Mapping short tandem repeats for liver gene expression traits helps prioritize potential causal variants for complex traits in pigs

Background Short tandem repeats (STRs) were recently found to have significant impacts on gene expression and diseases in humans, but their roles on gene expression and complex traits in pigs remain unexplored. This study investigates the effects of STRs on gene expression in liver tissues based on the whole-genome sequences and RNA-Seq data of a discovery cohort of 260 F6 individuals and a validation population of 296 F7 individuals from a heterogeneous population generated from crosses among eight pig breeds. Results We identified 5203 and 5868 significantly expression STRs (eSTRs, FDR < 1%) in the F6 and F7 populations, respectively, most of which could be reciprocally validated (π1 = 0.92). The eSTRs explained 27.5% of the cis-heritability of gene expression traits on average. We further identified 235 and 298 fine-mapped STRs through the Bayesian fine-mapping approach in the F6 and F7 pigs, respectively, which were significantly enriched in intron, ATAC peak, compartment A and H3K4me3 regions. We identified 20 fine-mapped STRs located in 100 kb windows upstream and downstream of published complex trait-associated SNPs, which colocalized with epigenetic markers such as H3K27ac and ATAC peaks. These included eSTR of the CLPB, PGLS, PSMD6 and DHDH genes, which are linked with genome-wide association study (GWAS) SNPs for blood-related traits, leg conformation, growth-related traits, and meat quality traits, respectively. Conclusions This study provides insights into the effects of STRs on gene expression traits. The identified eSTRs are valuable resources for prioritizing causal STRs for complex traits in pigs.

Breeding for disease resilience: opportunities to manage polymicrobial challenge and improve commercial performance in the pig industry

Disease resilience, defined as an animal’s ability to maintain productive performance in the face of infection, provides opportunities to manage the polymicrobial challenge common in pig production. Disease resilience can deliver a number of benefits, including more sustainable production as well as improved animal health and the potential for reduced antimicrobial use. However, little progress has been made to date in the application of disease resilience in breeding programs due to a number of factors, including (1) confusion around definitions of disease resilience and its component traits disease resistance and tolerance, and (2) the difficulty in characterizing such a complex trait consisting of multiple biological functions and dynamic elements of rates of response and recovery from infection. Accordingly, this review refines the definitions of disease resistance, tolerance, and resilience based on previous studies to help improve the understanding and application of these breeding goals and traits under different scenarios. We also describe and summarize results from a “natural disease challenge model” designed to provide inputs for selection of disease resilience. The next steps for managing polymicrobial challenges faced by the pig industry will include the development of large-scale multi-omics data, new phenotyping technologies, and mathematical and statistical methods adapted to these data. Genome editing to produce pigs resistant to major diseases may complement selection for disease resilience along with continued efforts in the more traditional areas of biosecurity, vaccination and treatment. Altogether genomic approaches provide exciting opportunities for the pig industry to overcome the challenges provided by hard-to-manage diseases as well as new environmental challenges associated with climate change.

TCF7L2 acts as a molecular switch in midbrain to control mammal vocalization through a transcriptional repression mechanism

Vocalization is an essential medium for sexual and social signaling in birds and mammals. Periaqueductal gray (PAG) a conserved midbrain structure is believed to be responsible for innate vocalizations, but its molecular regulation remains largely unknown. Here, through a mouse forward genetic screening we identified one of the key Wnt/β-catenin effectors TCF7L2/TCF4 controls ultrasonic vocalization (USV) production and syllable complexity during maternal deprivation and sexual encounter. Expression of TCF7L2 in PAG excitatory neurons is necessary for the complex trait, while TCF7L2 loss reduces neuronal gene expressions and synaptic transmission in PAG. TCF7L2-mediated vocal control is independent of its β-catenin-binding domain but dependent of its DNA binding ability. Patient mutations associated with severe speech delay disrupt the transcriptional repression effect of TCF7L2, while mice carrying those mutations display severe USV impairments. Therefore, we conclude that TCF7L2 orchestrates gene expression in midbrain to control vocal production through a transcriptional repression mechanism.

Internet-Related Disorders and Their Effects on Personality Development in Adolescents from Germany—Results from a Prospective Study

Internet-related disorders (IRD) are increasingly becoming a major health issue. IRD are defined as the predominant use of online content, related to a loss of control and continued use despite negative consequences. Despite findings from cross-sectional studies, the causality of pathways accelerating the development of IRD are unclear. While etiological models emphasize the role of personality as risk factor, mutual influences between IRD and personality have not been examined. A prospective study with two assessments was conducted with n = 941 adolescents (mean age of 13.1 years; 10–17 years). Our aim was to validate etiological assumptions and to examine the effects of IRD-symptoms on the maturation of personality. IRD were measured with the Scale of the Assessment of Internet and Computer game Addiction (AICA-S). Personality traits were assessed using the Brief Five Factor Inventory (BFI). Conscientiousness and neuroticism were predictive for IRD symptoms one year later, and were likewise prone to changes depending on incidence or remission of IRD. Conscientiousness and openness moderated the course of IRD symptoms. Our findings point to complex trait–pathology associations. Personality influences the risk of development and maintenance of IRD symptoms and pre-existing IRD-symptoms affect the development of personality. Adaptations to etiological models are discussed and perspectives for novel intervention strategies are suggested.

Genome-Wide Association Mapping of Crown and Brown Rust Resistance in Perennial Ryegrass

A population of 239 perennial ryegrass (Lolium perenne L.) genotypes was analyzed to identify marker-trait associations for crown rust (Puccinia coronata f. sp. lolii) and brown rust (Puccinia graminis f. sp. loliina) resistance. Phenotypic data from field trials showed a low correlation (r = 0.17) between the two traits. Genotypes were resequenced, and a total of 14,538,978 SNPs were used to analyze population structure, linkage disequilibrium (LD), and for genome-wide association study. The SNP heritability (h2SNP) was 0.4 and 0.8 for crown and brown rust resistance, respectively. The high-density SNP dataset allowed us to estimate LD decay with the highest possible precision to date for perennial ryegrass. Results showed a low LD extension with a rapid decay of r2 value below 0.2 after 520 bp on average. Additionally, QTL regions for both traits were detected, as well as candidate genes by applying Genome Complex Trait Analysis and Multi-marker Analysis of GenoMic Annotation. Moreover, two significant genes, LpPc6 and LpPl6, were identified for crown and brown rust resistance, respectively, when SNPs were aggregated to the gene level. The two candidate genes encode proteins with phosphatase activity, which putatively can be induced by the host to perceive, amplify and transfer signals to downstream components, thus activating a plant defense response.

Haplotype-Based Single-Step GWAS for Yearling Temperament in American Angus Cattle

Behavior is a complex trait and, therefore, understanding its genetic architecture is paramount for the development of effective breeding strategies. The objective of this study was to perform traditional and weighted single-step genome-wide association studies (ssGWAS and WssGWAS, respectively) for yearling temperament (YT) in North American Angus cattle using haplotypes. Approximately 266 K YT records and 70 K animals genotyped using a 50 K single nucleotide polymorphism (SNP) panel were used. Linkage disequilibrium thresholds (LD) of 0.15, 0.50, and 0.80 were used to create the haploblocks, and the inclusion of non-LD-clustered SNPs (NCSNP) with the haplotypes in the genomic models was also evaluated. WssGWAS did not perform better than ssGWAS. Cattle YT was found to be a highly polygenic trait, with genes and QTL broadly distributed across the whole genome. Association studies using LD-based haplotypes should include NCSNPs and different LD thresholds to increase the likelihood of finding the relevant genomic regions affecting the trait of interest. The main candidate genes identified, i.e., ATXN10, ADAM10, VAX2, ATP6V1B1, CRISPLD1, CAPRIN1, FA2H, SPEF2, PLXNA1, and CACNA2D3, are involved in important biological processes and metabolic pathways related to behavioral traits, social interactions, and aggressiveness in cattle. Future studies should further investigate the role of these genes.

Genetic Dissection of Temperament Personality Traits in Italian Isolates

Human personality (i.e., temperament and character) is a complex trait related to mental health, influenced by genetic and environmental factors. Despite the efforts performed during the past decades, its genetic background is only just beginning to be identified. With the aim of dissecting the genetic basis of temperament, we performed a Genome-Wide Association Study (GWAS) on Cloninger’s Temperament and Character Inventory in 587 individuals belonging to different Italian genetic isolates. Data analysis led to the identification of four new genes associated with different temperament scales, such as Novelty Seeking (NS), Harm Avoidance (HA), and Reward Dependence (RD). In detail, we identified suggestive and significant associations between: MAGI2 (highest p-value = 9.14 × 10−8), a gene already associated with schizophrenia and depressive disorder, and the NS–Extravagance scale; CALCB (highest p-value = 4.34 × 10−6), a gene likely involved in the behavioral evolution from wild wolf to domestic dog, and the NS–Disorderliness scale; BTBD3 (highest p-value = 2.152 × 10−8), a gene already linked to obsessive–compulsive disorder, and the HA–Fatigability scale; PRKN (highest p-value = 8.27 × 10−9), a gene described for early onset Parkinson’s disease, and the RD scale. Our work provides new relevant insights into the genetics of temperament, helping to elucidate the molecular basis of psychiatric disorders.

Effect of maternal intrinsic factors on productivity and efficiency at weaning in commercial flock of Pelibuey ewes in the tropic of Tabasco, Mexico

Evaluation of ewe efficiency or productivity is a complex trait because of several factors that are related to produce heavy litters (lamb growth traits) per ewe. The objective of present study was to evaluate maternal intrinsic effects (body weight, body condition score, udder type, litter size, lamb sex) on litter growth traits (litter weight at lambing [LBW] and at weaning adjusted for 70 days [LWW70]) as a criteria of productivity and some indexes of efficiency in Pelibuey ewes. Data of body weight (BW), body condition scores (BCS), and udder types (UT) were taken at lambing, likewise at weaning BW (WBW), on 48 multiparous Pelibuey ewes. Additionally, litter size, sex, birth and weaning weight, were recorded for each offspring; this information was used to calculate LBW, LWW70, average daily gain (ADG), and the following indexes: Ewe efficiency (EEF) expressed as kg of lamb weaned per kg ewe BW at lambing, EEF0.75 expressed as kg of lamb weaned per kg ewe metabolic BW (BW0.75) at lambing, and EEF2 expressed as kg of lamb weaned ± ewe BW gained or lost at waning per kg ewe BW at lambing. For statistical analysis, ewes were classified according to BW (low, medium and high), BCS (low and high) and udder type (I, II, III and IV) at lambing. High BW ewes had greater (P? 0.01) LLW and LWW70 than low BW ewes. Ewe BW at lambing did not affect (P> 0.05) any productivity index. Also, BCS from lambed ewes did not alter (P> 0.05) the productivity parameters. The udder type affected only LWW70 and productivity indexes, being similar among ewes with type-I, II and III udders, but lower in ewes with type-IV udders. Likewise, double litters were heavier at birth and weaning than single litters, affecting EEF and EEF0.75, but not EEF. The Pelibuey ewe’s productivity in humid tropic depends on the maternal BW, udder type at lambing and prolificacy, being a better productivity when ewes have a high BW, double lambing and non-misshapen udders.