Genome Mapping Research Articles

Single-molecule toxicogenomics: Optical genome mapping of DNA-damage in nanochannel arrays.

Quantitative genomic mapping of DNA damage may provide insights into the underlying mechanisms of damage and repair. Sequencing based approaches are bound to the limitations of PCR amplification bias and read length which hamper both the accurate quantitation of damage events and the ability to map them to structurally complex genomic regions. Optical Genome mapping in arrays of parallel nanochannels allows physical extension and genetic profiling of millions of long genomic DNA fragments, and has matured to clinical utility for characterization of complex structural aberrations in cancer genomes. Here we present a new mapping modality, Repair-Assisted Damage Detection - Optical Genome Mapping (RADD-OGM), a method for single-molecule level mapping of DNA damage on a genome-wide scale. Leveraging ultra-long reads to assemble the complex structure of a sarcoma cell-line genome, we mapped the genomic distribution of oxidative DNA damage, identifying regions more susceptible to DNA oxidation. We also investigated DNA repair by allowing cells to repair chemically induced DNA damage, pinpointing locations of concentrated repair activity, and highlighting variations in repair efficiency. Our results showcase the potential of the method for toxicogenomic studies, mapping the effect of DNA damaging agents such as drugs and radiation, as well as following specific DNA repair pathways by selective induction of DNA damage. The facile integration with optical genome mapping enables performing such analyses even in highly rearranged genomes such as those common in many cancers, a challenging task for sequencing-based approaches.

Utility of Optical Genome Mapping for Accurate Detection and Fine-Mapping of Structural Variants in Elusive Rare Diseases

Utility of Optical Genome Mapping for Accurate Detection and Fine-Mapping of Structural Variants in Elusive Rare Diseases

Chromoanagenesis Is Frequently Associated With Highly Complex Karyotypes, Extensive Clonal Heterogeneity, and Treatment Refractoriness in Acute Myeloid Leukemia.

Chromoanagenesis (CAG) encompasses a spectrum of catastrophic genomic events, including chromothripsis, chromoanasynthesis, and chromoplexy. We studied CAG in 410 patients with a diagnosis of acute myeloid leukemia (AML), 292 newly diagnosed (ND), and 118 refractory/relapsed, using optical genome mapping. CAG was identified by the presence of clusters (with 10 or more breakpoints) of structural abnormalities and/or segmental copy number alterations within one or more chromosomal regions. CAG was detected in 65 (16%) patients. Compared with patients without CAG, those with CAG showed significantly (p < 0.0001) higher frequencies of highly complex karyotype (92% vs. 11%), monosomal karyotype (88% vs. 12%), extensive clonal heterogeneity (75% vs. 7%), gene amplification (49% vs. 1%), and TP53 deletion/mutation (92% vs. 9%). Overall, CAG was detected in about two-thirds of AML patients who exhibited the abovementioned high-risk cytogenetic abnormalities/karyotype. Among the 42 patients with ND AML and CAG, 36 received treatments and follow-ups, and 28 (78%) had no or only partial response to therapy. Among patients with ND AML, those with CAG had a shorter overall survival than those without CAG (median survival: 5 vs. 14 months, p < 0.0001). However, in multivariate analysis, CAG did not appear to be an independent risk factor for survival. These results indicate that CAG is frequently associated with high-risk chromosomal alterations and genomic instability in AML and may contribute to treatment refractoriness and inferior survival in this subset of AML patients.

Comprehensive Analysis of Apigetrin's Effects on Liver Cancer Cells: Insights from Bioinformatics, In Vitro Studies, and Next-Generation Transcriptome Sequencing.

Despite numerous attempts to understand the molecular mechanisms behind the development of liver cancer, it continues to pose a significant worldwide health challenge. Transcriptome sequencing, a powerful tool in molecular biology, has played a pivotal role in uncovering the intricate gene expression profiles underlying hepatocellular carcinoma (HCC). In the present study, we identified a total of 808 differentially expressed genes (DEGs), with 584 exhibiting downregulation, and 224 showing upregulation following apigetrin treatment. We utilized a combination of bioinformatics tools and platforms, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and mapping, Protein-Protein Interaction (PPI), and GEPIA. We found that DEGs were related to the apoptotic cell death process and identified hub genes, namely CASP8, RB1, and TGFBR2. These genes were further validated through both GEPIA analysis and western blot experiments. Our findings collectively demonstrate that apigetrin has the potential to modulate genes related to liver cancer and trigger molecular pathways that lead to apoptotic cell death in liver cancer cells. This study underscores the potential of apigetrin as an innovative treatment strategy for HCC, emphasizing the need for additional research to elucidate its mechanisms of action and evaluate its clinical efficacy.

A genomic variation map provides insights into potato evolution and key agronomic traits.

Hybrid potato breeding based on diploid inbred lines is transforming the way of genetic improvement of this staple food crop, which requires a deep understanding of potato domestication and differentiation. Here, we resequenced 314 diploid wild and landrace accessions to generate a variome map of 47,203,407 variants. Using the variome map, we discovered the reshaping of tuber transcriptome during potato domestication, characterized genome-wide differentiation between landrace groups Stenotomum and Phureja, and identified a jasmonic acid biosynthetic gene possibly affecting tuber dormancy period. Genome-wide association studies revealed a UDP-glycosyltransferase gene for biosynthesis of antinutritional steroidal glycoalkaloids (SGAs), and a Dehydration Responsive Element Binding (DREB) transcription factor conferring increased average tuber weight. In addition, genome similarity and group-specific SNP analyses indicated tetraploid potatoes originated from the diploid S. tuberosum group Stenotomum. These findings shed light on the evolutionary trajectory of potato domestication and improvement, providing a solid foundation for advancing hybrid potato breeding practices.

How to combine multiple tools for the genetic diagnosis work-up of pediatric B-cell acute lymphoblastic leukemia.

This study investigated the importance of comprehensive genetic diagnosis in pediatric B-cell acute lymphoblastic leukemia (B-ALL). We analyzed 175 B-ALL employing karyotyping, FISH, MLPA, targeted next-generation sequencing (t-NGS), and Optical Genome Mapping (OGM). This approach achieved an 83% classification rate, identifying 17 distinct genetic subtypes. Specifically, within B-other subtype, seven different subgroups were identified (ZNF384, IGH, DUX4, NUTM1 rearrangements, PAX5 alterations, PAX5 P80R, and IKZF1 N159Y). Secondary genetic alterations were observed, with copy number alterations (CNA) present in 60% of cases and mutations detected in 70.6%. While these alterations exhibited specific associations with certain genetic subtypes, CNAs did not appear to significantly impact the prognosis within these genetic groups. HeH, ETV6::RUNX1, ZNF384-r, and PAX5 P80R exhibited excellent outcomes, contrasting with the poor prognoses observed in KMT2A-r, hypodiploidy, and CRLF2-r (5-year overall OS were 50%, 50%, and 52%, respectively). These findings underscore the value of integrated genetic diagnostics for accurate subtyping, risk stratification, and guiding personalized treatment in pediatric B-ALL. Therefore, optimizing diagnostic workflows for routine clinical practice is crucial. Our study confirms the utility of conventional techniques (karyotyping and FISH), combined with t-NGS and OGM, for comprehensive genetic diagnosis.

Probiotic potential and safety properties of Limosilactobacillus fermentum A51 with high exopolysaccharide production.

Exopolysaccharides (EPS) produced by Lactic acid bacteria have many health benefits and unique physicochemical properties. They are widely used in the food industry to improve viscosity, mouthfeel, and textural properties of foods. In our previous studies, Limosilactobacillus fermentum A51 (L. fermentum A51) isolated from yak yogurt exhibited high EPS production capacity and was applied to improve the texture of yogurt. In this study, whole genome sequencing analysis and corresponding in vitro assays were performed to investigate the probiotic potential and safety properties of L. fermentum A51. Scanning electron microscopy (SEM) observed that L. fermentum strain A51 adhered into clusters and its colony exhibited the obvious silk drawing phenomenon. Whole genome mapping revealed that L. fermentum A51 genome is 2,188,538 bp, and with an average guanine and cytosine (GC) content of 51.28%. PGAAP annotation identified 2,152 protein-encoding genes and 58 rRNAs, 15 tRNAs, and 5 5sRNAs. Hemolysis and antibiotic resistance tests, combined with the analysis of genes involved in antibiotic resistance, virulence factor, and hemolysins, suggested that L. fermentum A51 is safe. Fifty-one carbohydrate active enzyme genes in the whole genome sequence of L. fermentum A51 were annotated by carbohydrate active enzymes (CAZymes). Furthermore, L. fermentum A51 possesses adhesion, acid tolerance, bile salt tolerance, and heat tolerance genes (srtA, tuf, Bsh, nhaC, Ntn, cfa), antioxidant (nrfA, npr, nox2, tps), antibacterial genes (Idh and Dld) EPS synthesis-related genes (glf, epsG, gtf, Wzz, Wzx, Wzy), and signal molecule A1-2 synthesis-related genes (luxS, pfs). These probiotic genes were verified by quantitative real-time PCR. In vitro assays confirmed that L. fermentum A51 showed good tolerance to simulated gastrointestinal tract (8.49 log CFU/mL), 0.3% bile salt (39.06%), and possessed adhesion (86.92%), antioxidant (70.60-89.71%), and antimicrobial activities, as well as EPS and signaling molecule AI-2 synthesis capacities. Collectively, our findings have confirmed that L. fermentum A51 is safe and exhibits good probiotic properties, thus recommending its potential application in the production of value-added fermented dairy products.

Congenital muscular dystrophies and myopathies: the leading cause of genetic muscular disorders in eleven Chinese families

BackgroundCongenital muscular dystrophies (CMDs) and myopathies (CMYOs) are a clinically and genetically heterogeneous group of neuromuscular disorders that share common features, such as muscle weakness, hypotonia, characteristic changes on muscle biopsy and motor retardation. In this study, we recruited eleven families with early-onset neuromuscular disorders in China, aimed to clarify the underlying genetic etiology.MethodsEssential clinical tests, such as biomedical examination, electromyography and muscle biopsy, were applied to evaluate patient phenotypes. Whole exome sequencing was used to screen for prospective variants responsible for muscular diseases, followed by co-segregation analysis in the families and prenatal diagnosis via Sanger sequencing, if appropriate. Nanopore sequencing and optical genome mapping were applied for detecting complicated genome rearrangements.ResultsFourteen variants in nine genes (ATL1, LMNA, KLHL40, FKRP, DMD, ACTA1, MSTO1, RYR1 and LAMA2) associated with congenital muscular conditions were identified in the ten families mentioned above. Among them, five novel variants, c.1153_1155del in LMNA, c.577 A > G in ACTA1, c.694T > G in MSTO1, c.5938del in LAMA2, and a rare genome fusion ogm[GRCh38] fus(X; X)(p22.31;p21.1) involving DMD, have not been recorded in public databases to the best of our knowledge.ConclusionsCMDs and CMYOs were probably responsible for most of the cases (9/11) of genetic muscular defects in this study. Molecular analysis is highly beneficial for the precise diagnosis, genetic counseling and prenatal diagnosis of families suspected of having genetic muscular disorders.Clinical trial numberNot applicable.

Featured Cover

The cover image is based on the article Utility of Optical Genome Mapping in Repeat Disorders by Mehmet Burak Mutlu et al., https://doi.org/10.1111/cge.14633. image

Single-nucleotide-resolution genomic maps of O6-methylguanine from the glioblastoma drug temozolomide.

Temozolomide kills cancer cells by forming O6-methylguanine (O6-MeG), which leads to cell cycle arrest and apoptosis. However, O6-MeG repair by O6-methylguanine-DNA methyltransferase (MGMT) contributes to drug resistance. Characterizing genomic profiles of O6-MeG could elucidate how O6-MeG accumulation is influenced by repair, but there are no methods to map genomic locations of O6-MeG. Here, we developed an immunoprecipitation- and polymerase-stalling-based method, termed O6-MeG-seq, to locate O6-MeG across the whole genome at single-nucleotide resolution. We analyzed O6-MeG formation and repair across sequence contexts and functional genomic regions in relation to MGMT expression in a glioblastoma-derived cell line. O6-MeG signatures were highly similar to mutational signatures from patients previously treated with temozolomide. Furthermore, MGMT did not preferentially repair O6-MeG with respect to sequence context, chromatin state or gene expression level, however, may protect oncogenes from mutations. Finally, we found an MGMT-independent strand bias in O6-MeG accumulation in highly expressed genes. These data provide high resolution insight on how O6-MeG formation and repair are impacted by genome structure and nucleotide sequence. Further, O6-MeG-seq is expected to enable future studies of DNA modification signatures as diagnostic markers for addressing drug resistance and preventing secondary cancers.

Pervasive RNA-binding protein enrichment on TAD boundaries regulates TAD organization.

Mammalian genome is hierarchically organized by CTCF and cohesin through loop extrusion mechanism to facilitate the organization of topologically associating domains (TADs). Mounting evidence suggests additional factors/mechanisms exist to orchestrate TAD formation and maintenance. In this study, we investigate the potential role of RNA-binding proteins (RBPs) in TAD organization. By integrated analyses of global RBP binding and 3D genome mapping profiles from both K562 and HepG2 cells, our study unveils the prevalent enrichment of RBPs on TAD boundaries and define boundary-associated RBPs (baRBPs). We found that baRBP binding is correlated with enhanced TAD insulation strength and in a CTCF-independent manner. Moreover, baRBP binding is associated with nascent promoter transcription. Additional experimental testing was performed using RBFox2 as a paradigm. Knockdown of RBFox2 in K562 cells causes mild TAD reorganization. Moreover, RBFox2 enrichment on TAD boundaries is a conserved phenomenon in C2C12 myoblast (MB) cells. RBFox2 is downregulated and its bound boundaries are remodeled during MB differentiation into myotubes. Finally, transcriptional inhibition indeed decreases RBFox2 binding and disrupts TAD boundary insulation. Altogether, our findings demonstrate that RBPs can play an active role in modulating TAD organization through co-transcriptional association and synergistic actions with nascent promoter transcripts.

Long-read structural and epigenetic profiling of a kidney tumor-matched sample with nanopore sequencing and optical genome mapping.

Carcinogenesis often involves significant alterations in the cancer genome, marked by large structural variants (SVs)and copy number variations (CNVs) that are difficult to capture with short-read sequencing. Traditionally, cytogenetic techniques are applied to detect such aberrations, but they are limited in resolution and do not cover features smaller than several hundred kilobases. Optical genome mapping (OGM) and nanopore sequencing [Oxford Nanopore Technologies (ONT)] bridge this resolution gap and offer enhanced performance for cytogenetic applications. Additionally, both methods can capture epigenetic information as they profile native, individual DNA molecules. We compared the effectiveness of the two methods in characterizing the structural, copy number and epigenetic landscape of a clear cell renal cell carcinoma tumor. Both methods provided comparable results for basic karyotyping and CNVs, but differed in their ability to detect SVs of different sizes and types. ONT outperformed OGM in detecting small SVs, while OGM excelled in detecting larger SVs, including translocations. Differences were also observed among various ONT SV callers. Additionally, both methods provided insights into the tumor's methylome and hydroxymethylome. While ONT was superior in methylation calling, hydroxymethylation reports can be further optimized. Our findings underscore the importance of carefully selecting the most appropriate platform based on specific research questions.

Double or nothing: Ancient duplications in the amylase locus drove human adaptation.

Salivary and pancreatic amylase are encoded by AMY1 and AMY2, respectively, which are located within a single genomic locus that has undergone substantial structural variation, resulting in varying gene copy numbers across species. Using optical genome mapping and long-read sequencing, Yilmaz, Karageorgiou, Kim, etal. achieved nucleotide-level resolution of this locus across different human populations, offering new insights into how copy number variation contributes to human adaptation.

Structural Variant Analysis of Complex Karyotype Myelodysplastic Neoplasia Through Optical Genome Mapping.

Myelodysplastic neoplasia with complex karyotype (CK-MDS) poses significant clinical challenges and is associated with poor survival. Detection of structural variants (SVs) is crucial for diagnosis, prognostication, and treatment decision-making in MDS. However, the current standard-of-care (SOC) cytogenetic testing, relying on karyotyping, often yields ambiguous results in cases with CK. Here, SV detection by novel optical genome mapping (OGM) technique was explored in 15 CK-MDS cases, which collectively harbored 85 chromosomes with abnormalities reported by SOC. Additionally, OGM was utilized in the discovery of novel SVs. Altogether, OGM detected corresponding > 5 Mbp alterations for 73 out of 85 SOC reported abnormalities, resulting in an 86% concordance rate. OGM provided further specification of these abnormalities, revealing that 64% of the altered chromosomes were affected by multiple SVs or chromoanagenesis. Prominently, only 5% of missing chromosomes reported by SOC were true monosomies. In addition, OGM detected alterations in chromosomes not reported as abnormal by karyotyping in 93% of cases and provided clinically relevant gene-level information, such as SVs in TP53, MECOM, NUP98, IKZF1, and ETV6. Analysis of novel SVs revealed two previously unreported gene-fusions (SCFD1::ZNF592 and VPS8::LRBA), both confirmed by transcriptome sequencing. Furthermore, the repositioning of CCDC26 (8q24.21) was identified as a potential cause of inappropriate gene activation in two cases, affecting MECOM and SOX7, respectively. This study shows that OGM can significantly enhance the diagnostic analysis of SVs in CK-MDS and highlights the utility of OGM identifying novel SVs in complex cancer genomes.

Epigenomic and 3D genomic mapping reveals developmental dynamics and subgenomic asymmetry of transcriptional regulatory architecture in allotetraploid cotton

Although epigenetic modification has long been recognized as a vital force influencing gene regulation in plants, the dynamics of chromatin structure implicated in the intertwined transcriptional regulation of duplicated genes in polyploids have yet to be understood. Here, we document the dynamic organization of chromatin structure in two subgenomes of allotetraploid cotton (Gossypium hirsutum) by generating 3D genomic, epigenomic and transcriptomic datasets from 12 major tissues/developmental stages covering the life cycle. We systematically identify a subset of genes that are closely associated with specific tissue functions. Interestingly, these genes exhibit not only higher tissue specificity but also a more pronounced homoeologous bias. We comprehensively elucidate the intricate process of subgenomic collaboration and divergence across various tissues. A comparison among subgenomes in the 12 tissues reveals widespread differences in the reorganization of 3D genome structures, with the Dt subgenome exhibiting a higher extent of dynamic chromatin status than the At subgenome. Moreover, we construct a comprehensive atlas of putative functional genome elements and discover that 37 cis-regulatory elements (CREs) have selection signals acquired during domestication and improvement. These data and analyses are publicly available to the research community through a web portal. In summary, this study provides abundant resources and depicts the regulatory architecture of the genome, which thereby facilitates the understanding of biological processes and guides cotton breeding.

Understanding anaerobic germination in direct-seeded rice: a genomic mapping approach

BackgroundAnaerobic germination is a critical trait for rice cultivation, particularly in regions that experience flooding or waterlogging immediately after sowing. Under direct-seeded conditions, where rice is sown directly into the field without prior transplantation, the ability of seeds to germinate in anaerobic (oxygen-deficient) conditions becomes essential for successful crop establishment. This trait is especially relevant in areas prone to waterlogging, were traditional methods of rice cultivation, such as puddled transplanting, may be less viable. Understanding the genetic basis of anaerobic germination can lead to the development of rice varieties that are better adapted to such challenging conditions, thus supporting more sustainable agricultural practices.ResultsIn this study, a nested association mapping (NAM) population consisting of 384 breeding lines was utilized to identify genomic regions associated with anaerobic germination in rice. Through comprehensive analysis, 19 significant marker-trait associations (MTAs) were identified, including 12 associations specifically linked to percent seed germination under anaerobic conditions. These associations were distributed across six different chromosomes: 3, 4, 5, 6, 7, and 9. Notably, a cluster of single nucleotide polymorphisms (SNPs) spanning a 6.9 Mb genomic region on chromosome 3 (from 21,089,181 to 28,017,712 bp) was consistently associated with percent germination at 15 and 21 days after sowing over multiple years. Similarly, a 6.4 Mb genomic segment on chromosome 6 (from 18,028,538 to 24,492,161 bp) was also associated with percent germination at the same time points. Specific SNPs within this region, namely S6_18028538 and S6_24492161, were linked to germination at 15 and 21 days, respectively. In addition to these findings, one MTA was identified for days to 50% flowering on chromosome 1, and six MTAs were identified for grain yield across chromosomes 1, 2, 5, 8, and 10. The breeding lines that exhibited both high and stable yields, along with anaerobic germination traits, have the potential to be particularly valuable in genomics-assisted breeding programs aimed at improving rice varieties for flood-prone areas.ConclusionsThis study provides crucial insights into the genetic basis of anaerobic germination in rice, highlighting specific genomic regions associated with this trait under direct-seeded conditions. The identification of significant MTAs across multiple chromosomes, particularly the consistent associations found on chromosomes 3 and 6, underscores the potential for developing rice varieties with enhanced tolerance to anaerobic conditions. The high-yielding breeding lines identified in this research, which also exhibit strong anaerobic germination traits, represent valuable genetic resources for breeding programs. These findings support the use of direct-seeded rice (DSR) as a sustainable alternative to traditional puddled transplanting, particularly in regions prone to flooding, thereby contributing to the development of more resilient rice cultivation practices.

Detection of KMT2A Partial Tandem Duplication by Optical Genome Mapping in Myeloid Neoplasms: Associated Cytogenetics, Gene Mutations, Treatment Responses, and Patient Outcomes.

KMT2A partial tandem duplication (PTD) involves intragenic KMT2A duplications and has been associated with poorer prognosis. In this study, we evaluated KMT2A PTD in 1277 patients with hematological malignancies using optical genome mapping (OGM). KMT2A PTD was detected in 35 patients with acute myeloid leukemia (AML) (7%), 5 patients with myelodysplastic syndrome (MDS) (2.2%), and 5 patients with chronic myelomonocytic leukemia (CMML) (7.1%). The PTDs varied in size, region, and copy number. An Archer RNA fusion assay confirmed KMT2A PTD in all 25 patients tested: 15 spanning exons 2 to 8 and 10 spanning exons 2 to 10. Most patients exhibited a normal (n = 21) or non-complex (n = 20) karyotype. The most common chromosomal abnormalities included loss of 20q or 7q and trisomy 11/gain of 11q. All patients had gene mutations, with FLT3 ITD and DNMT3A prevalent in AML and DNMT3A and RUNX1 common in MDS and CMML. Among patients who received treatment and had at least one follow-up bone marrow evaluation, 82% of those with de novo AML achieved complete remission after initial induction chemotherapy, whereas 90% of patients with secondary or refractory/relapsed AML showed refractory or partial responses. All but one patient with MDS and CMML were refractory to therapy. We conclude that OGM is an effective tool for detecting KMT2A PTD. Neoplasms with KMT2A PTD frequently harbor gene mutations and display normal or non-complex karyotypes. Patients with KMT2A PTD are generally refractory to conventional therapy, except for de novo AML.

Unveiling the Complexity of KMT2A Rearrangements in Acute Myeloid Leukemias with Optical Genome Mapping.

Background:KMT2A rearrangements are major genetic entities in the classification of acute myeloid leukemias (AMLs), but their diverse and frequently cryptic nature makes their detection and characterization challenging. Karyotypic anomalies at the KMT2A locus and/or abnormal KMT2A Fluorescence in situ hybridization (FISH) results strongly indicate a KMT2A fusion, but the identification of the translocation partner gene often requires further investigation. KMT2A partial tandem duplications (PTDs), on the other hand, are undetectable by standard cytogenetics methods. Methods: We herein report the optical genome mapping (OGM) analysis of 38 AML samples: 12 cryptic/hard-to-characterize KMT2A fusions, 20 KMT2A-PTDs and 6 cases with no KMT2A anomaly. Results: In all the fusion cases, the rearrangement between 5'KMT2A and the 3'partner gene was identified as a translocation t(v;11q23.3)(v;118479068), and the analysis of co-occurring variants elucidated the formation of the rearrangement. The KMT2A variants detected in the KMT2A-PTD cases were surprisingly diverse. Combined with RNAseq data, OGM analysis identified 9 distinct in-frame KMT2A-PTD variants among the 20 cases analyzed. Conclusions: With the clinical development of menin inhibitors for the treatment of patients with KMT2A-rearranged acute leukemias, the characterization of these rearrangements is of utmost importance. Our results suggest that OGM is a promising tool for accurate genetic diagnosis in this context.

Enhancing aluminium resistance in wheat ( Triticum aestivum L.) by exploring for novel genes in the wheat genome

Abstract Aluminium (Al 3+ ) toxicity is a major constraint to crop production worldwide and is considered second only to drought for its importance as an agronomic challenge. A common practice to manage the impact is the application of lime but this is expensive, and it can take years for the lime to be effective in ameliorating the subsoil acidity. Plant species with a natural ability to adapt to Al 3+ toxicity offer an option to maintain production while amelioration efforts continue, especially in low-rainfall areas where yield responses to lime is less profitable. In wheat ( Triticum aestivum L.), the genes conferring Al 3+ resistance have been extensively researched over the years through classical inheritance, cytogenetic, quantitative trait locus (QTL) and genome-wide association studies, and transcriptional analyses. As a focal point for this discussion, we assembled a total of 212 QTL from research papers published between 2006 and 2024, and their physical positions were projected on the sequenced genome of the moderately Al 3+ -resistant hexaploid wheat variety, Chinese Spring. The markers were distributed across the 21 wheat chromosomes, with the highest numbers on chromosomes 3B, 4D and 7A and the lowest on chromosomes 3D and 5D. The physical mapping of significantly associated markers onto the reference genome map uncovered novel candidate genes. These include wheat aluminium-induced (Wali) genes, the ATP-binding cassette (ABC) transporters, phytosulfokine receptor (PSKR), PIN-formed (PIN, auxin transporter), NAC (NAC domain), WRKY (WRKY domain) and natural resistance-associated macrophage proteins (NRAMP). These were discussed to provide a contextual review of gaps that can be exploited in enhancing Al 3+ resistance in wheat, which can lead to the discovery of novel genes and the development of improved cultivars.

Optical genome mapping technology and its applications in genetic disease diagnosis

Optical genome mapping (OGM) is an emerging technology for the detection of genetic diseases based on physical mapping, which can detect numerical chromosomal abnormalities, copy number variation (CNV) and structural variation (SV) on a genome-wide scale. In recent years, a number of studies have proved that OGM, as a new generation of cytogenomic technique, has higher resolution and stronger ability to discover genomic variants compared with conventional genetic techniques. This article has systematically reviewed the principles, characteristics, advantages and limitations of OGM technology, and its applications in the diagnosis of genetic disorders.