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PubMed2026

Fine-Scale Landscape Genomics Show Asymmetric Patterns of Gene Flow for the Invasive Mosquito Aedes albopictus.

Mosquito-borne viruses like dengue, Zika, and chikungunya pose increasing health risks in the United States due to the expanding range of Aedes albopictus, a highly invasive mosquito species that now has a global distribution. Aedes albopictus thrive in artificial containers associated with anthropogenic land use, allowing populations to reach high numbers in urban and suburban environments. While the global spread of Ae. albopictus has been well characterized, the effects of heterogeneous urban landscapes on dispersal and gene flow at fine spatial scales remain unclear. This study analyzed the genetic connectivity of Aedes albopictus populations collected in Wake County, North Carolina in 2018. We used single nucleotide polymorphisms (SNP) data from double-digest restriction-enzyme associated DNA sequencing (ddRADseq) and examined genetic connectivity through principal component analysis (PCA) and genetic network analysis. We then evaluated migration and source-sink dynamics using a Bayesian approach for SNP data (BA3-SNP). We found little evidence of genetic clustering or isolated populations of Ae. albopictus in Wake County, suggesting high gene flow between sites. Migration analysis demonstrated asymmetric gene flow from rural to urban regions within Wake County, with greater gene flow occurring between and within urban regions. These findings suggest that the pattern of gene flow of Ae. albopictus populations within local metropolitan areas may involve urban city centers serving as genetic sinks and surrounding suburban and rural regions serving as sources. This study highlights how heterogeneous landscapes shape mosquito population connectivity and migration at fine spatial scales, which is critical for informing vector control and public health intervention strategies.

Aedes albopictus↗

PubMed2026

Shared candidate genes associated with variation in egg size in cold-adapted and artificially selected Drosophila melanogaster.

The development of most multicellular organisms begins with oogenesis, the production of the egg. In D. melanogaster, egg size is a highly polygenic trait closely related to fitness. Elements of shifts in egg size have been widely studied and modeled, but the genes underlying this variation are still poorly understood. This study aimed to identify candidate genes associated with processes underlying egg-size variation using D. melanogaster as a model. In selection experiments, we generated large-egg populations from a shared ancestral population using both cold-adaptation and artificial selection, and identified candidate genes for the large-egg phenotype. Using whole-genome DNA sequencing and strict computational filtering, we uncovered single-nucleotide polymorphisms in 10 genes. Characterization of these candidates revealed functions in cytoskeletal dynamics, DNA replication and repair, intracellular signaling, and stem cell maintenance and differentiation. RT-PCR and qPCR were used to validate gene expression differences between cold-adapted lines and the Oregon R control (OrR) in a subset of the candidates. In RT-PCR, stathmin demonstrated a modified expression pattern in all cold-adapted lines relative to OrR controls. In qPCR experiments, Pde1c had significantly higher expression (p < 0.05) in the cold-adapted flies compared to OrR controls for all three fly cages tested. For Ino80, significantly higher expression was observed for one of three cages while one cage showed lower expression. We have assembled a candidate list we hope will be a useful resource for researchers across specialties, from germ cells to cytoskeletal dynamics, to further investigate the genetic and developmental aspects of variation in egg size in D. melanogaster.

Animals↗

PubMed2026

Dissemination of blaKPC-3-harbouring Klebsiella pneumoniae across ST48 and ST628 in multiple healthcare facilities in the Republic of Korea.

Klebsiella pneumoniae carbapenemase-3 (KPC-3) remains rare in South Korea, where KPC-2 is the dominant carbapenemase, making the repeated detection of a concentrated blaKPC-3 signal over five years notable. We performed genomic analyses of blaKPC-3-harbouring K. pneumoniae from a regional healthcare network. Two chromosomally distinct lineages with concordant capsule loci (ST628/KL15 and ST48/KL62) presented multidrug-resistant phenotypes, and the virulence-associated loci were confined to ST48. Single-nucleotide polymorphism (SNP) analyses revealed near-clonal relatedness within lineages, with 0-38 pairwise SNPs among ST628 isolates and 8 SNPs between the two ST48 isolates. Core-genome multilocus sequence typing (cgMLST) supported this structure, as ST628 isolates were assigned to complex type 19149 with 0-7 allelic differences, and ST48 isolates were assigned to complex type 19150 with 5 allelic differences. These patterns support vertical spread via clonal expansion across multiple facilities. Despite substantial chromosomal separation, most isolates carried the same IncFII(K) plasmid backbone and blaKPC-3, and they were nearly indistinguishable from a plasmid previously reported in South Korea. One isolate carried blaKPC-3 on a distinct multireplicon IncFIB(K)/IncFII(K) plasmid, indicating that the signal was not confined to a single plasmid backbone. In both plasmids, blaKPC-3 was embedded within Tn4401b. These findings indicate that a rare blaKPC-3 genotype can persist regionally through sustained clonal dissemination and that cross-lineage linkage is compatible with past horizontal transfer involving a conserved plasmid. These findings underscore the need for subtype-resolved, regionally coordinated genomic surveillance in connected healthcare networks to detect uncommon carbapenemase variants early.

Klebsiella pneumoniae↗

PubMed2026

Multi-omics identification of ZFPM2 and CD44 as key candidates for testicular size in sheep.

Testicular size is a key determinant of ram fertility, yet its genetic architecture in sheep remains poorly understood. Crossbred sheep exhibit substantial testicular developmental variation and serve as ideal models for screening fertility-related genes. Here, we performed whole-genome sequencing (WGS)-based genome-wide association study (GWAS) on 115 rams, including seven crossbred populations (each derived from a distinct sire breed crossed with Hu sheep) and a purebred Hu sheep population. We identified two variants within ZFPM2, including an intronic single nucleotide polymorphism (SNP) rs421073404 and a missense SNP rs1086332841, both significantly correlated with testis weight, length, and width. Importantly, these variants exerted testis-specific effects, consistent with their weak correlation with body weight (r < 0.2). Genomic selection scans (FST and π-ratio) between rams with large (>150 g/side) and small (<75 g/side) testes revealed multiple divergent genomic regions, with prominent haplotype differentiation at the CD44 locus on chromosome 15. Notably, two linked missense variants (rs160734053 and rs414318703) in CD44 exerted opposing effects on testicular size, suggesting allelic heterogeneity at this locus. Integrative RNA-seq and ATAC-seq across 0-12 months further uncovered prepubertal stage-specific expression and chromatin accessibility patterns of ZFPM2 and CD44, providing mechanistic insights into their regulatory roles. Collectively, this study provides candidate SNPs for sheep marker-assisted selection and multi-omic evidence for dissecting the genetic basis of testicular development in ovine breeding.

Animals↗

PubMed2026

Dual-dimensional profiling of host genomic variations and HPV integration in PD-L1-stratified cervical cancer via Oxford Nanopore Technology.

BACKGROUND: The integration of human papillomavirus (HPV) DNA into the host genome is a key step in the development of HPV-associated cervical cancer (CC). However, the genomic characteristics of host genomic variations and HPV integration within the context of programmed death-ligand 1 (PD-L1) expression stratification have not been systematically investigated. METHODS: Whole-genome sequencing was performed using Oxford Nanopore Technology (ONT) on six samples (three from the high PD-L1 expression group and three from the low PD-L1 expression group). The characteristics of host genomic variations under different PD-L1 expression stratifications were explored, including structural variations (SV), copy number variations (CNV), single nucleotide polymorphisms (SNP), and insertion-deletions (Indel). Subsequently, the distribution features of HPV integration sites were analyzed, different integration types were identified, and pathway analysis was conducted. RESULTS: Whole-genome SV analysis revealed that the total number of SVs and the composition of mutation types were similar between the high and low PD-L1 expression groups, with insertions (INS) and deletions (DEL) predominating in both. These variations were primarily enriched in intergenic regions and introns. In the low PD-L1 expression group, integration events were observed at multiple chromosomal loci, with the most frequent integration occurring in the KLF5 gene region on chromosome 13. No frequently integrated loci were identified in the high PD-L1 expression group. Additionally, four distinct HPV integration breakpoint patterns were preliminarily identified and analyzed. CONCLUSION: PD-L1 expression stratification did not significantly alter the overall genomic instability of the host. However, differences were observed in the distribution patterns of HPV integration sites. These findings provide new insights into the genomic heterogeneity of CC under different PD-L1 expression backgrounds and may lay the groundwork for future research exploring stratified immunotherapy based on HPV integration features.

Humans↗

PubMed2025

Nested Admixture During and After the Trans-Atlantic Slave Trade on the Island of São Tomé.

Human genetic admixture, involving the contact between two or more previously isolated populations, can be a complex process influenced by social dynamics. In this study, we aim to reconstruct complex admixture histories in São Tomé, an island in the Gulf of Guinea where the Portuguese established one of the first plantation-based slave societies. Since the 15th century, migration waves from Africa and Europe, slavery, marooning, and indentured labour led to profound demographic shifts and social stratification on the island. Examining 2.5 million SNPs newly genotyped in 96 São Toméans, we observed patterns of genetic differentiation that were more complex than those of other populations descended from enslaved Africans on either side of the Atlantic. Using local ancestry inference and Identical-by-Descent methods, we identified five genetic clusters in São Tomé and reconstructed shared ancestries between each cluster and 70 African and European population samples, including an extensive sample from the Cabo Verde archipelago. Our findings align with historical records, retracing the major slave trade routes and labour-driven migrations after the abolition of slavery. We also identified gene flow between recently admixed groups that were previously isolated on the island. We call this process, creating multiple layers of genetic ancestry in admixed genomes, nested admixture. We suggest that changing social structures in São Tomé transformed the genetic structure of its population and influenced the admixture process. This study demonstrates how successive admixture and isolation events during and after the Trans-Atlantic Slave Trade shaped extant genetic diversity patterns at local scale in Africa.

Humans↗

PubMed2026

Concordance and divergence between self-declared ancestry and genome-derived ancestry composition in 10 250 participants from the HostSeq cohort.

Accurate characterization of human genetic diversity is essential for robust genomic analyses. We compared self-declared and genome-derived ancestry composition in 10 250 participants from the pan-Canadian HostSeq cohort using whole-genome sequencing data. Global and local ancestry were inferred at the continental super-population level using the alignment-free ntRoot algorithm and evaluated through both hard-label concordance and multiclass Brier score analyses incorporating full ancestry fraction profiles. Strong agreement was observed among East Asian / Pacific Islander (mean Brier score ± SD: 0.012 ± 0.052), Black (0.013 ± 0.042), White (0.055 ± 0.022), and South Asian (0.057 ± 0.098) participants, whereas higher scores among Hispanic (0.083 ± 0.060) and Middle Eastern or Central Asian (0.122 ± 0.034) participants reflected broader and more admixed ancestry profiles. Principal component analysis of centered log-ratio-transformed ancestry fractions revealed overlapping ancestry gradients rather than discrete continental groupings. Entropy- and dominance margin-based analyses further indicated that many discordant cases reflected diffuse admixture rather than categorical mismatch. Together, these findings support representing ancestry as a continuous compositional spectrum rather than discrete categories. Genome-derived ancestry estimates describe patterns of genomic variation and should not be interpreted as proxies for race.

Humans↗

PubMed2026

Lineage-specific transmission and spatial clustering of Mycobacterium tuberculosis in Kaohsiung, Taiwan, in 2019-23: a population-based genomic study.

BACKGROUND: The epidemiology of tuberculosis in Taiwan has been influenced by the introduction of multiple Mycobacterium tuberculosis lineages and by the ageing of the population. We conducted a population-based study to investigate M tuberculosis transmission in Kaohsiung, a city in southern Taiwan. METHODS: In this study, we performed whole-genome sequencing (WGS) of M tuberculosis isolates from all culture-positive cases of tuberculosis notified in Kaohsiung between Jan 1, 2019 and Dec 31, 2023. We obtained routine epidemiological data for each case collected through the national tuberculosis control programme. We characterised the lineage composition of the isolate collection and evaluated genomic clustering of isolates, defined as a difference of 12 or fewer single-nucleotide polymorphisms. Univariable and multivariable logistic regression analyses were performed to estimate the odds of a case belonging to a genomic cluster based on host factors (age, sex, sputum smear status, and residential region) and pathogen factors (drug resistance status and strain lineage). Spatial aggregation of large genomic clusters (including greater than or equal to ten isolates) was assessed using a non-parametric statistical clustering method. We used a Bayesian transmission tree inference method to explore the patterns of age-dependent transmission. FINDINGS: During the study period, 5667 tuberculosis cases were notified in Kaohsiung, 4916 (86·7%) of which were culture-positive. Of these 4916 cases, whole-genome sequencing was successfully performed for 4168 (84·8%) isolates. 1219 (29·2%) of 4168 individuals were female and 2947 (70·7%) were male; the median age was 69·7 years (IQR 57·4-80·7). The dominant lineages were lineage 1 (1749 [42·0%] of 4168 isolates), lineage 2 (1510 [36·2%]), and lineage 4 (905 [21·7%]). 1069 (25·6%) of 4168 were genomically linked and formed 287 clusters. Lineage 2 isolates had higher odds (aOR 2·15 [95% CI 1·80-2·52]) than lineage 1 isolates of genomic clustering across all regions, whereas lineage 4 isolates had a significantly higher risk (2·75 [1·16-6·89]) of genomic clustering than lineage 1 only in the rural northeast region, inhabited primarily by indigenous populations. Spatial clustering analysis corroborated these lineage-region interactions. Although younger adults (<35 years) had the highest individual-level odds (5·64 [4·16-7·68]) of clustering in the logistic regression analysis compared with those aged 80 years or older, the transmission inference indicated that individuals aged 55-74 years were responsible for a greater proportion of inferred transmission events, contributing 50·8% of all transmission events. INTERPRETATION: This sequencing study revealed that older adults (aged ≥65 years) might have played a substantial and under-recognised role in the transmission of tuberculosis in Taiwan. The lineage-specific clustering and spatial patterns suggested that both pathogen characteristics and host demographics shaped tuberculosis transmission dynamics. These findings support the use of integrated genomic surveillance to guide precision tuberculosis control and motivate further research on age-specific transmission pathways and targeted interventions to advance tuberculosis elimination efforts. FUNDING: Taiwan National Health Research Institutes and Taiwan National Science and Technology Council.

Mycobacterium tuberculosis↗

PubMed2026

Whole-Genome Analysis Reveals Antimicrobial Resistance and Population Structure of Environmental and Veterinary Acinetobacter baumannii.

Acinetobacter (A.) baumannii is an important multidrug-resistant pathogen increasingly recognized across animal and environmental settings, and carbapenem-resistant A. baumannii (CRAB) is classified as a critical-priority pathogen by the World Health Organization. This study investigated the antimicrobial resistance (AMR) and genomic characteristics of 122 A. baumannii isolates comprising 72 veterinary and 50 environmental isolates collected in Andhra Pradesh, India. Antimicrobial susceptibility testing, whole-genome sequencing (WGS), resistance and virulence gene profiling, multilocus sequence typing (MLST), core-genome analysis, single nucleotide polymorphism (SNP) phylogeny, and pan-genome analysis were performed. Overall, 58.2% of isolates were multidrug-resistant (MDR), and 41.8% were extensively drug-resistant (XDR). Sequence type (ST) 52 predominated among veterinary isolates, whereas ST2 was more frequent among environmental isolates. The presence of carbapenem-resistant isolates along with the ST2 lineage enhances the similarity to clinical A. baumannii. Several intrinsic resistance genes, including blaOXA-23, armA, aph(3″)-Ib, aph(6)-Id, tet(B), mph(E), and msr(E), were more prevalent in the ST2-associated population. Virulence-associated determinants were widely conserved. Core-genome MLST (cgMLST) and core-genome SNP (cgSNP) analyses identified highly related isolates within both lineages, while pairwise SNP differences were 0-7. Pan-genome analysis identified 4204 gene clusters and distinct accessory gene patterns between ST2 and ST52. These findings indicate that resistance gene distribution was closely associated with lineage structure and support integrated genomic surveillance of A. baumannii across animal and environmental reservoirs.

Acinetobacter baumannii↗

PubMed2025

Genomic Insights Into Local Adaptation Across Heterogeneous Understory Habitats and Climate Change Vulnerability.

Understanding adaptive evolution and survival risks in understory herbs is crucial for the effective conservation of biodiversity. How environmental gradients shape species local adaptation patterns is not well understood, nor is how populations of understory herbs respond to a changing climate. In this study, we conducted population genomic analyses of Adenocaulon himalaicum (Asteraceae) with a pan-East Asian distribution, representing a good model for dominant understory herbs to elucidate adaptation mechanisms in heterogeneous forest ecosystems. Based on 34,398 putatively neutral single nucleotide polymorphisms (SNPs) across 27 populations, we identified three genetic lineages accompanied by high levels of genetic differentiation between populations. Our isolation by environment results (IBE) indicated a significant effect of environmental gradients on genomic variation of A. himalaicum (r = 0.18, p = 0.03). To decompose the relative contributions of climate, geography and population structure in explaining genetic variance, our partial RDA found that the prominent contribution of environmental effects (climatic and soil variables) explained 29% and 36% of the neutral and adaptive genetic variation, respectively. Using two genotype-environment association (GEA) methods, we identified 13 SNPs as candidates for core climate-related adaptation loci, with two of these loci further validated by qRT-PCR experiments. Projections of spatiotemporal genomic vulnerability under different future climate scenarios revealed that populations in the southeastern edge of the Himalayas, near the Sichuan Basin, the southernmost region of Northeast China and the northern Korean Peninsula, as well as northern Japan, were identified as the most vulnerable and should be prioritised for conservation. Therefore, our current study provides the genomic foundations for conservation and management strategies to elucidate how these understory herbs cope with future climate changes.

Climate Change↗

PubMed2024

Genome-wide association studies with experimental validation identify a protective role for B lymphocytes against chronic post-surgical pain.

BACKGROUND: Chronic post-surgical pain (CPSP) significantly impacts patients' recovery and quality of life. Although environmental risk factors are well-established, genetic risk remains less understood. METHODS: A meta-analysis of genome-wide association studies followed by partitioned heritability was performed on 1350 individuals across five surgery types: hysterectomy, mastectomy, abdominal, hernia, and knee. In subsequent animal studies, withdrawal thresholds to evoked mechanical stimulation were measured in Rag1 null mutant and wild-type mice after plantar incision and laparotomy. Cell sorting by flow cytometry tracked recruitment of immune cell types. RESULTS: We discovered 77 genome-wide significant single-nucleotide polymorphism (SNP) hits, distributed among 24 loci and 244 genes. Meta-analysis of all cohorts estimated a SNP-based narrow-sense heritability for CPSP at ∼39%, indicating a substantial genetic contribution. Partitioned heritability analysis across a wide variety of tissues revealed enrichment of heritability in immune system-related genes, particularly those associated with B and T cells. Rag1 null mutant mice lacking both T and B cells exhibited exacerbated and prolonged allodynia up to 42 days after surgery, which was rescued by B-cell transfer. Recruitment patterns of B cells but not T cells differed significantly during the first 7 days after injury in the footpad, lymph nodes, and dorsal root ganglia. CONCLUSIONS: These findings suggest a key protective role for the adaptive immune system in the development of chronic post-surgical pain.

Animals↗

PubMed2026

Development and optimization of T-ARMS PCR assays for detection of lethal haplotypes of TADA2A, UR1B, and PORL1B in pigs in Vietnam.

Marker-assisted selection has increasingly relied on single-nucleotide polymorphisms (SNPs) as robust genetic markers, particularly in livestock breeding programs. In pig farming, embryonic mortality significantly affects litter size, and SNPs in reference genes have been implicated as potential causal factors. We developed and optimized a tetra-primer amplification refractory mutation system (T-ARMS) PCR assay for rapid, cost-effective detection of SNPs in 3 candidate genes-TADA2A, PORL1B, URB1-that are associated with embryonic lethality and reproductive performance. Primer sets were designed based on known mutation sites and validated using synthetic gene constructs and porcine genomic DNA from pigs of Duroc and Landrace breeds. Optimization of annealing temperatures and primer concentration ratios yielded distinct and reproducible allele-specific amplicon patterns that were corroborated by PCR-RFLP and Sanger sequencing. Our T-ARMS PCR protocol, which requires minimal equipment and reduces processing time to <3 h, had high specificity and efficiency in differentiating wild-type, heterozygous, and homozygous mutant genotypes in 20 Duroc and 20 Landrace pigs. Our Tetra-ARMS PCR assay is a robust and economically viable tool for SNP genotyping in pig breeding programs, potentially contributing to the reduction of embryonic lethality and the improvement of overall reproductive outcomes.

Sus scrofa↗

PubMed2026

Whole-genome sequencing reveals divergent and shared selection signatures of heat stress adaptation in indigenous Ethiopian zebu cattle from dry-hot and humid-hot environments.

African zebu cattle (Bos indicus) exhibit remarkable adaptations to extreme thermal conditions, yet the genomic basis of this resilience remains incompletely characterized. Ethiopia provides a unique natural setting in which closely related zebu populations have adapted divergently to dry-hot (DHETZ) and humid-hot (HHETZ) climates. In this study, we reanalyzed publicly available whole-genome sequencing datasets from 46 Ethiopian zebu cattle from five populations and compared them with Asian zebu, Sudanese zebu, African taurine, and European taurine breeds. By integrating genome-wide SNP analysis, population genetic structure assessment, and multiple selection scans (iHS, Hp, XP-EHH, and XP-CLR), we identified distinct and shared selection signatures between DHETZ and HHETZ. We detected 33.7 million and 34.2 million biallelic autosomal SNPs in DHETZ and HHETZ, respectively. Ethiopian zebu clustered closely with Sudanese zebu but showed clear divergence from Asian zebu and taurine breeds. DHETZ and HHETZ exhibited very low genetic differentiation (FST = 0.0063), consistent with their shared ancestry; however, each group displayed unique selection signals. In DHETZ, iHS and Hp detected 298 and 113 candidate regions, respectively, whereas in HHETZ, they detected 244 and 138 regions, respectively. Cross-population XP-EHH and XP-CLR analyses identified 163 and 227 divergent regions between DHETZ and HHETZ, respectively. Integration of the four selection scans identified 19 high-confidence candidate regions in DHETZ and 13 in HHETZ. DHETZ showed strong selection in genes involved in oxidative stress regulation, protein folding, mitochondrial function, and vascular remodeling, including SESN2, DNAJC8, GRPEL2, ABLIM3, and AFAP1L1. In contrast, HHETZ displayed signatures in genes associated with immune responses, energy metabolism, and angiogenesis inhibition, including MYD88, PRKACA, PRKACB, and WIF1. Several genes, including VEGFC, TNIP3, and DMXL2, were under selection in both groups, suggesting conserved mechanisms of thermotolerance and reproductive adaptation. The shared VEGFC signal and the HHETZ-specific WIF1 signal may indicate a distinct vascular regulatory mechanism in the dry-hot and humid-hot environments. Our results reveal a dual pattern of genomic adaptation in Ethiopian zebu cattle and provide candidate loci for future validation and climate-resilient livestock breeding.

Animals↗

PubMed2026

Genetic Association Between Sleep Traits and Vertigo Risk: A Two-sample Bidirectional Mendelian Randomization Study.

BACKGROUND: Observational studies suggest the potential association between sleep traits and vertigo; however, causal evidence remains limited. OBJECTIVE: This study aimed to explore the relationship between genetically predicted sleep traits and vertigo with the Mendelian randomization (MR) method. METHODS: Instrumental variables for sleep traits (snoring, sleep duration, insomnia, daytime sleepiness, daytime napping, and chronotype) were adopted from genomewide association studies (GWAS) data of European ancestry from UK Biobank. The summary-level datasets of vertigo were retrieved from the GWAS of FinnGen. Inversevariance weighted (IVW) method was adopted as the main analysis. RESULTS: IVW analysis revealed a significant association between genetically predicted daytime napping (OR = 1.51, 95% CI =1.08-2.12, P = 0.016) and chronotype (OR = 1.13, 95% CI =1.01-1.26, P = 0.033), both of which were associated with an increased risk of vertigo. However, we did not find evidence for a causal effect of snoring, overall sleep duration, long sleep duration, short sleep duration, insomnia, and excessive daytime sleepiness on vertigo. No reverse causality was detected. CONCLUSION: Our findings suggest that abnormal sleep patterns may serve as risk factors for vertigo disorders and offer opportunities for the prevention and management of vertigo disorders.

Humans↗

PubMed2026

Shared genetic basis and spatial cellular atlas of psoriasis and metabolic syndrome.

BACKGROUND: Psoriasis (PS) and metabolic syndrome (MetS) frequently co-occur. Characterizing their shared genetic architecture and spatially enriched cellular populations may clarify the context of their co-occurrence and generate hypotheses for functional validation. METHODS: We integrated genome-wide association study (GWAS) summary statistics for PS, MetS, and five related components with spatially resolved single-cell transcriptomic data. Global and local genetic correlations were assessed using linkage disequilibrium score regression, genetic covariance analysis, high-definition likelihood, and local analysis of variant association. A bivariate causal mixture model quantified polygenic overlap. Conditional/conjunctional false discovery rate and composite-null pleiotropy analyses identified shared susceptibility loci. Finally, gsMap evaluated trait-associated enrichment across annotated embryonic tissues at single-cell resolution. RESULTS: Genetic approaches identified significant genome-wide correlations and polygenic sharing between PS, MetS, and its components. Local and cross-trait analyses identified region-specific signals and cross-validated shared loci. gsMap revealed trait-specific tissue enrichment. PS showed the strongest enrichment in the epidermis (pCauchy = 1.0573 × 10  - ⁴), adipose tissue (pCauchy = 1.5366 × 10 - ⁴), and liver (pCauchy = 1.0167 × 10 - ³). Across MetS, FBG, HDL-C, hypertension, and TG, enriched regions mainly involved the liver, adipose tissue, and epidermis. WC enrichment was predominantly observed in adipose tissue (pCauchy = 1.7823 × 10 - ⁴), with no significant liver or epidermal enrichment. CONCLUSION: Integrating GWAS with single-cell transcriptomic and spatial information characterized shared genetic architecture between PS and MetS-related phenotypes and their spatial enrichment patterns. These findings provide a framework for generating testable hypotheses about comorbidity biology and guiding future functional and clinical validation.

Psoriasis↗

PubMed2026

Genome-wide characterization of heat shock protein genes reveals thermal stress-responsive candidates in Litopenaeus vannamei.

Heat shock proteins (HSPs) are conserved molecular chaperones involved in protein folding, refolding, aggregation prevention, and degradation of damaged proteins. However, the genomic organization and thermal responsiveness of HSP genes in the Pacific white shrimp (Litopenaeus vannamei) remain incompletely understood. Here, we performed a genome-wide analysis of the HSP gene family and examined its phylogenetic relationships, structural features, duplication patterns, sequence variation, interaction networks, and transcriptional responses to acute heat stress. A total of 34 HSP genes were identified and classified into the HSP90, HSP70, HSP40/DNAJ, HSP60, and small HSP families. Phylogenetic, motif, gene structure, synteny, and subcellular localization analyses revealed evolutionary conservation and structural diversification among family members. Three duplicated gene pairs were identified, comprising two segmental duplications and one tandem duplication. All pairs exhibited Ka/Ks ratios below 1, consistent with purifying selection of varying strength. Sequence analysis identified 295 nonsynonymous single-nucleotide polymorphisms, of which 12 were consistently predicted to be deleterious by multiple algorithms. Protein-protein interaction analysis indicated enrichment of protein-folding and cellular stress-response functions. RT-qPCR analysis showed significant induction of HSPA4, HSP90AA1, TRAP1, BiP, and DNAJA1 after 6, 12, and 24 h of exposure to 34 °C, whereas DNAJC3 was significantly induced only at 12 h. All six genes reached their highest transcript abundance at 12 h. These findings may provide a genomic framework for HSP genes in L. vannamei and identify candidate genes and variants associated with thermal stress responses.

Animals↗

PubMed2026

Genotypic and phenotypic consequences of domestication in dogs.

Runs of homozygosity (ROH) are genomic regions that arise when identical haplotypes are inherited from a shared ancestor. In this study, we explored ROH across 556 whole-genome sequences from domesticated and non-domesticated dogs. Then, we leveraged ROH from 466 breed dogs, representing 13 breed groups and 13 phenotypic traits, to investigate associations between genetic diversity and non-disease phenotypes. We identified significant associations between the ROH-based inbreeding coefficient (FROH) and multiple phenotypes. These include three quantitative traits (height, weight, lifespan) and ten morphological and coat-related traits. After correcting for population structure, we identified more than 45 genes associated with quantitative traits that exceeded suggestive or genome-wide significance (GWS) thresholds. We also observed distinct patterns of inbreeding across dog populations, including elevated levels of long ROH in modern breed dogs relative to more ancient breeds, consistent with intensive breeding practices during Victorian-era breed formation. Together, our results demonstrate how domestication, demographic bottlenecks, and selective breeding have shaped patterns of homozygosity and contributed to the genetic architecture of complex traits in dogs, highlighting an important role for non-additive genetic variation and polygenicity.

Animals↗

PubMed2025

Combined somatic mutation and transcriptome analysis reveals region-specific differences in clonal architecture in human cortex.

The human cerebral cortex is specialized into regions, but little is known about how human cellular lineages shape cortical regional variation and neuronal cell-type distribution during development. Here, we map single-cell lineages of human cortical regions and neuronal subtypes using >1,000 somatic single-nucleotide variants (sSNVs) identified from deep bulk whole-genome sequencing and analyzed over 25 regions and >72,000 single cells. In the fronto-parietal cortex, sSNVs are rarely restricted, marking neuron-generating clones that disperse into neighboring regions. In contrast, the primary visual cortex harbors 30%-70% more sSNVs than the neighboring secondary visual cortex. Clones at this border exhibit more restricted dispersion, suggesting late developmental lineage segregation. Single-nucleus sSNV and whole-transcriptome analysis reveal glutamatergic neuron clones with modest regional restrictions that share low-mosaic sSNVs with some GABAergic neurons, suggesting a recent dorsal cortical progenitor. Our analysis reveals human-specific cortical lineage patterns, regional differences in clonal patterns, and late divergence of some glutamatergic/GABAergic lineages.

Humans↗