Search Results (280)

Background: Endometriosis is a chronic inflammatory condition affecting 10–15% of women of reproductive age. Genome-wide association studies (GWASs) have accounted for only a fraction of its high heritability, indicating the need for alternative approaches to identify rare genetic variants contributing to its etiology. To this end, we performed whole-exome sequencing (WES) in a multi-affected family. Methods: A multigenerational family was studied, comprising three sisters, their mother, grandmother, and a daughter, all diagnosed with endometriosis. WES was conducted on the three sisters and their mother. We used the enGenome-Evai and Varelect software to perform our analysis, which mainly focused on rare, missense, frameshift, and stop variants. Results: Bioinformatic analysis identified 36 co-segregating rare variants. Six missense variants in genes associated with cancer growth were prioritized. The top candidates were c.3319G>A (p.Gly1107Arg) in the LAMB4 gene and c.1414G>A (p.Gly472Arg) in the EGFL6 gene. Variants in NAV3, ADAMTS18, SLIT1, and MLH1 may also contribute to disease onset through a synergistic and additive model. Conclusions: We identified novel candidate genes for endometriosis in a multigenerational affected family, supporting a polygenic model of the disease. Our study is an exploratory family-based WES study, and replication and functional studies are warranted to confirm these preliminary findings. Full article

The size of the gluteus medius muscle (GM) in swine significantly impacts both hindlimb conformation and carcass yield, while little is known about the genetic architecture of this trait. This study aims to estimate genetic parameters and identify candidate genes associated with this trait through a genome-wide association study (GWAS). A total of 439 commercial crossbred pigs, possessing both Landrace and Yorkshire ancestry, were genotyped using the Porcine 50K chip. The length and width of the GM were directly measured, and the area was then calculated from these values. The heritabilities were estimated by HIBLUP (V1.5.0) software, and the GWAS was conducted employing the BLINK model implemented in GAPIT3. The heritability estimates for the length, width, and area of the GM were 0.43, 0.40, and 0.46, respectively. The GWAS identified four genome-wide significant SNPs (rs81381267, rs697734475, rs81298447, and rs81458910) associated with the gluteus medius muscle area. The PDE4D gene was identified as a promising candidate gene potentially involved in the regulation of gluteus medius muscle development. Our analysis revealed moderate heritability estimates for gluteus medius muscle size traits. These findings enhance our understanding of the genetic architecture underlying porcine muscle development. Full article

Climate change is jeopardizing global food security, with at least 713 million people facing hunger. To face this challenge, legumes as common beans could offer a nature-based solution, sourcing nutrients and dietary fiber, especially for rural communities in Latin America and Africa. However, since common beans are generally heat and drought susceptible, it is imperative to speed up their molecular introgressive adaptive breeding so that they can be cultivated in regions affected by extreme weather. Therefore, this study aimed to couple an advanced panel of common bean (Phaseolus vulgaris L.) × tolerant Tepary bean (P. acutifolius A. Gray) interspecific lines with Bayesian regression algorithms to forecast adaptation to the humid and dry sub-regions at the Caribbean coast of Colombia, where the common bean typically exhibits maladaptation to extreme heat waves. A total of 87 advanced lines with hybrid ancestries were successfully bred, surpassing the interspecific incompatibilities. This hybrid panel was genotyped by sequencing (GBS), leading to the discovery of 15,645 single-nucleotide polymorphism (SNP) markers. Three yield components (yield per plant, and number of seeds and pods) and two biomass variables (vegetative and seed biomass) were recorded for each genotype and inputted in several Bayesian regression models to identify the top genotypes with the best genetic breeding values across three localities on the Colombian coast. We comparatively analyzed several regression approaches, and the model with the best performance for all traits and localities was BayesC. Also, we compared the utilization of all markers and only those determined as associated by a priori genome-wide association studies (GWAS) models. Better prediction ability with the complete SNP set was indicative of missing heritability as part of GWAS reconstructions. Furthermore, optimal SNP sets per trait and locality were determined as per the top 500 most explicative markers according to their β regression effects. These 500 SNPs, on average, overlapped in 5.24% across localities, which reinforced the locality-dependent nature of polygenic adaptation. Finally, we retrieved the genomic estimated breeding values (GEBVs) and selected the top 10 genotypes for each trait and locality as part of a recommendation scheme targeting narrow adaption in the Caribbean. After validation in field conditions and for screening stability, candidate genotypes and SNPs may be used in further introgressive breeding cycles for adaptation. Full article

Corn smut, caused by Ustilago maydis, significantly threatens maize production. This study evaluated 199 maize inbred lines at the seedling stage under greenhouse conditions for resistance to U. maydis, identifying 39 highly resistant lines. A genome-wide association study (GWAS) using the mrMLM model detected 19 significant single-nucleotide polymorphism (SNP) loci. Based on a linkage disequilibrium (LD) decay distance of 260 kb, 226 candidate genes were identified. Utilizing the significant loci chr1_244281660 and chr5_220156746, two kompetitive allele-specific PCR (KASP) markers were successfully developed. A PCR-based sequence-specific oligonucleotide probe hybridization technique applied to the 199 experimental lines and 60 validation lines confirmed polymorphism for both markers, with selection efficiencies of 48.12% and 43.33%, respectively. The tested materials were derived from foundational inbred lines of domestic and foreign origin. Analysis of 39 highly resistant lines showed that the advantageous alleles carrying thymine/cytosine (T/C) predominated at frequencies of 94.87% and 53.84%, respectively. The genotype TTCC conferred high resistance, while CCTT was highly susceptible. The resistance exhibited high heritability and significant gene-by-environment interaction. This work systematically dissects the genetic basis of common smut resistance in maize, identifies favorable alleles, and provides a novel KASP marker-based strategy for developing disease-resistant germplasm. Full article

Background/Objectives: Maternal exposures are known to influence the risk of isolated cleft lip with or without cleft palate (CL/P)—a common and highly heritable birth defect with a multifactorial etiology. Methods: To identify new risk loci, we conducted a genome-wide gene–environment interaction (GEI) analysis of CL/P with maternal smoking and vitamin use in Filipinos (N_cases = 540, N_controls = 260). Since GEI analyses are typically low in power and the results can be difficult to interpret, we applied multiple testing frameworks to evaluate potential GEI effects: a one degree-of-freedom (1df) GxE test, the 3df joint test, and the two-step EDGE approach. Results: While no genome-wide significant interactions were detected, we identified 11 suggestive GEIs with smoking and 24 with vitamin use. Several implicated loci contain biologically plausible genes. Notable interactions with smoking include loci near FEZF1, TWIST2, and NET1. While FEZF1 is involved in early neuronal development, TWIST2 and NET1 regulate epithelial–mesenchymal transition, which is required for proper lip and palate fusion. Interactions with vitamins encompass CECR2—a chromatin remodeling protein required for neural tube closure—and FURIN, a critical protease during early embryogenesis that activates various growth factors and extracellular matrix proteins. The activity of both proteins is influenced by folic acid. Conclusions: Our findings highlight the critical role of maternal exposures in identifying genes associated with structural birth defects such as CL/P and provide new paths to explore for CL/P genetics. Full article

Ischemic stroke is a complex, multifactorial disorder with a significant heritable component. Recent developments in genome-wide association studies (GWASs) have identified several common variants associated with clinical outcomes, stroke subtypes, and overall risk. Key loci implicated in biological pathways related to vascular integrity, lipid metabolism, inflammation, and atherogenesis include 9p21 (ANRIL), HDAC9, SORT1, and PITX2. Although polygenic risk scores (PRSs) hold promise for early risk prediction and stratification, their clinical utility remains limited by Eurocentric bias and missing heritability. Integrating multiomics approaches, such as functional genomics, transcriptomics, and epigenomics, enhances our understanding of stroke pathophysiology and paves the way for precision medicine. This review summarizes the current genetic landscape of ischemic stroke, emphasizing how evolving methodologies are shaping its prevention, diagnosis, and treatment. Full article

Lipopolysaccharide (LPS) endotoxin is a well-characterized microbe-associated molecular pattern (MAMP) that forms the outer membrane of both pathogenic and commensal Gram-negative bacteria. It plays a crucial role in triggering inflammatory disorders such as mastitis, acidosis, and septicemia. In heifers, an LPS challenge induces a dynamic stress response, marked by elevated cortisol levels, increased body temperature, and altered immune function. Research indicates that LPS administration leads to a significant rise in cortisol post-challenge. Building on this understanding, the present study aimed to estimate genetic parameters for serum cortisol response to LPS challenge in Holstein heifers and its linear associations with production, health, reproduction, and conformation traits. Additionally, a genome-wide association study (GWAS) was conducted to identify genetic regions associated with cortisol response. A total of 252 animals were evaluated for cortisol response, with correlations estimated between cortisol levels and 55 genomic breeding values for key traits. Genetic parameters and heritability for cortisol response were estimated using Residual Maximum Likelihood (REML) in the Blupf90+ v 2.57 software. Single-Step GWAS (ssGWAS) employing a 10-SNP window approach and 42,123 SNP markers was performed to identify genomic regions that explained at least 0.5% of additive genetic variance. Finally, candidate genes and QTLs located 50 kb up and downstream of those windows were identified. The cortisol response showed significant but weak linear associations with cystic ovaries, body maintenance requirements, lactation persistency, milk yield, and protein yield (p-value ≤ 0.05) and showed suggestive weak linear associations with udder texture, clinical ketosis, heel horn erosion, and milking speed (p-value ≤ 0.15). Cortisol response showed significant additive genetic variance, along with moderate heritability of 0.26 (±0.19). A total of 34 windows explained at least 0.5% of additive genetic variance, and 75 QTLs and 11 candidate genes, comprising the genes CCL20, DAW1, CSMD2, HMGB4, B3GAT2, PARD3, bta-mir-2285aw, CFH, CDH2, ENSBTAG00000052242, and ENSBTAG00000050498, were identified. The functional enrichment analysis allowed us to infer two instances where these gene products could interfere with cortisol production: the first instance is related to the complement system, and the second one is related to the EMT (Epithelium–Mesenchymal Transition) and pituitary gland formation. Among the QTLs, 13 were enriched in the dataset, corresponding to traits related to milk (potassium content), the exterior (udder traits, teat placement, foot angle, rear leg placement, and feet and leg conformation), production (length of productive life, net merit, and type), and reproduction (stillbirth and calving ease). In summary, the cortisol response to LPS challenge in Holstein heifers seems to be moderately heritable and has weak but significant linear associations with important production and health traits. Several candidate genes identified could perform important roles, in at least two ways, for cortisol production, and QTLs were identified close to regions of the genome that explained a significant amount of additive genetic variance for cortisol response. Therefore, further investigations are warranted to validate these findings with a larger dataset. Full article

(1) Background: Litter size traits are critical for pig breeding efficiency but pose challenges due to low heritability and sex-limited influences. This study aimed to elucidate the genetic architecture and identify candidate genes for these traits in Large White pigs using genomic selection (GS) and genome-wide association analyses (GWAS). (2) Methods: This study utilized phenotypic data from nine litter size traits in Large White sows. Genotyping-by-sequencing (GBS) was performed to obtain genotype data, retaining 153,782 high-quality SNPs after quality control. Genetic evaluation was conducted using single-step genomic best linear unbiased prediction (ssGBLUP), with genetic parameters (heritability and genetic correlations) estimated via an animal model (repeatability model). To assess prediction accuracy, 10-fold cross-validation was employed to compare traditional BLUP with ssGBLUP. Furthermore, a single-step genome-wide association study (ssGWAS) integrated genomic information and pedigree-based relationship matrices to screen for significant SNPs associated with litter size traits across the genome. Functional analysis of key candidate genes was subsequently conducted based on ssGWAS results. (3) Results: Heritabilities for litter traits ranged from 0.01 to 0.06. ssGBLUP improved genomic prediction accuracy by 6.38–13.33% over BLUP. Six genomic windows explaining 1.07–1.77% of genetic variance were identified via ssGWAS, highlighting GPR12 on SSC11 as a key candidate gene linked to oocyte development. (4) Conclusions: This study demonstrates the efficacy of ssGBLUP for low-heritability traits and identifies GPR12 as a pivotal gene for litter size. Prioritizing NHB and LBWT in breeding programs could enhance genetic gains while mitigating adverse effects on piglet health. These findings advance genomic strategies for improving reproductive efficiency in swine. Full article

Breast and endometrial cancer are prevalent and share both hormonal and environmental risk factors. This study aimed to identify shared germline genetic risk loci for these cancers. In total, 1116 endometrial cancer cases, 3200 breast cancer cases, and 5021 healthy controls were included in a merged sliding window haplotype genome-wide association study (GWAS). This analysis employed a logistic regression model in PLINK v1.07. The results from this merged analysis were compared with previous individual analyses of the same samples. The analysis identified three loci that influenced both the risk of breast and endometrial cancer: 8p21.1 (OR 2.1; p 1.6 × 10⁻⁸), 16q24.3 (OR 2.4; p 3.8 × 10⁻⁸) and 17q11.2 (OR 1.3; p 4.3 × 10⁻⁸). This combined haplotype GWAS of endometrial and breast cancers identified three loci associated with shared genetic risk, two of which were novel: 16q24.3 and 17q11.2. Further studies are warranted to replicate these findings and to determine its pathophysiological role and future clinical implications. Full article

Rapeseed (Brassica napus L., 2n = 38) is an important oil crop worldwide, providing vegetable oil and biofuel. Despite improvements in breeding, rapeseed’s harvest index and yield remain lower than other major crops. Plant height (PH) and first-branch height (FBH) are crucial plant architecture traits affecting yield, lodging resistance and efficiency of mechanical harvesting. Phenotypic analysis of 125 rapeseed accessions across four environments revealed wide variation in PH (100–198 cm) and FBH (15.56–112.4 cm), with high broad-sense heritability (H² = 81.59% for PH, 77.69% for FBH), and significant positive correlations between traits. To understand the genetic control of PH and FBH, a genome-wide association study (GWAS) of a natural population was conducted, covering 2,131,705 genome variants across four environments. The 13 QTLs for PH and 15 for FBH were identified. Meta-analysis revealed that 28.57% of these loci overlapped with previously reported QTLs. Haplotype analysis confirmed significant effects of these loci on the traits. Candidate genes for PH and FBH, respectively, were identified based on linkage disequilibrium and functional predictions. However, five novel loci lacked nearby annotated genes. The candidate genes are linked to traits in Arabidopsis and other species, as well as to phytohormone response and cell development, and cell development. Notably, MOS1 gene copies (BnaA03G0481200ZS and BnaC07G0459400ZS) were associated with PH and FBH, indicating their multifunctional potential. Additionally, BnaA05G0163200ZS, with no functional annotation, emerged as a crucial gene for plant architecture. This study provides new genetic insights and may enhance marker-based breeding for ideotypes in rapeseed. Full article

Swine inflammation and necrosis syndrome (SINS) is a widespread disease in pigs, causing pain, suffering, and damage. Inflammation is documented at different levels based on clinical signs, histopathology, clinical chemistry, metabolomics and transcriptomics. The influence of sow and boar, as well as a heritability of around 0.3, suggest a genetic component to the disease. The aim of the present study was to identify functional single nucleotide polymorphisms (SNPs) in the vicinity of gene markers previously mapped using GWAS. DNA samples were available from 234 already phenotyped piglets. These animals were re-sequenced with additional prior enrichment. The nine selected chromosomal regions cover a total length of 22 Mbp. The genome-wide association study (GWAS) revealed two series with a total of 15 significant missense polymorphisms on chromosomes 11, 14, and 15. The homozygous genotypes of the most discriminating SNPs in series 1 resulted in SINS scores of 3.5 and 17.9, respectively. Despite the partial linkage of the SNPs, interesting candidate genes were defined. The results allow a significant narrowing of the possible candidate genes for understanding the pathogenesis of SINS and for future use in selection breeding to overcome the syndrome. Further studies should be carried out on larger animal populations. Full article

Semen cryopreservation is a crucial technology in the artificial insemination of livestock and poultry. It not only contributes to the conservation of germplasm resources but also facilitates the cross-regional exchange of high-quality breeding stock. In this study, 165 Duroc boars were selected for genome-wide genotyping, and the sperm freezing/thawing motility ratio (sperm recovery rate) was used as phenotypic data for genome-wide association analysis (GWAS). Considerable individual variations in sperm recovery rates (SRRs) were detected, and the sperm structure after cyropreservation was significantly better in highly freeze-tolerant individuals compared to non-freeze-tolerant ones. The heritability of the SRR was calculated and found to be 0.199 ± 0.158, representing low heritability. Through GWAS, eight single-nucleotide polymorphism (SNP) loci and four candidate genes (SLC10A6, MYRF, GGA1, and UTRN) were identified as being significantly associated with sperm freezing tolerance. Moreover, the dominant genotypes of four SNPs were finally determined to be valuable for identifying individuals with high sperm freezing tolerance. This study reveals the heritability of the sperm recovery rate and identifies molecular markers associated with sperm freezing tolerance in Duroc boars, which is of great significance for accelerating boar genetic improvement and enhancing the economic efficiency of pig breeding industry. Full article

The pathogenesis of obesity is complex and incompletely understood, with an underlying interplay between our genetic architecture and obesogenic environment. The public understanding of the development of obesity is shrouded in myths with widespread societal misconceptions. Body Mass Index (BMI) is a highly heritable trait. However, despite reports from recent genome-wide association studies, only a small proportion of the overall heritability of BMI is known to be lurking within the human genome. Other non-genetic heritable traits may contribute to BMI. The gut microbiome is an excellent candidate, implicating complex interlinks with hypothalamic control of appetite and metabolism via entero-endocrine, autonomic, and neuro-humeral pathways. The neonatal gut microbiome derived from the mother via transgenerational transmission (vaginal delivery and breastfeeding) tends to have a permanence within the gut. Conversely, non-maternally derived gut microbiota manifest mutability that responds to changes in lifestyle and diet. We should all strive to optimize our lifestyles and ensure a diet that is replete with varied and unprocessed plant-based foods to establish and nurture a healthy gut microbiome. Women of reproductive age should optimize their gut microbiome, particularly pre-conception, ante- and postnatally to enable the establishment of a healthy neonatal gut microbiome in their offspring. Finally, we should redouble our efforts to educate the populace on the pathogenesis of obesity, and the role of heritable (but modifiable) factors such as the gut microbiome. Such renewed understanding and insights would help to promote the widespread adoption of healthy lifestyles and diets, and facilitate a transition from our current dispassionate and stigmatized societal approach towards people living with obesity towards one that is epitomized by understanding, support, and compassion. Full article

Fish are rich sources of amino acids (AAs), particularly human essential amino acids (HEAAs). Exploring the regulatory mechanisms behind the changes in the combined AA content in the fillet and enhancing the content of AAs, especially HEAAs, in fillets of farmed fish is crucial for meeting human nutritional needs. After hot acidic hydrolysis of 304 common carp fillets, we quantified the contents of 17 single AAs and 5 AA groups and observed significant variations among them. Except for Pro, 16 single AAs and all AA groups showed medium-to-high heritabilities over 0.2. Through a genome-wide association study (GWAS), we identified 1974 SNPs and candidate genes associated with at least one AA content. Using transcriptome data from groups with the highest and lowest contents for each AA, 7089 candidate genes were related to the concentrations of at least two AAs. For the total HEAA content, 121 SNPs and their associated genes preferred ATPase-coupled transmembrane transporter activity, and 4727 differentially expressed genes were enriched in cytokine activity, chemokine activity, oxidoreductase activity, and ion binding. With the optimal genomic selection programs and associated SNPs, the correlation between the actual AA contents and estimated breeding values was high and positive, ranging from 0.76 to 0.90. These findings revealed the major-effect processes and regulatory mechanisms modulating the differences in fillet AA contents. The genomic selection programs will guide the future selection of common carp with high AA contents. Full article

Understanding the genetic basis of economically important traits is essential for enhancing the productivity, fertility, and health of dairy cattle. This study aimed to identify the pleiotropic genes associated with the 305-day milk yield (MY305), days open (DO), and milk fat-to-protein ratio (FPR) in Thai-Holstein crossbred dairy cattle using a genome-wide association study (GWAS) approach. The dataset included 18,843 records of MY305 and milk FPR, as well as 48,274 records of DO, collected from first-lactation Thai-Holstein crossbred dairy cattle. A total of 868 genotyped animals and 43,284 informative SNPs out of 50,905 were used for the analysis. The single-nucleotide polymorphism (SNP) effects were evaluated using a weighted single-step GWAS (wssGWAS), which estimated these effects based on genomic breeding values (GEBVs) through a multi-trait animal model with single-step genomic BLUP (ssGBLUP). Genomic regions explaining at least 5% of the total genetic variance were selected for candidate gene analysis. Single-step genomic REML (ssGREML) with a multi-trait animal model was used to estimate components of (co)variance. The heritability estimates from additive genetic variance were 0.262 for MY305, 0.029 for DO, and 0.102 for milk FPR, indicating a moderate genetic influence on milk yield and a lower genetic impact on fertility and milk FPR. The genetic correlations were 0.559 (MY305 and DO), −0.306 (MY305 and milk FPR), and −0.501 (DO and milk FPR), indicating potential compromises in genetic selection. wssGBLUP showed a higher accuracy than ssGBLUP, although the improvement was modest. A total of 24, 46, and 33 candidate genes were identified for MY305, DO, and milk FPR, respectively. Pleiotropic effects, identified by SNPs showing significant influence with more than trait, were observed in 14 genes shared among all three traits, 17 genes common between MY305 and DO, 14 genes common between MY305 and milk FPR, and 26 genes common between DO and milk FPR. Overall, wssGBLUP is a promising approach for improving the genomic prediction of economic traits in multi-trait analyses, outperforming ssGBLUP. This presents a viable alternative for genetic evaluation in dairy cattle breeding programs in Thailand. However, further studies are needed to validate these candidate genes and refine marker selection for production, fertility, and health traits in dairy cattle. Full article