Genome-wide Single Nucleotide Polymorphism Research Articles

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.

Missing genotype imputation in non-model species using self-organizing maps.

Current methodologies of genome-wide single-nucleotide polymorphism (SNP) genotyping produce large amounts of missing data that may affect statistical inference and bias the outcome of experiments. Genotype imputation is routinely used in well-studied species to buffer the impact in downstream analysis, and several algorithms are available to fill in missing genotypes. The lack of reference haplotype panels precludes the use of these methods in genomic studies on non-model organisms. As an alternative, machine learning algorithms are employed to explore the genotype data and to estimate the missing genotypes. Here, we propose an imputation method based on self-organizing maps (SOM), a widely used neural networks formed by spatially distributed neurons that cluster similar inputs into close neurons. The method explores genotype datasets to select SNP loci to build binary vectors from the genotypes, and initializes and trains neural networks for each query missing SNP genotype. The SOM-derived clustering is then used to impute the best genotype. To automate the imputation process, we have implemented gtImputation, an open-source application programmed in Python3 and with a user-friendly GUI to facilitate the whole process. The method performance was validated by comparing its accuracy, precision and sensitivity on several benchmark genotype datasets with other available imputation algorithms. Our approach produced highly accurate and precise genotype imputations even for SNPs with alleles at low frequency and outperformed other algorithms, especially for datasets from mixed populations with unrelated individuals.

Genetic and morphological evidence support the specific status of the endemic Ericaandevalensis (Ericales, Ericaceae).

Assessing the taxonomic status of closely related taxa is crucial in plant systematics and can have important implications for conservation and human plant use. Ericaandevalensis Cabezudo & Rivera is a metallophyte endemic species from highly metal-polluted soils of SW Iberian Peninsula, an area with a mining history going back more than 5,000 years. Ericaandevalensis is closely related to Ericamackayana Bab., a northern Iberian species also present in western Ireland. The status of E.andevalensis as a species or subspecies subordinated to E.mackayana is subject to debate. Here, we assessed the genetic and phenotypic relationship between both species, including the population structure of E.andevalensis. We used high throughput sequencing to determine genome-wide Single Nucleotide Polymorphisms (SNPs), and morphometric analyses from 35 reproductive and vegetative traits. The morphological analysis showed at least eight characters that can discriminate the two species, from which ovary hairiness and the size of leaf glandular hairs were the most informative. Genetic analyses showed that each species formed a monophyletic cluster with full support, separated by an interspecific genetic distance >4-fold higher than intra-specific distance. Population genetic analyses of E.andevalensis shows that populations are highly structured, with the Portuguese one as the most isolated and less variable. These results support the recognition of E.andevalensis as a distinct species with a highly constrained ecological requirements and a narrow geographic distribution, but with a limited gene flow between populations. We discuss the implications of these outcomes in conservation policies and potential uses of E.andevalensis such as decontamination of polluted soils.

Drivers of genomic diversity and phenotypic development in early phases of domestication in Hermetia illucens.

The black soldier fly (BSF), Hermetia illucens, has the ability to efficiently bioremediate organic waste into usable bio-compounds. Understanding the impact of domestication and mass rearing on fitness and production traits is therefore important for sustainable production. This study aimed to assess patterns of genomic diversity and its association to phenotypic development across early generations of mass rearing under two selection strategies: selection for greater larval mass (SEL lines) and no direct artificial selection (NS lines). Genome-wide single nucleotide polymorphism (SNP) data were generated using 2bRAD sequencing, while phenotypic traits relating to production and population fitness were measured. Declining patterns of genomic diversity were observed across three generations of captive breeding, with the lowest diversity recorded for the F3 generation of both selection lines, most likely due to founder effects. The SEL cohort displayed statistically significantly greater larval weight com the NS lines with pronounced genetic and phenotypic directional changes across generations. Furthermore, lower genetic and phenotypic diversity, particularly for fitness traits, were evident for SEL lines, illustrating the trade-off between selecting for mass and the resulting decline in population fitness. SNP-based heritability was significant for growth, but was low or non-significant for fitness traits. Genotype-phenotype correlations were observed for traits, but individual locus effect sizes where small and very few of these loci demonstrated a signature for selection. Pronounced genetic drift, due to small effective population sizes, is likely overshadowing the impacts of selection on genomic diversity and consequently phenotypic development. The results hold particular relevance for genetic management and selective breeding for BSF in future.

Respiratory infection- and asthma-prone, low vaccine responder children demonstrate distinct mononuclear cell DNA methylation pathways

BackgroundInfants with frequent viral and bacterial respiratory infections exhibit compromised immunity to routine immunizations. They are also more likely to develop chronic respiratory diseases in later childhood. This study investigated the feasibility of epigenetic profiling to reveal endotype-specific molecular pathways with potential for early identification and immuno-modulation. Peripheral blood mononuclear cells from respiratory infection allergy/asthma-prone (IAP) infants and non-infection allergy/asthma prone (NIAP) were retrospectively selected for genome-wide DNA methylation and single nucleotide polymorphism analysis. The IAP infants were enriched for the low vaccine responsiveness (LVR) phenotype (Fisher's exact p-value = 0.02).ResultsAn endotype signature of 813 differentially methylated regions (DMRs) comprising 238 lead CpG associations (FDR < 0.05) emerged, implicating pathways related to asthma, mucin production, antigen presentation and inflammasome activation. Allelic variation explained only a minor portion of this signature. Stimulation of mononuclear cells with monophosphoryl lipid A (MPL), a TLR agonist, partially reversed this signature at a subset of CpGs, suggesting the potential for epigenetic remodeling.ConclusionsThis proof-of-concept study establishes a foundation for precision endotyping of IAP children and highlights the potential for immune modulation strategies using adjuvants for future investigation.

O-271 Two component resolution of mosaic samples in PGT-A: primary template amplification (PTA) and independent analysis using copy-number variation and allelic balance

Abstract Study question How does accurate, unbiased whole genome amplification and tiered, independent, two component analysis impact PGT-A results? Summary answer When compared to previous methods a PGT-A workflow utilizing PTA followed by a CNV and allelic balance-based analysis generated more conclusive results. What is known already Accurate PGT-A results require unbiased error-free whole genome amplification from the trophectoderm biopsy and smart bioinformatics utilities to fully analyze and consider the large complex datasets. PTA generates fewer errors, greater coverage, and reduced allele drop-out offering the best starting point to interpret the genome of each embryo. Current PGT-A platforms leverage either normalized CNV data OR allelic balance at single nucleotide polymorphisms (SNPs), to detect alterations in the embryonic genome. A pipeline leveraging improved amplification technology and consolidated CNV and SNP data, particularly for putative mosaic and segmental mosaic calls, could reduce uncertainty and provide more accurate PGT-A results. Study design, size, duration A retrospective analysis of PGT-A results was undertaken with samples originating from multiple clinics and processed in a single laboratory, from January through December, 2023. Approximately 500 samples were processed simultaneously through two independent PGT-A pipelines. The primary objective was to compare the performance of CNV-only PGT-A with a test leveraging both CNV and SNP data. A secondary objective was to observe the resolution of mosaic embryos. Participants/materials, setting, methods De-identified samples were amplified with PTA and sequenced with both shotgun (coverage-based CNV) and capture (SNP-based)-approaches. Method specific analysis was applied to the resulting data. An initial bioinformatics approach analyzed CNV data only for variations in copy-number along the genome, proposing stretches of aneuploidy or mosaicism. A second, tiered analysis extended this data and incorporated SNP-based allelic balance to evaluate candidate regions and confirm the presence of aneuploidy and/or quantify mosaic levels. Main results and the role of chance Genome-wide read coverage and SNP data confirmed that PTA accurately and completely amplified the genetic material in each sample with broad distribution of informative data and a low allele drop-out rate. High concordance (95%) was observed for euploid and full aneuploid (whole chromosome and segmental) embryos classified with CNV-alone and CNV/SNV combined analysis. SNP data was processed, and B-allele ratios were used to confirm aneuploidies with particular utility in resolving the location of segmental changes. The classification of mosaic samples was altered in the pipeline leveraging both CNV and SNP data. Of 54 mosaic samples tested, 75% remained mosaic after independent consideration of SNP data, ∼15% and 6% of high-level mosaics were resolved to full aneuploid and euploid, respectively, and ∼25% of low-level mosaics reverted to a euploid classification. The deep SNP data produced during targeted sequencing confirmed the altered allele ratio predicted by CNV data and re-confirmed the presence and proportion of aneuploid cells. Mosaic levels were highly correlated in 90% of re-confirmed mosaic samples. This suggests that the classification of these samples as mosaic is precise and accurate and suggests a strong utility for a two component PGT-A pipeline leveraging CNV and SNV data generated from PTA embryos. Limitations, reasons for caution This was a retrospective study with limited sample numbers. Wider implications of the findings The study highlights the strong advantages of a hybrid PGT-A pipeline, leveraging PTA and two component analysis of coverage and allelic balance, particularly to resolve mosaic embryos more accurately. Overall, this could reduce uncertainty and deliver more confident PGT-A results for embryo transfer decision making. Trial registration number not applicable

On the road to losing connectivity: Faecal samples provide genome-wide insights into anthropogenic impacts on two large herbivore species in central India.

Humans have impacted most of the planet, and the ensuing fragmentation results in small, isolated habitat patches posing a risk of genetic diversity loss, inbreeding, and genetic load. Understanding how natural and anthropogenic landscape features affect gene flow among habitat patches is critical for maintaining connectivity. Genome-wide data are required to comprehend the impacts of recent fragmentation, which can be challenging when only non-invasive samples are available. Here, we build upon advancements in conservation genomics to address connectivity of two large herbivores, gaur (Bos gaurus) and sambar (Rusa unicolor) in central India. Given their habitat associations, we expected these species to respond similarly to habitat fragmentation. We used faecal-DNA and methylation-based host-DNA enrichment with modified ddRAD protocol to generate genome-wide single-nucleotide polymorphism (SNP) data for 124 gaur and 99 sambar individuals. Our findings reveal that gaur populations in central India are fragmented, displaying high genetic differentiation, with drift significantly affecting small populations like Umred Karhandla Wildlife Sanctuary. Although sambar shows low genetic structure, another small population, Bor Tiger Reserve is genetically differentiated. Our results suggest that although land cover change and roads restrict animal movement, the extent of this impact varies across the two species. We show that different species respond differently to landscape features, even with similar habitat associations. We highlight small and isolated populations requiring urgent conservation intervention. Such multi-species approaches enhance our understanding of cross-species connectivity patterns. We suggest shifting from single-species to multi-species holistic conservation approach in rapidly developing landscapes to better manage co-occurring endangered species.

Genome-wide association study provided insights into the polled phenotype and polled intersex syndrome (PIS) in goats

BackgroundBreeding polled goats is a welfare-friendly approach for horn removal in comparison to invasive methods. To gain a comprehensive understanding of the genetic basis underlying polledness in goats, we conducted whole-genome sequencing of 106 Xinong Saanen dairy goats, including 33 horned individuals, 70 polled individuals, and 3 polled intersexuality syndrome (PIS) individuals.MethodsThe present study employed a genome-wide association study (GWAS) and linkage disequilibrium (LD) analysis to precisely map the genetic locus underlying the polled phenotype in goats.ResultsThe analysis conducted in our study revealed a total of 320 genome-wide significant single nucleotide polymorphisms (SNPs) associated with the horned/polled phenotype in goats. These SNPs exhibited two distinct peaks on chromosome 1, spanning from 128,817,052 to 133,005,441 bp and from 150,336,143 to 150,808,639 bp. The present study identified three genome-wide significant SNPs, namely Chr1:129789816, Chr1:129791507, and Chr1:129791577, as potential markers of PIS-affected goats. The results of our LD analysis suggested a potential association between MRPS22 and infertile intersex individuals, as well as a potential association between ERG and the polled trait in goats.ConclusionWe have successfully identified three marker SNPs closely linked to PIS, as well as several candidate genes associated with the polled trait in goats. These results may contribute to the development of SNP chips for early prediction of PIS in goats, thereby facilitating breeding programs aimed at producing fertile herds with polled traits.

Genetic characterization of cucumber genetic resources in the NARO Genebank indicates their multiple dispersal trajectories to the East

Key messageGenotyping-by-sequencing of 723 worldwide cucumber genetic resources revealed that cucumbers were dispersed eastward via at least three distinct routes, one to Southeast Asia and two from different directions to East Asia.The cucumber (Cucumis sativus) is an economically important vegetable crop cultivated and consumed worldwide. Despite its popularity, the manner in which cucumbers were dispersed from their origin in South Asia to the rest of the world, particularly to the east, remains a mystery due to the lack of written records. In this study, we performed genotyping-by-sequencing (GBS) on 723 worldwide cucumber accessions, mainly deposited in the Japanese National Agriculture and Food Research Organization (NARO) Genebank, to characterize their genetic diversity, relationships, and population structure. Analyses based on over 60,000 genome-wide single-nucleotide polymorphisms identified by GBS revealed clear genetic differentiation between Southeast and East Asian populations, suggesting that they reached their respective region independently, not progressively. A deeper investigation of the East Asian population identified two subpopulations with different fruit characteristics, supporting the traditional classification of East Asian cucumbers into two types thought to have been introduced by independent routes. Finally, we developed a core collection of 100 accessions representing at least 93.2% of the genetic diversity present in the entire collection. The genetic relationships and population structure, their associations with geographic distribution and phenotypic traits, and the core collection presented in this study are valuable resources for elucidating the dispersal history and promoting the efficient use and management of genetic resources for research and breeding in cucumber.

Impact of gene-by-trauma interaction in MDD-related multimorbidity clusters

BackgroundMajor depressive disorder (MDD) is considerably heterogeneous in terms of comorbidities, which may hamper the disentanglement of its biological mechanism. In a previous study, we classified the lifetime trajectories of MDD-related multimorbidities into seven distinct clusters, each characterized by unique genetic and environmental risk-factor profiles. The current objective was to investigate genome-wide gene-by-environment (G × E) interactions with childhood trauma burden, within the context of these clusters. MethodsWe analyzed 77,519 participants and 6,266,189 single-nucleotide polymorphisms (SNPs) of the UK Biobank database. Childhood trauma burden was assessed using the Childhood Trauma Screener (CTS). For each cluster, Plink 2.0 was used to calculate SNP × CTS interaction effects on the participants' cluster membership probabilities. We especially focused on the effects of 31 candidate genes and associated SNPs selected from previous G × E studies for childhood maltreatment's association with depression. ResultsAt SNP-level, only the high-multimorbidity Cluster 6 revealed a genome-wide significant SNP rs145772219. At gene-level, MPST and PRH2 were genome-wide significant for the low-multimorbidity Clusters 1 and 3, respectively. Regarding candidate SNPs for G × E interactions, individual SNP results could be replicated for specific clusters. The candidate genes CREB1, DBH, and MTHFR (Cluster 5) as well as TPH1 (Cluster 6) survived multiple testing correction. LimitationsCTS is a short retrospective self-reported measurement. Clusters could be influenced by genetics of individual disorders. ConclusionsThe first G × E GWAS for MDD-related multimorbidity trajectories successfully replicated findings from previous G × E studies related to depression, and revealed risk clusters for the contribution of childhood trauma.

Intraspecific divergence in a coastal plant, Euphorbia jolkinii, at a major biogeographic boundary in East Asia.

Quaternary climatic fluctuations and long-distance seed dispersal across the sea are critical factors affecting the distribution of coastal plants, but the spatiotemporal nature of population expansion and distribution change of East Asian coastal plants during this period are rarely examined. To explore this process, we investigated the genome-wide phylogenetic patterns of Euphorbia jolkinii Boiss. (Euphorbiaceae), which grows widely on littoral areas of Japan, Korea, and Taiwan. We used plastome sequences and genome-wide single nucleotide polymorphisms in samples across the species range to reveal phylogeographic patterns and spatiotemporal distributional changes. We conducted ecological niche modeling for the present and the last glacial maximum (LGM). Genetic differentiation was observed between the northern and southern populations of E. jolkinii, separated by the major biogeographic boundary, the Tokara Gap. These two groups of populations differentiated during the glacial period and subsequently intermingled in the intermorainic areas of the central Ryukyu Islands after the LGM. Ecological niche models suggested that the potential range of E. jolkinii was restricted to southern Kyushu; however, it was widespread in the southern Ryukyu Islands and Taiwan during the LGM. This study provides evidence of genetic differentiation among coastal plant populations separated by the prominent biogeographical boundary. Although coastal plants are typically expected to maintain population connectivity through sea-drifted seed dispersal, our findings suggest that genetic differences may arise because of a combination of limited gene flow and changes in climate during the glacial period.

Novel insights into rosacea's role in cancer risk: A Mendelian randomization approach.

Chronic inflammation has been shown to promote cancer progression. Rosacea is indeed a long-term inflammatory skin condition and had been reported to link with increased risk for several types of malignancies, but evidence for causality is lacking. To systematically estimate the causal relationship between rosacea and several types of cancer, including cutaneous malignant melanoma (CMM), cutaneous squamous cell carcinoma (cSCC), basal cell carcinoma (BCC), actinic keratosis (AK), thyroid cancer, breast cancer, glioma and hepatic cancer, as well as explore the potential underlying pathogenesis. We conducted a bidirectional two-sample Mendelian randomization study to probe the potential causal relationships between rosacea and several types of cancer. Instrumental variables were established using genome-wide significant single nucleotide polymorphisms associated with rosacea and cancers. The assessment of causality was carried out through multiple methods, and the robustness of the results was evaluated via sensitivity analyses. There was no significant indication of causal effects of rosacea on CMM (pivw=0.71), cSCC (pivw=0.45), BCC (pivw=0.90), AK (pivw=0.73), thyroid cancer (pivw=0.59), glioma (pivw=0.15), and hepatic cancer (pivw=0.07), but the genetic risk of rosacea was associated with an increased susceptibility to human epidermal growth factor receptor (HER)-negative malignant neoplasm of breast (odds ratio [OR], 1.10; 95% confidence interval [CI], 1.02-1.18; pivw=0.01). TANK (TRAF family member associated nuclear factor kappa B (NFKB) activator) was identified as a common protective gene for both rosacea (OR, 0.90; 95% CI, 0.82-0.99; pivw=0.048) and HER-negative malignant neoplasm of the breast (OR, 0.86; 95% CI, 0.75-0.98; pivw=0.032), which was primarily enriched in the negative regulation of NF-κB signal transduction and may contribute to the genetic links between rosacea and this subtype of breast cancer. Our findings provide suggestive evidence for causal links between rosacea and HER-negative malignant neoplasm of the breast risk.

Causal association of metformin treatment with diverse cardiovascular diseases: a Mendelian randomization analysis.

The cardiovascular effects of metformin continue to be a subject of debate within the medical community. The Mendelian randomization (MR) study used data from genome-wide association studies (GWAS) to explore the causal association with six diseases that are associated with bimatoprost treatment and myocardial infarction, chronic heart failure, atrial fibrillation, hypertrophic and dilated cardiomyopathy, and valvular disease. Genome-wide significant single nucleotide polymorphisms (SNPs), that are associated with metformin use were selected as the instrumental variables. To determine the causal relationship between metformin use and various cardiovascular diseases, MR analysis was conducted, employing methods such as Instrumental Variable Weighting (IVW). The IVW analysis demonstrated a positive association between metformin treatment and the risk of myocardial infarction (OR = 22.67, 95% CI 3.22-34.01; P = 0.002). Conversely, metformin treatment exhibited a negative association with the risk of developing valvular disease (OR = 0.98, 95% CI 0.95-1.00; P = 0.046) and hypertrophic cardiomyopathy (OR = 0.01, 95% CI 0.00-0.22; P = 0.016). Multiple test correction found that metformin treatment was causally associated with the risk of both hypertrophic cardiomyopathy (PFDR = 0.048) and myocardial infarction (PFDR = 0.012). The analysis revealed limited heterogeneity in the individual results, absence of pleiotropy evidence, and indications of stability in the findings. The MR study discovered from a genetic standpoint that metformin may lower the risk of hypertrophic cardiomyopathy and valvular heart disease, yet it could elevate the risk of myocardial infarction.

Genetic history of esophageal cancer group in southwestern China revealed by Y‐chromosome STRs and genomic evolutionary connection analysis

Genetic and environmental factors play crucial roles in the development of esophageal cancer (EC) and contribute uniquely or cooperatively to human cancer susceptibility. Sichuan is located in the interior of southwestern China, and the northern part of Sichuan is one of the regions with a high occurrence of EC. However, the factors influencing the high incidence rate of EC in the Sichuan Han Chinese population and its corresponding genetic background and origins are still poorly understood. Here, we utilized genome-wide single nucleotide polymorphisms (SNPs) and Y-chromosome short tandem repeats (Y-STRs) to characterize the genetic structure, connection, and origin of cancer groups and general populations. We generated Y-STR-based haplotype data from 214 Sichuan individuals, including the Han Chinese EC population and a control group of Han Chinese individuals. Our results, obtained from Y-STR-based population statistical methods (analysis of molecular variance (AMOVA), principal component analysis (PCA), and phylogenetic analysis), demonstrated that there was a genetic substructure difference between the EC population in the high-incidence area of northern Sichuan Province and the control population. Additionally, there was a strong genetic relationship between the EC population in the northern Sichuan high-incidence area and those at high risk in both the Fujian and Chaoshan areas. In addition, we obtained high-density SNP data from saliva samples of 60 healthy Han Chinese individuals from three high-prevalence areas of EC in China: Sichuan Nanchong, Fujian Quanzhou, and Henan Xinxiang. As inferred from the allele frequency of SNPs and sharing patterns of haplotype segments, the evolutionary history and admixture events suggested that the Han population from Nanchong in northern Sichuan Province shared a close genetic relationship with the Han populations from Xinxiang in Henan Province and Quanzhou in Fujian Province, both of which are regions with a high prevalence of EC. Our study illuminated the genetic profile and connection of the Northern Sichuan Han population and enriched the genomic resources and features of the Han Chinese populations in China, especially for the Y-STR genetic data of the Han Chinese EC population. Populations living in different regions with high incidences of EC may share similar genetic backgrounds, which offers new insights for further exploring the genetic mechanisms underlying EC.

PM2.5 associates with blood pressure: a Mendelian randomization analysis

ABSTRACT The relationship between fine particulate matter (PM2.5) and blood pressure (BP) is a controversial issue. We conducted a two-sample Mendelian randomization (MR) analysis and identified 58 genome-wide significant single-nucleotide polymorphisms associated with PM2.5 as instrument variables. Inverse-variance weighted (IVW) was used as the primary analysis approach. MR-Egger, weighted median, simple model, and weighted model methods were selected for quality control. We found a significant negative causal association of higher genetically predicted PM2.5 levels with lower systolic BP (SBP), while no causal relationship was identified between PM2.5 and diastolic BP (DBP). For each 1 standard deviation increase in genetically predicted PM2.5 levels, the beta value (95% CI) of SBP was -0.14 (-0.25, -0.03) for IVW (p=0.02), and -0.13 (-0.22, -0.04) for weighted median (p=0.005). Increased PM2.5 concentrations can lead to decreased SBP levels. Our findings provided novel insights into the controversial topic on the causal relationship between PM2.5 and BP.

Genome-wide single nucleotide polymorphisms reveal the genetic diversity and population structure of Creole goats from northern Peru

Goat farming constitutes a significant source of income for farmers in northern Peru. There is currently an absence of information about the genetics of Peruvian Creole goats that would enable us to understand their origins and genetic spread. The objective of this study was to estimate the genetic diversity of Creole goats from northern Peru using SNP markers. This study involved the collection of 192 male Creole goats from three key goat production geographical departments in northern Peru. These goat samples were genotyped using the GGPGoat70k SNP panel. To explore the genetic influence of other breeds on Peruvian Creole goats, our dataset was combined with previously published SNP genotypes. External data set includes multiple breeds genotypes sampled from Argentina, Brazil, Spain, and Alpine breed from Italy, France, and Switzerland. After quality control 52,832 autosomal SNPs were used to assess genetic diversity in the Peruvian goats. For the population structure analysis of the merged data 20,513 common SNPs were used. Estimations for expected heterozygosity (He), observed heterozygosity (Ho), and inbreeding coefficient (FIS) were computed for the Peruvian groups. AMOVA, principal component analysis and ADMIXTURE were conducted to evaluate the population structure in the two data sets, Peru and merged. The results revealed a considerable genetic diversity, with Ho values ranging from 0.40 to 0.41 for the Peruvian sampling groups, and inbreeding coefficient was notably low for Peruvian goat. The population structure analysis demonstrated a distinction (p < 0.05) from other breeds. These findings suggest a level of genetic differentiation of the Peruvian goat population among other breeds, although further research is needed considering samples from other Peruvian areas. We expect this study will contribute to define genetic management strategies to prevent the loss of genetic diversity in Peruvian goat populations and for upcoming advancements in this field.

Comprehensive genome assembly reveals genetic diversity and carcass consumption insights in critically endangered Asian king vultures

The Asian king vulture (AKV), a vital forest scavenger, is facing globally critical endangerment. This study aimed to construct a reference genome to unveil the mechanisms underlying its scavenger abilities and to assess the genetic relatedness of the captive population in Thailand. A reference genome of a female AKV was assembled from sequencing reads obtained from both PacBio long-read and MGI short-read sequencing platforms. Comparative genomics with New World vultures (NWVs) and other birds in the Family Accipitridae revealed unique gene families in AKV associated with retroviral genome integration and feather keratin, contrasting with NWVs’ genes related to olfactory reception. Expanded gene families in AKV were linked to inflammatory response, iron regulation and spermatogenesis. Positively selected genes included those associated with anti-apoptosis, immune response and muscle cell development, shedding light on adaptations for carcass consumption and high-altitude soaring. Using restriction site-associated DNA sequencing (RADseq)-based genome-wide single nucleotide polymorphisms (SNPs), genetic relatedness and inbreeding status of five captive AKVs were determined, revealing high genomic inbreeding in two females. In conclusion, the AKV reference genome was established, providing insights into its unique characteristics. Additionally, the potential of RADseq-based genome-wide SNPs for selecting AKV breeders was demonstrated.

Tasmanian devil (Sarcophilus harrisii) gene flow and source-sink dynamics

Increased access to genetic data has substantially improved how we manage threatened species. The Tasmanian devil (Sarcophilus harrisii) is listed as endangered due to the ongoing threat of a highly contagious cancer, devil facial tumour disease (DFTD), causing more than 80% population reductions. To assist future management interventions (e.g. releases into wild sites) we expanded upon previous studies of gene flow for the devil by assessing more recent and broad-scale patterns. We use genome-wide single nucleotide polymorphisms generated via DArTSeq across 21 devil sites to delineate source-sink dynamics across the species’ range. Our findings revealed gene flow is stronger on the northeast and central regions of Tasmania, with high rates of bidirectional gene flow among central sites. The northwest exhibits weaker connectivity relative to other regions of Tasmania, while gene flow appears to be non-existent between the southwest and other areas. Northeast coastal sites tend to serve as ‘sources’ for inland central sites, whereas gene flow appears restricted to the coastline in the northwest. These results are consistent with genetic structure of devil sites and spatial spread of DFTD, which has yet to arrive in the southwest region of Tasmania. Southwest isolation is probably due to mountain ranges and lack of roadways. Interestingly, some waterbodies did not appear to restrict devil movement among sites. Conversely, areas of high elevation act as apparent barriers, as evidenced by limited gene flow observed between eastern and western sites. Integrating source-sink dynamics into conservation management planning will be crucial in developing effective strategies to safeguard the Tasmanian devil and other threatened species facing similar threats (i.e. disease, habitat loss).