Late stage colorectal carcinoma is very complicated in its molecular mechanisms. One hundred andnine cases of colorectal carcinomas were analyzed with RFLP method for the allelic deletion of chromosome 17short arms (A...Late stage colorectal carcinoma is very complicated in its molecular mechanisms. One hundred andnine cases of colorectal carcinomas were analyzed with RFLP method for the allelic deletion of chromosome 17short arms (ADCC17p) In this study. The results showed that frs(luency of allelic deletion of chromosome 17short arms (FADC17P) in Dukes’ D stage (95 % ) was higher than those in Dukes’ A, B. C stages (54% 68% ); Fisher’s exact test P <0. 01; FADC17p in colorectal carcinomas with distant metastasis (95 % ) washigher than those without distant metastasis, Fisher’s exact test P <0. 01 However, there were no significant differences in FADC 1 7p between the colorectal carcinomas with lymph node metastasis and those without lymph node metastasis (P >0. 05). Therefore, it is considered that ADC17p is an important diagnosticmarker of late stage colorectal carcinomas, and indicates a poor prognosis.展开更多
A collection of 167 Thai and exotic rice accessions was subjected for evaluation of genetic diversity and assessment of relationship by simple sequence repeat (SSR) markers. Among a total of 49 SSR markers, 13 markers...A collection of 167 Thai and exotic rice accessions was subjected for evaluation of genetic diversity and assessment of relationship by simple sequence repeat (SSR) markers. Among a total of 49 SSR markers, 13 markers distributing over 12 rice chromosomes showed clear polymorphic band patterns, and they were selected for genetic assessment. A total of 110 alleles were detected with an average of 8.46 alleles per locus. The averages of gene diversity, heterozygosity and polymorphic information content were 0.59, 0.02 and 0.56, respectively. The unweighted-pair group method with arithmetic averages (UPGMA) clustering analysis was performed for genetic distance, and phylogenetic tree was constructed. The result showed that this rice collection was divided into two major groups, classified as japonica and indica subspecies. Within the japonica group, temperate japonica and tropical japonica subgroups can be clearly separated. Three-dimensional principal component analysis projection and model-based population structure analysis showed consistent clustering results with two major groups of UPGMA analysis, supporting the classification of japonica and indica subspecies. The indica allelic frequency was also investigated to provide an indicative guide for breeders to overcome the practical problems on sterility of inter-subspecies hybrid offspring. This rice collection and information obtained in this study will be useful for rice breeding programs.展开更多
This paper studies the offspring＇s genotype frequency of the selfing population on multiple alleles with limited loci.A recursive algorithm is given for it.It is discovered that the genotype frequency of homozygous g...This paper studies the offspring＇s genotype frequency of the selfing population on multiple alleles with limited loci.A recursive algorithm is given for it.It is discovered that the genotype frequency of homozygous gene of limited loci increases by generations.Relative increment reduces by generations and the genotype frequency tends to a definite value finally.The genotype frequency of limited loci with hybrid gene tends to 0 finally.But it is possibility that the genotype frequency increases in previous generations then reduces later.It is found that the number of the hybrid gene are more,the speeds tending to 0 are quicker.展开更多
Genomic selection has been demonstrated as a powerful technology to revolutionize animal breeding. However, marker density and minor allele frequency can affect the predictive ability of genomic estimated breeding val...Genomic selection has been demonstrated as a powerful technology to revolutionize animal breeding. However, marker density and minor allele frequency can affect the predictive ability of genomic estimated breeding values （GEBVs）. To investigate the impact of marker density and minor allele frequency on predictive ability, we estimated GEBVs by constructing the different subsets of single nucleotide polymorphisms （SNPs） based on varying markers densities and minor allele frequency （MAF） for average daily gain （ADG）, live weight （LW） and carcass weight （CW） in 1 059 Chinese Simmental beef cattle. Two strategies were proposed for SNP selection to construct different marker densities： 1） select evenly-spaced SNPs （Strategy 1 ）, and 2） select SNPs with large effects estimated from BayesB （Strategy 2）. Furthermore, predictive ability was assessed in terms of the correlation between predicted genomic values and corrected phenotypes from 10-fold cross-validation. Predictive ability for ADG, LW and CW using autosomal SNPs were 0.13＋0.002, 0.21＋0.003 and 0.25＋0.003, respectively. In our study, the predictive ability increased dramatically as more SNPs were included in analysis until 200K for Strategy 1. Under Strategy 2, we found the predictive ability slightly increased when marker densities increased from 5K to 20K, which indicated the predictive ability of 20K （3% of 770K） SNPs with large effects was equal to the predictive ability of using all SNPs. For different MAF bins, we obtained the highest predictive ability for three traits with MAF bin 0.01-0.1. Our result suggested that designing a low-density chip by selecting low frequency markers with large SNP effects sizes should be helpful for commercial application in Chinese Simmental cattle.展开更多
Growth performance as well as marbling is the main breeding objectives in Japanese Black cattle, the major beef breed in Japan. A previous study has identified the c.1326T>G single nucleotide polymorphism (SNP) in ...Growth performance as well as marbling is the main breeding objectives in Japanese Black cattle, the major beef breed in Japan. A previous study has identified the c.1326T>G single nucleotide polymorphism (SNP) in the NCAPG (non-SMC condensin I complex, subunit G) gene that leads to the amino acid change p.Ile442Met in the NCAPG protein, which is a candidate causative variation for a bovine carcass weight (CWT) quantitative trait locus (QTL). In this study, we first confirmed the association of the c.1326T>G SNP with the growth-related traits, CWT, rib eye area (REA) and rib thickness (RT), and showed significant effect of the SNP genotypes on the marbling trait, beef marbling score (BMS), in the Japanese Black beef cattle population of the Niigata prefecture, with the G allele being associated with a favorable phenotype of these traits. Thus, we concluded that the c.1326T>G SNP is useful for effective marker-assisted selection to increase meat quality and meat productivity in Japanese Black beef cattle of the Niigata prefecture. Furthermore the frequency of the favorable G allele of the c.1326T>G SNP in the Niigata prefecture population was significantly lower than the frequency of this allele in Japanese Black cattle population of the Kagoshima prefecture. However, no statistically significant difference was detected between the allele frequencies estimated by maternal alleles in the half-sib progeny steers in the Niigata prefecture population and obtained in Japanese Black cattle population of the Kagoshima prefecture.展开更多
Anaplastic lymphoma kinase(ALK)is the most common fusion gene involved in non-small cell lung cancer(NSCLC),and remarkable response has been achieved with the use of ALK tyrosine kinase inhibitors(ALK-TKIs).However,th...Anaplastic lymphoma kinase(ALK)is the most common fusion gene involved in non-small cell lung cancer(NSCLC),and remarkable response has been achieved with the use of ALK tyrosine kinase inhibitors(ALK-TKIs).However,the clinical efficacy is highly variable.Pre-existing intratumoral heterogeneity(ITH)has been proven to contribute to the poor treatment response and the resistance to targeted therapies.In this work,we investigated whether the variant allele frequencies(VAFs)of ALK fusions can help assess ITH and predict targeted therapy efficacy.Through the application of next-generation sequencing(NGS),7.2%(326/4548)of patients were detected to be ALK positive.On the basis of the adjusted VAF(adjVAF,VAF normalization for tumor purity)of four different threshold values(adjVAF<50%,40%,30%,or 20%),the association of ALK subclonality with crizotinib efficacy was assessed.Nonetheless,no statistical association was observed between median progression-free survival(PFS)and ALK subclonality assessed by adjVAF,and a poor correlation of adjVAF with PFS was found among the 85 patients who received first-line crizotinib.Results suggest that the ALK VAF determined by hybrid capture-based NGS is probably unreliable for ITH assessment and targeted therapy efficacy prediction in NSCLC.展开更多
New clinical approaches are imperative beyond the widely adopted National Comprehensive Cancer Network (NCCN) guidelines, utilized by prominent cancer institutions. Cancer is the leading cause of death among individua...New clinical approaches are imperative beyond the widely adopted National Comprehensive Cancer Network (NCCN) guidelines, utilized by prominent cancer institutions. Cancer is the leading cause of death among individuals younger than 85 years within the United States. Despite significant technological advances, including the expenditure of hundreds of billions, treatment outcomes and overall survival have not notably improved for most types of advanced cancer over the last several decades. Over the past 24 years, Envita Medical Centers has pioneered a unique form of personalized treatment approach for late-stage and refractory cancer patients, introducing groundbreaking innovations in the field. Our integrated algorithm utilizes advanced genomics, transcriptomics, and highly tailored immunotherapy, resulting in remarkable outcome improvements. This study presents Envita’s innovative personalized treatment algorithms and examines the response outcomes of 199 late-stage cancer patients treated at Envita Medical Centers over a two-year period. Compared to standard of care and palliative chemotherapy, Envita’s treatment demonstrated a remarkable 35-fold improvement in overall response rates (Figure 1). Moreover, 88% of the patients, the majority presenting with Stage 3 or 4 cancer, experienced a 43-fold improvement in quality of life with minimal side effects, as compared to standard of care chemotherapy and palliative care. This revolutionary success is attributed to Envita’s personalized therapeutic algorithms, which incorporate customized immunotherapy. Envita’s precision care approach has also achieved a 100% better response rate compared to over 65 global chemotherapy clinical trials with more than 2700 patients. The results from this study suggest that a wider utilization of Envita’s personalized approach can significantly benefit patients with late-stage and refractory cancer.展开更多
X-linked redegreen color blindness is the most widespread form of vision impairment.The study aimed to determine the prevalence and gene frequencies of redegreen color vision impairments among children of six differen...X-linked redegreen color blindness is the most widespread form of vision impairment.The study aimed to determine the prevalence and gene frequencies of redegreen color vision impairments among children of six different human populations of Jammu province.A total of 1028 healthy subjects(6e15 years of age)were selected from five Muslim populations and the color vision impairments were determined using the Ishihara’s test of color deficiency.The gene frequency was calculated using HardyeWeinberg equilibrium method.The prevalence of color vision deficiency(CVD)ranged from 5.26%to 11.36%among males and 0.00%e3.03%among females of six different populations.The gender based differences in the frequency of CVD was found to be statistically significant(p<0.0001),with a higher prevalence among male(7.52%)as compared to female(0.83%)children.We observed high frequency of deutan as compared to protan defects.The incidences of deuteranomaly(5.68%)and deuteranopia(2.27%)were higher among male children of Syed population while the frequencies of protanomaly(1.94%),protanopia(1.28%)and achromacy(2.27%)were the highest among male subjects of Khan,Malik and Syed populations,respectively.The allele and genotype frequencies showed cogent differences among six populations.The population based assessment of CVDs help patients to follow adaptive strategies that could minimize the risks of the disease.展开更多
Knowledge of allelic frequencies at loci associated with kernel weight and effects on kernel weight-related traits is crucial for yield improvement in wheat. Kernel weight-related traits were evaluated in 200 Chinese ...Knowledge of allelic frequencies at loci associated with kernel weight and effects on kernel weight-related traits is crucial for yield improvement in wheat. Kernel weight-related traits were evaluated in 200 Chinese winter wheat cultivars(lines) grown at the Xinxiang Experimental Station, Chinese Academy of Agricultural Sciences, Xinxiang in Henan Province, for three consecutive years from 2014 to 2016. Alleles associated with kernel weight at nine loci, TaCKX6-D1, TaCwi-A1, TaCWI-4A, TaGS1a, TaGS5-A1, TaGS3-3A, TaGW2-6A, TaSus2-2B, and TaTGW6-A1, were determined for all cultivars(lines). ANOVA showed that genotypes, years and their interactions had significant effects on thousand-kernel weight(TKW), kernel length(KL) and kernel width(KW). The overall mean frequencies of alleles conferring high and low TKW at the nine loci were 65.9% and 33.4%, with the ranges of 37.0%–85.0% and 13.5%–63.0% for single loci. The frequencies of high-TKW alleles were over 50.0% at eight of the loci. Genotypes at each locus with the high-TKW allele had higher TKW than those with the low-TKW allele. The high-TKW allele Hap-H at the TaSus2-2B locus can be preferably used to increase grain yield due to its high TKW(49.32 g). A total of 18 main allelic combinations(ACs) at nine loci were detected. Three ACs(AC1–AC3) had significantly higher TKW than AC6 with high-TKW alleles at all nine loci even though they contained some low-TKW alleles. This indicated that other loci controlling kernel weight were present in the high-TKW cultivars. This work provides important information for parental selection and marker-assisted selection for breeding.展开更多
AIM: To estimate the frequency of microdeletions in the long arm of Y-chromosome of 20 infertile males from South India. METHODS: Polymerase chain reaction (PCR) amplification using Y-specific STS of azoospermia facto...AIM: To estimate the frequency of microdeletions in the long arm of Y-chromosome of 20 infertile males from South India. METHODS: Polymerase chain reaction (PCR) amplification using Y-specific STS of azoospermia factor (AZF) regions i.e., SY 84 for AZFa, SY 127 for AZFb and SY 254 for AZFc. RESULTS: Of the 20 infertile subjects 3 (15 %), one azoospermic and two oligozoospermic, showed microdeletions in the AZF region of Y-chromosome. CONCLUSION: The frequency of deletions involving AZF region of the Y-chromosome is 15 % in azoospermic and severely oligozoospermic infertile men. PCR amplification of AZF locus is useful for the diagnosis of microdeletions in the Y-chromosome.展开更多
To overcome the obstacle of the fascinating relation in predicting animal phenotype value, we have developed a neural network model to detect the complex non-linear relationships between the genotypes and phenotypes a...To overcome the obstacle of the fascinating relation in predicting animal phenotype value, we have developed a neural network model to detect the complex non-linear relationships between the genotypes and phenotypes and the possible interactions that cannot be expressed with equations. In this paper, back-propagation neural network is used to discuss the influences of different allele frequencies on estimating the polygenic phenotype value. To ensure the precision of prediction, normalization was needed to train the prediction model. The results show that back-propagation artificial neural networks can be used to predict the phenotype value and perform very well in allele frequency from 0.2 to 0.8, when the allele frequency is very small （less than 0.2） or big （more than 0.8）; however, the prediction model was not reliable and the predicted value should be carefully tested.展开更多
Hypoxia represents one of the most extreme environmental conditions for both human beings and animals living at high al- titudes （Zhao et al., 2009）. Over the past few years, great attention has been focused on the ...Hypoxia represents one of the most extreme environmental conditions for both human beings and animals living at high al- titudes （Zhao et al., 2009）. Over the past few years, great attention has been focused on the genetic bases of adaption to high-altitude environments （Bigham et al., 2010; Simonson et al., 2010）. The domestic dog （Canisfamiliaris） is the first animal that developed an intimate relationship with human beings. Dogs migrated with human beings and have adapted to variety of ecological niches （Savolainen et al., 2002）. Our previous research revealed parallel evolution and convergent evolution in the adaptation of dogs and humans to the high-altitude environment of the Tibetan plateau （Wang et al., 2013, 2014）, suggesting that exploring the adaption of domestic dogs to high-altitude hypoxia is an interesting and important question.展开更多
The allele frequency spectrum(AFS), or site frequency spectrum, is commonly used to summarize the genomic polymorphism pattern of a sample, which is informative for inferring population history and detecting natural s...The allele frequency spectrum(AFS), or site frequency spectrum, is commonly used to summarize the genomic polymorphism pattern of a sample, which is informative for inferring population history and detecting natural selection. In 2013, Chen and Chen developed a method for analytically deriving the AFS for populations with temporally varying size through the coalescence time-scaling function. However, their approach is only applicable to population history scenarios in which the analytical form of the time-scaling function is tractable. In this paper, we propose a computational approach to extend the method to populations with arbitrary complex varying size by numerically approximating the time-scaling function. We demonstrate the performance of the approach by constructing the AFS for two population history scenarios: the logistic growth model and the Gompertz growth model, for which the AFS are unavailable with existing approaches. Software for implementing the algorithm can be downloaded at http://chenlab.big.ac.cn/software/.展开更多
目的探讨弥漫大B细胞淋巴瘤(Diffuse large B-cell lymphoma,DLBCL)中TP53基因状态与免疫微环境相关因子CD4蛋白、CD8蛋白、白细胞介素-6(IL-6)水平之间的相关性,以及与各临床病理参数的关系。方法收集174例DLBCL标本,制备组织芯片。应...目的探讨弥漫大B细胞淋巴瘤(Diffuse large B-cell lymphoma,DLBCL)中TP53基因状态与免疫微环境相关因子CD4蛋白、CD8蛋白、白细胞介素-6(IL-6)水平之间的相关性,以及与各临床病理参数的关系。方法收集174例DLBCL标本,制备组织芯片。应用荧光原位杂交(Fluorescence in situ hybridization,FISH)检测TP53等位基因缺失情况,免疫组织化学法检测p53、CD4、CD8蛋白表达情况。收集伴TP53等位基因缺失及未缺失DLBCL患者的血液标本各10例,电化学发光免疫分析法检测IL-6水平。结果TP53等位基因缺失率为21.8%(38/174)。p53蛋白总阳性率为40.8%(71/174)。CD4、CD8蛋白的阳性率分别为1.72%(3/174)、81.03%(141/174)。发生TP53等位基因缺失的病例p53、CD8蛋白的阳性率更高(P<0.05),血清IL-6均值水平也更高(P<0.05)。TP53等位基因缺失、结外侵犯、疾病复发是DLBCL的不良预后独立影响因素(P<0.05)。结论TP53等位基因缺失的DLBCL病例中p53、CD8蛋白阳性率较高,血清IL-6水平升高,总生存率降低,表明TP53等位基因缺失影响DLBCL免疫微环境,是不良预后因子,可能成为免疫检测和/或治疗靶点。展开更多
文摘Late stage colorectal carcinoma is very complicated in its molecular mechanisms. One hundred andnine cases of colorectal carcinomas were analyzed with RFLP method for the allelic deletion of chromosome 17short arms (ADCC17p) In this study. The results showed that frs(luency of allelic deletion of chromosome 17short arms (FADC17P) in Dukes’ D stage (95 % ) was higher than those in Dukes’ A, B. C stages (54% 68% ); Fisher’s exact test P <0. 01; FADC17p in colorectal carcinomas with distant metastasis (95 % ) washigher than those without distant metastasis, Fisher’s exact test P <0. 01 However, there were no significant differences in FADC 1 7p between the colorectal carcinomas with lymph node metastasis and those without lymph node metastasis (P >0. 05). Therefore, it is considered that ADC17p is an important diagnosticmarker of late stage colorectal carcinomas, and indicates a poor prognosis.
基金supported by the Center of Excellence on Agricultural Biotechnology,Science and Technology Postgraduate Education and Research Development Office,Office of Higher Education Commission,Ministry of Education(AG-BIO/PERDO-CHE)Agricultural Research Development Agency(ARDA)National Science and Technology Development Agency in Thailand
文摘A collection of 167 Thai and exotic rice accessions was subjected for evaluation of genetic diversity and assessment of relationship by simple sequence repeat (SSR) markers. Among a total of 49 SSR markers, 13 markers distributing over 12 rice chromosomes showed clear polymorphic band patterns, and they were selected for genetic assessment. A total of 110 alleles were detected with an average of 8.46 alleles per locus. The averages of gene diversity, heterozygosity and polymorphic information content were 0.59, 0.02 and 0.56, respectively. The unweighted-pair group method with arithmetic averages (UPGMA) clustering analysis was performed for genetic distance, and phylogenetic tree was constructed. The result showed that this rice collection was divided into two major groups, classified as japonica and indica subspecies. Within the japonica group, temperate japonica and tropical japonica subgroups can be clearly separated. Three-dimensional principal component analysis projection and model-based population structure analysis showed consistent clustering results with two major groups of UPGMA analysis, supporting the classification of japonica and indica subspecies. The indica allelic frequency was also investigated to provide an indicative guide for breeders to overcome the practical problems on sterility of inter-subspecies hybrid offspring. This rice collection and information obtained in this study will be useful for rice breeding programs.
基金Supported by Research Project from Education Department of Guangxi(200807MS065)Mathematical Modeling in Population Genetics from Talents Scheme of Universities in Guangxi~~
文摘This paper studies the offspring＇s genotype frequency of the selfing population on multiple alleles with limited loci.A recursive algorithm is given for it.It is discovered that the genotype frequency of homozygous gene of limited loci increases by generations.Relative increment reduces by generations and the genotype frequency tends to a definite value finally.The genotype frequency of limited loci with hybrid gene tends to 0 finally.But it is possibility that the genotype frequency increases in previous generations then reduces later.It is found that the number of the hybrid gene are more,the speeds tending to 0 are quicker.
基金supported by the National Natural Science Foundation of China(31201782,31672384 and 31372294)the Agricultural Science and Technology Innovation Program of Chinese Academy of Agricultural Sciences(ASTIPIAS03)+3 种基金the Cattle Breeding Innovative Research Team of Chinese Academy of Agricultural Sciences(cxgc-ias-03)the Key Technology R&D Program of China during the 12th Five-Year Plan period(2011BAD28B04)the National High Technology Research and Development Program of China(863 Program 2013AA102505-4)the Beijing Natural Science Foundation,China(6154032)
文摘Genomic selection has been demonstrated as a powerful technology to revolutionize animal breeding. However, marker density and minor allele frequency can affect the predictive ability of genomic estimated breeding values （GEBVs）. To investigate the impact of marker density and minor allele frequency on predictive ability, we estimated GEBVs by constructing the different subsets of single nucleotide polymorphisms （SNPs） based on varying markers densities and minor allele frequency （MAF） for average daily gain （ADG）, live weight （LW） and carcass weight （CW） in 1 059 Chinese Simmental beef cattle. Two strategies were proposed for SNP selection to construct different marker densities： 1） select evenly-spaced SNPs （Strategy 1 ）, and 2） select SNPs with large effects estimated from BayesB （Strategy 2）. Furthermore, predictive ability was assessed in terms of the correlation between predicted genomic values and corrected phenotypes from 10-fold cross-validation. Predictive ability for ADG, LW and CW using autosomal SNPs were 0.13＋0.002, 0.21＋0.003 and 0.25＋0.003, respectively. In our study, the predictive ability increased dramatically as more SNPs were included in analysis until 200K for Strategy 1. Under Strategy 2, we found the predictive ability slightly increased when marker densities increased from 5K to 20K, which indicated the predictive ability of 20K （3% of 770K） SNPs with large effects was equal to the predictive ability of using all SNPs. For different MAF bins, we obtained the highest predictive ability for three traits with MAF bin 0.01-0.1. Our result suggested that designing a low-density chip by selecting low frequency markers with large SNP effects sizes should be helpful for commercial application in Chinese Simmental cattle.
文摘Growth performance as well as marbling is the main breeding objectives in Japanese Black cattle, the major beef breed in Japan. A previous study has identified the c.1326T>G single nucleotide polymorphism (SNP) in the NCAPG (non-SMC condensin I complex, subunit G) gene that leads to the amino acid change p.Ile442Met in the NCAPG protein, which is a candidate causative variation for a bovine carcass weight (CWT) quantitative trait locus (QTL). In this study, we first confirmed the association of the c.1326T>G SNP with the growth-related traits, CWT, rib eye area (REA) and rib thickness (RT), and showed significant effect of the SNP genotypes on the marbling trait, beef marbling score (BMS), in the Japanese Black beef cattle population of the Niigata prefecture, with the G allele being associated with a favorable phenotype of these traits. Thus, we concluded that the c.1326T>G SNP is useful for effective marker-assisted selection to increase meat quality and meat productivity in Japanese Black beef cattle of the Niigata prefecture. Furthermore the frequency of the favorable G allele of the c.1326T>G SNP in the Niigata prefecture population was significantly lower than the frequency of this allele in Japanese Black cattle population of the Kagoshima prefecture. However, no statistically significant difference was detected between the allele frequencies estimated by maternal alleles in the half-sib progeny steers in the Niigata prefecture population and obtained in Japanese Black cattle population of the Kagoshima prefecture.
基金supported by grants from the National Natural Science Foundation of China(No.81802294)the Beijing Hope Run Special Fund of Cancer Foundation of the People's Republic of China(No.LC2019L04).
文摘Anaplastic lymphoma kinase(ALK)is the most common fusion gene involved in non-small cell lung cancer(NSCLC),and remarkable response has been achieved with the use of ALK tyrosine kinase inhibitors(ALK-TKIs).However,the clinical efficacy is highly variable.Pre-existing intratumoral heterogeneity(ITH)has been proven to contribute to the poor treatment response and the resistance to targeted therapies.In this work,we investigated whether the variant allele frequencies(VAFs)of ALK fusions can help assess ITH and predict targeted therapy efficacy.Through the application of next-generation sequencing(NGS),7.2%(326/4548)of patients were detected to be ALK positive.On the basis of the adjusted VAF(adjVAF,VAF normalization for tumor purity)of four different threshold values(adjVAF<50%,40%,30%,or 20%),the association of ALK subclonality with crizotinib efficacy was assessed.Nonetheless,no statistical association was observed between median progression-free survival(PFS)and ALK subclonality assessed by adjVAF,and a poor correlation of adjVAF with PFS was found among the 85 patients who received first-line crizotinib.Results suggest that the ALK VAF determined by hybrid capture-based NGS is probably unreliable for ITH assessment and targeted therapy efficacy prediction in NSCLC.
文摘New clinical approaches are imperative beyond the widely adopted National Comprehensive Cancer Network (NCCN) guidelines, utilized by prominent cancer institutions. Cancer is the leading cause of death among individuals younger than 85 years within the United States. Despite significant technological advances, including the expenditure of hundreds of billions, treatment outcomes and overall survival have not notably improved for most types of advanced cancer over the last several decades. Over the past 24 years, Envita Medical Centers has pioneered a unique form of personalized treatment approach for late-stage and refractory cancer patients, introducing groundbreaking innovations in the field. Our integrated algorithm utilizes advanced genomics, transcriptomics, and highly tailored immunotherapy, resulting in remarkable outcome improvements. This study presents Envita’s innovative personalized treatment algorithms and examines the response outcomes of 199 late-stage cancer patients treated at Envita Medical Centers over a two-year period. Compared to standard of care and palliative chemotherapy, Envita’s treatment demonstrated a remarkable 35-fold improvement in overall response rates (Figure 1). Moreover, 88% of the patients, the majority presenting with Stage 3 or 4 cancer, experienced a 43-fold improvement in quality of life with minimal side effects, as compared to standard of care chemotherapy and palliative care. This revolutionary success is attributed to Envita’s personalized therapeutic algorithms, which incorporate customized immunotherapy. Envita’s precision care approach has also achieved a 100% better response rate compared to over 65 global chemotherapy clinical trials with more than 2700 patients. The results from this study suggest that a wider utilization of Envita’s personalized approach can significantly benefit patients with late-stage and refractory cancer.
文摘X-linked redegreen color blindness is the most widespread form of vision impairment.The study aimed to determine the prevalence and gene frequencies of redegreen color vision impairments among children of six different human populations of Jammu province.A total of 1028 healthy subjects(6e15 years of age)were selected from five Muslim populations and the color vision impairments were determined using the Ishihara’s test of color deficiency.The gene frequency was calculated using HardyeWeinberg equilibrium method.The prevalence of color vision deficiency(CVD)ranged from 5.26%to 11.36%among males and 0.00%e3.03%among females of six different populations.The gender based differences in the frequency of CVD was found to be statistically significant(p<0.0001),with a higher prevalence among male(7.52%)as compared to female(0.83%)children.We observed high frequency of deutan as compared to protan defects.The incidences of deuteranomaly(5.68%)and deuteranopia(2.27%)were higher among male children of Syed population while the frequencies of protanomaly(1.94%),protanopia(1.28%)and achromacy(2.27%)were the highest among male subjects of Khan,Malik and Syed populations,respectively.The allele and genotype frequencies showed cogent differences among six populations.The population based assessment of CVDs help patients to follow adaptive strategies that could minimize the risks of the disease.
基金supported by the National Key Research and Development Program of China (2017YFD0101000, 2016YFD0101004)the National Natural Science Foundation of China (31771881, 31401468)the CAAS Innovation Team and the National Engineering Laboratory of Crop Molecular Breeding
文摘Knowledge of allelic frequencies at loci associated with kernel weight and effects on kernel weight-related traits is crucial for yield improvement in wheat. Kernel weight-related traits were evaluated in 200 Chinese winter wheat cultivars(lines) grown at the Xinxiang Experimental Station, Chinese Academy of Agricultural Sciences, Xinxiang in Henan Province, for three consecutive years from 2014 to 2016. Alleles associated with kernel weight at nine loci, TaCKX6-D1, TaCwi-A1, TaCWI-4A, TaGS1a, TaGS5-A1, TaGS3-3A, TaGW2-6A, TaSus2-2B, and TaTGW6-A1, were determined for all cultivars(lines). ANOVA showed that genotypes, years and their interactions had significant effects on thousand-kernel weight(TKW), kernel length(KL) and kernel width(KW). The overall mean frequencies of alleles conferring high and low TKW at the nine loci were 65.9% and 33.4%, with the ranges of 37.0%–85.0% and 13.5%–63.0% for single loci. The frequencies of high-TKW alleles were over 50.0% at eight of the loci. Genotypes at each locus with the high-TKW allele had higher TKW than those with the low-TKW allele. The high-TKW allele Hap-H at the TaSus2-2B locus can be preferably used to increase grain yield due to its high TKW(49.32 g). A total of 18 main allelic combinations(ACs) at nine loci were detected. Three ACs(AC1–AC3) had significantly higher TKW than AC6 with high-TKW alleles at all nine loci even though they contained some low-TKW alleles. This indicated that other loci controlling kernel weight were present in the high-TKW cultivars. This work provides important information for parental selection and marker-assisted selection for breeding.
文摘AIM: To estimate the frequency of microdeletions in the long arm of Y-chromosome of 20 infertile males from South India. METHODS: Polymerase chain reaction (PCR) amplification using Y-specific STS of azoospermia factor (AZF) regions i.e., SY 84 for AZFa, SY 127 for AZFb and SY 254 for AZFc. RESULTS: Of the 20 infertile subjects 3 (15 %), one azoospermic and two oligozoospermic, showed microdeletions in the AZF region of Y-chromosome. CONCLUSION: The frequency of deletions involving AZF region of the Y-chromosome is 15 % in azoospermic and severely oligozoospermic infertile men. PCR amplification of AZF locus is useful for the diagnosis of microdeletions in the Y-chromosome.
基金Supported by the Scientific Research Starting Foundation for Doctors, Henan Institute of Science and Technology of China
文摘To overcome the obstacle of the fascinating relation in predicting animal phenotype value, we have developed a neural network model to detect the complex non-linear relationships between the genotypes and phenotypes and the possible interactions that cannot be expressed with equations. In this paper, back-propagation neural network is used to discuss the influences of different allele frequencies on estimating the polygenic phenotype value. To ensure the precision of prediction, normalization was needed to train the prediction model. The results show that back-propagation artificial neural networks can be used to predict the phenotype value and perform very well in allele frequency from 0.2 to 0.8, when the allele frequency is very small （less than 0.2） or big （more than 0.8）; however, the prediction model was not reliable and the predicted value should be carefully tested.
基金supported by the National Natural Science Foundation of China(No.91231108)the Breakthrough Project of Strategic Priority Program of the Chinese Academy of Sciences(No.XDB13000000)+1 种基金the Key Research Program of the Chinese Academy of Sciencesthe Youth Innovation Promotion Association,Chinese Academy of Sciences(to GDW)
文摘Hypoxia represents one of the most extreme environmental conditions for both human beings and animals living at high al- titudes （Zhao et al., 2009）. Over the past few years, great attention has been focused on the genetic bases of adaption to high-altitude environments （Bigham et al., 2010; Simonson et al., 2010）. The domestic dog （Canisfamiliaris） is the first animal that developed an intimate relationship with human beings. Dogs migrated with human beings and have adapted to variety of ecological niches （Savolainen et al., 2002）. Our previous research revealed parallel evolution and convergent evolution in the adaptation of dogs and humans to the high-altitude environment of the Tibetan plateau （Wang et al., 2013, 2014）, suggesting that exploring the adaption of domestic dogs to high-altitude hypoxia is an interesting and important question.
基金supported by the National Natural Science Foundation of China(Grant Nos.91731302,31571370,and91631106)the National Key R&D Program of China(Grant No.2018YFC1406902)+2 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences(Grant No.XDB13000000)Shanghai Municipal Science and Technology Major Project(Grant No.2017SHZDZX01)the “100-Talent” Program of the Chinese Academy of Sciences,China.
文摘The allele frequency spectrum(AFS), or site frequency spectrum, is commonly used to summarize the genomic polymorphism pattern of a sample, which is informative for inferring population history and detecting natural selection. In 2013, Chen and Chen developed a method for analytically deriving the AFS for populations with temporally varying size through the coalescence time-scaling function. However, their approach is only applicable to population history scenarios in which the analytical form of the time-scaling function is tractable. In this paper, we propose a computational approach to extend the method to populations with arbitrary complex varying size by numerically approximating the time-scaling function. We demonstrate the performance of the approach by constructing the AFS for two population history scenarios: the logistic growth model and the Gompertz growth model, for which the AFS are unavailable with existing approaches. Software for implementing the algorithm can be downloaded at http://chenlab.big.ac.cn/software/.
文摘目的探讨弥漫大B细胞淋巴瘤(Diffuse large B-cell lymphoma,DLBCL)中TP53基因状态与免疫微环境相关因子CD4蛋白、CD8蛋白、白细胞介素-6(IL-6)水平之间的相关性,以及与各临床病理参数的关系。方法收集174例DLBCL标本,制备组织芯片。应用荧光原位杂交(Fluorescence in situ hybridization,FISH)检测TP53等位基因缺失情况,免疫组织化学法检测p53、CD4、CD8蛋白表达情况。收集伴TP53等位基因缺失及未缺失DLBCL患者的血液标本各10例,电化学发光免疫分析法检测IL-6水平。结果TP53等位基因缺失率为21.8%(38/174)。p53蛋白总阳性率为40.8%(71/174)。CD4、CD8蛋白的阳性率分别为1.72%(3/174)、81.03%(141/174)。发生TP53等位基因缺失的病例p53、CD8蛋白的阳性率更高(P<0.05),血清IL-6均值水平也更高(P<0.05)。TP53等位基因缺失、结外侵犯、疾病复发是DLBCL的不良预后独立影响因素(P<0.05)。结论TP53等位基因缺失的DLBCL病例中p53、CD8蛋白阳性率较高,血清IL-6水平升高,总生存率降低,表明TP53等位基因缺失影响DLBCL免疫微环境,是不良预后因子,可能成为免疫检测和/或治疗靶点。
