BMI (29±5 kg/m

Resolving fine-scale population structure and fishery exploitation using sequenced microsatellites in a northern fish

Funding Information Natural Sciences and Engineering Research Council of Canada (NSERC) Strategic Project Atlantic Canada Opportunities Agency and Department of Tourism, Culture, Industry and Innovation grants allocated to the Labrador Institute (MC) Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Genomics Research and Development Initiative (GRDI) Weston Family AwardPeer reviewedPublisher PD

A cardinal role for cathepsin D in co-ordinating the host-mediated apoptosis of macrophages and killing of pneumococci

The bactericidal function of macrophages against pneumococci is enhanced by their apoptotic demise, which is controlled by the anti-apoptotic protein Mcl-1. Here, we show that lysosomal membrane permeabilization (LMP) and cytosolic translocation of activated cathepsin D occur prior to activation of a mitochondrial pathway of macrophage apoptosis. Pharmacological inhibition or knockout of cathepsin D during pneumococcal infection blocked macrophage apoptosis. As a result of cathepsin D activation, Mcl-1 interacted with its ubiquitin ligase Mule and expression declined. Inhibition of cathepsin D had no effect on early bacterial killing but inhibited the late phase of apoptosis-associated killing of pneumococci in vitro. Mice bearing a cathepsin D-/- hematopoietic system demonstrated reduced macrophage apoptosis in vivo, with decreased clearance of pneumococci and enhanced recruitment of neutrophils to control pulmonary infection. These findings establish an unexpected role for a cathepsin D-mediated lysosomal pathway of apoptosis in pulmonary host defense and underscore the importance of apoptosis-associated microbial killing to macrophage function