Clinical studies have shown similarities in the genetic background and biological functional characteristics between Hashimoto's thyroiditis (HT) and papillary thyroid carcinoma (PTC), and that HT ...may increase risks of PTC. Here, we set to determine the gene expression specificity of HT and PTC by screening related genes or co-expressed genes and exploring their genetic correlation. Referencing the Oncomine database, HT-related genes were discovered to be expressed in many different types of thyroid cancer, such as TSHR that is highly expressed in thyroid cancer. An in-depth genetic analysis and verification of 35 cancer and paracancerous tissue pairs from patients with thyroid cancer, and 35 tissues and blood cells pairs from patients with Hashimoto's thyroiditis was conducted. Gene chip technology research showed that TSHR, BACH2, FOXE1, RNASET2, CTLA4, PTPN22, IL2RA and other HT-related genes were all expressed in PTC, in which TSHR was significantly over-expressed in PTC patients sensitive to radioactive iodine therapy, while BACH2 was significantly under-expressed in these patients. The biologically significant candidate Tag SNP highlighted from HT-related genes was screened by the high-throughput detection method. Somatic mutations in patients with HT and PTC were detected by target region capture technique, and 75 mutations were found in patients with HT and PTC. The upstream regulatory factors of the different genes shared by HT and PTC were analyzed based on Ingenuity Pathway Analysis (IPA), and it was found that HIF-1α and PD-L1 could be used as important upstream regulatory signal molecules. These results provide a basis for screening key diagnostic genes of PTC by highlighting the relationship between some HT-related genes and their polymorphisms in the pathogenesis of PTC.
A well-functioning placenta is essential for fetal and maternal health throughout pregnancy. Using placental weight as a proxy for placental growth, we report genome-wide association analyses in the ...fetal (n = 65,405), maternal (n = 61,228) and paternal (n = 52,392) genomes, yielding 40 independent association signals. Twenty-six signals are classified as fetal, four maternal and three fetal and maternal. A maternal parent-of-origin effect is seen near KCNQ1. Genetic correlation and colocalization analyses reveal overlap with birth weight genetics, but 12 loci are classified as predominantly or only affecting placental weight, with connections to placental development and morphology, and transport of antibodies and amino acids. Mendelian randomization analyses indicate that fetal genetically mediated higher placental weight is causally associated with preeclampsia risk and shorter gestational duration. Moreover, these analyses support the role of fetal insulin in regulating placental weight, providing a key link between fetal and placental growth.
1. Production of antiherbivore chemical defences is generally assumed to be costly in terms of fitness, although some studies have failed to detect such costs. A convincing explanation is that the ...expression of fitness costs depends on environmental conditions such as nutrient availability. 2. We performed a greenhouse experiment with 33 half-sib families in order to study the phenotypic plasticity of constitutive and methyl jasmonate-induced chemical defences to soil phosphorus (P) availability, the existence of genetic trade-offs (costs) between growth and the production of those defences and the extent to which P availability may modulate the expression of those costs. 3. We measured some proxies of vegetative fitness (primary growth, secondary growth and total biomass), plant reserves (soluble sugars and starch) and the concentration of quantitative chemical defences (diterpene content in the stem, total polyphenolics and condensed tannins in the needles). 4. Phosphorus availability had a considerable effect, both on the allocation of resources to constitutive and induced defences and on the expression of vegetative costs associated with those chemical defences. Constitutive investment in chemical defences was greater under P-limited conditions for all studied traits. Inducibility of foliar phenolic compounds was greater under P-limited conditions, and it was strongly constrained under high P availability. Availability of P did not affect the inducibility of stem diterpenes. 5. All defensive traits showed significant genetic variation, with different levels of genetic control in constitutive and induced modes, and genetic variation in their inducibility. We found significant negative genetic correlations (i.e. trade-offs) between growth and defensive investment, but costs of chemical defences emerged only in P-limited conditions. Vegetative costs of constitutive defences were detected for stem diterpenes but not for needle phenolics, while costs of induced defences were found for leaf phenolics but not for stem diterpenes. 6. Synthesis. Our results indicate that P availability controls the production of chemical defences in this pine species, influencing the resource allocation to constitutive defences, the inducibility of those defences and the emergence of related vegetative costs. Phosphorus availability thus appears as a major driver in the evolution of pine resistance to insects and a potential factor in maintaining genetic variation in defences.
Best linear unbiased prediction (BLUP) is a standard method for estimating random effects of a mixed model. This method was originally developed in animal breeding for estimation of breeding values ...and is now widely used in many areas of research. It does not, however, seem to have gained the same popularity in plant breeding and variety testing as it has in animal breeding. In plants, application of mixed models with random genetic effects has up until recently been mainly restricted to the estimation of genetic and non-genetic components of variance, whereas estimation of genotypic values is mostly based on a model with fixed effects. This paper reviews recent developments in the application of BLUP in plant breeding and variety testing. These include the use of pedigree information to model and exploit genetic correlation among relatives and the use of flexible variance-covariance structures for genotype-by-environment interaction. We demonstrate that BLUP has good predictive accuracy compared to other procedures. While pedigree information is often included via the so-called numerator relationship matrix graphic removed , we stress that it is frequently straightforward to exploit the same information by a simple mixed model without explicit reference to the graphic removed -matrix.
Linear or nonlinear genetic relationships between productive life and functional productive life at 72 mo, with final score (SCO), stature, strength, dairyness (DAI), teat diameter, rear legs (side ...view), rump angle, rump width (RUW), fore udder attachment (FUA), rear udder height, rear udder arch, udder depth (UDD), suspensory ligament (SUS), and teat placement, as well as heritabilities and correlations were estimated from multibreed US dairy goat records. Productive life was defined as the total days in production until 72 mo of age (PL72) for goats having the opportunity to express the trait. Functional productive life (FPL72) was analyzed by incorporating first lactation milk yield, fat yield, protein yield, and SCO in the statistical model. Heritabilities and correlations were estimated using linear mixed models with pedigree additive genetic relationships and ASReml software. Nonlinearity of genetic relationships was assessed based on second-degree polynomial (quadratic) regression models, with the breeding values of PL72 or FPL72 as responses and the breeding values for each type trait (linear and quadratic) as predictor variables. Heritability estimates were 0.19, 0.14, 0.18, 0.20, 0.14, 0.07, 0.28, 0.20, 0.15, 0.13, 0.25, 0.18, 0.20, 0.21, 0.21, and 0.32 for PL72, FPL72, SCO, stature, strength, DAI, teat diameter, rear legs, rump angle, RUW, FUA, rear udder height, rear udder arch, UDD, SUS, and teat placement, respectively. The type traits SCO, RUW, and FUA were the most correlated with PL72 and FPL72, so these may be used as selection criteria to increase longevity in dairy goats. An increase in the coefficient of determination >1% for the second degree, compared with that for the linear model for either PL72 or FPL72, was taken as evidence of a nonlinear genetic relationship. Using this criterion, PL72 showed maximum values at intermediate scores in DAI, UDD, and RUW, and maximum values at extreme scores in FUA and SUS, whereas FPL72 showed maximum values at intermediate scores in DAI and UDD, and maximum values at extreme scores in FUA, RUW, and SUS. Selecting for increased SCO, RUW, and FUA will lead to an increase of FPL72 in goats. Consideration of nonlinear relationships between DAI, FUA, RUW, SUS, and UDD may help in the design of more efficient breeding programs for dairy goats using conformation traits.
The objective of the current study was to assess the extent of genotype by environment interaction for growth of sole (Solea solea) grown in an intensive recirculation aquaculture system (RAS) and in ...a semi-natural outdoor pond (POND). The RAS environment consisted of four indoor shallow raceways without sand, where fish were stocked at a density of 40fish/m2 and fed with dry pelleted feed. The POND environment consisted of one 100m2 outdoor pond, where fish were stocked at densities of 1.4fish/m2, and fish could prey on live ragworms present in the sediment. S. solea (n=2800) offspring, produced by natural mating of wild broodstock, and with initial body weight of 64±20g, were randomly divided over the two environments. After a growing period of 165days, all fish were harvested and harvest weight (HW, g), specific growth rate (SGR, %BW/d) and sex of all fish was assessed; molecular relatedness between animals was estimated using 9 microsatellite markers. In POND 980 fish and in RAS 774 fish were successfully genotyped and used in the analysis. SGR was higher for sole reared in POND compared to RAS (0.60±0.01 vs. 0.57±0.01). Pearson correlation of initial body weight with SGR was negative, and more so in POND compared to RAS (−0.30 vs. −0.16, respectively). Genetic variance and heritability estimates for SGR were higher in POND (h2=0.20±0.05) than in RAS (h2=0.04±0.02). Genetic correlations for HW and SGR of sole reared in RAS and in POND were 0.56±0.34 and 0.27±0.3, respectively. The differences in heritable variation and the low genetic correlations of growth of sole between environments suggest strong genotype by environment interaction. These results are important in developing breeding programs for sole because the accuracy of selection and genetic gain for growth of sole may differ between environments. Low genetic correlations for growth between environments imply that the best genotypes in an intensive aquaculture environment are not to be necessarily the best genotypes in more natural environments such as ponds.
•First G×E study for genetically wild sole reared in RAS and in semi-natural POND•Different heritability estimates for growth in RAS and in semi-natural POND•Low genetic correlations for growth between RAS and semi-natural POND
The heritability of chimpanzee and human brain asymmetry Gómez-Robles, Aida; Hopkins, William D.; Schapiro, Steven J. ...
Proceedings of the Royal Society. B, Biological sciences,
12/2016, Letnik:
283, Številka:
1845
Journal Article
Recenzirano
Human brains are markedly asymmetric in structure and lateralized in function, which suggests a relationship between these two properties. The brains of other closely related primates, such as ...chimpanzees, show similar patterns of asymmetry, but to a lesser degree, indicating an increase in anatomical and functional asymmetry during hominin evolution. We analysed the heritability of cerebral asymmetry in chimpanzees and humans using classic morphometries, geometric morphometries, and quantitative genetic techniques. In our analyses, we separated directional asymmetry and fluctuating asymmetry (FA), which is indicative of environmental influences during development. We show that directional patterns of asymmetry, those that are consistently present in most individuals in a population, do not have significant heritability when measured through simple linear metrics, but they have marginally significant heritability in humans when assessed through three-dimensional configurations of landmarks that reflect variation in the size, position, and orientation of different cortical regions with respect to each other. Furthermore, genetic correlations between left and right hemispheres are substantially lower in humans than in chimpanzees, which points to a relatively stronger environmental influence on left–right differences in humans. We also show that the level of FA has significant heritability in both species in some regions of the cerebral cortex. This suggests that brain responsiveness to environmental influences, which may reflect neural plasticity, has genetic bases in both species. These results have implications for the evolvability of brain asymmetry and plasticity among humans and our close relatives.
To understand the origins of interhemispheric differences and commonalities/coupling in human brain wiring, it is crucial to determine how homologous interregional connectivities of the left and ...right hemispheres are genetically determined and related. To address this, in the present study, we analyzed human twin and pedigree samples with high-quality diffusion magnetic resonance imaging tractography and estimated the heritability and genetic correlation of homologous left and right white matter (WM) connections. The results showed that the heritability of WM connectivity was similar and coupled between the 2 hemispheres and that the degree of overlap in genetic factors underlying homologous WM connectivity (i.e., interhemispheric genetic correlation) varied substantially across the human brain: from complete overlap to complete nonoverlap. Particularly, the heritability was significantly stronger and the chance of interhemispheric complete overlap in genetic factors was higher in subcortical WM connections than in cortical WM connections. In addition, the heritability and interhemispheric genetic correlations were stronger for long-range connections than for short-range connections. These findings highlight the determinants of the genetics underlying WM connectivity and its interhemispheric relationships, and provide insight into genetic basis of WM connectivity asymmetries in both healthy and disease states.
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