Progress in clinical diagnosis and treatment of colorectal cancer with rare genetic variants

Targeted therapy is crucial for advanced colorectal cancer(CRC) positive for genetic drivers. With advances in deep sequencing technology and new targeted drugs, existing standard molecular pathological detection systems and therapeutic strategies can no longer meet the requirements for careful management of patients with advanced CRC. Thus, rare genetic variations require diagnosis and targeted therapy in clinical practice. Rare gene mutations, amplifications, and rearrangements are usually associated with poor prognosis and poor response to conventional therapy. This review summarizes the clinical diagnosis and treatment of rare genetic variations, in genes including erb-b2 receptor tyrosine kinase 2(ERBB2), B-Raf proto-oncogene, serine/threonine kinase(BRAF), ALK receptor tyrosine kinase/ROS proto-oncogene 1, receptor tyrosine kinase(ALK/ROS1), neurotrophic receptor tyrosine kinases(NTRKs), ret proto-oncogene(RET), fibroblast growth factor receptor 2(FGFR2), and epidermal growth factor receptor(EGFR), to enhance understanding and identify more accurate personalized treatments for patients with rare genetic variations.

A Theory of Bio-Quantum Genetics

The physical mechanism of heredity or inheritance of genes is a quantum mechanical and/or quantum computational process. A theory of bio-quantum genetics is established in this paper. Principle of Bio-quantum Genetics is suggested. I propose and define the soft-genes of genetics controlling the processes of heredity or inheritance of genes. This research deals with the quantum mechanisms of Mendel plant heredity and family inheritance as examples of bio-quantum genetics, deepening our understanding of heredity or inheritance. I believe that more contributions will be made to promote researches of bio-quantum genetics or quantum biology at large.

Mobile genetic elements facilitate the transmission of antibiotic resistance genes in multidrug-resistant Enterobacteriaceae from duck farms

Multidrug-resistant(MDR)Enterobacteriaceae critically threaten duck farming and public health.The phenotypes,genotypes,and associated mobile genetic elements(MGEs)of MDR Enterobacteriaceae isolated from 6 duck farms in Zhejiang Province,China,were investigated.A total of 215 isolates were identified as Escherichia coli(64.65%),Klebsiella pneumoniae(12.09%),Proteus mirabilis(10.23%),Salmonella(8.84%),and Enterobacter cloacae(4.19%).Meanwhile,all isolates were resistant to at least two antibiotics.Most isolates carried tet(A)(85.12%),blaTEM(78.60%)and sul1(67.44%)resistance genes.Gene co-occurrence analysis showed that the resistance genes were associated with IS26 and integrons.A conjugative IncFII plasmid pSDM004 containing all the above MGEs was detected in Proteus mirabilis isolate SDM004.This isolate was resistant to 18 antibiotics and carried the blaNDM-5 gene.MGEs,especially plasmids,are the primary antibiotic resistance gene transmission route in duck farms.These findings provide a theoretical basis for the rational use of antibiotics in farms which are substantial for evaluating public health and food safety.

Rapid Prototype Development Approach for Genetic Programming

Genetic Programming (GP) is an important approach to deal with complex problem analysis and modeling, and has been applied in a wide range of areas. The development of GP involves various aspects, including design of genetic operators, evolutionary controls and implementations of heuristic strategy, evaluations and other mechanisms. When designing genetic operators, it is necessary to consider the possible limitations of encoding methods of individuals. And when selecting evolutionary control strategies, it is also necessary to balance search efficiency and diversity based on representation characteristics as well as the problem itself. More importantly, all of these matters, among others, have to be implemented through tedious coding work. Therefore, GP development is both complex and time-consuming. To overcome some of these difficulties that hinder the enhancement of GP development efficiency, we explore the feasibility of mutual assistance among GP variants, and then propose a rapid GP prototyping development method based on πGrammatical Evolution (πGE). It is demonstrated through regression analysis experiments that not only is this method beneficial for the GP developers to get rid of some tedious implementations, but also enables them to concentrate on the essence of the referred problem, such as individual representation, decoding means and evaluation. Additionally, it provides new insights into the roles of individual delineations in phenotypes and semantic research of individuals.

Epidemiological Surveillance: Genetic Diversity of Rotavirus Group A in the Pearl River Delta, Guangdong, China in 2019

Objective This study aimed to understand the epidemic status and phylogenetic relationships of rotavirus group A(RVA)in the Pearl River Delta region of Guangdong Province,China.Methods This study included individuals aged 28 days–85 years.A total of 706 stool samples from patients with acute gastroenteritis collected between January 2019 and January 2020 were analyzed for 17 causative pathogens,including RVA,using a Gastrointestinal Pathogen Panel,followed by genotyping,virus isolation,and complete sequencing to assess the genetic diversity of RVA.Results The overall RVA infection rate was 14.59%(103/706),with an irregular epidemiological pattern.The proportion of co-infection with RVA and other pathogens was 39.81%(41/103).Acute gastroenteritis is highly prevalent in young children aged 0–1 year,and RVA is the key pathogen circulating in patients 6–10 months of age with diarrhea.G9P[8](58.25%,60/103)was found to be the predominant genotype in the RVA strains,and the 41 RVA-positive strains that were successfully sequenced belonged to three different RVA genotypes in the phylogenetic analysis.Recombination analysis showed that gene reassortment events,selection pressure,codon usage bias,gene polymorphism,and post-translational modifications(PTMs)occurred in the G9P[8]and G3P[8]strains.Conclusion This study provides molecular evidence of RVA prevalence in the Pearl River Delta region of China,further enriching the existing information on its genetics and evolutionary characteristics and suggesting the emergence of genetic diversity.Strengthening the surveillance of genotypic changes and gene reassortment in RVA strains is essential for further research and a better understanding of strain variations for further vaccine development.

CRISPR-based genetic control strategies for insect pests

Genetic control strategies such as the sterile insect technique have successfully fought insect pests worldwide. The CRISPR(clustered regularly interspaced short palindromic repeats) technology, together with high-quality genomic resources obtained in more and more species, greatly facilitates the development of novel genetic control insect strains that can be used in area-wide and species-specific pest control programs. Here, we review the research progress towards state-of-art CRISPR-based genetic control strategies, including gene drive, sex ratio distortion, CRISPRengineered genetic sexing strains, and precision-guided sterile insect technique. These strategies’ working mechanisms,potential resistance development mechanisms, and regulations are illustrated and discussed. In addition, recent developments such as stacked and conditional systems are introduced. We envision that the advances in genetic technology will continue to be one of the driving forces for developing the next generation of pest control strategies.

Genetic diversity and population structure of Marsh Grassbird (Locustella pryeri sinensis) in China

We used sequences of mitochondrial control region （807bp） in 75 samples from three breeding colonies and one wintering population to investigate the genetic diversity and population structure of Marsh Grassbird （Locustella pryeri sinensis） in different regions of China. Marsh Grassbird retained a moderate amount of haplotype （0.759 ± 0.056） and nucleotide diversity （0.002）. The results of FST among 3 phy-logeographic units and ФST between breeding and wintering sites revealed little evidence of genetic distinction between different colonies. Neither UPGMA tree structure analysis nor Network picture analysis showed obvious divergence between populations at different locations. Analysis of molecular variance also showed a lack of regional subdivision within Locustella pryeri sinesis, 98.5% of source of variation within populations and only 1.5% among populations. The neutrality test showed negative Fu’s FS value, which, in combination with detection of the mismatch distribution, suggested that population expansion occurred in the evolu-tionary history of this species. This hypothesis was further supported by Tajima’s D test and Fu’s test （D = -1.80, p = 0.02; Fs = -22.11, p = 0.001）, this expansion was estimated to occur about 28,700 years ago.

Genetics of non-alcoholic fatty liver disease: From susceptibility and nutrient interactions to management

Genetics plays an important role in determining the susceptibility of an individual to develop a disease. Complex, multi factorial diseases of modern day(diabetes, cardiovascular disease, hypertension and obesity) are a result of disparity between the type of food consumed and genes, suggesting that food which does not match the host genes is probably one of the major reasons for developing life style diseases. Non-alcoholic fatty liver is becoming a global epidemic leading to substantial morbidity. While various genotyping approaches such as whole exome sequencing using next generation sequencers and genome wide association studies have identified susceptibility loci for non-alcoholic fatty liver disease(NAFLD) including variants in patatin-like phospholipase domain containing 3 and transmembrane 6 superfamily member 2 genes apart from others; nutrient based studies emphasized on a combination of vitamin D, E and omega-3 fatty acids to manage fatty liver disease. However majority of the studies were conducted independent of each other and very few studies explored the interactions between the genetic susceptibility and nutrient interactions. Identifying such interactions will aid in optimizing the nutrition tailor made to an individual's genetic makeup, thereby aiding in delaying the onset of the disease and its progression. The present topic focuses on studies that identified the genetic susceptibility for NAFLD, nutritional recommendations, and their interactions for better management of NAFLD.

Genetic segregation analysis of unsaturated fatty acids content in the filial generations of high-linolenic-acid rapeseed(Brassica napus)

Alpha linolenic acid(ALA)is an essential polyunsaturated fatty acids that can improve human health.Rapeseed is the second largest oil crop in the world but the ALA content in its seed fatty acids is only about 10%.Two rapeseed germplasms YH25005 and R8Q10 with high content(up to 21%)ALA were developed by intervarietal crossing.They were used as the maternal parent(P_(1))when crossed with a low ALA parent SW(P2)to produce the seeds of the F1 hybrid,F2,and backcrosses to P1(BCP1)and P2(BCP2).A multigeneration joint segregation analysis was conducted to determine major gene t polygene effects of the content of three major unsaturated fatty acids including oleic(OA),linoleic(LA)and ALA.The results showed that,although some genes favorable to ALA accumulation were not allelic in R8Q10 and YH25005,all the inheritances of OA,LA and ALA in YH25005×SW and R8Q10×SW followed a genetic model of‘two pairs of additive major genes t additive-dominant polygenes’.It is suggested that the contents of OA,LA and ALA are closely related and the major genes in the parent SW containing loss-of-function mutations in FAD2 and FAD3 loci had strong effect to reduce ALA and elevate OA.However,total genetic effect of the polygenes was greater than that of the two major genes,especial on ALA content.It indicated that it is necessary to employ a larger F2 population to find the plant that accumulate enough minor-effect polygenes for high ALA content.The results are useful for high ALA rapeseed breeding and future work of gene mapping.

Genetic relatedness and association mapping of horticulturally valuable traits for the Ceiba plants using ddRAD sequencing

Ceiba species have high ornamental value and are widely cultivated in tropical regions.However,genetic background of cultivated Ceiba plants remains unclear.To understand the genetic relatedness of cultivated Ceiba plants and genetic basis of key horticultural traits,here we explored the genetic relatedness of 153 accessions of Ceiba plants cultivated in Southern China and identified SNPs associated with five horticultural traits,based on 11704 SNPs derived from double-digest restriction-site associated DNA sequencing(ddRAD-seq).Clustering analysis revealed that these accessions were composed of three groups:C.speciosa group,C.insignis group,and hybrid group.The GWAS identified two,four,two,three,and four SNPs related to petal color,petal striation number,flowering time,trunk shape,and prickles on the trunk and branches,respectively.One to two candidate genes were found near the SNPs strongly associated with these traits.This study revealed the genetic relatedness in the Ceiba plants cultivated in Southern China and presented the first GWAS analysis for five horticultural traits for them,laying a foundation for phenotype-related marker selection and molecular breeding.

Genetic variation features of neonatal hyperbilirubinemia caused by inherited diseases

BACKGROUND Genetic factors play an important role in neonatal hyperbilirubinemia(NH)caused by genetic diseases.AIM To explore the characteristics of genetic mutations associated with NH and analyze the correlation with genetic diseases.METHODS This was a retrospective cohort study.One hundred and five newborn patients diagnosed with NH caused by genetic diseases were enrolled in this study between September 2020 and June 2023 at the Second Affiliated Hospital of Xiamen Medical College.A 24-gene panel was used for gene sequencing to analyze gene mutations in patients.The data were analyzed via Statistical Package for the Social Sciences 20.0 software.RESULTS Seventeen frequently mutated genes were found in the 105 patients.Uridine 5'-diphospho-glucuronosyltransferase 1A1(UGT1A1)variants were identified among the 68 cases of neonatal Gilbert syndrome.In patients with sodium taurocholate cotransporting polypeptide deficiency,the primary mutation identified was Na+/taurocholate cotransporting polypeptide Ntcp(SLC10A1).Adenosine triphosphatase 7B(ATP7B)mutations primarily occur in patients with hepatolenticular degeneration(Wilson's disease).In addition,we found that UGT1A1 and glucose-6-phosphate dehydrogenase mutations were more common in the high-risk group than in the low-risk group,whereas mutations in SLC10A1,ATP7B,and heterozygous 851del4 mutation were more common in the low-risk group.CONCLUSION Genetic mutations are associated with NH and significantly increase the risk of disease in affected newborns.

Genetic Structure of the Oriental River Prawn (Macrobrachium nipponense) from the Yangtze and Lancang Rivers, Inferred from COI Gene Sequence

This study analyzed nueleotide sequences from the mitochondrial eytochrome oxidase submit （COI） gene region （450 bp） to investigate the genetic structure of the oriental river prawn （ Macrobrachium nipponense ） among nine populations from the Yangtze and Lancang Rivers. A total of 79 individuals were collected for this work. Eighty-nine nucleotides were found to be variable, resulting in 46 haplotypes. Among the nine populations, the population from Kunming shows the greatest level of variability （h = 1.000, π = 0.028）, whereas the population from Cbongqing exhibits the lowest level of variability （h = 0.700,π = 0.008）. Analysis of molecular variance suggested that of the total genetic diversity, 9.66% was attributable to inter-population diversity and the remainder （90.34%） to differences within populations. A molecular phylogenetic tree constructed using the Neighbor-joining （N J） method showed that the 46 haplotypes were assigned to two clades associated with geographic regions. These results provide basic information for the conservation and sustainable exploitation of this species.

Novel treatments and genetics of age-related macular degeneration-a narrative review

Age-related macular degeneration(AMD)remains a leading cause of severe visual impairment in developing countries.Although dry-type AMD and geographic atrophy(GA)are progressive conditions with the associated decrease of visual functions,no well-established treatment regimen was proposed for the disease.Wet-type AMD is effectively treated with intravitreal anti-angiogenic agents,but frequent injections are a major issue for the affected patients.Recent advances in AMD genetics have provided new insights into the pathogenesis and novel therapeutic targets of AMD,but the benefits of using genetic testing and genotype-based risk models for AMD development and progression still lacks evidence.Novel AMD treatments aim to increase the interval among intravitreal injections through new therapeutic agents and modern delivery devices.Simultaneously,gene therapy for dry and wet AMD is widely studied.Although gene therapy possesses a major superiority over other novel treatments regarding a persistent cure of disease,many challenges exist in the way of its broad impact on the ocular health of AMD patients.

Effects of non-procedural factors in Brassica napus genetic transformation

Rapeseed (Brassica napus) is the second largest oil crop in the world. However, transformation efficiency of rapeseed still needs to be improved. To evaluate non-procedural factors (e.g. explants, section of explant, marker genes and number of exogenous genes) effects on transformation efficiency, 6-day-old hypocotyl explants from in vitro grown seedlings were co-cultivated with Agrobacterium strain GV3101 harboring a binary vector using optimized transformation procedure. Results showed that normal maturing variety ‘Zhongshuang 6 (ZS6)’ had the highest overall capacity to produce rooted shoots among 5 common varieties and 6 early maturing varieties, with green callus induction rate 81.45% and shoot regeneration rate 21.66%. Early maturing variety 14M645 has relatively high regeneration rate (4.69%) and one of the shortest growth periods (107.54 d). Data showed that choosing neomycin phosphotransferase II gene (NPTII) as selectable marker led to the best transformation rate (17.38%). Selecting upper hypocotyl segments near cotyledon as explant provided the higest transformation efficiency, with regeneration rate of 25.59% when using NPTII as selectable marker and 22.19% for Bar. B. napus transformed with single gene showed higher transformation frequency than vectors with multiple genes,highlighting difficulty of multiple gene transformation. This work helped to further improve genetic transformation of B. napus by optimizing factors that impact transformation efficiency,and it would ultimately improve research in transgenic B. napus varieties with commercial potential.

Comparative Study on Genetic Diversity of Beauveria bassiana in Different Forest Ecosystems

ISSR molecular marker technology was adopted to conduct comparison analysis on genetic diversity level and population genetic structure of Beauveria bassiana population in natural secondary forest （Langyashan national forest park） in Chuzhou City of Anhui Province and artificial pure pine forest （Magushan forest farm） in Xuancheng City of Anhui Province.Seven primers were selected to conduct PCR amplification on total 222 strains of B.bassiana in two populations,a total of 58 unique amplified loci were obtained through amplification,the number of polymorphic loci was 56,the percentage of polymorphic loci was 96.55%,Nei＇s genetic diversity was 0.299 3,Shannon information index was 0.459 3,genetic differentiation coefficient among populations （Gst） was 0.128 3,gene flow Nm=3.398 4;the gene flow between the two populations was small,genetic differentiation was relatively large,being 12.83%,this may be caused by human selective pressures and barrier of gene flow;the genetic variation level of B.bassiana populations in Langyashan was relatively high（PPL=96.55%,H=0.278 1,I= 0.429 9）;the genetic variation level of B.bassiana populations in Magushan was relatively low（PPL=93.10%,H=0.255 2,I= 0.382 5）.The genetic diversity of B.bassiana from the primary forest in Dabieshan was studied（PPL=81.00%,H=0.318 7,I= 0.478 2）,indicating that the genetic diversity of B.bassiana populations in Dabieshan with complex ecological environment was the highest,followed by the populations in natural secondary forest,and the genetic diversity in artificial pure pine forest was the lowest.Nei＇s genetic distance was adopted to construct the genetic relationship dendrogram of B.bassiana individuals collected from Langyashan and Magushan,from the cluster analysis of UPGMA,the strains from the same collection places clustered together.

Plant Regeneration from Immature Inflorescence Culture and Genetic Transformation of Wheatgrass(Agropyron cristatum×A. desertorum cv. Hycrest-Mengnong)

The plants of hybrid wheatgrass （A. cristatum×A. desertorum cv. Hycrest-Mengnong） were directly induced from embryogenic callus regenerated from immature inflorescence. Immature inflorescence was cultured on improved MS medium containing 2.0-3.0 mg L^-1 2,4-D to regenerate callus. The calli were then transferred to hormone-free MS medium for differentiation and 1/2 MS medium for rooting. Results showed that callus initiation frequency was 83.4% and plant regeneration frequency was 59.6%. Phosphinothricin acetyltransferase （bar） gene was transformed into the hybrid wheatgrass by particle bombardment. Resistant callus was obtained using selecting agent, herbicide glufosinate of 0.5 mg L^-1, and some transgenic plants were recovered in vitro. The transgenic plants were identified by PCR and Southern blot analysis and these plants developed normally in the glufosinate medium, whereas the nontransgenic plants did not. The results demonstrated that bar cDNA integrated into the genomic DNA of the transgenic plants. The transgenic frequencies of bar gene were 1.1%.

Genome-wide identification,evolutionary selection,and genetic variation of DNA methylation-related genes in Brassica rapa and Brassica oleracea

DNA methylation plays an important role in plant growth and development,and in regulating the activity of transposable elements(TEs).Research on DNA methylation-related(DMR)genes has been reported in Arabidopsis,but little research on DMR genes has been reported in Brassica rapa and Brassica oleracea,the genomes of which exhibit significant differences in TE content.In this study,we identified 78 and 77 DMR genes in Brassica rapa and Brassica oleracea,respectively.Detailed analysis revealed that the numbers of DMR genes in different DMR pathways varied in B.rapa and B.oleracea.The evolutionary selection pressure of DMR genes in B.rapa and B.oleracea was compared,and the DMR genes showed differential evolution between these two species.The nucleotide diversity(π)and selective sweep(Tajima’s D)revealed footprints of selection in the B.rapa and B.oleracea populations.Transcriptome analysis showed that most DMR genes exhibited similar expression characteristics in B.rapa and B.oleracea.This study dissects the evolutionary differences and genetic variations of the DMR genes in B.rapa and B.oleracea,and will provide valuable resources for future research on the divergent evolution of DNA methylation between B.rapa and B.oleracea.

Genetic Transformation of Brassica campestris L.ssp.pekinensis via Agrobacterium-with Bt Gene

By means of Agrobacterium-mediated transformation, 43 kanamycin-resistant buds of Chinese cabbage were got. PCR, PCR-Southern blot and dot blot analysis were used to identify and characterize the putative transgenic plants. 26 plants had the predicted bands of the fragment of npt Ⅱ gene. Insect bioassays of 4 transformants showed that toxic protein had been translated and the translation levels were different among these transformants.

Major Results and Research Challenges in Cotton Molecular Genetics at CIRAD(France)

CIRAD(Montpellier,France) develops research activities centered on tropical and sub-tropical agricultural systems.Among others crops,cotton is the focus of a series of research programs in different disciplines from economics to breeding.Major areas in genetics and breeding relate to(1) genetic diversity,(2) cultivar development through classical and molecular breeding,and(3)

Genetic Diversity in the Camel Tick <i>Hyalomma dromedarii</i>(Acari: Ixodidae) Based on Mitochondrial Cytochrome c Oxidase Subunit I (COI) and Randomly Amplified Polymorphic DNA Polymerase Chain Reaction (RAPD-PCR)

Hyalomma dromedarii ticks are important disease vectors to camels in the UAE and worldwide. Ticks can be identified using DNA-based techniques. In addition, such techniques could be utilized to study the intraspecific genetic diversity in tick populations. In this study, the genetic diversity of four H. dromedarii populations was investigated using mitochondrial cytochrome c oxidase subunit I (COI) gene and randomly amplified polymorphic DNA polymerase chain reaction (RAPD-PCR). The results showed that both of the aforementioned techniques produced similar grouping patterns. Moreover, they revealed that the four tick populations had high levels of genetic similarity. However, one population was slightly different from the three other populations. The current study demonstrated that H. dromedarii ticks in the UAE are very similar at the genetic level and that investigating more locations and screening larger numbers of ticks could reveal larger genetic differences.