BACKGROUND: Wheat landraces are considered a valuable source of genetic diversity for breeding programs. It is useful to evaluate the genetic diversity in breeding studies such as marker-assisted selection (MAS), genome-wide association studies (GWAS), and genomic selection. In addition, constructing a core germplasm set that represents the genetic diversity of the entire variety set is of great significance for the efficient conservation and utilization of wheat landrace germplasms.
RESULTS: To understand the genetic diversity in wheat landrace, 2,023 accessions in the Jiangsu Provincial Crop Germplasm Resource Bank were used to explore the molecular diversity and population structure using the Illumina 15 K single nucleotide polymorphism (SNP) chip. These accessions were divided into five subpopulations based on population structure, principal coordinate and kinship analysis. A significant variation was found within and among the subpopulations based on the molecular variance analysis (AMOVA). Subpopulation 3 showed more genetic variability based on the different allelic patterns (Na, Ne and I). The M strategy as implemented in MStratv 4.1 software was used to construct the representative core collection. A core collection with a total of 311 accessions (15.37%) was selected from the entire landrace germplasm based on genotype and 12 different phenotypic traits. Compared to the initial landrace collections, the core collection displayed higher gene diversity (0.31) and polymorphism information content (PIC) (0.25), and represented almost all phenotypic variation.
CONCLUSIONS: A core collection comprising 311 accessions containing 100% of the genetic variation in the initial population was developed. This collection provides a germplasm base for effective management, conservation, and utilization of the variation in the original set.

The genus Euphorbia (Euphorbiaceae) has near-cosmopolitan distribution and serves as a significant resource for both ornamental and medicinal purposes. Despite its economic importance, Euphorbia\'s taxonomy has long been challenged by the intricate nature of morphological traits exhibiting high levels of convergence. While molecular markers are essential for phylogenetic studies, their availability for Euphorbia has been limited. To address this gap, we conducted comparative analyses focusing on the chloroplast (CP) genomes of nine Euphorbia species, incorporating three newly sequenced and annotated accessions. In addition, phylogenetic informativeness and nucleotide diversity were computed to identify candidate markers for phylogenetic analyses among closely related taxa in the genus. Our investigation revealed relatively conserved sizes and structures of CP genomes across the studied species, with notable interspecific variations observed primarily in non-coding regions and IR/SC borders. By leveraging phylogenetic informativeness and nucleotide diversity, we identified rpoB gene as the optimal candidate for species delimitation and shallow-level phylogenetic inference within the genus. Through this comprehensive analysis of CP genomes across multiple taxa, our study sheds light on the evolutionary dynamics and taxonomic intricacies of Euphorbia, offering valuable insights into its CP genome evolution and taxonomy.

Meiotic recombination is a fundamental feature of sexually reproducing species. It is often required for proper chromosome segregation and plays important role in adaptation and the maintenance of genetic diversity. The molecular mechanisms of recombination are remarkably conserved across eukaryotes, yet meiotic genes and proteins show substantial variation in their sequence and function, even between closely related species. Furthermore, the rate and distribution of recombination shows a huge diversity within and between chromosomes, individuals, sexes, populations, and species. This variation has implications for many molecular and evolutionary processes, yet how and why this diversity has evolved is not well understood. A key step in understanding trait evolution is to determine its genetic basis-that is, the number, effect sizes, and distribution of loci underpinning variation. In this perspective, I discuss past and current knowledge on the genetic basis of variation in recombination rate and distribution, explore its evolutionary implications, and present open questions for future research.

Force Field X (FFX) is an open-source software package for atomic resolution modeling of genetic variants and organic crystals that leverages advanced potential energy functions and experimental data. FFX currently consists of nine modular packages with novel algorithms that include global optimization via a many-body expansion, acid-base chemistry using polarizable constant-pH molecular dynamics, estimation of free energy differences, generalized Kirkwood implicit solvent models, and many more. Applications of FFX focus on the use and development of a crystal structure prediction pipeline, biomolecular structure refinement against experimental datasets, and estimation of the thermodynamic effects of genetic variants on both proteins and nucleic acids. The use of Parallel Java and OpenMM combines to offer shared memory, message passing, and graphics processing unit parallelization for high performance simulations. Overall, the FFX platform serves as a computational microscope to study systems ranging from organic crystals to solvated biomolecular systems.

Clade 2.3.4.4b highly pathogenic avian influenza (HPAI) H5N1 virus was detected in the South American sea lions found dead in Santa Catarina, Brazil, in October 2023. Whole genome sequencing and comparative phylogenetic analysis were conducted to investigate the origin, genetic diversity, and zoonotic potentials of the H5N1 viruses. The H5N1 viruses belonged to the genotype B3.2 of clade 2.3.4.4b H5N1 virus, which was identified in North America and disseminated to South America. They have acquired new amino acid substitutions related to mammalian host affinity. Our study provides insights into the genetic landscape of HPAI H5N1 viruses in Brazil, highlighting the continuous evolutionary processes contributing to their possible adaptation to mammalian hosts.

CONCLUSIONS: Genotyping-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.

Schistosomiasis is of medical and veterinary importance. Despite the critical situation of schistosomiasis in sub-Saharan Africa, few molecular epidemiological studies have been carried out to determine the role of animals in its transmission. In Mali, it has been over three decades since the last molecular study of animal schistosomes was carried out. It is now urgent to identify circulating strains of the parasite because of potential interactions with other schistosome species, which could complicate disease control. The aim of our work was to study the composition and genetic structure of schistosome populations collected from cattle. The prevalence of schistosome was 23.9%, with the prevalences of Schistosoma bovis (Sb) and S. curassoni (Sc) estimated at 12.6% and 9.8%, respectively. No hybrid strains or S. haematobium were found. The parasites displayed distinct geographical distribution with Sb dominant in Bamako (78.8% and 98% in Central Bamako Slaughterhouse and Sabalibougou Slaughterhouses, respectively) and Sc dominant in Kayes (95.3%). Of the 476 parasites with a complete genetic profile, 60.4% were pure Sc, and were mainly from Kayes. We identified two clusters at the site level (Fst of 0.057 and 0.042 for Sb and Sc, respectively). Cluster 1 was predominantly composed of pure Sb parasites and cluster 2 was mainly composed of pure Sc parasites, from Bamako and Kayes, respectively. Our study shows that cattle schistosomiasis remains endemic in Mali with S. bovis and S. curassoni. A robust genetic structure between the different schistosome populations was identified, which included two clusters based on the geographical distribution of the parasites.
UNASSIGNED: Structure génétique des populations de Schistosoma bovis et S. curassoni collectées chez des bovins au Mali.
UNASSIGNED: La schistosomiase revêt une grande importance médicale et vétérinaire. Malgré la situation critique de la schistosomiase en Afrique subsaharienne, peu d’études épidémiologiques moléculaires ont été réalisées pour déterminer le rôle des animaux dans sa transmission. Au Mali, cela fait plus de trois décennies que la dernière étude moléculaire des schistosomes animaux a été réalisée. Il est désormais urgent d’identifier les souches circulantes du parasite en raison des interactions potentielles avec d’autres espèces de schistosomes, ce qui pourrait compliquer la lutte contre la maladie. Le but de notre travail était d’étudier la composition et la structure génétique des populations de schistosomes collectées chez des bovins. La prévalence des schistosomes était de 23,9 %, celles de Schistosoma bovis (Sb) et de S. curassoni (Sc) étant respectivement estimées à 12,6 % et 9,8 %. Aucune souche hybride ni S. haematobium n’ont été trouvés. Les parasites présentaient une répartition géographique distincte avec Sb dominant à Bamako (respectivement 78,8 % et 98 % aux Abattoirs Centraux de Bamako et aux Abattoirs de Sabalibougou) et Sc dominant à Kayes (95,3 %). Sur les 476 parasites ayant un profil génétique complet, 60,4 % étaient des Sc purs, et provenaient principalement de Kayes. Nous avons identifié deux clusters au niveau du site (Fst de 0,057 et 0,042 pour Sb et Sc, respectivement). Le groupe 1 était principalement composé de parasites Sb purs et le groupe 2 était principalement composé de parasites Sc purs, provenant respectivement de Bamako et de Kayes. Notre étude montre que la schistosomiase bovine reste endémique au Mali, avec S. bovis and S. curassoni. Une structure génétique robuste entre les différentes populations de schistosomes a été identifiée, comprenant deux groupes basés sur la répartition géographique des parasites.

Computational variant effect predictors offer a scalable and increasingly reliable means of interpreting human genetic variation, but concerns of circularity and bias have limited previous methods for evaluating and comparing predictors. Population-level cohorts of genotyped and phenotyped participants that have not been used in predictor training can facilitate an unbiased benchmarking of available methods. Using a curated set of human gene-trait associations with a reported rare-variant burden association, we evaluate the correlations of 24 computational variant effect predictors with associated human traits in the UK Biobank and All of Us cohorts.
AlphaMissense outperformed all other predictors in inferring human traits based on rare missense variants in UK Biobank and All of Us participants. The overall rankings of computational variant effect predictors in these two cohorts showed a significant positive correlation.
We describe a method to assess computational variant effect predictors that sidesteps the limitations of previous evaluations. This approach is generalizable to future predictors and could continue to inform predictor choice for personal and clinical genetics.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting over 300,000 people worldwide. It is characterized by the progressive decline of the nervous system that leads to the weakening of muscles which impacts physical function. Approximately, 15% of individuals diagnosed with ALS have a known genetic variant that contributes to their disease. As therapies that slow or prevent symptoms continue to develop, such as antisense oligonucleotides, it is important to discover novel genes that could be targets for treatment. Additionally, as cohorts continue to grow, performing analyses in ALS subtypes, such as primary lateral sclerosis (PLS), becomes possible due to an increase in power. These analyses could highlight novel pathways in disease manifestation.
METHODS: Building on our previous discoveries using rare variant association analyses, we conducted rare variant burden testing on a substantially larger multi-ethnic cohort of 6,970 ALS patients, 166 PLS patients, and 22,524 controls. We used intolerant domain percentiles based on sub-region Residual Variation Intolerance Score (subRVIS) that have been described previously in conjunction with gene based collapsing approaches to conduct burden testing to identify genes that associate with ALS and PLS.
RESULTS: A gene based collapsing model showed significant associations with SOD1, TARDBP, and TBK1 (OR = 19.18, p = 3.67 × 10-39; OR = 4.73, p = 2 × 10-10; OR = 2.3, p = 7.49 × 10-9, respectively). These genes have been previously associated with ALS. Additionally, a significant novel control enriched gene, ALKBH3 (p = 4.88 × 10-7), was protective for ALS in this model. An intolerant domain-based collapsing model showed a significant improvement in identifying regions in TARDBP that associated with ALS (OR = 10.08, p = 3.62 × 10-16). Our PLS protein truncating variant collapsing analysis demonstrated significant case enrichment in ANTXR2 (p = 8.38 × 10-6).
CONCLUSIONS: In a large multi-ethnic cohort of 6,970 ALS patients, collapsing analyses validated known ALS genes and identified a novel potentially protective gene, ALKBH3. A first-ever analysis in 166 patients with PLS found a candidate association with loss-of-function mutations in ANTXR2.

Widespread species often experience significant environmental clines over the area they naturally occupy. We investigated a widespread livebearing fish, the Sailfin molly (Poecilia latipinna) combining genetic, life-history, and environmental data, asking how structured populations are. Sailfin mollies can be found in coastal freshwater and brackish habitats from roughly Tampico, Veracruz in Mexico to Wilmington, North Carolina, in the USA. In addition, they are found inland on the Florida peninsula. Using microsatellite DNA, we genotyped 168 individuals from 18 populations covering most of the natural range of the Sailfin molly. We further determined standard life-history parameters for both males and females for these populations. Finally, we measured biotic and abiotic parameters in the field. We found six distinct genetic clusters based on microsatellite data, with very strong indication of isolation by distance. However, we also found significant numbers of migrants between adjacent populations. Despite genetic structuring we did not find evidence of cryptic speciation. The genetic clusters and the migration patterns do not match paleodrainages. Life histories vary between populations but not in a way that is easy to interpret. We suggest a role of humans in migration in the sailfin molly, for example in the form of a ship channel that connects southern Texas with Louisiana which might be a conduit for fish migration.