Heritability of corticosterone response and changes in life history traits during selection in the zebra finch

Vertebrates respond to environmental stressors through the neuro-endocrine stress response, which involves the production of glucocorticoids. We have selected independent, duplicate divergent lines of zebra finches for high, low and control corticosterone responses to a mild stressor. This experiment has shown that over the first four generations, the high lines have demonstrated a significant realized heritability of about 20%. However, the low lines have apparently not changed significantly from controls. This asymmetry in response is potentially because of the fact that all birds appear to be showing increased adaptation to the environment in which they are housed, with significant declines in corticosterone response in control lines as well as low lines. Despite the existence of two- to threefold difference in mean corticosterone titre between high and low lines, there were no observed differences in testosterone titre in adult male birds from the different groups. In addition, there were no consistent, significant differences between the lines in any of the life history variables measured – number of eggs laid per clutch, number of clutches or broods produced per pair, number of fledglings produced per breeding attempt, nor in any of egg, nestling and fledgling mortality. These results highlight the fact that the mechanisms that underlie variation in the avian physiological system can be modified to respond to differences between environments through selection. This adds an additional level of flexibility to the avian physiological system, which will allow it to respond to environmental circumstances.

Does subjective well-being show a relationship between parents and their children?

The relationship between the subjective well-being of parents and their own 12–16-year-old children was explored in a Spanish sample of N = 266 families. A positive relationship was expected due to both a shared environment and the possibility of the genetic transmission of subjective well-being ‘set-points’. A positive significant relationship was found for the summated scale of satisfaction domains forming the Personal Well-being Index, and for the specific domains of health and security for the future. However, no relationship was found for the other five domains that make up this Index or for satisfaction with life as a whole. We conclude while these results provide some evidence for the expected influence of a shared environment, they have failed to provide evidence for high heritability of set-points for subjective well-being.

Polyunsaturated fats in meat from Merino, first- and second-cross sheep slaughtered as yearlings

This study examined the level of long chain omega-3 and omega-6 polyunsaturated fats, the ratio of polyunsaturated fat to saturated fat (PUFA/SFA) and the ratio of omega-6 to omega-3 (n-6/n-3) fat in sheep grown under grazing conditions in Australia. The sheep genotypes used were Poll Dorset_growth × Border Leicester Merino (PDg × BLM), Poll Dorset_growth × Merino (PDg × M), Poll Dorsetmuscling × Merino (PDm × M), Border Leicester × Merino (BL × M) and Merino × Merino (M × M). Loin muscles (Longissimus lumborum) collected from 40 ewe and wether sheep slaughtered at 14 months of age were processed for fatty acid determination. After frozen storage, 20 g samples were minced and a 7 g homogenate was processed for muscle lipid extraction using a chloroform:methanol (2:1) procedure. There was an increase in PUFA/SFA as the proportion of Merino genetics increased in the progeny (second-cross < first-cross < Merino), but this was not shown in the n-6/n-3 ratio. The PUFA/SFA trend appeared to be associated with an increase in the level of total polyunsaturated fats, but not a decrease in the level of total saturated fats. The results demonstrate that there is a need to improve the PUFA/SFA content in first- and second-cross animals which are mainly used for meat production in Australia so as to maintain the healthy lipids in meat. Nutritional manipulation through feeding systems or selection of sires for greater heritability of omega-3 fat deposition may be suitable pathways to elevate the ratio of polyunsaturated fatty acids, and in particular omega-3.

Genetic and environmental influences on variation in balance performance among female twin pairs aged 21-82 years

Genetic and environmental influences on variation in balance performance were measured in 93 monozygous and 83 dizygous female twin pairs aged 21–82 years (mean age, 50.5 years) in Melbourne, Australia, between 1999 and 2003. The authors administered clinical (Lord's Balance Test and Step Test) and laboratory tests of static and dynamic balance from the Chattecx Balance System with and without distractor tasks. The authors conducted factor analysis and estimated genetic and environmental variance components and heritability (defined as additive genetic variance as a proportion of all variance, after adjustment for age) using a multivariate normal model with the statistical package FISHER. Three factors were identified and adjusted for age. Heritability was 46% (standard error (SE), 9) for the "sensory balance tests" factor and 30% (SE, 9) for the "static and dynamic perturbations" factor. For both factors, the remaining variance was attributed to unique environmental effects. There was no evidence that genetic factors influenced variation in the "dynamic weight shift tests" factor, with environmental effects shared by twins accounting for 38% (SE, 7) of variance. Neither genetic nor environmental proportions of variance differed significantly between twin subgroups by age (≤50/>50 years). An age-related decline in performance measures was found across the whole sample. These results imply that balance impairments may have a heritable element.

A population-based study of the effect of the HFE C282Y and H63D mutations on iron metabolism

The C282Y and H63D mutations in the HFE gene are important causes of hemochromatosis. In the elderly, these mutations might be associated with increased morbidity because of the lifelong accumulation of iron. In a population-based sample of the elderly, we determined the value of genotyping for HFE mutations to screen for subclinical hemochromatosis. HFE genotype frequencies were determined in a random group of 2095 subjects (55 years and over). In this random group, we selected within the six genotype groups a total of 342 individuals and measured their serum transferrin saturation, iron and ferritin levels. We also estimated the heritability and parameters needed to evaluate screening, including the sensitivity, specificity, positive and negative predictive values (PPV, NPV) of HFE genotypes. Iron parameters were significantly increased in subjects homozygous, heterozygous or compound heterozygous. The effect of the mutations was more pronounced in men than in women. For the H63D mutation, an allele dose effect was observed. The HFE gene explained about 5% of the variability in serum iron indices. The PPV for hemochromatosis for the C282Y homozygous was 100% in men and 67% in women. The NPV of the wild-type allele was 97% for both men and women. The sensitivity of both mutations was 70% for men and 52% for women and the specificity was 62% for men and 64% for women. Our study shows that the HFE C282Y and H63D are determinants of iron parameters in the elderly and will be effective in detecting individuals at high risk of hemochromatosis. However, when screening based on these two mutations, some individuals with subclinical hemochromatosis will be missed.

Variation of mohair staple length across Angora goat fleeces : implications for animal selection and fleece evaluation

The present study aimed to determine how the average mohair staple length (SL) differences between nine sampling sites vary between sex and flock, to identify differences in SL variability between sampling sites as a result of between-animal and between-sire variability and to determine SL correlations between sampling sites in between-animal and between-sire variability. Australian Angora goats (n=301) from two farms in southern Australia were sampled at 12 and 18 months of age at nine sites (mid side, belly, brisket, hind flank, hip, hock, mid back, neck and shoulder). Staples were taken prior to shearing at skin level and stretched SL determined. For each shearing, differences in SL between sampling sites, how these differences were affected by farm, sex and sire, and the covariance between sites for sire and individual animal effects were investigated by restricted maximum likelihood (REML) analyses. The median mid-side SL at 12 and 18 months of age was 110 and 130 mm, respectively, but the actual range in mid-side SL was 65–165 mm. There was an anterior–posterior decline in SL with the hock being particularly short. There was no evidence that the between-site correlation of the sire effects differed from 1, indicating that genetic selection for SL at one site will be reflected in SL over the whole fleece. However, low heritabilities of SL at the hock, belly and brisket or at any site at 12 months of age were obtained. There was more variability between sites than between sires, but the between-animal variation was greater. The hip and mid-back sites can be recommended for within-flock (culling) and genetic selection for SL due to their low sampling variability, moderate heritability and ease of location.

Identification and genetic determination of an early life risk disposition for depressive disorder : atypical stress-related behaviour in early childhood

Progress in psychiatric genetics has been slow despite evidence of high heritability for most mental disorders. We argue that greater use of early detectable intermediate traits (endophenotypes) with the highest likely aetiological significance to depression, rather than complex clinical phenotypes, would be advantageous. Longitudinal data from the Western Australian Pregnancy Cohort (Raine) Study were used to identify an early life behavioural endophenotype for atypical hypothalamic-pituitaryadrenocortical function in adolescence, a neurobiological indicator of anxiety and depression. A set of descriptors representing rigid and reactive behaviour at age 1 year discriminated those in the top 20% of the free salivary cortisol exposure at age 17 years. Genetic association analysis revealed a male-sensitive effect to variation in three specific single nucleotide polymorphisms within selected genes underpinning the overall stress response. Furthermore, support for a polygenic effect on stress-related behaviour in childhood is presented.

Association of differential gene expression with imatinib mesylate and omacetaxine mepesuccinate toxicity in lymphoblastoid cell lines

Background

Imatinib mesylate is currently the drug of choice to treat chronic myeloid leukemia. However, patient resistance and cytotoxicity make secondary lines of treatment, such as omacetaxine mepesuccinate, a necessity. Given that drug cytotoxicity represents a major problem during treatment, it is essential to understand the biological pathways affected to better predict poor drug response and prioritize a treatment regime.
Methods

We conducted cell viability and gene expression assays to determine heritability and gene expression changes associated with imatinib and omacetaxine treatment of 55 non-cancerous lymphoblastoid cell lines, derived from 17 pedigrees. In total, 48,803 transcripts derived from Illumina Human WG-6 BeadChips were analyzed for each sample using SOLAR, whilst correcting for kinship structure.
Results

Cytotoxicity within cell lines was highly heritable following imatinib treatment (h2 = 0.60-0.73), but not omacetaxine treatment. Cell lines treated with an IC20 dose of imatinib or omacetaxine showed differential gene expression for 956 (1.96%) and 3,892 transcripts (7.97%), respectively; 395 of these (0.8%) were significantly influenced by both imatinib and omacetaxine treatment. k-means clustering and DAVID functional annotation showed expression changes in genes related to kinase binding and vacuole-related functions following imatinib treatment, whilst expression changes in genes related to cell division and apoptosis were evident following treatment with omacetaxine. The enrichment scores for these ontologies were very high (mostly >10).
Conclusions

Induction of gene expression changes related to different pathways following imatinib and omacetaxine treatment suggests that the cytotoxicity of such drugs may be differentially tolerated by individuals based on their genetic background.

Genetic basis for the increased expression of vacuolar H+ translocating ATPase genes upon imatinib treatment in human lymphoblastoid cells

Purpose The role of v-ATPases in cancer biology is being increasingly recognized. Yeast studies indicate that the tyrosine kinase inhibitor imatinib may interact with the v-ATPase genes and alter the course of cancer progression. Data from humans in this regard are lacking.

Methods We constructed 55 lymphoblastoid cell lines from pedigreed, cancer-free human subjects and treated them with IC20 concentration of imatinib mesylate. Using these cell lines, we (i) estimated the heritability and differential expression of 19 genes encoding several subunits of the v-ATPase protein in response to imatinib treatment; (ii) estimated the genetic similarity among these genes; and (iii) conducted a high-density scan to find cis-regulating genetic variation associated with differential expression of these genes.

Results We found that the imatinib response of the genes encoding v-ATPase subunits is significantly heritable and can be clustered to identify novel drug targets in imatinib therapy. Further, five of these genes were significantly cis-regulated and together represented nearly half-log fold change in response to imatinib (p = 0.0107) that was homogenous (p = 0.2598).

Conclusions Our results proffer support to the growing view that personalized regimens using proton pump inhibitors or v-ATPase inhibitors may improve outcomes of imatinib therapy in various cancers.

Genetic correlation between resting metabolic rate and exploratory behaviour in deer mice (Peromyscus maniculatus)

According to the ‘pace-of-life’ syndrome hypothesis, differences in resting metabolic rate (RMR) should be genetically associated with exploratory behaviour. A large number of studies reported significant heritability for both RMR and exploratory behaviour, but the genetic correlation between the two has yet to be documented. We used a quantitative genetic approach to decompose the phenotypic (co)variance of several metabolic and behavioural measures into components of additive genetic, common environment and permanent environment variance in captive deer mice. We found significant additive genetic variance for two mass-independent metabolic measures (RMR and the average metabolic rate throughout the respirometry run) and two behavioural measures (time spent in centre and distance moved in a novel environment). We also detected positive additive genetic correlation between mass-independent RMR and distance moved (rA = 0.78 ± 0.23). Our results suggest that RMR and exploratory behaviour are functionally integrated traits in deer mice, providing empirical support for one of the connections within the pace-of-life syndrome hypothesis.

Individual (co)variation in standard metabolic rate, feeding rate, and exploratory behavior in wild-caught semiaquatic salamanders

Repeatability is an important concept in evolutionary analyses because it provides information regarding the benefit of repeated measurements and, in most cases, a putative upper limit to heritability estimates. Repeatability (R) of different aspects of energy metabolism and behavior has been demonstrated in a variety of organisms over short and long time intervals. Recent research suggests that consistent individual differences in behavior and energy metabolism might covary. Here we present new data on the repeatability of body mass, standard metabolic rate (SMR), voluntary exploratory behavior, and feeding rate in a semiaquatic salamander and ask whether individual variation in behavioral traits is correlated with individual variation in metabolism on a whole-animal basis and after conditioning on body mass. All measured traits were repeatable, but the repeatability estimates ranged from very high for body mass (R = 0.98), to intermediate for SMR (R = 0.39) and food intake (R = 0.58), to low for exploratory behavior (R = 0.25). Moreover, repeatability estimates for all traits except body mass declined over time (i.e., from 3 to 9 wk), although this pattern could be a consequence of the relatively low sample size used in this study. Despite significant repeatability in all traits, we find little evidence that behaviors are correlated with SMR at the phenotypic and among-individual levels when conditioned on body mass. Specifically, the phenotypic correlations between SMR and exploratory behavior were negative in all trials but significantly so in one trial only. Salamanders in this study showed individual variation in how their exploratory behavior changed across trials (but not body mass, SMR, and feed intake), which might have contributed to observed changing correlations across trials.

Hierarchical analysis of avian re-nesting behavior: mean, across-individual, and intra-individual responses

© 2015, Springer-Verlag Berlin Heidelberg. Anti-predator behavior is a key aspect of life history evolution, usually studied at the population (mean), or across-individual levels. However individuals can also differ in their intra-individual (residual) variation, but to our knowledge, this has only been studied once before in free-living animals. Here we studied the distances moved and changes in nest height and concealment between successive nesting attempts of marked pairs of grey fantails (Rhipidura albiscapa) in relation to nest fate, across the breeding season. We predicted that females (gender that decides where the nest is placed) should on average show adaptive behavioral responses to the experience of prior predation risk such that after an unsuccessful nesting attempt, replacement nests should be further away, higher from the ground, and more concealed compared with replacement nests after successful nesting attempts. We found that, on average, females moved greater distances to re-nest after unsuccessful nesting attempts (abandoned or depredated) in contrast to after a successful attempt, suggesting that re-nesting decisions are sensitive to risk. We found no consistent across-individual differences in distances moved, heights, or concealment. However, females differed by 53-fold (or more) in their intra-individual variability (i.e., predictability) with respect to distances moved and changes in nest height between nesting attempts, indicating that either some systematic variation went unexplained and/or females have inherently different predictability. Ignoring these individual differences in residual variance in our models obscured the effect of nest fate on re-nesting decisions that were evident at the mean level.