Genome-wide Single Nucleotide Polymorphism Research Articles

Genome-wide assessment of population structure and association mapping for agronomic and grain nutritional traits in proso millet (Panicum miliaceum L.)

Proso millet is an important but under-researched and underutilized crop with the potential to become a future smart crop because of its climate-resilient features and high nutrient content. Assessing diversity and marker-trait associations are essential to support the genomics-assisted improvement of proso millet. This study aimed to assess the population structure and diversity of a proso millet diversity panel and identify marker-trait associations for agronomic and grain nutrient traits. In this study, genome-wide single nucleotide polymorphisms (SNPs) were identified by mapping raw genotyping-by-sequencing (GBS) data onto the proso millet genome, resulting in 5621 quality-filtered SNPs in 160 diverse accessions. The modified Roger's Distance assessment indicated an average distance of 0.268 among accessions, with the race miliaceum exhibiting the highest diversity and ovatum the lowest. Proso millet germplasm diversity was structured according to geographic centers of origin and domestication. Genome-wide association mapping identified 40 marker-trait associations (MTAs), including 34 MTAs for agronomic traits and 6 for grain nutrients; 20 of these MTAs were located within genes. Favourable alleles and phenotypic values were estimated for all MTAs. This study provides valuable insights into the population structure and diversity of proso millet, identified marker-trait associations, and reported favourable alleles and their phenotypic values for supporting genomics-assisted improvement efforts in proso millet.

DNA Methylation signatures underpinning blood neutrophil to lymphocyte ratio during first week of human life

Understanding of newborn immune ontogeny in the first week of life will enable age-appropriate strategies for safeguarding vulnerable newborns against infectious diseases. Here we conducted an observational study exploring the immunological profile of infants longitudinally throughout their first week of life. Our Expanded Program on Immunization - Human Immunology Project Consortium (EPIC-HIPC) studies the epigenetic regulation of systemic immunity using small volumes of peripheral blood samples collected from West African neonates on days of life (DOL) 0, 1, 3, and 7. Genome-wide DNA methylation and single nucleotide polymorphism markers are examined alongside matched transcriptomic and flow cytometric data. Integrative analysis reveals that a core network of transcription factors mediates dynamic shifts in neutrophil-to-lymphocyte ratios (NLR), which are underpinned by cell-type specific methylation patterns in the two cell types. Genetic variants are associated with lower NLRs at birth, and healthy newborns with lower NLRs at birth are more likely to subsequently develop sepsis. These findings provide valuable insights into the early-life determinants of immune system development.

Sleep duration and heart failure risk: Insights from a Mendelian Randomization Study.

To investigate the causal relationship between sleep duration and heart failure (HF) in a European population. We focused on the continuous sleep duration of 460,099 European individuals as our primary exposure. Genome-wide significant single nucleotide polymorphisms (SNPs, n = 9851,867) linked to continuous sleep duration were adopted as instrumental variables. The outcome of interest was based on HF events in a European cohort (n = 977,323; with 930,014 controls and 47,309 cases). We employed a two-sample Mendelian randomization (MR) approach to infer causality between sleep duration and the incidence of HF. For validation purposes, an additional cohort of 336,965 European individuals diagnosed with insomnia was selected as a secondary exposure group. Using its SNPs, a subsequent two-sample MR analysis was conducted with the HF cohort to further corroborate our initial findings. Employing the MR methodology, we selected 57 SNPs that are associated with sleep duration, and 24 SNPs that are associated with insomnia as instrumental variables. We discerned a substantial association between genetically inferred sleep duration and HF risk (odds ratio: 0.61; 95% confidence interval: 0.47-0.78, P < .0001). Our subsequent analysis highlighted a pronounced increased HF risk associated with insomnia (odds ratio: 1.54; 95% confidence interval: 1.08-2.17, P < .02). These conclusions were further bolstered by consistent results from sensitivity analyses. Our study suggests a causal linkage between sleep duration and the onset risk of HF in the European population. Notably, shorter sleep durations were associated with a heightened risk of HF.

Conservation genomic study of Hopea hainanensis (Dipterocarpaceae), an endangered tree with extremely small populations on Hainan Island, China.

Hopea hainanensis Merrill & Chun is considered a keystone and indicator species in the tropical lowland rainforests of Hainan Island. Owing to its high-quality timber, H. hainanensis has been heavily exploited, leading to its classification as a first-class national protected plant in China and a plant species with extremely small populations (PSESPs). This study analyzed genome-wide single nucleotide polymorphisms obtained through restriction site-associated DNA sequencing from 78 adult trees across 10 H. hainanensis populations on Hainan Island. The nucleotide diversity of the sampled populations ranged from 0.00096 to 0.00138, which is lower than that observed in several other PSESPs and endangered tree species. Bayesian unsupervised clustering, principal component analysis, and neighbor-joining tree reconstruction identified three to five genetic clusters in H. hainanensis, most of which were geographically widespread and shared by multiple populations. Demographic history analysis based on pooled samples indicated that the decline in the H. hainanensis population began approximately 20,000 years ago, starting from an ancestral population size of approximately 10,000 individuals. The reduction in population size accelerated approximately 4,000 years ago and has continued to the present, resulting in a severely reduced population on Hainan Island. Intensified genetic drift in small and isolated H. hainanensis populations may contribute to moderate differentiation between some of them, as revealed by pairwise F st. In conclusion, our conservation genomic study confirms a severe population decline and an extremely low level of nucleotide variation in H. hainanensis on Hainan Island. These findings provide critical insights for the sustainable management and genetic restoration of H. hainanensis on Hainan Island.

Genome-wide discovery of selection signatures in four Anatolian sheep breeds revealed by ddRADseq

High-density genomic data analyzed by accurate statistical methods are of potential to enlighten past breeding practices such as selection by unraveling fixed regions. In this study, four native Turkish sheep breeds (80 samples) were genotyped via 296.097 single nucleotide polymorphisms (SNPs) detected by double-digest restriction site-associated DNA (ddRADseq) library preparation combined with the Illumina HiSeq X Ten instrument in order to identify genes under selection pressure. A total of 32, 136, 133, and 119 protein-coding genes were detected under selection pressure by runs of homozygosity (ROH), integrated haplotype score (iHS), the ratio of extended haplotype homozygosity (Rsb), and fixation index (FST) approaches, respectively. Of these, a total of 129 genes were identified by at least two statistical models which overlapped with a total of 52 quantitative trait loci (QTL)-associated SNPs, known to be related to fiber diameter, milk content, body weight, carcass traits, some blood parameters, and entropion. A total of six genes under selection pressure were validated by three statistical approaches five of which are of potential to be integrated into animal breeding since they were associated with wool fiber diameter (ZNF208B), behaviors related to neurocognitive development (CBX1 and NFE2L1), adaptation to high-altitude (SDK1), and anxiety causing internal stress (GSG1L). The sixth gene (COPZ1) turned out to play an important role in coping with different types of cancer in mammals. In particular, ROH analysis uncovered significant findings that the Güney Karaman (GKR) had experienced different selection practices than the Akkaraman (AKR) breed. Moreover, some genes specifically under selection in the GKR breed turned out to be associated with olfaction (OR6K6, OR6N1, OR6N2, and OR4C16), survival during the gestation period (PRR15L), and heat stress (CDK5RAP9). The results of this study imply that GKR may become genetically different from the AKR breed at the genome level due to most probably experiencing different adaptation processes occurring in raised climatic conditions. These differences should be conserved to face future challenges, while other native Turkish sheep breeds could be monitored via genome-wide high-density SNP data to obtain deeper knowledge about the effects of natural selection.

Association of the ABCG2 rs2231142 variant with the Framingham Cardiovascular Disease Risk score in the Taiwanese population

BackgroundSerum uric acid (SUA) is an important predictor of cardiovascular events and mortality. The ABCG2 rs2231142 variant (TT genotype) is associated with hyperuricemia (HUA), but the relationship between ABCG2 gene polymorphisms and coronary artery disease (CAD) risk is poorly elucidated. We investigated the association between ABCG2 rs2231142 genetic variants and the Framingham Risk Score for Cardiovascular Disease (FRS-CVD) in a Taiwanese population. MethodsThis cross-sectional study enrolled 139,508 Taiwanese participants aged 30–70 years based on data from the Taiwan Biobank (TWB) database that was obtained from questionnaires, laboratory investigations, anthropometry, and Affymetrix TWB genome-wide single-nucleotide polymorphism (SNP) chip data analysis. The association between ABCG2 rs2231142 and FRS-CVD risk was evaluated using logistic regression analysis. ResultsCompared to those with the GG genotype, participants with the ABCG2 rs2231142 TT genotype had a significantly lower systolic blood pressure, smoking rate, body mass index, triglyceride level, waist circumference, waist–hip ratio, and body fat percentage, but had higher high-density lipoprotein cholesterol level. Despite the same FRS-CVD score, participants with TT genotypes had higher SUA. Even with the same SUA, TT carriers had a lower FRS-CVD than GT and GG carriers. Participants with the TT genotype had significantly lower CVD risk, particularly female participants with HUA and BMI <27 (OR: 0.760, 95 % CI: 0.587–0.985; p = 0.0381) group. ConclusionThe ABCG2 rs2231142 TT genotype is associated with a lower FRS-CVD, particularly in non-obese hyperuricemic female individuals. The complicated interplay among genetic variations, metabolic profile, and CVD risk provides insights for precision health.

Genetic analysis of asymptomatic antinuclear antibody production.

Antinuclear antibodies (ANA) are detected in up to 14% of the population and the majority of individuals with ANA are asymptomatic. The literature on the genetic contribution to asymptomatic ANA positivity in the population is limited. In this study, we aimed to perform a multi-ancestry genome-wide association study (GWAS) of asymptomatic ANA positivity. Asymptomatic ANA positive and negative individuals from the All of Us Research Program were included in this study, selecting those with an ANA test by immunofluorescence and no evidence of autoimmune disease. Imputation was performed and a multi-ancestry meta-analysis including approximately 6 million single-nucleotide polymorphisms (SNPs) was conducted. Genome-wide SNP based heritability was estimated using the GCTA software. A cumulative genetic risk score for lupus was constructed using previously reported genome-wide significant loci. 1,955 asymptomatic ANA positive and 3,634 asymptomatic ANA negative individuals were included across three genetic ancestries. The multi-ancestry meta-analysis revealed SNPs with a suggestive association (p-value < 1×10 -5 ) across 8 different loci, but no genome-wide significant loci were identified. A gene variant upstream of HLA-DQB1 (rs17211748, P = 1.4×10 -6 , OR = 0.82, 95% CI 0.76-0.89) showed the most significant association. The heritability of asymptomatic ANA positivity was estimated to be 24.9%. Asymptomatic ANA positive individuals did not exhibit increased cumulative genetic risk for lupus compared to ANA negative individuals. ANA production is not associated with significant genetic risk and is primarily determined by non-genetic, likely environmental, factors.

Mapping genome-wide diversity and population dynamics in Indian chicken breeds for targeted conservation and breeding

ABSTRACT 1. Genetic improvement and widespread use of artificial selection may have impacted the genetic make-up of Indian chicken breeds. The genetic architecture of contemporary chicken population of India needs to be assessed for future improvement and conservation programmes. This study utilised whole-genome sequences in 180 chicken samples from 16 indigenous breeds, along with the Red Jungle Fowl and the commercial White Leghorn. 2. A panel of 76 978 genome-wide single-nucleotide polymorphisms (SNP) was selected for comparative genome analysis after stringent screening. Breeds originating from the eastern regions of India exhibited higher genomic diversity, indicative of a rich repository of distinct germplasm. Conversely, the Uttara breed, from the northern hilly areas, display considerable genetic differentiation with diminished diversity compared to others, underscoring conservation concerns. The average coefficient (FIS) of 0.084 caution the need to mitigate risks associated with inbreeding. 3. The study revealed that the analysis of 76 978 genome-wide SNP will serve as a cornerstone in refining conservation strategies, to design interventions with greater precision. 4. The contribution of Red Jungle Fowl to the gene pool of all native breeds was supported by this study. Genetic structuring indicated a relationship among breeds based on geographical proximity, underscored by varying levels of admixture.

Exploring causal effects of sarcopenia on risk and progression of Parkinson disease by Mendelian randomization

Previous observational studies suggested that sarcopenia is associated with Parkinson disease (PD), but it is unclear whether this association is causal. The objective of this study was to examine causal associations between sarcopenia-related traits and the risk or progression of PD using a Mendelian randomization (MR) approach. Two-sample bidirectional MR analyses were conducted to evaluate causal relationships. Genome-wide association study (GWAS) summary statistics for sarcopenia-related traits, including right handgrip strength (n = 461,089), left handgrip strength (n = 461,026), and appendicular lean mass (n = 450,243), were retrieved from the IEU OpenGWAS database. GWAS data for the risk of PD were derived from the FinnGen database (4235 cases; 373,042 controls). Summary-level data for progression of PD, including progression to Hoehn and Yahr stage 3, progression to dementia, and development of levodopa-induced dyskinesia, were obtained from a recent GWAS publication on progression of PD in 4093 patients from 12 longitudinal cohorts. Significant causal associations identified in MR analysis were verified through a polygenic score (PGS)-based approach and pathway enrichment analysis using genotype data from the Parkinson’s Progression Markers Initiative. MR results supported a significant causal influence of right handgrip strength (odds ratio [OR] = 0.152, 95% confidence interval [CI] = 0.055–0.423, adjusted P = 0.0036) and appendicular lean mass (OR = 0.597, 95% CI = 0.440–0.810, adjusted P = 0.0111) on development of levodopa-induced dyskinesia. In Cox proportional hazard analysis, higher PGSs for right handgrip strength (hazard ratio [HR] = 0.225, 95% CI = 0.095–0.530, adjusted P = 0.0019) and left handgrip strength (HR = 0.303, 95% CI = 0.121–0.59, adjusted P = 0.0323) were significantly associated with a lower risk of developing levodopa-induced dyskinesia, after adjusting for covariates. Pathway enrichment analysis revealed that genome-wide significant single-nucleotide polymorphisms for right handgrip strength were substantially enriched in biological pathways involved in the control of synaptic plasticity. This study provides genetic evidence of the protective role of handgrip strength or appendicular lean mass on the development of levodopa-induced dyskinesia in PD. Sarcopenia-related traits can be promising prognostic markers for levodopa-induced dyskinesia and potential therapeutic targets for preventing levodopa-induced dyskinesia in patients with PD.

Improving complex agronomic and domestication traits in the perennial grain crop intermediate wheatgrass with genetic mapping and genomic prediction.

The perennial grass Thinopyrum intermedium (intermediate wheatgrass [IWG]) is being domesticated as a food crop. With a deep root system and high biomass, IWG can help reduce soil and water erosion and limit nutrient runoff. As a novel grain crop undergoing domestication, IWG lags in yield, seed size, and other agronomic traits compared to annual grains. Better characterization of trait variation and identification of genetic markers associated with loci controlling the traits could help in further improving this crop. The University of Minnesota's Cycle 5 IWG breeding population of 595 spaced plants was evaluated at two locations in 2021 and 2022 for agronomic traits plant height, grain yield, and spike weight, and domestication traits shatter resistance, free grain threshing, and seed size. Pairwise trait correlations were weak to moderate with the highest correlation observed between seed size and height (0.41). Broad-sense trait heritabilities were high (0.68-0.77) except for spike weight (0.49) and yield (0.44). Association mapping using 24,284 genome-wide single nucleotide polymorphism markers identified 30 main quantitative trait loci (QTLs) across all environments and 32 QTL-by-environment interactions (QTE) at each environment. The genomic prediction model significantly improved predictions when parents were used in the training set and significant QTLs and QTEs used as covariates. Seed size was the best predicted trait with model predictive ability (r) of 0.72; yield was predicted moderately well (r=0.45). We expect this discovery of significant genomic loci and mostly high trait predictions from genomic prediction models to help improve future IWG breeding populations.

Identification of interactions between genetic risk scores and dietary patterns for personalized prevention of kidney dysfunction in a population-based cohort

Background & AimChronic kidney disease (CKD) is a heterogeneous disorder that affects the kidney structure and function. This study investigated the effect of the interaction between genetic factors and dietary pattern on kidney dysfunction in Korean adults.MethodsBaseline data were obtained from the Ansan and Ansung Study of the Korean Genome and Epidemiology Study involving 8230 participants aged 40–69 years. Kidney dysfunction was defined as an estimated glomerular filtration rate < 90 mL/minute/1.73 m2. Genomic DNAs genotyped on the Affymetrix® Genome-Wide Human SNP array 5.0 were isolated from peripheral blood. A genome-wide association study using a generalized linear model was performed on 1,590,162 single-nucleotide polymorphisms (SNPs). To select significant SNPs, the threshold criterion was set at P-value < 5 × 10−8. Linkage disequilibrium clumping was performed based on the R2 value, and 94 SNPs had a significant effect. Participants were divided into two groups based on their generic risk score (GRS): the low-GR group had GRS > 0, while the high-GR group had GRS ≤ 0.ResultsThree distinct dietary patterns were extracted, namely, the “prudent pattern,” “flour-based and animal food pattern,” and “white rice pattern,” to analyze the effect of dietary pattern on kidney function. In the “flour-based and animal food pattern,” higher pattern scores were associated with a higher prevalence of kidney dysfunction in both the low and high GR groups (P for trend < 0.0001 in the low-, high-GR groups of model 1; 0.0050 and 0.0065 in the low-, high-GR groups of model 2, respectively).ConclusionsThe results highlight a significant association between the ‘flour-based and animal food pattern’ and higher kidney dysfunction prevalence in individuals with both low and high GR. These findings suggest that personalized nutritional interventions based on GR profiles may become the basis for presenting GR-based individual dietary patterns for kidney dysfunction.

Urbanisation has impacted the population genetic structure of the Eurasian red squirrel in Japan within a short period of 30 years

Human activities often induce maladaptive effects in urban wildlife, such as increased inbreeding and decreased gene flow, consequently leading to a loss of biodiversity. Although maladaptive effects are commonly reported in urban wildlife, some wildlife species are not affected. Understanding the conditions and factors that affect the genetic structure of wildlife is crucial for its conservation in urban environments. Eurasian red squirrels Sciurus vulgaris in Obihiro City, Hokkaido, Japan, have settled in large residential lots with a high risk of vehicle collisions for approximately 30 years, raising the possibility that the urban population would be genetically isolated from nearby rural populations and may experience a rapid decrease in genetic diversity. In this study, we analysed the population structure, genetic distance, and nucleotide diversity of squirrels in the Obihiro area using genome-wide single nucleotide polymorphisms (SNPs). Principal component analysis and ADMIXTURE showed that urban and rural squirrel populations formed distinct clusters with intermediate urban and rural boundary populations. Genetic distances between the urban populations were greater than that of other pairs. Nucleotide diversities were lower in urban populations than in other populations, suggesting limited gene flow between urban and other populations, possibly due to urbanisation. The change in the genetic characteristics of urban squirrel populations during this short period demonstrates the strong impact of urbanisation. Our findings suggest that a genome-wide approach to the genetic structure of wildlife contributes to its conservation in urban environments.

Genome-Wide Association Study Meta-Analysis Uncovers Novel Genetic Variants Associated with Olfactory Dysfunction.

Olfactory dysfunction is among the earliest signs of many age-related neurodegenerative diseases and has been associated with increased mortality in older adults; however, its genetic basis remains largely unknown. To identify the genetic loci associated with olfactory dysfunction in the general population. This genome-wide association study meta-analysis (GWMA) included participants of European ancestry (N = 22,730) enrolled in four different large population-based studies, followed by a multi-ancestry GWMA including participants of African ancestry (N = 1,030). The data analysis was performed from March 2023 through June 2024. Genome-wide single nucleotide polymorphisms. Olfactory dysfunction was the outcome and assessed using a 12-item smell identification test. GWMA revealed a novel genome-wide significant locus (tagged by rs11228623 at 11q12) associated with olfactory dysfunction. Gene-based analysis revealed a high enrichment for olfactory receptor genes in this region. Phenome-wide association studies demonstrated associations between genetic variants related to olfactory dysfunction and blood cell counts, kidney function, skeletal muscle mass, cholesterol levels and cardiovascular disease. Using individual-level data, we also confirmed and quantified the strength of these associations on a phenotypic level. Moreover, employing two-sample Mendelian Randomization analyses, we found evidence for causal associations between olfactory dysfunction and these phenotypes. These findings provide novel insights into the genetic architecture of the sense of smell and highlight its importance for many aspects of human health.

Screening of heat stress-tolerant weedy rice and SNP identification of heat-tolerance-related genes

AbstractRice, a staple crop that feeds more than one-third of the world’s population, encounters a wide range of biotic and abiotic stresses due to climate change. Rising temperature is one of the significant abiotic stresses affecting rice productivity worldwide. The development of heat-tolerant rice cultivars is critical in this regard. Weedy rice could potentially serve as a natural resource for genes conferring agronomically important traits beneficial to cultivated rice. However, heat tolerance in both cultivated and weedy rice is still understudied. This study screened a set of 180 weedy rice accessions for heat stress tolerance and further characterised them using genome-wide single-nucleotide polymorphisms (SNPs) analysis. Five heat-tolerant (HT) accessions (MU244, MU235, MU249, MU260 and MU237), along with five heat-susceptible (HS) accessions (MU100, MU114, MU264, MU251 and MU005), were subjected to relative electrical conductivity (REC) test and reactive oxidative species assay (ROS). These tests verified that the five HT accessions performed better under heat stress than their HS counterparts. In addition, whole-genome sequences of three HT (MU235, MU237 and MU066) and four HS (MU100, MU114, MU022 and MU005) accessions were selected for the genome-wide SNPs comparison, revealing substantial amino acid variation in the heat-tolerance-related genes between the HT and HS rice groups. The proposed genes and genome-wide SNP markers may help rice breeders better understand how different rice cultivars respond to heat stress.

Imputation of single nucleotide polymorphism genotypes in ungenotyped sport horses from the genotypes of their progeny

Many sport horse studbooks worldwide use microsatellite markers for parentage verification. However, many have expressed a desire to introduce genomic selection using genome-wide dense single nucleotide polymorphism (SNP) genotypes to complement their current breeding programmes. Hence, it does not make sense to genotype the same animal for both microsatellite markers and SNP markers. Transitioning to SNP-based parentage verification is an obvious solution but one barrier to this transition is the lack of SNP data on parents from which to verify parentage against. Therefore, the objective of this study was to assess the ability to impute the SNP genotype of a stallion from the genotypes of its progeny, with or without the consideration of the genotype of the progeny’s dam. Genotype information from 55 935 SNPs was available on 13 327 horses. A total of 98 stallions had genotype data on 10 progeny and the genotypes of these stallions were used as a test population. Genome-wide genotype imputation was undertaken by combining a family- and population-based imputation approach. Several different scenarios were assessed to quantify the ability to accurately impute the genotype of a stallion based on genotype data of incrementally more half-sibling progeny. Using genomic information from four progeny the average genotype concordance of the imputed sire genotype compared to the actual sire’s genotype was 0.932. The average genotype concordance rate increased to 0.960 when the genotypes of 10 progeny were included in the imputation process. The inclusion of the genotypes of the dams of the progeny improved the concordance rate from 0.932 to 0.977 when based on the genotype of just four progeny and their dams and from 0.960 to 0.996 when based on the genotype of 10 progeny and their dams. These results suggest it is possible to impute the genotype of a non-genotyped horse from the genotypes of its progeny and that the inclusion of the genotypes of the dams of the progeny improves this imputation accuracy further.

Genome-wide SNPs and candidate genes underlying the genetic variations for protein and amino acids in pearl millet (Pennisetum glaucum) germplasm

Main conclusionA total of 544 significant marker-trait associations and 286 candidate genes associated with total protein and 18 amino acids were identified. Thirty-three candidate genes were found near the strong marker trait associations (– log10P ≥ 5.5).Pearl millet (Pennisetum glaucum) is largely grown as a subsistence crop in South Asia and sub-Saharan Africa. It serves as a major source of daily protein intake in these regions. Despite its importance, no systematic effort has been made to study the genetic variations of protein and amino acid content in pearl millet germplasm. The present study was undertaken to dissect the global genetic variations of total protein and 18 essential and non-essential amino acids in pearl millet, using a set of 435 K Single Nucleotide Polymorphisms (SNPs) and 161 genotypes of the Pearl Millet Inbred Germplasm Association Panel (PMiGAP). A total of 544 significant marker-trait associations (at P < 0.0001; – log10P ≥ 4) were detected and 23 strong marker-trait associations were identified using Bonferroni’s correction method. Forty-eight pleiotropic loci were found in the genome for the studied traits. In total, 286 candidate genes associated with total protein and 18 amino acids were identified. Thirty-three candidate genes were found near strongly associated SNPs. The associated markers and the candidate genes provide an insight into the genetic architecture of the traits studied and are going to be useful in breeding improved pearl millet varieties in the future. Availabilities of improved pearl millet varieties possessing higher protein and amino acid compositions will help combat the rising malnutrition problem via diet.

Mapping quantitative trait loci for seminal root angle in a selected durum wheat population.

Seminal root angle (SRA) is an important root architectural trait associated with drought adaptation in cereal crops. To date, all attempts to dissect the genetic architecture of SRA in durum wheat (Triticum durum Desf.) have used large association panels or structured mapping populations. Identifying changes in allele frequency generated by selection provides an alternative genetic mapping approach that can increase the power and precision of QTL detection. This study aimed to map quantitative trait loci (QTL) for SRA by genotyping durum lines created through divergent selection using a combination of marker-assisted selection (MAS) for the major SRA QTL (qSRA-6A) and phenotypic selection for SRA over multiple generations. The created 11 lines (BC1F2:5) were genotyped with genome-wide single-nucleotide polymorphism (SNP) markers to map QTL by identifying markers that displayed segregation distortion significantly different from the Mendelian expectation. QTL regions were further assessed in an independent validation population to confirm their associations with SRA. The experiment revealed 14 genomic regions under selection, 12 of which have not previously been reported for SRA. Five regions, including qSRA-6A, were confirmed in the validation population. The genomic regions identified in this study indicate that the genetic control of SRA is more complex than previously anticipated. Our study demonstrates that selection mapping is a powerful approach to complement genome-wide association studies for QTL detection. Moreover, the verification of qSRA-6A in an elite genetic background highlights the potential for MAS, although it is necessary to combine additional QTL to develop new cultivars with extreme SRA phenotypes.

Functional ex vivo DNA fibre assay to measure replication dynamics in breast cancer tissue.

Replication stress (RS) is a key trait of cancer cells, and a potential actionable target in cancer treatment. Accurate methods to measure RS in tumour samples are currently lacking. DNA fibre analysis has been used as a common technique to measure RS in cell lines. Here, we investigated DNA fibre analysis on fresh breast cancer specimens and correlated DNA replication kinetics to known RS markers and genomic alterations. Fresh, treatment-naïve primary breast cancer samples (n = 74) were subjected to ex vivo DNA fibre analysis to measure DNA replication kinetics. Tumour cell proliferation was confirmed by EdU incorporation and cytokeratin AE1/AE3 (CK) staining. The RS markers phospho-S33-RPA and γH2AX and the RS-inducing proto-oncogenes Cyclin E1 and c-Myc were analysed by immunohistochemistry. Copy number variations (CNVs) were assessed from genome-wide single nucleotide polymorphism (SNP) arrays. We found that the majority of proliferating (EdU-positive) cells in each sample were CK-positive and therefore considered to be tumour cells. DNA fibre lengths varied largely in most tumour samples. The median DNA fibre length showed a significant inverse correlation with pRPA expression (r = -0.29, p = 0.033) but was not correlated with Cyclin E1 or c-Myc expression and global CNVs in this study. Nuclear Cyclin E1 expression showed a positive correlation with pRPA levels (r = 0.481, p < 0.0001), while cytoplasmic Cyclin E1 expression exhibited an inverse association with pRPA expression (r = -0.353, p = 0.002) and a positive association with global CNVs (r = 0.318, p = 0.016). In conclusion, DNA fibre analysis performed with fresh primary breast cancer samples is feasible. Fibre lengths were associated with pRPA expression. Cyclin E1 expression was associated with pRPA and the percentage of CNVs. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Phylogeography and genetic structure of Papaver bracteatum populations in Iran based on genotyping-by-sequencing (GBS)

Papaver bracteatum, known for its high thebaine content and absence of morphine, has emerged as a promising alternative to opium poppy for codeine production. In this study, our objective was to create a diverse panel representing the natural variation of this species in Iran. To achieve this, we employed genotyping-by-sequencing to obtain genome-wide distributed single-nucleotide polymorphisms (SNPs) for phylogeographic analysis, population structure assessment, and evaluation of genetic diversity within P. bracteatum populations. A total of 244 P. bracteatum individuals from 13 distinct populations formed seven genetic groups, along with one highly admixed population. We observed a clear split between the populations inhabiting the Alborz Mts. in the east and Zagros Mts. in the west. In between these mountain ranges, the population of Kachal Mangan exhibited a high degree of genetic admixture between both genetic groups. At or after the end of the last glacial maximum, when climate conditions rapidly changed, all P. bracteatum populations experienced a strong demographic bottleneck reducing the already small effective population sizes further before they increased to their recent strengths. Our results suggest that the ongoing climate change together with human pressure on the species’ habitats and limited seed-dispersal ability are potential factors contributing today to rising genetic isolation of P. bracteatum populations. Our results provide genetic data that can be used for conservation measures to safeguard the species’ genetic diversity as a resource for future breeding approaches in this medicinally important species.

Phylogenetic relationships and genetic diversity of the Korean endemic Phedimus latiovalifolius (Crassulaceae) and its close relatives

Phedimus latiovalifolius (Y.N.Lee) D.C.Son & H.J.Kim is exclusively distributed in the high mountains in the Korean Peninsula, mainly along the Baekdudaegan mountain range. Despite its morphological and distributional distinction from other Phedimus Raf. species, its taxonomic identity and phylogenetic relationship with congeneric species remain unclear. This study employs genotyping-by-sequencing-derived genome-wide single nucleotide polymorphisms to establish the monophyly of P. latiovalifolius and its relationship with closely related species. Genetic diversity and population differentiation of P. latiovalifolius are also assessed to provide baseline genetic information for future conservation and management strategies. Our phylogenetic analyses robustly demonstrate the monophyletic nature of P. latiovalifolius, with P. aizoon (L.) ‘t Hart identified as its closest sister lineage. There is no genetic evidence supporting a hybrid origin of P. latiovalifolius from P. aizoon involving either P. ellacombeanus (Praeger) ‘t Hart or P. kamtschaticus (Fisch.) ‘t Hart. Population genetic analyses reveal two major groups within P. latiovalifolius. A higher genetic variation is observed in P. ellacombeanus than in the congeneric species. Notably, most of the genetic variation exists within P. latiovalifolius populations. Given its distribution and the potential role of Baekdudaegan as an East Asian Pleistocene refugia, P. latiovalifolius could be considered rare and endemic, persisting in the refugium across glacial/interglacial cycles.