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Summary The rubber tree (Hevea brasiliensis) is grown in tropical regions and is the major source of natural rubber. Using traditional breeding approaches, the latex yield has increased by sixfold in the last century. However, the underlying genetic basis of rubber yield improvement is largely unknown. Here, we present a high‐quality, chromosome‐level genome sequence of the wild rubber tree, the first report on selection signatures and a genome‐wide association study (GWAS) of its yield traits. Population genomic analysis revealed a moderate population divergence between the Wickham clones and wild accessions. Interestingly, it is suggestive that H. brasiliensis and six relatives of the Hevea genus might belong to the same species. The selective sweep analysis found 361 obvious signatures in the domesticated clones associated with 245 genes. In a 15‐year field trial, GWAS identified 155 marker–trait associations with latex yield, in which 326 candidate genes were found. Notably, six genes related to sugar transport and metabolism, and four genes related to ethylene biosynthesis and signalling are associated with latex yield. The homozygote frequencies of the causal nonsynonymous SNPs have been greatly increased under selection, which may have contributed to the fast latex yield improvement during the short domestication history. Our study provides insights into the genetic basis of the latex yield trait and has implications for genomic‐assisted breeding by offering valuable resources in this new domesticated crop.

Hennekam Lymphangiectasia–Lymphedema Syndrome 3 (HKLLS3) is a rare genetical disorder caused by mutations in a few genes including ADAMTS3. It is characterized by lymphatic dysplasia, intestinal lymphangiectasia, severe lymphedema and distinctive facial appearance. Up till now, no extensive studies have been conducted to elucidate the mechanism of the disease caused by various mutations. As a preliminary investigation of HKLLS3, we sorted out the most deleterious nonsynonymous single nucleotide polymorphisms (nsSNPs) that might affect the structure and function of ADAMTS3 protein by using a variety of in silico tools. A total of 919 nsSNPs in the ADAMTS3 gene were identified. 50 nsSNPs were predicted to be deleterious by multiple computational tools. 5 nsSNPs (G298R, C567Y, A370T, C567R and G374S) were found to be the most dangerous and can be associated with the disease as predicted by different bioinformatics tools. Modelling of the protein shows it can be divided into segments 1, 2 and 3, which are connected by short loops. Segment 3 mainly consists of loops without substantial secondary structures. With prediction tools and molecular dynamics simulation, some SNPs were found to significantly destabilize the protein structure and disrupt the secondary structures, especially in segment 2. The deleterious effects of mutations in segment 1 are possibly not from destabilization but from other factors such as the change in phosphorylation as suggested by post-translational modification (PTM) studies. This is the first-ever study of ADAMTS3 gene polymorphism, and the predicted nsSNPs in ADAMST3, some of which have not been reported yet in patients, will serve for diagnostic purposes and further therapeutic implications in Hennekam syndrome, contributing to better diagnosis and treatment.

To map resistance genes for Fusarium wilt (FW) and sterility mosaic disease (SMD) in pigeonpea, sequencing-based bulked segregant analysis (Seq-BSA) was used. Resistant (R) and susceptible (S) bulks from the extreme recombinant inbred lines of ICPL 20096 × ICPL 332 were sequenced. Subsequently, SNP index was calculated between R- and S-bulks with the help of draft genome sequence and reference-guided assembly of ICPL 20096 (resistant parent). Seq-BSA has provided seven candidate SNPs for FW and SMD resistance in pigeonpea. In parallel, four additional genotypes were re-sequenced and their combined analysis with R- and S-bulks has provided a total of 8362 nonsynonymous (ns) SNPs. Of 8362 nsSNPs, 60 were found within the 2-Mb flanking regions of seven candidate SNPs identified through Seq-BSA. Haplotype analysis narrowed down to eight nsSNPs in seven genes. These eight nsSNPs were further validated by re-sequencing 11 genotypes that are resistant and susceptible to FW and SMD. This analysis revealed association of four candidate nsSNPs in four genes with FW resistance and four candidate nsSNPs in three genes with SMD resistance. Further, In silico protein analysis and expression profiling identified two most promising candidate genes namely C.cajan_01839 for SMD resistance and C.cajan_03203 for FW resistance. Identified candidate genomic regions/SNPs will be useful for genomics-assisted breeding in pigeonpea.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation, pain, swelling, and stiffness, with matrix metalloproteinase-9 (MMP9) playing a critical role in extracellular matrix remodelling and joint degradation. Elevated MMP9 levels are closely associated with RA severity and progression. This study aimed to identify and characterize functional and pathogenic variants of the MMP9 gene and assess their impact on RA susceptibility and severity. Various computational tools were used to identify deleterious non-synonymous single nucleotide polymorphisms (nsSNPs). These nsSNPs were further evaluated for their conservation profiles, influence on protein structure, function, and phenotypic stability. Models for all the mutant and wild type were generated and validated by ERRAT, VERIFY3D and QMEAN. Further, molecular dynamics simulations, molecular docking and gene-gene interactions were analysed. Nine damaging missense nsSNPs within the MMP9 catalytic region were identified, all of which were highly conserved, with Y262C notably resulting in the loss of a phosphorylation site. Most mutations were associated with decreased protein stability, and HOPE analysis revealed their localization in essential functional domains of MMP9. MD simulations indicated greater structural instability in these variants compared to the wild type, with Y262C, P180L, G438A, and D434N exhibiting the highest root-mean-square deviation (RMSD) values. Gene-gene interaction analysis further emphasized the significant role of MMP9 in RA-related pathways. This study offers key insights into pathogenic nsSNPs affecting MMP9 structure and function, highlighting their importance in genetic screening and potential therapeutic strategies for RA.

Background: Genetic diversity and genetic differentiation between Gossypium hirsutum-Gossypium barbadense introgression lines (ILs) and early-maturing upland cotton lines are critical for resolving the core breeding contradiction in Xinjiang cotton region: narrow genetic basis of early-maturing cultivars and late maturity of ILs with superior fiber quality. Xinjiang is one of the major cotton-producing regions in China, and breeding high-quality early-maturing upland cotton adapted to local ecological conditions is essential for improving cotton yield and quality. However, the genetic relationship and differentiation between the two types of cotton germplasm remain unclear, which hinders the efficient utilization of germplasm resources in breeding. Therefore, this study aimed to clarify the genetic diversity and differentiation between the two germplasm types and identify key candidate loci related to early maturity and fiber quality, providing support for cotton breeding. Results: Here, we used a 40K Single Nucleotide Polymorphism chip to genotype core cotton germplasm in northern Xinjiang, and analyzed their population structure, genetic diversity and functional SNP loci associated with early maturity and fiber quality. The tested materials were clearly divided into two subgroups (ILs and early-maturing lines). Genetic diversity analysis revealed a significantly narrow genetic basis in the early-maturing subgroup, while the IL subgroup had higher genetic diversity. Specifically, the early-maturing subgroup showed lower nucleotide diversity and polymorphism information content compared with the IL subgroup, indicating that the genetic variation of early-maturing cotton germplasm in northern Xinjiang is relatively limited. A total of 25 non-synonymous SNPs were identified, among which the c.A613G:p.T205A mutation in GH_D09G1484 (mRNA-decapping enzyme 1, DCP1) was a characteristic variation of early-maturing cotton, and a possible non-synonymous mutation in GH_A09G2400 (Heat shock transcription factor A6b, HSFA6B) was associated with fiber development. These two candidate genes were annotated to be involved in plant growth and development, further supporting their potential roles in regulating cotton early maturity and fiber quality. Conclusions: This study clarified the genetic differentiation between the two types of germplasms and identified key candidate loci for early maturity and fiber quality, providing precise molecular markers and theoretical support for breeding high-quality early-maturing upland cotton adapted to Xinjiang’s ecological conditions. The results also highlight the value of Gossypium hirsutum–Gossypium barbadense introgression lines in enriching the genetic basis of early-maturing cotton, which can be further utilized to solve the core breeding contradiction in the Xinjiang cotton region.

Sperm motility, a key determinant of male fertility, is often impaired by genetic variations affecting flagellar formation. The ( ) gene encodes a protein essential for sperm flagella biogenesis and structural integrity. This study investigates genetic variations within exon 3 of the gene, identifying novel heterozygous variants associated with sperm tail-specific abnormalities and motility impairments. Among 34 individuals diagnosed with asthenozoospermia (ASZ) and 26 individuals with normal sperm parameters (NZ) from Jordan, eight unique heterozygous variants (c.123 G>T, c.133 G>C, c.138A>G, c.170A>C, c.189C>G, c.190T>C, c.195A>T, and c.204A>T) were exclusive to the ASZ group, while four variants (c.136 G>A, c.145A>C, c.179T>G, and c.180T>G) were found only in NZ. These variants were absent from major genetic databases, suggesting their potential novelty, while two variants (c.206C>T and c.189C>T) were linked to known SNP cluster IDs rs73996306 and rs1567790525, respectively. Four non-synonymous SNPs (c.136 G>A, c.145A>C, c.170A>C, and c.204A>T) were predicted to be functionally and structurally damaging, underscoring their significance. Additionally, five variants overlapped with previously reported mutation sites, indicating potential mutation hotspots. Statistical analysis revealed a significant association between mutations and tail defects (  < 0.021). These findings highlight the critical role of heterozygous mutations in mild-to-moderate ASZ, even in NZ individuals. Despite some carriers meeting WHO criteria for NZ, notable morphological abnormalities suggest the need for refined diagnostic benchmarks. Screening for mutations is essential for accurate molecular diagnosis and should be integrated into genetic counseling, particularly in regions like Jordan. Further research into the cumulative effects of heterozygous mutations and their environmental interactions is needed to expand our understanding of idiopathic male infertility and to enhance diagnostic and therapeutic strategies for male infertility.

Background In veterinary medicine, congenital methemoglobinemia associated with nicotinamide adenine dinucleotide (NADH)‐cytochrome b5 reductase (b5R) deficiency is rare. It has been reported in several breeds of dogs, but little information is available about its etiology. Objectives To analyze the NADH‐cytochrome b5 reductase gene, CYB5R3, in a Pomeranian dog family with methemoglobinemia suspected to be caused by congenital b5R deficiency. Animals Three Pomeranian dogs from a family with methemoglobinemia were analyzed. Five healthy beagles and 5 nonrelated Pomeranian dogs without methemoglobinemia were used as controls. Methods Methemoglobin concentration, b5R activity, and reduced glutathione (GSH) concentration were measured, and a turbidity index was used to evaluate Heinz body formation. The CYB5R3 genes of the affected dog and healthy dogs were analyzed by direct sequencing. Results Methemoglobin concentrations in erythrocytes of the affected dogs were remarkably higher than those of the control dogs. The b5R activity of the affected dogs was notably lower than that of the control dogs. DNA sequencing indicated that this Pomeranian family carried a CYB5R3 gene missense variant (ATC→CTC at codon 194) that resulted in the replacement of isoleucine (Ile) by leucine (Leu). Conclusions and Clinical Importance This dog family had familial congenital methemoglobinemia caused by b5R deficiency, which resulted from a nonsynonymous variant in the CYB5R3 gene. This variation (c.580A>C) led to an amino acid substitution (p.Ile194Leu), and Ile194 was located in the proximal region of the NADH‐binding motif. Our data suggested that this variant in the canine CYB5R3 gene would affect function of the b5R in erythrocytes.

Rhododendron canescens (Michaux) Sweet is a deciduous azalea from the southeastern United States that is used as an ornamental landscaping plant. We identified and characterized allelic variation in R. canescens architecture genes as the first step towards breeding a more compact phenotype for urban settings. The transcriptome of R. canescens vegetative and reproductive tissues was sequenced and analyzed using PacBio Iso-Seq methods. The analysis generated 24,244 full-length isoform sequences, of which 16,825 were annotated. Orthologs were identified of genes that have been shown to control height or branching across multiple plant species. These included genes for regulatory factors and components of phytohormone biosynthesis and signaling pathways. Exons of these genes were captured and sequenced from DNA libraries of 216 R. canescens plants, including a dwarf genotype. In this germplasm collection, 40 non-synonymous single-nucleotide polymorphisms (nsSNPs) were identified in R. canescens orthologs of GA INSENSITIVE (GAI), PHOTOPERIOD RESPONSIVE1 (PHOR1), GA-INSENSITIVE DWARF1 (GID1), BRASSINOSTEROID INSENSITIVE1 (BRI1), FLOWERING LOCUS C (FLC), MORE AXILLARY BRANCHING2 (MAX2), and BRANCHED1 (BRC1). The effect of amino acid changes on the primary and tertiary protein structure was examined in silico and several nsSNPs were found to be deleterious to protein function. Missense mutations were identified in RcMAX2 of the dwarf genotype. Discriminant Analysis of Principal Components found that RcMAX2 could be responsible for the difference between the dwarf and other R. canescens accessions. This investigation provides a pathway for breeding R. canescens with architectural traits better suited for urban environments.

BReast CAncer gene 1 (BRCA1)—a tumor suppressor gene plays an important role in the DNA repair mechanism. Several BRCA1 variants perturb its structure and function, including synonymous and nonsynonymous single nucleotide polymorphisms (SNPs). In the present study, we performed in-silico analyses of nonsynonymous SNPs (nsSNPs) of the BRCA1 gene. In total, 122 nsSNPs were retrieved from the NCBI SNP database and in-silico analyses were performed using computational prediction tools: SIFT, PROVEAN, Mutation Taster, PolyPhen-2, MutPred, and ConSurf. Of these tools, SIFT, PROVEAN, and Mutation Taster predicted 61 out of 122 nsSNPs as “damaging”, based on structural homology analysis. PolyPhen-2 classified 22 nsSNPs as “probably damaging”. These nsSNPs were further analyzed by MutPred to predict basic molecular mechanisms of amino acid alteration. ConSurf analysis predicted eleven conserved amino acid residues with structural and functional consequences. We identified five amino acid residues in the RING finger domain (L22, C39, H41, C44, and C47) and two in the BRCT domain (P1771 and I1707) with the potential to deter the BRCA1 protein function. This study provides insights into the effect of nsSNPs and amino acid substitutions in BRCA1.

Gene-based molecular markers are increasingly used in crop breeding programs for marker-assisted selection. However, identification of genetic variants associated with important agronomic traits has remained a difficult task in soybean. RNA-Seq provides an efficient way, other than assessing global expression variations of coding genes, to discover gene-based SNPs at the whole genome level. In this study, RNA isolated from four soybean accessions each with three replications was subjected to high-throughput sequencing and a range of 44.2–65.9 million paired-end reads were generated for each library. A total of 75,209 SNPs were identified among different genotypes after combination of replications, 89.1% of which were located in expressed regions and 27.0% resulted in amino acid changes. GO enrichment analysis revealed that most significant enriched genes with nonsynonymous SNPs were involved in ribonucleotide binding or catalytic activity. Of 22 SNPs subjected to PCR amplification and Sanger sequencing, all of them were validated. To test the utility of identified SNPs, these validated SNPs were also assessed by genotyping a relative large population with 393 wild and cultivated soybean accessions. These SNPs identified by RNA-Seq provide a useful resource for genetic and genomic studies of soybean. Moreover, the collection of nonsynonymous SNPs annotated with their predicted functional effects also provides a valuable asset for further discovery of genes, identification of gene variants, and development of functional markers.