Additional Genetic Features Research Articles

A Novel Natural Graph for Efficient Clustering of Virus Genome Sequences

Background: This study addresses the need for analyzing viral genome sequences and understanding their genetic relationships. The focus is on introducing a novel natural graph approach as a solution. Objective: The objective of this study is to demonstrate the effectiveness and advantages of the proposed natural graph approach in clustering viral genome sequences into distinct clades, subtypes, or districts. Additionally, the aim is to explore its interpretability, potential applications, and implications for pandemic control and public health interventions. Methods: The study utilizes the proposed natural graph algorithm to cluster viral genome sequences. The results are compared with existing methods and multidimensional scaling to evaluate the performance and effectiveness of the approach. Results: The natural graph approach successfully clusters viral genome sequences, providing valuable insights into viral evolution and transmission dynamics. The ability to generate directed connections between nodes enhances the interpretability of the results, facilitating the investigation of transmission pathways and viral fitness. Conclusion: The findings highlight the potential applications of the natural graph algorithm in pandemic control, transmission tracing, and vaccine design. Future research directions may involve scaling up the analysis to larger datasets and incorporating additional genetic features for improved resolution. : The natural graph approach presents a promising tool for viral genomics research with implications for public health interventions.

Evaluating the persistence and utility of five wild Vitis species in the context of climate change.

Crop wild relatives (CWRs) have the capacity to contribute novel traits to agriculture. Given climate change, these contributions may be especially vital for the persistence of perennial crops, because perennials are often clonally propagated and consequently do not evolve rapidly. By studying the landscape genomics of samples from five Vitis CWRs (V. arizonica, V. mustangensis, V. riparia, V. berlandieri and V. girdiana) in the context of projected climate change, we addressed two goals. The first was to assess the relative potential of different CWR accessions to persist in the face of climate change. By integrating species distribution models with adaptive genetic variation, additional genetic features such as genomic load and a phenotype (resistance to Pierce's Disease), we predicted that accessions from one species (V. mustangensis) are particularly well-suited to persist in future climates. The second goal was to identify which CWR accessions may contribute to bioclimatic adaptation for grapevine (V. vinifera) cultivation. To do so, we evaluated whether CWR accessions have the allelic capacity to persist if moved to locations where grapevines are cultivated in the United States. We identified six candidates from V. mustangensis and hypothesized that they may prove useful for contributing alleles that can mitigate climate impacts on viticulture. By identifying candidate germplasm, this study takes a conceptual step toward assessing the genomic and bioclimatic characteristics of CWRs.

Germline DNA replication timing shapes mammalian genome composition.

Mammalian DNA replication is a highly organized and regulated process. Large, Mb-sized regions are replicated at defined times along S-phase. Replication Timing (RT) is thought to play a role in shaping the mammalian genome by affecting mutation rates. Previous analyses relied on somatic RT profiles. However, only germline mutations are passed on to offspring and affect genomic composition. Therefore, germ cell RT information is necessary to evaluate the influences of RT on the mammalian genome. We adapted the RT mapping technique for limited amounts of cells, and measured RT from two stages in the mouse germline - primordial germ cells (PGCs) and spermatogonial stem cells (SSCs). RT in germline cells exhibited stronger correlations to both mutation rate and recombination hotspots density than those of RT in somatic tissues, emphasizing the importance of using correct tissues-of-origin for RT profiling. Germline RT maps exhibited stronger correlations to additional genetic features including GC-content, transposable elements (SINEs and LINEs), and gene density. GC content stratification and multiple regression analysis revealed independent contributions of RT to SINE, gene, mutation, and recombination hotspot densities. Together, our results establish a central role for RT in shaping multiple levels of mammalian genome composition.

‘Candidatus Phytoplasma noviguineense’, a novel taxon associated with Bogia coconut syndrome and banana wilt disease on the island of New Guinea

Bogia coconut syndrome (BCS) is one of the lethal yellowing (LY)-type diseases associated with phytoplasma presence that are seriously threatening coconut cultivation worldwide. It has recently emerged, and is rapidly spreading in northern parts of the island of New Guinea. BCS-associated phytoplasmas collected in different regions were compared in terms of 16S rRNA gene sequences, revealing high identity among them represented by strain BCS-BoR. Comparative analysis of the 16S rRNA gene sequences revealed that BCS-BoR shared less than a 97.5 % similarity with other species of 'Candidatus Phytoplasma', with a maximum value of 96.08 % (with strain LY; GenBank accession no. U18747). This result indicates the necessity and propriety of a novel taxon for BCS phytoplasmas according to the recommendations of the IRPCM. Phylogenetic analysis was also conducted on 16S rRNA gene sequences, resulting in a monophyletic cluster composed of BCS-BoR and other LY-associated phytoplasmas. Other phytoplasmas on the island of New Guinea associated with banana wilt and arecanut yellow leaf diseases showed high similarities to BCS-BoR and were closely related to BCS phytoplasmas. Based on the uniqueness of their 16S rRNA gene sequences, a novel taxon 'Ca.Phytoplasma noviguineense' is proposed for these phytoplasmas found on the island of New Guinea, with strain BCS-BoR (GenBank accession no. LC228755) as the reference strain. The novel taxon is described in detail, including information on the symptoms of associated diseases and additional genetic features of the secY gene and rp operon.

Plasma Cell Leukemia.

Abstract SCI-4 IntroductionPlasma cell leukemia (PCL) represents an aggressive variant of multiple myeloma (MM) characterized by the presence of large number of circulating plasma cells (PC) in the peripheral blood. While some boundaries have been defined to establish a diagnosis of PCL (PC in the peripheral blood greater than 2×109/l-1 or 20% of leukocytes being plasma cells), these values are artificial, and most cases of PCL show extreme numbers of circulating plasma cells. PCL is part of a spectrum of the PC neoplasms where increasing numbers of circulating PC identify aggressive MM, yet many cases do not satisfy criteria for PCL. Historically PLC has been divided into “Primary PCL” (pPCL) when it represents the initial manifestation of a PC neoplasm, and “Secondary PCL”, or MM with leukemic transformation (MM-LT). Both entities share biologic and clinical similarities as aggressive variants of MM, but the latter represents a fulminant PC neoplasm with historic survival of only 1-2 months. In contrast, pPCL, while nevertheless aggressive, often will respond to induction treatment and can occasionally result in a durable response. BiologyBecause of the rarity of PCL (1% or less of all MM) the genetic description of the disease has been limited by lack of material for study. Nevertheless most PCL cases harbor IgH translocations (87% of pPCL and 82% in MM-LT). In particularly the t(11;14)(q13;q32) is common; observed in 35 to 70% of cases of pPCL. In contrast MM-LT contains most other genetic aberrations associated with MM pathogenesis, including the more benign genetic variants of the disease (e.g. hyperdiploid MM), and these cells are presumed to have acquired additional genetic features resulting in aggressive clonal proliferation and expansion. When karyotypes are informative (frequently in PCL) they are almost always non-hyperdiploid variant, mostly hypodiploid. Rare cases of hyperdiploid karyotypes have been observed in association with MM-LT. Monoallelic deletions of 17p13.1, at the TP53 locus and similar to those seen in MM, can be detected in 50% of pPCL and 75% of MM-LT. While mutations of TP53 area rare in MM they are common in PCL (24%), contributing to a substantial overall prevalence of TP53 inactivation of 56% in pPCL and 83% in MM-LT. Furthermore, we found the upstream tumor suppressor p14ARF, whose product directly binds MDM2 enhancing p53 function, to be inactivated by methylation in 29% of MM-LT. MYC abnormalities are only observed in 15% of cases and the distribution of chromosome 13 deletion/monosomy is similar to what would be expected for the corresponding karyotypic aberrations (85% in the hypodiploid pPCL and 50% in MM-LT). Treatment and future directionsHistorically the treatment of PCL has been unsatisfactory with few patients achieving durable remissions, and most dying within weeks to months after diagnosis. The impact of more intensive regimens (including autologous and allogeneic stem cell transplant) and of novel agents such as bortezomib and lenalidomide are not known. However, early data suggest, that the historic survival rates of pPCL (∼12 months) and MM-LT (∼1-2 months) will be improved by the aforementioned interventions. It is likely that with increasing survival of MM patients, MM-LT will become an increasingly common and difficult problem to manage. DisclosuresFonseca:Various: CME lectures; Halozyme: Consultancy; BMS: Consultancy; Medtronic: Consultancy; AMGEN: Consultancy. Off Label Use: Multiple agents to be used for the treatment of plasma cell leukemia. No agents are specifically approved for this indication although this is a variant of myeloma.

Previously documented mutations in the epidermal growth factor receptor (EGFR) gene in a non-small cell lung cancer (NSCLC) population treated with gefitinib are not associated with response

7163 Background: Mutations in the tyrosine kinase domain of EGFR that may correlate with clinical features and response of NSCLC to EGFR tyrosine kinase inhibitors have been described. But, varying methodologies have contributed to an uncertain relationship between EGFR mutational status and response. This study sought to characterize EGFR mutations in microdissected tumour tissue from pts with advanced NSCLC treated with gefitinib and correlate their clinical data. Methods: Biopsy material from pts treated with gefitinib for advanced NSCLC at the British Columbia Cancer Agency was analyzed. Malignant cells (cytology specimens) or tissue (paraffin embedded biopsies) was reviewed and tumour cells isolated by laser- capture microdissection or manual scrape. Genomic DNA was extracted and exons coding for the EGFR tyrosine kinase domain (18 - 24) were amplified by PCR and sequenced. When insufficient, the priority was 18, 19, 21, followed by 20, 23, 22, and 24. EGFR mutational analyses were correlated with response to gefitinib and clinical features. Results: 61 pts were identified, 14 (23%) radiological responders (CR, PR): 10 Asian, 10 female, 8 non-smokers, 8 adenocarcinoma, 2 BAC. Of 51 tumour samples available, 39 had adequate tissue for sequencing analysis. EGFR copy number by FISH is pending. Laser-capture microdissection allowed for high quality DNA to be extracted almost exclusively from tumour. Exons 18, 19, 20, 21, 22, 23 and 24 have been sequenced in 37, 34, 30, 33, 12, 10, and 13 patients, respectively. 4 mutations were identified: 2 in 2 non-smoking Asian pts (exon 19; deletion or substitution of L747-T751) and 2 in Caucasians (exon 20 point mutation resulting in a L798F substitution). None of these pts had a response to gefitinib. Conclusions: As with other series, most responders were female, non-smokers of Asian origin. Our results support the relationship between Asian ethnicity and EGFR mutations but question the role of EGFR mutational status in predicting response. Prospective studies will need to focus the detection of additional genetic features using accurate and reproducible techniques before recommendations for selecting populations to be treated can be made. No significant financial relationships to disclose.

Molecular genetics of RH and its clinical application : Génétique moléculaire sur système RH et ses applications cliniques

Background The RH genes RHD and RHCE encode two proteins that represent the clinically most important blood group system defined by the sequences of red cell membrane proteins. In the last five years the field has been moving from defining the underlying molecular genetics to applying the molecular genetics in clinical practice. Materials and methods The state of the current knowledge is briefly summarized using recent reviews and original work since 2000. Results The RHD and RHCE genes are strongly homologous and located closely adjacent at the human chromosomal position 1p36.11. Part of the genetic complexity is explained by the clustered orientation of both genes with their tail ends facing each other. The SMP1 gene is located interspersed between both RH genes. Using additional genetic features of the RH gene locus, RHCE was shown to represent the ancestral RH position, while RHD is the duplicated gene. More than 150 alleles have been defined for RHD alone. They were classified based on antigenic and clinical properties into phenotypes like partial D, weak D and DEL. Among the D negative phenotype a large variety of non-functional alleles were found. The frequencies of these distinct alleles vary widely among human populations, which has consequences for clinical practice. Conclusion Rhesus is a model system for the correlation of genotype and phenotype, facilitating the understanding of underlying genetic mechanisms in clustered genes. With regard to clinical practice, the genetic diagnostics of blood group antigens will advance the cost-effective development of transfusion medicine.

A comparative study of the superior fertility of ‘Smoothee Golden Delicious’ apple

SummaryApple (Malus domestica) has a gametophytically determined self-incompatibility system, which limits inbreeding. As a consequence, apple trees depend on cross-fertilization for fruit-set, which may be enhanced by honeybees (Apis mellifera). In this study honeybee pollination effectiveness and setting potential of two important apple cultivars, ‘Smoothee Golden Delicious’ and ‘Topred Red Delicious’, were investigated to shed light on the high fruit-sets and yields of ‘Smoothee’, as compared with ‘Topred’. Analysis of floral features and honeybee behaviour revealed that the differences between the two cultivars in flower size and nectar traits did not affect honeybee visitation frequency, which was the same for both cultivars. Due to the wide basal gaps between the stamen filaments in ‘Smoothee’ and ‘Topred’ flowers, which enabled “sideworking”, a low proportion of “topworkers” was found in both cultivars.Yet, more than double the number of “topworkers” was found in ‘Smoothee’, as compared to ‘Topred’, probably because of the wider diameter of the stamen filament spread of the ‘Smoothee’ flowers, facilitating nectar collection from the top and thus increasing pollination effectiveness. ‘Smoothee’ fruit-set was significantly higher than ‘Topred’ in all stages of flower development, in accordance with the assumption that ‘Topred’ has a shorter ovule longevity than ‘Smoothee’. However, higher fruit-set of ‘Smoothee’ flowers pollinated before anthesis, at the “Balloon” stage, was also found.This implies that the high fruit-set and fertility of ‘Smoothee’ are also due to additional genetic features.

Chromosomal and Gene Amplification in Diffuse Large B-Cell Lymphoma

Chromosomal translocations leading to deregulation of specific oncogenes characterize approximately 50% of cases of diffuse large B-cell lymphomas (DLBL). To characterize additional genetic features that may be of value in delineating the clinical characteristics of DLBL, we studied a panel of 96 cases at diagnosis consecutively ascertained at the Memorial Sloan-Kettering Cancer Center (MSKCC) for incidence of gene amplification, a genetic abnormality previously shown to be associated with tumor progression and clinical outcome. A subset of 20 cases was subjected to comparative genomic hybridization (CGH) analysis, which identified nine sites of chromosomal amplification (1q21-23, 2p12-16, 8q24, 9q34, 12q12-14, 13q32, 16p12, 18q21-22, and 22q12). Candidate amplified genes mapped to these sites were selected for further analysis based on their known roles in lymphoid cell and lymphoma development, and/or history of amplification in tumors. Probes for six genes, which fulfilled these criteria, REL (2p12-16), MYC (8q24), BCL2 (18q21), GLI, CDK4, and MDM2 (12q13-14), were used in a quantitative Southern blotting analysis of the 96 DLBL DNAs. Each of these genes was amplified (four or more copies) with incidence ranging from 11% to 23%. This analysis is consistent with our previous finding that REL amplification is associated with extranodal presentation. In addition, BCL2 rearrangement and/or REL, MYC, BCL2, GLI, CDK4, and MDM2 amplification was associated with advanced stage disease. These data show, for the first time, that amplification of chromosomal regions and genes is a frequent phenomenon in DLBL and demonstrates their potential significance in lymphomagenesis.