Identification of transcriptional regulatory variants in pig duodenum, liver, and muscle tissues

Background In humans and livestock species, genome-wide association studies (GWAS) have been applied to study the association between variants distributed across the genome and a phenotype of interest. To discover genetic polymorphisms affecting the duodenum, liver, and muscle transcriptomes of 300 pigs from 3 different breeds (Duroc, Landrace, and Large White), we performed expression GWAS between 25,315,878 polymorphisms and the expression of 13,891 genes in duodenum, 12,748 genes in liver, and 11,617 genes in muscle. Results More than 9.68 × 1011 association tests were performed, yielding 14,096,080 significantly associated variants, which were grouped in 26,414 expression quantitative trait locus (eQTL) regions. Over 56% of the variants were within 1 Mb of their associated gene. In addition to the 100-kb region upstream of the transcription start site, we identified the importance of the 100-kb region downstream of the 3′UTR for gene regulation, as most of the cis-regulatory variants were located within these 2 regions. We also observed 39,874 hotspot regulatory polymorphisms associated with the expression of 10 or more genes that could modify the protein structure or the expression of a regulator gene. In addition, 2 motifs (5′-GATCCNGYGTTGCYG-3′ and a poly(A) sequence) were enriched across the 3 tissues within the neighboring sequences of the most significant single-nucleotide polymorphisms in each cis-eQTL region. Conclusions The 14 million significant associations obtained in this study are publicly available and have enabled the identification of expression-associated cis-, trans-, and hotspot regulatory variants within and across tissues, thus shedding light on the molecular mechanisms of regulatory variations that shape end-trait phenotypes.info:eu-repo/semantics/publishedVersio

Gender Differences in White Matter Microstructure

Sexual dimorphism in human brain structure is well recognised, but little is known about gender differences in white matter microstructure. We used diffusion tensor imaging to explore differences in fractional anisotropy (FA), an index of microstructural integrity.A whole brain analysis of 135 matched subjects (90 men and 45 women) using a 1.5 T scanner. A region of interest (ROI) analysis was used to confirm those results where proximity to CSF raised the possibility of partial-volume artefact.Men had higher fractional anisotropy (FA) in cerebellar white matter and in the left superior longitudinal fasciculus; women had higher FA in the corpus callosum, confirmed by ROI.The size of the differences was substantial--of the same order as that attributed to some pathology--suggesting gender may be a potentially significant confound in unbalanced clinical studies. There are several previous reports of difference in the corpus callosum, though they disagree on the direction of difference; our findings in the cerebellum and the superior longitudinal fasciculus have not previously been noted. The higher FA in women may reflect greater efficiency of a smaller corpus callosum. The relatively increased superior longitudinal fasciculus and cerebellar FA in men may reflect their increased language lateralisation and enhanced motor development, respectively

Fetal and infant origins of asthma

Previous studies have suggested that asthma, like other common diseases, has at least part of its origin early in life. Low birth weight has been shown to be associated with increased risks of asthma, chronic obstructive airway disease, and impaired lung function in adults, and increased risks of respiratory symptoms in early childhood. The developmental plasticity hypothesis suggests that the associations between low birth weight and diseases in later life are explained by adaptation mechanisms in fetal life and infancy in response to various adverse exposures. Various pathways leading from adverse fetal and infant exposures to growth adaptations and respiratory health outcomes have been studied, including fetal and early infant growth patterns, maternal smoking and diet, children’s diet, respiratory tract infections and acetaminophen use, and genetic susceptibility. Still, the specific adverse exposures in fetal and early postnatal life leading to respiratory disease in adult life are not yet fully understood. Current studies suggest that both environmental and genetic factors in various periods of life, and their epigenetic mechanisms may underlie the complex associations of low birth weight with respiratory disease in later life. New well-designed epidemiological studies are needed to identify the specific underlying mechanisms. This review is focused on specific adverse fetal and infant growth patterns and exposures, genetic susceptibility, possible respiratory adaptations and perspectives for new studies

What genetic group structure to fit?: A Bayesian approach applied to yearling worm egg count data in Merino sheep

Genetic groups need to be fitted in a genetic evaluation model to accommodate animals with unknown parents that come from a wide variety of sources. Different genetic grouping strategies were investigated for worm egg count data extracted from Sheep Genetics Australia's Merino database. A Bayesian approach was implemented that tested whether the genetic group variance was significantly different from zero. Four genetic grouping strategies were compared, 1) grouping on average fibre diameter, 2) groups by flock, 3) groups by flock-period, and 4) groups by flock-year. Two additional strategies were grouping strategies 3 and 4 with an assumed autocorrelation structure between genetic groups within flock

Genetic parameters for ultrasound scan and wool traits at yearling and hogget age in Merino sheep

The Australian Merino is the most important genetic resource for the wool and the lamb and sheep meat industries of Australia. In this paper estimated genetic parameters for ultrasound scan and wool traits at yearling and hogget age are presented for Merino sheep. Results indicate that it is possible to breed Merino sheep that perform well for both ultrasound scan and wool characteristics when both are measured

Predictive ability of sire weaning weight breeding values estimated across environments in terminal sire sheep breeds

Data used for the genetic evaluation of terminal sire sheep breeds in Australia originates from a wide array of genotypes and environments. As a result there are large differences in the levels of production and therefore contemporary group means within the data. Differing variances within contemporary groups results in scale effects on the estimated breeding values (EBVs), as there is a tendency for standard deviations to increase with the mean level of expression, groups with a higher phenotypic mean often have more phenotypic variation and, without adjustment, animals from these groups have greater variation in their EBVs. Consequently, animals are likely to be selected from the more variable groups, especially if selection is intense (Hill, 1984). This heterogeneity in variances across contemporary groups results in EBVs that do not reliably predict progeny performance across the whole range of production environments, and this in turn leads to lower confidence in the use of breeding values across flocks where environments and management practices may differ. A relatively simple way of accounting for heterogeneity in variances across fixed effect levels is the transformation of observations to a proportion of their contemporary group mean, an approach regularly used in the Merino sheep industry, as was previously shown by Brown et al. (2005) for wool traits in Merino sheep. The aim of this work was to investigate the predictive ability of terminal sire EBVs for progeny performance in low, medium and high production environments in Australia using weaning weight using different data transformations

Genetic parameters for daily feed intake patterns of growing Dutch Landrace gilts

Daily feed intake (DFI) was described as a function of days on test using a spline random regression model. Order of fit for the spline random regression model was varied, models were compared using Schwarz's Bayesian Information Criterion. The objective was to investigate whether there are genetic differences in DFI patterns. Data were DFI records of 257 growing gilts, which had ad libitum access to food. Gilts were 94 days old at start of test. All gilts were from a Dutch Landrace line. Number of random regression coefficients was varied from zero to nine for both random effects (animal and permanent environment), the model with four random regression coefficients resulted in the most optimal fit. Six traits were derived to capture differences in DFI patterns, average DFI over test, variance of DFI over test, DFI at day 5 on test, DFI at day 50 on test, DFI at day 95 on test and the difference between DFI at day 95 and day 5. Heritability for DFI decreased from 0.53 at 5 days on test to 0.24 at 95 days on test. Genetic correlations between DFI at 5 days on test and 95 days on test, and between DFI at 50 days on test and 95 days on test were low (around 0.3). The results suggested that DFI at different days on test could not be regarded as repeated measurements of a single trait with constant variance and heritability. Based on the results presented, it can be concluded that changes in feed intake patterns through selection are possible

Multiple trait linkage across flocks

To estimate contrasts between groups of animals or herds or flocks, or to compare groups of animals or herds or flocks, there has to be genetic linkage between those groups. A common problem for all extensively farmed livestock is the absence of such linkage. The main objective of assessing linkage is to determine the accuracy of comparisons between EBVs estimated in different herds or flocks. Several methods have been proposed to evaluate connectedness. However if the main objective of a linkage statistic is to identify flocks where EBVs are poorly contrasted in comparison to EBVs from other flocks, then a method which assesses the accuracy of such comparisons is most appropriate. This paper describes and gives an example from a multiple trait linkage analysis tool for data extracted from the Sheep Genetics Australia database

The influence of ewe weight at mating on lamb performance and reproduction of the ewe

The condition score and body weight of ewes at mating have well-established effects on reproductive performance and future performance of the progeny in commercial flocks. The aim of this study is to investigate one of these effects, that of ewe weight at mating on ewe reproductive performance and lamb performance in LAMBPLAN flocks (Terminal and Maternal sire breeds). Ewe weight at mating had a significant (