Significant Non-additive Effects Research Articles

Structural, physicochemical, and pasting properties of native cassava (Manihot esculenta) and yam (Dioscorea alata) starch blends

Starch blends are a technological alternative aimed at the development of starchy matrices that exhibit improvements in some physicochemical properties from interactions between their individual components. Native cassava and yam starches were mixed in different proportions and the effect of the blend on the structural, physicochemical, and pasting properties was evaluated. The viscosity behavior as a function of temperature revealed a significant non-additive effect on the pasting parameters of all the blends with respect to the individual native starches. Similarly, non-additive variations were evident in the crystallinity index of some mix ratios (NSB-2: 40.11%). Likewise, the difference in the amylose content of each native starch (20.88-25.66%) possibly exerted an effect on the resulting semicrystalline characteristics of the blends and the gelatinization behavior. Hence, the botanical origin and the proportion of starch blends play an important role in the behavior of the resulting physicochemical properties and in vitro digestibility. Polymeric blends were obtained with a low tendency to retrogradation and lower crystallinity index values compared to their native counterparts and a regulated water absorption capacity, all potentially desirable characteristics in the food industry.

Identifying QTLs involved in hybrid performance and heterotic group complementarity: new GWAS models applied to factorial and admixed diallel maize hybrid panels

Key messageAn original GWAS model integrating the ancestry of alleles was proposed and allowed the detection of background specific additive and dominance QTLs involved in heterotic group complementarity and hybrid performance. Maize genetic diversity is structured into genetic groups selected and improved relative to each other. This process increases group complementarity and differentiation over time and ensures that the hybrids produced from inter-group crosses exhibit high performances and heterosis. To identify loci involved in hybrid performance and heterotic group complementarity, we introduced an original association study model that disentangles allelic effects from the heterotic group origin of the alleles and compared it with a conventional additive/dominance model. This new model was applied on a factorial between Dent and Flint lines and a diallel between Dent-Flint admixed lines with two different layers of analysis: within each environment and in a multiple-environment context. We identified several strong additive QTLs for all traits, including some well-known additive QTLs for flowering time (in the region of Vgt1/2 on chromosome 8). Yield trait displayed significant non-additive effects in the diallel panel. Most of the detected Yield QTLs exhibited overdominance or, more likely, pseudo-overdominance effects. Apparent overdominance at these QTLs contributed to a part of the genetic group complementarity. The comparison between environments revealed a higher stability of additive QTL effects than non-additive ones. Several QTLs showed variations of effects according to the local heterotic group origin. We also revealed large chromosomic regions that display genetic group origin effects. Altogether, our results illustrate how admixed panels combined with dedicated GWAS modeling allow the identification of new QTLs that could not be revealed by a classical hybrid panel analyzed with traditional modeling.

COMBINATION ABILITY OF SOYBEAN VARIETIES BY PRODUCTIVITY IN TOPCROSS CROSSES

Two-tester analysis of topcross crossings of soybean varieties, which differ in valuable economic traits and ecological and geographical origin, was used in the research. According to the indicators of combining ability, the value of soybean varieties was determined by the elements of the crop structure. In hybrid populations, the degree and frequency of positive transgressions have been determined, which is a selection material for the creation of new varieties by hybridization. High effects of ZKZ on plant height and attachment of lower beans were established in Sawyer 2-95 variety and KiVin tester; by the number of productive nodes - in the varieties Sawyer 2-95, Medea, Kyivska 97 and tester KyVin; according to the number of beans per plant - in varieties Ustya, Kyivska 97 and tester KyVin; according to the number of seeds on the plant - in the Medea, Kyivska 97 and Hoverla tester varieties; by the weight of 1000 seeds - in varieties Sawyer 2-95, Kyivska 97 and Hoverla tester; according to the mass of grain from the plant - in the varieties Medea, Kyivska 97 and tester Hoverla; in terms of productivity - in Medea, Kyivska 97 and tester Hoverla varieties. It was established that additive effects of genes were dominant in the genetic control of plant height traits and attachment of lower beans, elements of crop structure and productivity, but there was also a significant non-additive effect. According to the number of beans per plant, the number of seeds per plant, and the weight of seeds per plant, in the vast majority of hybrid populations, inheritance by the type of overdominance and dominance of the parental form with a higher manifestation of the trait was noted. The analysis of dominance indicators made it possible to identify crossbreeding combinations that are distinguished by the overdominance of the specified traits and have significant breeding value: Sawyer 2-95 × Hoverla, Kyivska 97 × Hoverla, Kharkivska precocious × Hoverla, Sawyer 2-95 × KiVin, Kharkivska precocious × KiVin.

A simple theory for interfacial properties of dilute solutions.

Recent studies suggest that cosolute mixtures may exert significant non-additive effects upon protein stability. The corresponding liquid-vapor interfaces may provide useful insight into these non-additive effects. Accordingly, in this work, we relate the interfacial properties of dilute multicomponent solutions to the interactions between solutes. We first derive a simple model for the surface excess of solutes in terms of thermodynamic observables. We then develop a lattice-based statistical mechanical perturbation theory to derive these observables from microscopic interactions. Rather than adopting a random mixing approximation, this dilute solution theory (DST) exactly treats solute-solute interactions to lowest order in perturbation theory. Although it cannot treat concentrated solutions, Monte Carlo (MC) simulations demonstrate that DST describes the interactions in dilute solutions with much greater accuracy than regular solution theory. Importantly, DST emphasizes a fundamental distinction between the "intrinsic" and "effective" preferences of solutes for interfaces. DST predicts that three classes of solutes can be distinguished by their intrinsic preference for interfaces. While the surface preference of strong depletants is relatively insensitive to interactions, the surface preference of strong surfactants can be modulated by interactions at the interface. Moreover, DST predicts that the surface preference of weak depletants and weak surfactants can be qualitatively inverted by interactions in the bulk. We also demonstrate that DST can be extended to treat surface polarization effects and to model experimental data. MC simulations validate the accuracy of DST predictions for lattice systems that correspond to molar concentrations.

Genome-wide detection of non-additive quantitative trait loci for semen production traits in beef and dairy bulls

Semen production traits are important aspects of bull fertility, because semen quantity leads to direct profits for artificial insemination centres, and semen quality is associated with the probability of achieving a pregnancy. Most genome-wide association studies (GWASs) for semen production traits have assumed that each quantitative trait locus (QTL) has an additive effect. However, GWASs that account for non-additive effects are also important in fitness traits, such as bull fertility. Here, we performed a GWAS using models that accounted for additive and non-additive effects to evaluate the importance of non-additive effects on five semen production traits in beef and dairy bulls. A total of 65 463 records for 615 Japanese Black bulls (JB) and 50 734 records for 873 Holstein bulls (HOL), which were previously genotyped using the Illumina BovineSNP50 BeadChip, were used to estimate genetic parameters and perform GWAS. The heritability estimates were low (ranged from 0.11 to 0.23), and the repeatability estimates were low to moderate (ranged from 0.28 to 0.45) in both breeds. The estimated repeatability was approximately twice as high as the estimated heritability for all traits. In this study, only one significant region with an additive effect was detected in each breed, but multiple significant regions with non-additive effects were detected for each breed. In particular, the region at approximately 64 Mbp on Bos taurus autosome 17 had the highest significant non-additive effect on four semen production traits in HOL. The rs41843851 single nucleotide polymorphism (SNP) in the region had a much lower P-value for the non-additive effect (P-value = 1.1 × 10−31) than for the additive effect (P-value = 1.1 × 10−8) in sperm motility. The AA and AB genotypes on the SNP had a higher phenotype than the BB genotype in HOL, and there was no bull with the BB genotype in JB. Our results showed that non-additive QTLs affect semen production traits, and a novel QTL accounting for non-additive effects could be detected by GWAS. This study provides new insights into non-additive QTLs that affect fitness traits, such as semen production traits in beef and dairy bulls.

Genetic control of soybean seed quality using partial diallel

Abstract: The selection of soybean genotypes with seeds of high physiological quality is key to increasing the likelihood of establishment and success in the field and thus reaping higher yields. The aim of this study was to evaluate the genetic control of the physiological quality of soybean seeds from a partial diallel cross. Six previously selected soybean cultivars, group 1 (CD 201, CA 115, MS 8400) and group 2 (CD 202, Syn 1263, Syn 1279), were intercrossed by a partial diallel cross, totalizing 24 treatments. Seeds from these cultivars and crosses were evaluated for seed physiological quality based on germination tests, first germination count, accelerated aging, seedlings emergence, and emergence speed index. The lignin content in the soybean seed coat was evaluated. The effects on general and specific combining ability and reciprocal effects were analyzed. There were significant additive and non-additive effects of the genes on the seed quality traits and pronounced effects on the reciprocal traits, which suggest the presence of a maternal effect. Lignin content was not correlated with the physiological test results in the studied genotypes.

Generation mean analysis for resistance to bacterial brown spot disease in dry bean

ABSTRACT Dry bean (Phaseolus vulgaris L.) is a key protein and income source grown worldwide. This study determined gene effects influencing resistance to the bacterial brown spot (BBS) disease caused by Pseudomonas syringae pv. syringae, and estimated heritability in a dry bean cross between A55 (resistant) and cultivar RS7 (susceptible). Generations derived from the parents, namely F1, F2, two backcross generations, and the parents themselves were analysed. The six generations were cultivated in a randomised block design with two replications and inoculated with BBS isolates at two weeks after planting. Disease scoring was done at two weeks after inoculation using standard scale (1–9), where 1 represented highly resistant, and 9 represented highly susceptible. Generation means differed (P < 0.001), and scaling test parameters A and C were significant (P < 0.001) revealing that variation in data was not sufficiently explained by additive [d] and dominance [h] components. Five parameters viz. mean [m], [d], [h], additive × additive epistasis [i], and dominance × dominance epistasis [l] were significant (P < 0.001). The [h] and [l] effects had contrasting signs, indicating duplicate epistasis. Significant non-additive gene effects, together with moderate heritability, suggested that phenotypic selection for resistance, especially in early segregating generations, would be ineffective in conventional breeding.

The Stability Landscape of de novo TIM Barrels Explored by a Modular Design Approach

The ability to design stable proteins with custom-made functions is a major goal in biochemistry with practical relevance for our environment and society. Understanding and manipulating protein stability provide crucial information on the molecular determinants that modulate structure and stability, and expand the applications of de novo proteins. Since the (β/⍺)8-barrel or TIM-barrel fold is one of the most common functional scaffolds, in this work we designed a collection of stable de novo TIM barrels (DeNovoTIMs), using a computational fixed-backbone and modular approach based on improved hydrophobic packing of sTIM11, the first validated de novo TIM barrel, and subjected them to a thorough folding analysis. DeNovoTIMs navigate a region of the stability landscape previously uncharted by natural TIM barrels, with variations spanning 60 degrees in melting temperature and 22 kcal per mol in conformational stability throughout the designs. Significant non-additive or epistatic effects were observed when stabilizing mutations from different regions of the barrel were combined. The molecular basis of epistasis in DeNovoTIMs appears to be related to the extension of the hydrophobic cores. This study is an important step towards the fine-tuned modulation of protein stability by design.

Improved genomic prediction of clonal performance in sugarcane by exploiting non-additive genetic effects

Key messageNon-additive genetic effects seem to play a substantial role in the expression of complex traits in sugarcane. Including non-additive effects in genomic prediction models significantly improves the prediction accuracy of clonal performance.In the recent decade, genetic progress has been slow in sugarcane. One reason might be that non-additive genetic effects contribute substantially to complex traits. Dense marker information provides the opportunity to exploit non-additive effects in genomic prediction. In this study, a series of genomic best linear unbiased prediction (GBLUP) models that account for additive and non-additive effects were assessed to improve the accuracy of clonal prediction. The reproducible kernel Hilbert space model, which captures non-additive genetic effects, was also tested. The models were compared using 3,006 genotyped elite clones measured for cane per hectare (TCH), commercial cane sugar (CCS), and Fibre content. Three forward prediction scenarios were considered to investigate the robustness of genomic prediction. By using a pseudo-diploid parameterization, we found significant non-additive effects that accounted for almost two-thirds of the total genetic variance for TCH. Average heterozygosity also had a major impact on TCH, indicating that directional dominance may be an important source of phenotypic variation for this trait. The extended-GBLUP model improved the prediction accuracies by at least 17% for TCH, but no improvement was observed for CCS and Fibre. Our results imply that non-additive genetic variance is important for complex traits in sugarcane, although further work is required to better understand the variance component partitioning in a highly polyploid context. Genomics-based breeding will likely benefit from exploiting non-additive genetic effects, especially in designing crossing schemes. These findings can help to improve clonal prediction, enabling a more accurate identification of variety candidates for the sugarcane industry.

Evidence that genetic compatibility underpins female mate choice in a monandrous amphibian.

Mate choice for genetic benefits remains controversial, largely because few studies have estimated the relative contributions of additive and non-additive sources of genetic variation to offspring fitness. Moreover, there remains a deficit of these estimates for species where female-mate preferences have been quantified in the wild, especially species characterized by monandry or monogamy. Here, we use artificial fertilization techniques combined with a cross-classified breeding design to simultaneously test for "good genes" and "compatible genes" benefits of mate choice in the monandrous red backed toadlet (Pseudophryne coriacea). In addition, we used a genomic approach to estimate effects of parental-genetic relatedness (assessed using 27, 768 single nucleotide polymorphisms) on offspring fitness. Our results revealed no significant additive genetic effects (sire effects), but highly significant non-additive genetic effects (sire × dam interaction effects), on fertilization success, survival during embryonic development, and hatching success. We also found significant associations between parental genetic similarity and offspring survival (whereby survival was higher when parents were more related), and significant positive relationships between fertilization success and embryo survival through to hatching. These results indicate that offspring viability is significantly influenced by the genetic compatibility of parental genotypes, that more related parents are more genetically compatible, and that gametes with greater compatibility at fertilization produce more viable offspring. More broadly, our findings provide new quantitative genetic evidence that genetic incompatibility underpins female mate preferences. Continued quantitative genetic assessment of the relative importance of good genes versus compatible genes is needed to ascertain the general importance of genetic benefits as a driver of female mate choice.

Quantitative Genetic Variation in Bark Stripping of Pinus radiata

Bark stripping by mammals is a major problem for conifer forestry worldwide. In Australia, bark stripping in the exotic plantations of Pinus radiata is mainly caused by native marsupials. As a sustainable management option, we explored the extent to which natural variation in the susceptibility of P. radiata is under genetic control and is thus amenable to genetic improvement. Bark stripping was assessed at ages four and five years in two sister trials comprising 101 and 138 open-pollinated half-sib families. A third younger trial comprising 74 full-sib control-pollinated families was assessed at two and three years after planting. Significant additive genetic variation in bark stripping was demonstrated in all trials, with narrow-sense heritability estimates between 0.06 and 0.14. Within sites, the amount of additive genetic variation detected increased with the level of bark stripping. When strongly expressed across the two sister trials, the genetic signal was stable (i.e., there was little genotype × environment interaction). No significant non-additive effect (specific combining ability effect) on bark stripping was detected in the full-sib family trial, where it was estimated that up to 22.1% reduction in bark stripping might be achieved by selecting 20% of the less susceptible families. Physical traits that were genetically correlated, and likely influenced the amount of bark removed from the trees by the marsupials, appeared to depend upon tree age. In the older trials, these traits included bark features (presence of rough bark, rough bark height, and bark thickness), whereas in the younger trial where rough bark was not developed, it was the presence of obstructive branches or needles on the stem. In the younger trial, a positive genetic correlation between prior height and bark stripping was detected, suggesting that initially faster growing trees exhibit more bark stripping than slower growing trees but later develop rough bark faster and became less susceptible. While the presence of unexplained genetic variation after accounting for these physical factors suggests that other explanatory plant traits may be involved, such as chemical traits, overall the results indicate that selection for reduced susceptibility is possible, with potential genetic gains for deployment and breeding.

An in vitro mimic of in-cell solvation for protein folding studies.

Ficoll, an inert macromolecule, is a common in vitro crowder, but by itself it does not reproduce in-cell stability or kinetic trends for protein folding. Lysis buffer, which contains ions, glycerol as a simple kosmotrope, and mimics small crowders with hydrophilic/hydrophobic patches, can reproduce sticking trends observed in cells but not the crowding. We previously suggested that the proper combination of Ficoll and lysis buffer could reproduce the opposite in-cell folding stability trend of two proteins: variable major protein-like sequence expressed (VlsE) is destabilized in eukaryotic cells and phosphoglycerate kinase (PGK) is stabilized. Here, to discover a well-characterized solvation environment that mimics in-cell stabilities for these two very differently behaved proteins, we conduct a two-dimensional scan of Ficoll (0-250 mg/ml) and lysis buffer (0-75%) mixtures. Contrary to our previous expectation, we show that mixtures of Ficoll and lysis buffer have a significant nonadditive effect on the folding stability. Lysis buffer enhances the stabilizing effect of Ficoll on PGK and inhibits the stabilizing effect of Ficoll on VlsE. We demonstrate that a combination of 150 mg/ml Ficoll and 60% lysis buffer can be used as an in vitro mimic to account for both crowding and non-steric effects on PGK and VlsE stability and folding kinetics in the cell. Our results also suggest that this mixture is close to the point where phase separation will occur. The simple mixture proposed here, based on commercially available reagents, could be a useful tool to study a variety of cytoplasmic protein interactions, such as folding, binding and assembly, and enzymatic reactions. SIGNIFICANCE STATEMENT: The complexity of the in-cell environment is difficult to reproduce in the test tube. Here we validate a mimic of cellular crowding and sticking interactions in a test tube using two proteins that are differently impacted by the cell: one is stabilized and the other is destabilized. This mimic is a starting point to reproduce cellular effects on a variety of protein and biomolecular interactions, such as folding and binding.

Genetic benefits of extreme sequential polyandry in a terrestrial-breeding frog.

Sequential polyandry may evolve as an insurance mechanism to reduce the risk of females choosing mates who are genetically inferior (intrinsic male quality hypothesis) or genetically incompatible (genetic incompatibility hypothesis). The prevalence of such indirect benefits remains controversial, however, because studies estimating the contributions of additive and nonadditive sources of genetic variation to offspring fitness have been limited to a small number of taxonomic groups. Here, we used artificial fertilization techniques combined with a crossclassified breeding design (North Carolina Type II) to simultaneously test the "good genes hypothesis" and the "genetic incompatibility hypothesis" in the brown toadlet (Pseudophryne bibronii); a terrestrial-breeding species with extreme sequential polyandry. Our results revealed no significant additive or nonadditive genetic effects on fertilization success. Moreover, they revealed no significant additive genetic effects, but highly significant nonadditive genetic effects (sire by dam interaction effects), on hatching success and larval survival to initial and complete metamorphosis. Taken together, these results indicate that offspring viability is significantly influenced by the combination of parental genotypes, and that negative interactions between parental genetic elements manifest during embryonic and larval development. More broadly, our findings provide quantitative genetic evidence that insurance against genetic incompatibility favors the evolution and maintenance of sequential polyandry.

The effect of tree diversity on the resistance and recovery of forest stands in the French Alps may depend on species differences in hydraulic features

As climate change should lead to an increase in the vulnerability and the sensitivity of forests to extreme climatic events, quantifying and predicting their response to more severe droughts remains a key task for foresters. Furthermore, recent works have suggested that tree diversity may affect forest ecosystem functioning, including their response to extreme events. In this study we aimed at testing whether the growth response of forest stands to stressful climatic events varied between mixed and monospecific stands, under various environmental conditions. We focused on beech-fir forests (Fagus sylvatica [L.] and Abies alba [L.]) and beech-oak forests (F. sylvatica [L.] and Quercus pubescent [L.]) in the French Alps. We used a dendrochronological dataset sampled in forest plots organized by triplets (one mixture and two monospecific stands) distributed in six sites along a latitudinal gradient. We tested (1) whether stand diversity (two-species stands vs monospecific stands) modulates the stands’ response to drought events in terms of productivity, (2) whether species identity may drive the diversity effect on resistance and recovery, and (3) whether this can be explained by interspecific interactions. We found that (1) interspecific differences in response to extreme drought events (possibly due to interspecific differences in hydraulic characteristics) can induce a mixture effect on stand growth, although it appeared (2) to be strongly depending on species identity (positive effect only found for beech-fir mixed stands), while (3) there were no significant non-additive effects of diversity on stand resistance and recovery, except for some specific cases. Overall, our study shows that promoting selected mixed stands management may buffer extreme drought effect on stand productivity.

Consequences of multiple flower-insect interactions for subsequent plant-insect interactions and plant reproduction.

Plants often interact simultaneously with multiple antagonists and mutualists that can alter plant traits at the phenotypic or genetic level, subsequent plant-insect interactions, and reproduction. Although many studies have examined the effects of single floral antagonisms on subsequent pollination and plant reproduction, we know very little about the combined, potentially non-additive effects of multiple flower-insect interactions. We simulated increased florivory, nectar robbing, and pollination on field-grown Impatiens capensis, which allowed us to determine interactive effects on five subsequent plant-insect interactions and 16 plant traits, including traits related to plant growth, floral attractiveness, floral defenses, and plant reproduction. All three manipulative treatments had significant non-additive effects on the behavior of subsequent floral visitors, indicating that the effect of floral visitors generally depended on the presence or behavior of others. Pollination increased visitation by both pollinators and nectar larcenists (robbers and thieves), while florivory reduced pollinator and larcenist visits. Surprisingly, supplemental pollination also increased leaf herbivory. Florivores often responded to manipulations in opposite ways than did nectar larcenists and pollinators, suggesting different mechanisms influencing visitors that consume nectar compared to floral tissue. While our treatments did not affect any floral trait measured, they non-additively impacted plant reproduction, with florivory having a larger overall impact than either nectar robbing or pollination. These results emphasize the importance of understanding the context in which flower-insect interactions occur because the composition of the interacting community can have large and non-additive impacts on subsequent insect behavior and plant reproduction.

Litter species richness and composition effects on fungal richness and community structure in decomposing foliar and root litter

Litter species richness influences fungal diversity because of resource heterogeneity. Litter species composition effects on decomposition have been studied mostly in aboveground litter. However, little is known about the effects of litter diversity of roots and litter type effect on fungal diversity in general. We addressed litter species composition and richness effects on diversity of ectomycorrhizal (EcM), saprotrophic and pathogenic fungi in decomposing foliar and root litter in the Satakunta forest diversity experiment by varying litter species richness from one to four species in 560 litter bags incubated under tree canopies. After one year of decomposition, there were no significant non-additive effects of litter mixtures on mass loss. Litter species composition was the strongest predictor for saprotroph and plant pathogen community structure in foliar litter, but its effect on root litter fungal composition was much weaker. Litter diversity strongly enhanced fungal richness in foliar but not in root substrate. We found no evidence for host litter preferences in host-specific EcM fungi. Our study suggests that litter species richness and especially certain litter species may influence decomposition through modifying fungal community composition both in foliar and root litter.

Genetic and non-genetic factors influencing the live weight of artificially-reared lambs

The Spooner Agricultural Research Station (ARS) of the University of Wisconsin-Madison housed the only dairy sheep research flock in North America at the time of its closing in 2016. Multiple experiments conducted at the Spooner ARS determined that raising dairy lambs on milk replacer can be profitable and has since become a common practice in many U.S. dairy flocks. While the genetic basis of early growth traits in naturally-reared lambs has been extensively researched, little is known about the extent to which direct and maternal additive effects influence these traits in artificially-reared animals. The traits analyzed were birth weight (BW0) and 30 d adjusted weaning weight (BW30). Univariate models first determined the significant non-additive genetic effects on BW traits. Lacaune breed composition negatively affected (P < 0.01) both BW traits. Individual heterosis positively influenced (P ≤ 0.04) both BW traits, but only BW0 was positively influenced by maternal heterosis (P < 0.001). A bivariate model was used to estimate genetic and non-genetic relationships among BW0 and BW30. The estimated direct heritabilities of BW0 and BW30 were 0.27 ± 0.04 and 0.39 ± 0.05, respectively. The higher than generally reported heritability for BW30 was likely due to a decrease in environmental variation associated with artificial rearing. Lamb BW traits were estimated to be highly phenotypically (0.54 ± 0.02) and genetically (0.63 ± 0.07) correlated. Additive maternal genetic effects explained a substantial proportion of the phenotypic variation of BW0 (0.25 ± 0.02). Although only artificially-reared lambs were included in the analyses of BW30, additive maternal genetic effects were non-zero (0.13 ± 0.02). The sale of market lambs represents a significant source of revenue for U.S. dairy sheep producers, and knowledge of the factors affecting lamb performance has important economic implications.

Whole-genome scan reveals significant non-additive effects for sire conception rate in Holstein cattle

BackgroundService sire has a considerable impact on reproductive success in dairy cattle. Most gene mapping studies for bull fertility have focused on additive effects, while non-additive effects have been largely ignored. The main goal of this study was to assess the relevance of non-additive effects on Sire Conception Rate (SCR) in Holstein dairy cattle. The analysis included 7.5 k Holstein bulls with both SCR records and 57.8 k single nucleotide polymorphism (SNP) markers spanning the entire genome.ResultsThe importance of non-additive effects was evaluated using an efficient two-step mixed model-based approach. Four genomic regions located on chromosomes BTA8, BTA9, BTA13 and BTA17 showed marked dominance and/or recessive effects. Most of these regions harbor genes, such as ADAM28, DNAJA1, TBC1D20, SPO11, PIWIL3 and TMEM119, that are directly implicated in testis development, male germ line maintenance, and sperm maturation.ConclusionsThis study provides further evidence for the relevance of non-additive effects in fitness-related traits, such as male fertility. In addition, these findings may point out new strategies for improving service sire fertility in dairy cattle via marker-assisted selection.

The genetic and environmental architecture of substance use development from early adolescence into young adulthood: a longitudinal twin study of comorbidity of alcohol, tobacco and illicit drug use

To investigate how use of alcohol, illicit drugs and tobacco come from substance-specific pathways and from pathways general to all three substances through adolescent development. Analysis of population-based survey. Adolescent twins reported alcohol use (AU), tobacco use (TU) and illicit drug use (IDU) in three waves (2006, 2008, 2010). Restructuring data by age allowed for variance decomposition into age- and substance-specific and common genetic and environmental variance components. Norway. Seven national twin birth cohorts from 1988 to 1994, totalling 1483 pairs (558 monozygotic; 925 dizygotic, same and opposite sex). Six-point Likert scores of AU, TU and IDU on items from the Monitoring the Future Study. Substance use was found to be highly heritable; a2 =0.73 [95% confidence interval (CI) =0.61-0.94] for AU, a2 =0.36 (CI=0.18-0.52); d2 =0.49 (95% CI=0.29-0.62) for IDU and a2 =0.46 (95% CI=0.23-0.54); d2 =0.05 (95% CI=0.00-0.07) for TU during the whole adolescence period. General substance use (GSU) was also highly heritable at each age and averaged a2 =0.57 (95% CI=0.48-0.66). There was a high genetic carry-over from earlier age to later age. Genetic effects on GSU at ages 12-14years were still detectable 4years later. New substance (general and specific)-genetic effects also appeared. IDU demonstrated significant non-additive genetic effects (ages 12-14years). Shared environment had a small impact on AU only. There was almost no non-shared environmental carry-over from age to age, the effect probably due partly to reliability deficiency. Common genetic effects among substance and substance-specific genetic effects were observed at each age-period. Among Norwegian adolescents, there appear to be strong genetic effects on both substance-specific and comorbid use of alcohol, illicit drugs and tobacco; individual differences in alcohol use can be explained partially by family background.

Genetic landscape of interactive effects of HLA-DRB1 alleles on susceptibility to ACPA(+) rheumatoid arthritis and ACPA levels in Japanese population

BackgroundHLA-DRB1 is the strongest susceptibility gene to rheumatoid arthritis (RA). HLA-DRB1 alleles showed significant non-additive and interactive effects on susceptibility to RA in the European population, but these effects on...