Search Results (576)

Background/Objectives: Family history is a known risk factor for multiple myeloma (MM) and its precursor condition, monoclonal gammopathy of undetermined significance (MGUS). Previous genome-wide association studies (GWASs) have identified 35 common loci associated with MM risk and 21 associated with MGUS. The objective of this study was to identify less common and rare genetic loci predisposing to MM/MGUS through whole-exome sequencing (WES)-based linkage analysis. Methods:Multipoint linkage analysis was conducted using the Multipoint Engine for Rapid Likelihood Inference (MERLIN) with the Lander–Green algorithm on germline WES data from 79 pedigrees with 2 or more affected relatives (120 MM, 86 MGUS, and 21 unaffected). Genome-wide linkage was evaluated using 12,946 independent single-nucleotide variants (linkage disequilibrium r² < 0.05). Results: Significant linkage was observed at chromosome 6q22.33–q24.2 by the non-parametric model (logarithm-of-odds (LOD) = 3.3) and suggestive linkage by the dominant parametric model (heterogeneity LOD (HLOD) = 2.5). Fourteen rare variants within this region were prioritized using family-specific partial LOD scores and in silico functional prediction tools. Nine of these variants, REPS1, THEMIS, TAAR6, AHI1, VNN1, VNN3, MTFR2/FAM54A, LAMA2, and PHACTR2, overlapped immune-regulatory regions in blood cell lines and were not previously identified in GWASs. Conclusions: This study demonstrates the utility of applying a linkage analysis framework to familial WES data for identifying genomic regions and candidate genes that may contribute to MM/MGUS predisposition. These findings provide new insight into the inherited risk and etiology of familial MM and MGUS. Full article

The cultivated potato (Solanum tuberosum L.) is a globally important crop with a narrow genetic pool, making it vulnerable to biotic and abiotic stresses. The present study analyzed the relative content of the nuclear, mitochondrial, and plastid genomes and their contributions to agronomic traits in 30 diploid interspecific potato hybrids with diverse cytoplasmic types and pedigrees. The nuclear genome size (2C-value) was estimated using flow cytometry, while the organelle DNA content and cytoplasm types were determined by quantitative polymerase chain reaction (qPCR) and multiplex PCR, respectively. The genome size of individual diploid genotypes remained stable across cultivation conditions, such as in vitro or greenhouse environments. Significant variation was observed in genome size, organelle content, and cytoplasmic types, which were associated with differences in pollen fertility and starch content. Kendall’s correlation analysis revealed a strong positive correlation between the content of plastid and mitochondrial DNA, and between starch content and chip colour after cold storage. Principal component analysis (PCA) demonstrated that variation in plastid and mitochondrial DNA content explained differences among genotypes, with nuclear DNA content contributing independently. Notably, cytoplasmic male sterility was observed in some T-type cytoplasm genotypes, thus highlighting the role of nuclear–cytoplasmic interactions. The results obtained demonstrate that organelle genome composition exerts a significant influence on agronomic traits and offer valuable insights into the potential for the enhancement of potato breeding programmes through the analysis of cytoplasm and nuclear genomes. Full article

Background/Objectives: High differentiation rates provided by Y-chromosomal short tandem repeats (Y-STRs) are highly advantageous in most forensic and genealogical casework, as they enhance the ability to exclude close or moderately related individuals, refine an individual’s position within a pedigree, and uncover the population substructure in otherwise homogeneous groups. However, the impact for historical remains identification casework is underexplored. Methods: We present a pedigree analysis of 366 males from 183 pedigrees, separated by 4 to 16 meioses at 27 Y-STR loci, from the Yfiler Plus kit. The differentiation rate for a given degree of separation was defined as the proportion of pairs at that specific number of meioses showing at least one allelic difference, relative to the total number of such pairs. Results: Our pedigree-based locus-specific mutation rates were consistent with published father–son values for 22 of 25 loci, with 3 loci (DYS389II, DYS449, and DYS570) being significantly different (p < 0.05). These results were consistent with previous pedigree-based estimates, and the strong agreement between father–son and pedigree-based mutation rates supports the use of pedigrees as a reliable method for estimating mutation rates. The probability of differentiating male relatives reached 60.1%, which is similar to previous studies using the Yfiler Plus kit. Conclusions: This high male differentiation rate is advantageous for distinguishing unrelated individuals within the same population, reducing false inclusions. However, when comparing distantly related individuals, excessive mutations accumulated over many generations may obscure genuine patrilineal relationships, increasing the risk of false exclusions. Our findings are likely to be highly valuable for future interpretation of Y-STR haplotypes from patrilineal relatives across a wide range of applications, with significant relevance to historical remains identification casework. Full article

Heike 88, a new soybean variety developed through strategic hybridization of Heijiao 08-1611 × Heihe 43 followed by pedigree selection, was evaluated across seven locations in Heilongjiang Province from 2019 to 2022. The variety demonstrated stable performance with a 10.3% average yield advantage over regional check varieties and mean yields of 3188 kg ha⁻¹. Principal component analysis revealed that genetic variation accounted for 43.4% and 32.6% of performance variance in the first two components, indicating successful transgressive segregation where the pure line exceeded both parental lines through complementary gene action. Performance relative to parental averages ranged from −20% to +40% across the temperature gradient, demonstrating strong genotype-environment interaction effects. Machine learning analysis identified year effect (13% importance), accumulated temperature (7.6% importance), and oil content (4% importance) as primary yield drivers. Complete resistance to soybean mosaic virous (SMV) and cyst nematode attack was observed across all locations, with excellent gray leaf spot resistance (grades 0–1) maintained under natural pathogen pressure. Seed quality parameters remained stable across environments, with protein content ranging from 41.69% to 42.25% and oil content from 19.74% to 20.13%, indicating minimal environmental effects on compositional traits. Yield stability improved progressively over the evaluation period, with the coefficient of variation decreasing from 18.7% in 2019 to 6.7% in 2022, while absolute yields increased from 2550 to 3200 kg ha⁻¹. These results demonstrate successful exploitation of transgressive segregation for regional adaptation through strategic parent selection and pedigree breeding, supporting commercial deployment in northern China’s challenging production environments while providing methodological guidance for future breeding programs targeting environmental specificity. Full article

The objective of this study was to evaluate the impact of blending, tuning, and scaling adjustments in ssGBLUP on the accuracy of genomic estimated breeding values (GEBVs) for South African Holstein cattle. The edited dataset included pedigree information for 541,325 animals, 696,413 phenotypic records (milk, protein, and fat yields), and genotypes for 1221 Holstein cattle. The accuracy of GEBVs was evaluated based on different parameter settings for blending (β = 0.05, 0.10, 0.20, 0.30, and 0.40), tuning (τ), and scaling (τ and ω), ranging from 0.60 to 1.00. The results show that ssGBLUP outperformed the traditional pedigree-based approach (ABLUP), with realized accuracies increasing from 0.01 to 0.23 for milk yield, 0.03 to 0.29 for protein yield, and 0.03 to 0.30 for fat yield. Blending with β = 0.30–0.40 slightly increased the accuracy, while tuning adjustments showed limited influence on the prediction results. Scaling factors had a significant influence on accuracy, with ω = 0.60 yielding the highest values (0.26 for milk, 0.32 for protein, and 0.34 for fat). The results of this study show the importance of optimizing the integration of pedigree and genomic information in ssGBLUP to improve the accuracy of genomic predictions, ultimately enhancing selection decisions and genetic progress in South African Holstein cattle. Full article

Background/Objectives: Executive functioning (EF) and prospective memory (PM) difficulties have been documented in adults with developmental dyslexia. However, research has tended to focus on university students with a formal diagnosis, overlooking adults who may experience symptoms of dyslexia without ever being formally diagnosed. The present online study aimed to investigate the effects of dyslexia traits on EF and PM in a larger, community-based sample by prioritising the use of self-report measures that include and differentiate between underexplored aspects of EF and PM in the dyslexia literature. Methods: One hundred and eighty adult volunteers of a wide range of ages were included in the final analysis. Participants completed four self-report questionnaires with good pedigrees assessing dyslexia traits and ADHD symptomatology, as well as everyday experiences of five distinct EFs, PM and PM strategies. Results: Hierarchical regression analyses revealed that, after controlling for age and ADHD symptomatology, more self-reported dyslexia traits were associated with more frequent EF problems overall and lower confidence in PM Abilities. Elevated dyslexia traits were significantly associated with self-reports of more difficulties with time-management, organisation and self-restraint, but not with more difficulties with motivation and regulation of emotion. No significant associations were found between dyslexia traits and the self-reported use of PM-enhancing strategies. Conclusions: The findings are considered in the light of potential metacognition deficits and theoretical and practical implications are discussed. Full article

In small, closed populations such as the Lipizzan horse, maintaining genetic diversity while limiting inbreeding is a key challenge in conservation breeding. The Lipizzan is an indigenous Slovenian breed with a small population and restricted gene flow from other subpopulations. Inbreeding is traditionally monitored with pedigree-based coefficients, but these often underestimate realised autozygosity, particularly when pedigree depth is limited. This study compared pedigree-based inbreeding (F_PED) with four genomic estimators (F_HOM, F_ROH, F_HBD, F_GRM) in 329 Slovenian Lipizzan horses genotyped with a 70K SNP array. Data were processed in PLINK and R. Segment-based estimators (F_ROH, F_HBD) revealed higher inbreeding than F_PED and partitioned autozygosity into recent and distant components. F_ROH identified long homozygous segments reflecting recent inbreeding, whereas HBD classification showed that most autozygosity came from distant ancestors. Correlations between pedigree- and genomic-based coefficients were moderate (ρ = −0.18–0.56), while genomic estimators showed strong agreement. These results demonstrate that genomic measures complement pedigree-based metrics by providing a fuller picture of inbreeding and its temporal origin. Incorporating genomic estimators into routine monitoring can improve mate selection, reduce inbreeding depression, and support sustainable management of genetic diversity in the Lipizzan horse, while offering a case study for other small populations with conservation goals. Full article

Allele-specific expression (ASE) reflects the unequal expression of the parental alleles and can imply functional variants in cis-regulatory elements. The conventional ASE detection methods often depend on the presence of heterozygous variants in transcripts or sequencing a large number of individuals, both of which are often limited. In this study, we present a family-based strategy for detecting ASE and potential cis-regulatory elements utilizing both RNA-seq and whole-genome sequencing (WGS) from a pedigree. Using a rabbit family consisting of two divergent parents and their eight offspring, we identified 913 ASE genes by analyzing inheritance patterns of gene expression levels. Expression was classified into three levels—high, medium, and low—and used to define seven distinct expression groups across the family (e.g., H_L: high in the mother, low in the father, and intermediate in the offspring). Many ASE genes lacked heterozygous exonic variants, and inference was achieved via RNA read count patterns. We also pinpointed conserved transcription factor binding sites (TFBS) with sequence variants showing similar inherited genotypic patterns (e.g., AAxBB), suggesting their regulatory roles as eQTLs. Differential gene expression (DEG) analysis between the parents highlighted some candidate genes related to meat production and quality traits. Our findings show that the family-based method using RNA-seq and WGS data is promising for exploring ASE and mapping possible eQTLs. Full article

The Peruano de Paso is a horse breed renowned for its smooth gait, traditionally selected based on breeders’ empirical knowledge. Recently, the frequency of chestnut horses, a recessive trait, has increased substantially within the official studbook. This study evaluated whether preference for chestnut coat colour has influenced morphological traits and genetic diversity within the breed. A total of 8376 records of seven morphological traits, collected by the Peruano de Paso Breeders Association over eight years, were analysed, along with a pedigree including 41,357 individuals. Morphological traits were studied through univariate genetic models that considered potential heterogeneity of additive genetic variance between chestnut and non-chestnut horses. Results indicated moderate to high heritability estimates across traits. No significant differences were observed between groups, except for croup width, with heritability of 0.28 ± 0.08 in chestnuts and 0.44 ± 0.08 in non-chestnuts. Genetic correlations between groups could not be precisely estimated due to limited data. The main effect of selection for chestnut coat colour was a reduction in genetic variability, an increase in inbreeding and relatedness. However, this selection has had little impact on morphology, indicating that the traits valued by breeders remain almost unaffected despite the loss of diversity. Full article

Improving reproductive efficiency in beef cattle remains a key objective for sustainable genetic progress, particularly in extensively managed autochthonous breeds such as the Spanish Retinta. In this study, we applied a weighted single-step genome-wide association approach (wssGWAS) to identify genomic regions associated with four fertility-related traits: age at first calving (AFC), interval between first and second calving (IC12), average calving interval (ACI), and reproductive efficiency (RE). A total of 215,125 calving records from 44,032 cows and the genomic information of 1030 animals (Axiom™ Bovine Genotyping v3 Array 65k) were analyzed. Heritability was estimated using a single-step genomic best linear unbiased prediction (ssGBLUP) that incorporated both pedigree and genomic data, and estimates ranged from 0.15 (0.008) for AFC to 0.27 (0.012) for ACI. The wssGWAS identified 96 1 Mb-windows explaining over 1% of additive genetic variance (40 of them are common for more than one trait and 46 windows are unique), notably on chromosomes 2 and 5. Candidate genes related to folliculogenesis, steroidogenesis, immune modulation, and cell cycle control were identified, including ACVR1B, AMHR2, CYP27B1, CDK2, and IFNG. Additionally, a significant proportion of lncRNAs were detected, suggesting regulatory roles in reproductive processes through the modulation of gene expression at different levels. These findings enhance our understanding of the genetic architecture underlying female fertility in beef cattle and provide valuable markers for incorporation into genomic selection programs aimed at improving reproductive performance and long-term sustainability in the Retinta breed. Full article

High genetic variation in African indigenous chicken populations provides opportunities for long-term genetic improvement. This study estimated genetic parameters for economic traits based on data derived from a nucleus flock comprising two generations, derived from 40 sires and 200 dams in a line breeding program through mass selection. Body weight (BW) at different weeks was analyzed for 1370 chickens. Similarly, egg performance was evaluated on 473 hens kept for 44 weeks. Genetic parameters were estimated using a multi-trait animal model based on an average information-restricted maximum likelihood (AI-REML) algorithm in WOMBAT software. Body weight showed significant heritability (p < 0.001), ranging from 0.251 for body weight at 8 weeks of age (BW8) to 0.34 for body weight at 16 weeks of age (BW16), indicating a good genetic improvement potential. Egg production traits had low to moderate heritability (0.08–0.37). Positive genetic correlations among growth traits, particularly BW8 and body weight at 12 weeks of age, BW12 (rG = 0.94), suggest shared genetic influences and the possibility of improving multiple traits simultaneously. The genetic correlation between BW16 and the cumulative egg number varied from low and negative (−0.02) in the first two months to high (0.51) in the cumulative egg number over six months, suggesting that heavier birds lay more eggs over time. Our limited dataset based on two generations and pedigree demonstrates that BW16 with egg production has moderate heritability and strong genetic correlations that can lead to genetic progress toward the development of a dual-purpose breed, and this offers a scientific basis for breeders to develop selection indices to develop a dual-purpose breed for smallholder production systems. Full article

Chamomile (Matricaria chamomilla L.) is a popular herb of great economic and medicinal value. Despite its significant potential, there are currently no commercially available varieties specifically adapted to Mediterranean low-input farming systems. The present study aimed to develop a genetically improved breeding population derived from indigenous Greek chamomile germplasm, following a multi-year strategy, based on pedigree selection under low-input conditions. This selection process constituted the first phase of the breeding program, during which selection focused on improving inflorescence dry weight and essential oil quality, particularly with respect to α-bisabolol and chamazulene content. After three cycles of selection, considerable genetic gains were achieved. The realized heritability values exceeded 0.5 for all assessed traits, confirming strong genetic control. In the fourth year, representing the second phase of the breeding program, the breeding population—developed through selection during the first phase—was evaluated alongside the initial population and commercial diploid and tetraploid varieties. The breeding population exhibited significant observed gains compared to the initial population: inflorescence dry weight increased by 12.17%, α-bisabolol content by 71.45%, and chamazulene content by 6.57%. Additionally, the breeding population not only surpassed all evaluated diploid genotypes in essential oil composition, but also displayed a chemotypic shift, indicating successful alignment with tetraploid varieties characterized by high-value chemical profiles. Furthermore, this selection process targeting specific commercial chamomile traits indirectly contributed to improvement in plant height and inflorescence morphology. Overall, these results demonstrate that conventional breeding, when applied effectively to native resources, can enhance both agronomic performance and essential oil profile. The newly developed breeding population provides a strong foundation for future cultivar development tailored to Mediterranean low-input sustainable farming systems. Full article

UNC13D, which encodes the Munc13–4 protein, is a critical gene implicated in type 3 familial hemophagocytic lymphohistiocytosis (HLH). While biallelic nucleotide variants in HLH-related genes, including UNC13D, are traditionally linked to recessive inheritance patterns in HLH, emerging evidence suggests that heterozygous variants may also contribute to the onset of adult-onset HLH. However, the pathogenicity of heterozygous UNC13D variants is still not fully understood. Here, we present a 29-year-old male patient with Epstein–Barr virus (EBV)-triggered adult-onset HLH, who was found to carry compound heterozygous variants in the UNC13D gene (c.2588G>A and c.1978_1979insATTACCG) with complete T/NK cytotoxicity dysfunction. We conducted NK-cell function assay in this pedigree to link the genotype to phenotype and demonstrated that the monoallelic UNC13D c.2588G>A variant could partially impair NK cell cytotoxicity, in contrast to the completely recessive inheritance observed with UNC13D c.1978_1979insATTACCG and other familial HLH-related variants. In addition, to explore the implication of UNC13D c.2588G>A variant in various diseases, we reviewed 16 published studies, including data on 35 patients carrying this variant. Data showed the heterozygous variant of UNC13D c.2588G>A might act as a genetic risk factor predisposing carriers to conditions like HLH, lymphoma, etc. This study underscores the pathogenic role of the UNC13D c.2588G>A variant and expands our understanding of the genetic basis of adult-onset HLH. Full article

South African cattle comprise diverse breeds with distinct evolutionary histories, potentially reflecting differences in recombination landscapes. This study assessed genome-wide recombination rates and hotspots in Bonsmara (n = 190) and Nguni (n = 119) cattle using three-generation half-sib pedigrees genotyped with the Illumina Bovine SNP50 BeadChip. Phasing across 29 autosomes was conducted using SHAPEIT v2, and crossover events were inferred using the DuoHMM algorithm. The total number of crossover events detected was higher in Nguni (n = 8982) than in Bonsmara (n = 7462); however, the average recombination rate per 1 Mb window was significantly higher in Bonsmara (0.31) compared to Nguni (0.18) (p < 0.01). This apparent discrepancy reflects differences in genomic distribution and crossover clustering across breeds, rather than overall recombination frequency. A critical limitation of the study is the reliance on half-sib families with small family sizes, which may underestimate recombination rates due to limited meiotic sampling and increased variance in crossover detection. We identified 407 recombination hotspots in Bonsmara and 179 in Nguni, defined as intervals exceeding 2.5 standard deviations above the mean recombination rate. Genes such as PDE1B and FP which are associated with productions traits were located within hotspot-enriched regions. However, functional causality between these genes and local recombination activity remains unverified. Our results provide statistically supported evidence for breed-specific recombination patterns and hotspot distributions, underscoring the importance of incorporating recombination architecture into genetic improvement strategies for South African cattle. Full article

Background/Objectives: Dilated cardiomyopathy (DCM), defined as dilation and contractile dysfunction of the left or both cardiac ventricles, remains the most common category of primary myocardial disease worldwide. It is the most prevalent cause of chronic heart failure and the most common indication for cardiac transplantation in young subjects. Accumulating evidence increasingly highlights the substantial genetic defects underlying DCM. Nevertheless, the genetic ingredients accountable for DCM in a major percentage of patients remain indefinite. Methods: A multigenerational pedigree suffering from DCM and a total of 276 healthy volunteers employed as controls were recruited from the Chinese Han-ethnicity population. A whole-exome sequencing (WES) assay followed by a Sanger sequencing analysis of the genomic DNAs from the available family members was implemented. Functional characterization of the identified genetic variant was completed by dual-luciferase analysis. Results: A new heterozygous variation in the ETS1 (erythroblast transformation-specific 1) gene, NM_005238.4:c.447T>G;p.(Tyr149*), was identified by WES and validated by Sanger sequencing analysis to co-segregate with DCM in the whole DCM family. This nonsense ETS1 variant was not found in 276 control subjects. Functional examination elucidated that Tyr149*-mutant ETS1 lost the ability to transactivate its downstream target genes CLDN5 (claudin 5) and ALK1 (activin receptor-like kinase 1), two genes crucial for cardiovascular embryonic development and postnatal structural remodeling. Conclusions: The present investigation reveals ETS1 as a new gene predisposed to human DCM and indicates ETS1 haploinsufficiency as an alternative molecular pathogenesis underlying DCM, providing a potential molecular target for genetic counseling and early diagnosis as well as personalized prophylaxis of DCM. Full article