BACKGROUND Recent evidence shows that long non-coding RNAs(lncRNAs) are closely related to hepatogenesis and a few aggressive features of hepatocellular carcinoma(HCC). Increasing studies demonstrate that lncRNAs are ...BACKGROUND Recent evidence shows that long non-coding RNAs(lncRNAs) are closely related to hepatogenesis and a few aggressive features of hepatocellular carcinoma(HCC). Increasing studies demonstrate that lncRNAs are potential prognostic factors for HCC. Moreover, several studies reported the combination of lncRNAs for predicting the overall survival(OS) of HCC, but the results varied. Thus,more effort including more accurate statistical approaches is needed for exploring the prognostic value of lncRNAs in HCC.AIM To develop a robust lncRNA signature associated with HCC recurrence to improve prognosis prediction of HCC.METHODS Univariate COX regression analysis was performed to screen the lncRNAs significantly associated with recurrence-free survival(RFS) of HCC in GSE76427 for the least absolute shrinkage and selection operator(LASSO) modelling. The established lncRNA signature was validated and developed in The Cancer Genome Atlas(TCGA) series using Kaplan-Meier curves. The expression values of the identified lncRNAs were compared between the tumor and non-tumor tissues. Pathway enrichment of these lncRNAs was conducted based on the significantly co-expressed genes. A prognostic nomogram combining the lncRNA signature and clinical characteristics was constructed.RESULTS The lncRNA signature consisted of six lncRNAs: MSC-AS1, POLR2 J4, EIF3 J-AS1,SERHL, RMST, and PVT1. This risk model was significantly associated with the RFS of HCC in the TCGA cohort with a hazard ratio(HR) being 1.807(95%CI[confidence interval]: 1.329-2.457) and log-rank P-value being less than 0.001. The best candidates of the six-lncRNA signature were younger male patients with HBV infection in relatively early tumor-stage and better physical condition but with higher preoperative alpha-fetoprotein. All the lncRNAs were significantly upregulated in tumor samples compared to non-tumor samples(P < 0.05). The most significantly enriched pathways of the lncRNAs were TGF-β signaling pathway, cellular apoptosis-associated pathways, etc. The nomog展开更多
The phenotypic diversity resulting from artificial or natural selection of sheep has made a significant contribution to human civilization.Hu sheep are a local sheep breed unique to China with high reproductive rates ...The phenotypic diversity resulting from artificial or natural selection of sheep has made a significant contribution to human civilization.Hu sheep are a local sheep breed unique to China with high reproductive rates and rapid growth.Genomic selection signatures have been widely used to investigate the genetic mechanisms underlying phenotypic variation in livestock.Here,we conduct whole-genome sequencing of 207 Hu sheep and compare them with the wild ancestors of domestic sheep(Asiatic mouflon)to investigate the genetic characteristics and selection signatures of Hu sheep.Based on six signatures of selection approaches,we detect genomic regions containing genes related to reproduction(BMPR1B,BMP2,PGFS,CYP19,CAMK4,GGT5,and GNAQ),vision(ALDH1A2,SAG,and PDE6B),nervous system(NAV1),and immune response(GPR35,SH2B2,PIK3R3,and HRAS).Association analysis with a population of 1299 Hu sheep reveals that those missense mutations in the GPR35(GPR35 g.952651 A>G;GPR35 g.952496 C>T)and NAV1(NAV1 g.84216190 C>T;NAV1 g.84227412 G>A)genes are significantly associated(P<0.05)with immune and growth traits in Hu sheep,respectively.This research offers unique insights into the selection characteristics of Hu sheep and facilitates further genetic improvement and molecular investigations.展开更多
BACKGROUND Hepatitis B virus,together with hepatitis C virus,has been recognized as the leading causes of hepatocellular carcinoma(HCC).Long non-coding RNAs(lncRNAs)have been suggested in increasing studies to be the ...BACKGROUND Hepatitis B virus,together with hepatitis C virus,has been recognized as the leading causes of hepatocellular carcinoma(HCC).Long non-coding RNAs(lncRNAs)have been suggested in increasing studies to be the potential prognostic factors for HCC.However,the role of combined application of lncRNAs in estimating overall survival(OS)for hepatitis virus positive HCC(VHCC)is uncertain.AIM To construct an lncRNA signature related to the OS of VHCC patients to enhance the accuracy of prognosis prediction.METHODS The expression patterns of lncRNAs,as well as related clinical data were collected from 149 VHCC patients from The Cancer Genome Atlas database.The R package was adopted to obtain the differentially expressed lncRNAs(DElncRNAs).LncRNAs significantly associated with OS were screened by means of univariate Cox regression analysis,so as to construct a least absolute shrinkage and selection operator(LASSO)model.Subsequently,the constructed lncRNA signature was developed and validated.Afterwards,the prognostic nomogram was established,which combined the as-established lncRNA signature as well as the clinical features.Meanwhile,subgroup analysis stratified by the virus type was also performed.Finally,the above-mentioned lncRNAs were enriched to corresponding pathways according to the markedly coexpressed genes.RESULTS A total of 1420 DElncRNAs were identified,among which 406 were significant in univariate Cox regression analysis.LASSO regression confirmed 8 out of the 406 lncRNAs,including AC005722.2,AC107959.3,AL353803.1,AL589182.1,AP000844.2,AP002478.1,FLJ36000,and NPSR1-AS1.Then,the prognostic risk score was calculated.Our results displayed a significant association between the risk model and the OS of VHCC[hazard ratio=1.94,95%confidence interval(CI):1.61-2.34,log-rank P=2e-10].The inference tree suggested that the established lncRNA signature was useful in the risk stratification of VHCC.Furthermore,a nomogram was plotted,and the concordance index of internal validation was 0.763(95%CI:0.700-0.826).Moreov展开更多
We performed a genome-wide scan to detect selection signatures that showed evidence of positive selection in the domestication process by re-sequencing the whole genomes of Landrace and Yorkshire pigs.Fifteen annotate...We performed a genome-wide scan to detect selection signatures that showed evidence of positive selection in the domestication process by re-sequencing the whole genomes of Landrace and Yorkshire pigs.Fifteen annotated elements with 13 associated genes were identified using the Z-transformed FST(Z(FST))method,and 208 annotated elements with 140 associated genes were identified using the Z-transformed heterozygosity(ZHp)method.The functional analysis and the results of previous studies showed that most of the candidate genes were associated with basic metabolism,disease resistance,cellular processes,and biochemical signals,and several were related to body morphology and organs.They included PPP3CA,which plays an essential role in the transduction of intracellular Ca2+-mediated signals,and WWTR1,which plays a pivotal role in organ size control and tumor suppression.These results suggest that genes associated with body morphology were subject to selection pressure during domestication,whereas genes involved in basic metabolism and disease resistance were subject to selection during artificial breeding.Our findings provide new insights into the potential genetic variation of phenotypic diversity in different pig breeds and will help to better understand the selection effects of modern breeding in Landrace and Yorkshire pigs.展开更多
The abundance of domesticated sheep varieties and phenotypes is largely the result of long-term natural and artificial selection. However, there is limited information regarding the genetic mechanisms underlying pheno...The abundance of domesticated sheep varieties and phenotypes is largely the result of long-term natural and artificial selection. However, there is limited information regarding the genetic mechanisms underlying phenotypic variation induced by the domestication and improvement of sheep. In this study, to explore genomic diversity and selective regions at the genome level, we sequenced the genomes of 100 sheep across 10 breeds and combined these results with publicly available genomic data from 225 individuals, including improved breeds, Chinese indigenous breeds,African indigenous breeds, and their Asian mouflon ancestor. Based on population structure, the domesticated sheep formed a monophyletic group,while the Chinese indigenous sheep showed a clear geographical distribution trend. Comparative genomic analysis of domestication identified several selective signatures, including IFI44 and IFI44L genes and PANK2 and RNF24 genes, associated with immune response and visual function.Population genomic analysis of improvement demonstrated that candidate genes of selected regions were mainly associated with pigmentation,energy metabolism, and growth development.Furthermore, the IFI44 and IFI44L genes showed a common selection signature in the genomes of 30domesticated sheep breeds. The IFI44 c. 54413058C>G mutation was selected for genotyping and population genetic validation. Results showed that the IFI44 polymorphism was significantly associated with partial immune traits. Our findings identified the population genetic basis of domesticated sheep at the whole-genome level, providing theoretical insights into the molecular mechanism underlying breed characteristics and phenotypic changes during sheep domestication and improvement.展开更多
Wild castor grows in the high-altitude tropical desert of the African Plateau,a region known for high ultraviolet radiation,strong light,and extremely dry condition.To investigate the potential genetic basis of adapta...Wild castor grows in the high-altitude tropical desert of the African Plateau,a region known for high ultraviolet radiation,strong light,and extremely dry condition.To investigate the potential genetic basis of adaptation to both highland and tropical deserts,we generated a chromosome-level genome sequence assembly of the wild castor accession WT05,with a genome size of 316 Mb,a scaffold N50 of 31.93 Mb,and a contig N50 of 8.96 Mb,respectively.Compared with cultivated castor and other Euphorbiaceae species,the wild castor exhibits positive selection and gene family expansion for genes involved in DNA repair,photosynthesis,and abiotic stress responses.Genetic variations associated with positive selection were identified in several key genes,such as LIG1,DDB2,and RECG1,involved in nucleotide excision repair.Moreover,a study of genomic diversity among wild and cultivated accessions revealed genomic regions containing selection signatures associated with the adaptation to extreme environments.The identification of the genes and alleles with selection signatures provides insights into the genetic mechanisms underlying the adaptation of wild castor to the high-altitude tropical desert and would facilitate direct improvement of modern castor varieties.展开更多
Identifying targets of positive selection in farm animals has, until recently, been frustratingly slow, relying on the analysis of individual candidate genes. Genomics, however, has provided the necessary resources to...Identifying targets of positive selection in farm animals has, until recently, been frustratingly slow, relying on the analysis of individual candidate genes. Genomics, however, has provided the necessary resources to systematically interrogate the entire genome for signatures of selection. This review described important recent results derived from the application of genome-wide scan to the study of genetic changes in farm animals. These included findings of regions of the genome that showed breed differentiation, evidence of selective sweeps within individual genomes and signatures of demographic events. Particular attention is focused on the study of the implications for domestication. To date, sixteen genome-wide scans for recent or ongoing positive selection have been performed in farm animals. A key challenge is to begin synthesizing these newly constructed maps of selection into a coherent narrative of animal breed evolutionary history and derive a deeper mechanistic understanding of how animal populations improve or evolve. The major insights from the surveyed studies are highlighted and directions for future study are suggested.展开更多
Personalized medicine is critical for lung cancer treatment. Different gene signatures that can classify lung cancer patients as high- or low-risk for cancer recurrence have been found. The aim of this study is to ide...Personalized medicine is critical for lung cancer treatment. Different gene signatures that can classify lung cancer patients as high- or low-risk for cancer recurrence have been found. The aim of this study is to identify a novel gene signature that has higher recurrence risk prediction accuracy for non-small cell lung cancer patients than previous re-search, which can clearly differentiate the high- and low-risk groups. To accomplish this we employed an ensemble of feature selection algorithms, an ensemble of classification algorithms, and a genetic algorithm, an evolutionary search algorithm. Compared to one previous study, our 12-gene signature more accurately classifies the patients in the training set (n = 256), 57.32% compared to 50.78%, as well as in the two test sets (n = 104 and n = 82), 67.07% compared to 54.9% and 57.32% compared to 54.8%;where the prediction accuracy was determined by the average of the four classifiers. Through Kaplan-Meier analysis on high- and low-risk patients our 12-gene signature revealed statistically significant risk differentiation in each data set: the training set had a p-value less than 0.001 (log-rank) and the two test sets had (log-rank) p-values less than 0.05. Analysis of the posterior probabilities revealed strong correlation between 5-year survival and the 12-gene signature. Also, functional pathway analysis uncovered associations between the 12-gene signature and cancer causing genes in the literature.展开更多
To track the selection evident along the genome segment of OsLEA27?gene, a member of dehydrin gene family, 2.9-kbp nucleotide sequence containing the promoter 5’ upstream and transcribed region of OsLEA27?was determi...To track the selection evident along the genome segment of OsLEA27?gene, a member of dehydrin gene family, 2.9-kbp nucleotide sequence containing the promoter 5’ upstream and transcribed region of OsLEA27?was determined for 35 upland and dryland Myanmar landraces from drought-prone areas. Nucleotide diversity, neutrality tests, haplotype network analysis, and linkage disequilibrium (LD) analysis were performed to infer the impact of selection and to investigate nonrandom associations of SNPs within all or part of the entire OsLEA27?region. The evidence for LD, the presence of two distinct haplotype groups across four different geographical regions, and the significant values obtained in a sliding-window analysis of mutation-drift tests all suggest the effects of selection on OsLEA27?in a set of 30 landraces. The neutrality test values for 5’ upstream region of OsLEA27?were significantly negative (p OsLEA27 region was significantly negative in accessions of the northern group, indicating a recent increase in population size or selection pressure. This evidence for selection signatures at OsLEA27 in this study sample provides insight into the roles of selection, crop adaptation, and genetic diversity in establishing present-day variation at the OsLEA27 locus.展开更多
Improving the production of broiler chicken meat has been a goal of broiler breeding programs worldwide for many years. However, the genetic architectures of skeletal muscle production traits in chickens have not yet ...Improving the production of broiler chicken meat has been a goal of broiler breeding programs worldwide for many years. However, the genetic architectures of skeletal muscle production traits in chickens have not yet been fully elucidated. In the present study, a total of 519 F_(2) birds, derived from a cross of Arbor Acres broiler and Baier layer, were re-sequenced(26 F_(0) individuals were re-sequenced at a 10-fold depth;519 F_(2) individuals were re-sequenced at a 3-fold depth) and the coupling of genome-wide association study(GWAS) and selection signatures(FST(fixation index) and θπ(nucleotide diversity)) was carried out to pinpoint the associated loci and genes that contribute to pectoral muscle weight(PMW) and thigh muscle weight(TMW). A total of 7 890 258 single nucleotide polymorphisms(SNPs) remained to be analyzed after quality control and imputation. The integration of GWAS and selection signature analyses revealed that genetic determinants responsible for skeletal muscle production traits were mainly localized on chromosomes 1(168.95–172.43 Mb) and 4(74.37–75.23 Mb). A total of 17 positional candidate genes(PCGs)(LRCH1, CDADC1, CAB39 L, LOC112531568, LOC112531569, FAM124 A, FOXO1, NBEA, GPALPP1, RUBCNL, ARL11, KPNA3, LHFP, GBA3, LOC112532426, KCNIP4, and SLIT2) were identified in these regions. In particular, KPNA3 and FOXO1 were the most promising candidates for meat production in chickens. These findings will help enhance our understanding of the genetic architecture of chicken muscle production traits, and the significant SNPs identified could be promising candidates for integration into practical breeding programs such as genome-wide selection(GS) to improve the meat yield of chickens.展开更多
基金Supported by The National Natural Science Foundation of China,No.81773128 and No.81871998the Natural Science Basic Research Plan in Shaanxi Province of China,No.2017JM8039+1 种基金China Postdoctoral Science Foundation,No.2018m641000Research Fund for Young Star of Science and Technology in Shaanxi Province,No.2018KJXX-022
文摘BACKGROUND Recent evidence shows that long non-coding RNAs(lncRNAs) are closely related to hepatogenesis and a few aggressive features of hepatocellular carcinoma(HCC). Increasing studies demonstrate that lncRNAs are potential prognostic factors for HCC. Moreover, several studies reported the combination of lncRNAs for predicting the overall survival(OS) of HCC, but the results varied. Thus,more effort including more accurate statistical approaches is needed for exploring the prognostic value of lncRNAs in HCC.AIM To develop a robust lncRNA signature associated with HCC recurrence to improve prognosis prediction of HCC.METHODS Univariate COX regression analysis was performed to screen the lncRNAs significantly associated with recurrence-free survival(RFS) of HCC in GSE76427 for the least absolute shrinkage and selection operator(LASSO) modelling. The established lncRNA signature was validated and developed in The Cancer Genome Atlas(TCGA) series using Kaplan-Meier curves. The expression values of the identified lncRNAs were compared between the tumor and non-tumor tissues. Pathway enrichment of these lncRNAs was conducted based on the significantly co-expressed genes. A prognostic nomogram combining the lncRNA signature and clinical characteristics was constructed.RESULTS The lncRNA signature consisted of six lncRNAs: MSC-AS1, POLR2 J4, EIF3 J-AS1,SERHL, RMST, and PVT1. This risk model was significantly associated with the RFS of HCC in the TCGA cohort with a hazard ratio(HR) being 1.807(95%CI[confidence interval]: 1.329-2.457) and log-rank P-value being less than 0.001. The best candidates of the six-lncRNA signature were younger male patients with HBV infection in relatively early tumor-stage and better physical condition but with higher preoperative alpha-fetoprotein. All the lncRNAs were significantly upregulated in tumor samples compared to non-tumor samples(P < 0.05). The most significantly enriched pathways of the lncRNAs were TGF-β signaling pathway, cellular apoptosis-associated pathways, etc. The nomog
基金supported by the National Key Research and Development Program of China(2021YFD1300901,2022YFD1302000)National Natural Science Foundation of China(32260818,31960653)。
文摘The phenotypic diversity resulting from artificial or natural selection of sheep has made a significant contribution to human civilization.Hu sheep are a local sheep breed unique to China with high reproductive rates and rapid growth.Genomic selection signatures have been widely used to investigate the genetic mechanisms underlying phenotypic variation in livestock.Here,we conduct whole-genome sequencing of 207 Hu sheep and compare them with the wild ancestors of domestic sheep(Asiatic mouflon)to investigate the genetic characteristics and selection signatures of Hu sheep.Based on six signatures of selection approaches,we detect genomic regions containing genes related to reproduction(BMPR1B,BMP2,PGFS,CYP19,CAMK4,GGT5,and GNAQ),vision(ALDH1A2,SAG,and PDE6B),nervous system(NAV1),and immune response(GPR35,SH2B2,PIK3R3,and HRAS).Association analysis with a population of 1299 Hu sheep reveals that those missense mutations in the GPR35(GPR35 g.952651 A>G;GPR35 g.952496 C>T)and NAV1(NAV1 g.84216190 C>T;NAV1 g.84227412 G>A)genes are significantly associated(P<0.05)with immune and growth traits in Hu sheep,respectively.This research offers unique insights into the selection characteristics of Hu sheep and facilitates further genetic improvement and molecular investigations.
文摘BACKGROUND Hepatitis B virus,together with hepatitis C virus,has been recognized as the leading causes of hepatocellular carcinoma(HCC).Long non-coding RNAs(lncRNAs)have been suggested in increasing studies to be the potential prognostic factors for HCC.However,the role of combined application of lncRNAs in estimating overall survival(OS)for hepatitis virus positive HCC(VHCC)is uncertain.AIM To construct an lncRNA signature related to the OS of VHCC patients to enhance the accuracy of prognosis prediction.METHODS The expression patterns of lncRNAs,as well as related clinical data were collected from 149 VHCC patients from The Cancer Genome Atlas database.The R package was adopted to obtain the differentially expressed lncRNAs(DElncRNAs).LncRNAs significantly associated with OS were screened by means of univariate Cox regression analysis,so as to construct a least absolute shrinkage and selection operator(LASSO)model.Subsequently,the constructed lncRNA signature was developed and validated.Afterwards,the prognostic nomogram was established,which combined the as-established lncRNA signature as well as the clinical features.Meanwhile,subgroup analysis stratified by the virus type was also performed.Finally,the above-mentioned lncRNAs were enriched to corresponding pathways according to the markedly coexpressed genes.RESULTS A total of 1420 DElncRNAs were identified,among which 406 were significant in univariate Cox regression analysis.LASSO regression confirmed 8 out of the 406 lncRNAs,including AC005722.2,AC107959.3,AL353803.1,AL589182.1,AP000844.2,AP002478.1,FLJ36000,and NPSR1-AS1.Then,the prognostic risk score was calculated.Our results displayed a significant association between the risk model and the OS of VHCC[hazard ratio=1.94,95%confidence interval(CI):1.61-2.34,log-rank P=2e-10].The inference tree suggested that the established lncRNA signature was useful in the risk stratification of VHCC.Furthermore,a nomogram was plotted,and the concordance index of internal validation was 0.763(95%CI:0.700-0.826).Moreov
基金supported by the grants from the Sichuan Science and Technology Program,China(2020YFN0024)the earmarked fund for the China Agriculture Research System(CARS-35-01A)+2 种基金the National Key R&D Program of China(2018YFD0501204)the National Natural Science Foundation of China(C170102)the Sichuan Innovation Team of Pig,China(sccxtd-2021-08)。
文摘We performed a genome-wide scan to detect selection signatures that showed evidence of positive selection in the domestication process by re-sequencing the whole genomes of Landrace and Yorkshire pigs.Fifteen annotated elements with 13 associated genes were identified using the Z-transformed FST(Z(FST))method,and 208 annotated elements with 140 associated genes were identified using the Z-transformed heterozygosity(ZHp)method.The functional analysis and the results of previous studies showed that most of the candidate genes were associated with basic metabolism,disease resistance,cellular processes,and biochemical signals,and several were related to body morphology and organs.They included PPP3CA,which plays an essential role in the transduction of intracellular Ca2+-mediated signals,and WWTR1,which plays a pivotal role in organ size control and tumor suppression.These results suggest that genes associated with body morphology were subject to selection pressure during domestication,whereas genes involved in basic metabolism and disease resistance were subject to selection during artificial breeding.Our findings provide new insights into the potential genetic variation of phenotypic diversity in different pig breeds and will help to better understand the selection effects of modern breeding in Landrace and Yorkshire pigs.
基金supported by the National Key R&D Program of China (2021YFD1300901)National Natural Science Foundation of China (31960653)+1 种基金West Light Foundation of the Chinese Academy of SciencesNational Joint Research on Improved Breeds of Livestock and Poultry (19210365)。
文摘The abundance of domesticated sheep varieties and phenotypes is largely the result of long-term natural and artificial selection. However, there is limited information regarding the genetic mechanisms underlying phenotypic variation induced by the domestication and improvement of sheep. In this study, to explore genomic diversity and selective regions at the genome level, we sequenced the genomes of 100 sheep across 10 breeds and combined these results with publicly available genomic data from 225 individuals, including improved breeds, Chinese indigenous breeds,African indigenous breeds, and their Asian mouflon ancestor. Based on population structure, the domesticated sheep formed a monophyletic group,while the Chinese indigenous sheep showed a clear geographical distribution trend. Comparative genomic analysis of domestication identified several selective signatures, including IFI44 and IFI44L genes and PANK2 and RNF24 genes, associated with immune response and visual function.Population genomic analysis of improvement demonstrated that candidate genes of selected regions were mainly associated with pigmentation,energy metabolism, and growth development.Furthermore, the IFI44 and IFI44L genes showed a common selection signature in the genomes of 30domesticated sheep breeds. The IFI44 c. 54413058C>G mutation was selected for genotyping and population genetic validation. Results showed that the IFI44 polymorphism was significantly associated with partial immune traits. Our findings identified the population genetic basis of domesticated sheep at the whole-genome level, providing theoretical insights into the molecular mechanism underlying breed characteristics and phenotypic changes during sheep domestication and improvement.
基金supported by the National Key R&D Program of China(Grant No.2018YFA0901800)the National Natural Science Foundation of China(Grant No.32072101)+1 种基金the Guangdong Basic and Applied Basic Research Foundation,China(Grant No.2019A1515111150)the Shenzhen Science and Technology Program,China(Grant No.KQTD20180411143628272)。
文摘Wild castor grows in the high-altitude tropical desert of the African Plateau,a region known for high ultraviolet radiation,strong light,and extremely dry condition.To investigate the potential genetic basis of adaptation to both highland and tropical deserts,we generated a chromosome-level genome sequence assembly of the wild castor accession WT05,with a genome size of 316 Mb,a scaffold N50 of 31.93 Mb,and a contig N50 of 8.96 Mb,respectively.Compared with cultivated castor and other Euphorbiaceae species,the wild castor exhibits positive selection and gene family expansion for genes involved in DNA repair,photosynthesis,and abiotic stress responses.Genetic variations associated with positive selection were identified in several key genes,such as LIG1,DDB2,and RECG1,involved in nucleotide excision repair.Moreover,a study of genomic diversity among wild and cultivated accessions revealed genomic regions containing selection signatures associated with the adaptation to extreme environments.The identification of the genes and alleles with selection signatures provides insights into the genetic mechanisms underlying the adaptation of wild castor to the high-altitude tropical desert and would facilitate direct improvement of modern castor varieties.
基金Support for this work was provided by the Inner Mongolia Autonomous Region(2010ZD11)the National Natural Science Foundation of China(30960246,31260538)the Key Projects in the National Science&Technology Pillar Program(30960242011BAD28B05)
文摘Identifying targets of positive selection in farm animals has, until recently, been frustratingly slow, relying on the analysis of individual candidate genes. Genomics, however, has provided the necessary resources to systematically interrogate the entire genome for signatures of selection. This review described important recent results derived from the application of genome-wide scan to the study of genetic changes in farm animals. These included findings of regions of the genome that showed breed differentiation, evidence of selective sweeps within individual genomes and signatures of demographic events. Particular attention is focused on the study of the implications for domestication. To date, sixteen genome-wide scans for recent or ongoing positive selection have been performed in farm animals. A key challenge is to begin synthesizing these newly constructed maps of selection into a coherent narrative of animal breed evolutionary history and derive a deeper mechanistic understanding of how animal populations improve or evolve. The major insights from the surveyed studies are highlighted and directions for future study are suggested.
文摘Personalized medicine is critical for lung cancer treatment. Different gene signatures that can classify lung cancer patients as high- or low-risk for cancer recurrence have been found. The aim of this study is to identify a novel gene signature that has higher recurrence risk prediction accuracy for non-small cell lung cancer patients than previous re-search, which can clearly differentiate the high- and low-risk groups. To accomplish this we employed an ensemble of feature selection algorithms, an ensemble of classification algorithms, and a genetic algorithm, an evolutionary search algorithm. Compared to one previous study, our 12-gene signature more accurately classifies the patients in the training set (n = 256), 57.32% compared to 50.78%, as well as in the two test sets (n = 104 and n = 82), 67.07% compared to 54.9% and 57.32% compared to 54.8%;where the prediction accuracy was determined by the average of the four classifiers. Through Kaplan-Meier analysis on high- and low-risk patients our 12-gene signature revealed statistically significant risk differentiation in each data set: the training set had a p-value less than 0.001 (log-rank) and the two test sets had (log-rank) p-values less than 0.05. Analysis of the posterior probabilities revealed strong correlation between 5-year survival and the 12-gene signature. Also, functional pathway analysis uncovered associations between the 12-gene signature and cancer causing genes in the literature.
文摘To track the selection evident along the genome segment of OsLEA27?gene, a member of dehydrin gene family, 2.9-kbp nucleotide sequence containing the promoter 5’ upstream and transcribed region of OsLEA27?was determined for 35 upland and dryland Myanmar landraces from drought-prone areas. Nucleotide diversity, neutrality tests, haplotype network analysis, and linkage disequilibrium (LD) analysis were performed to infer the impact of selection and to investigate nonrandom associations of SNPs within all or part of the entire OsLEA27?region. The evidence for LD, the presence of two distinct haplotype groups across four different geographical regions, and the significant values obtained in a sliding-window analysis of mutation-drift tests all suggest the effects of selection on OsLEA27?in a set of 30 landraces. The neutrality test values for 5’ upstream region of OsLEA27?were significantly negative (p OsLEA27 region was significantly negative in accessions of the northern group, indicating a recent increase in population size or selection pressure. This evidence for selection signatures at OsLEA27 in this study sample provides insight into the roles of selection, crop adaptation, and genetic diversity in establishing present-day variation at the OsLEA27 locus.
基金supported by the National Natural Science Foundation of China(31572394)the China Agriculture Research System of MOF and MARA(CARS-41)the White Feather Broiler Breeding Joint Project of the Ministry of Agriculture and Rural Affairs of China(19190526)。
文摘Improving the production of broiler chicken meat has been a goal of broiler breeding programs worldwide for many years. However, the genetic architectures of skeletal muscle production traits in chickens have not yet been fully elucidated. In the present study, a total of 519 F_(2) birds, derived from a cross of Arbor Acres broiler and Baier layer, were re-sequenced(26 F_(0) individuals were re-sequenced at a 10-fold depth;519 F_(2) individuals were re-sequenced at a 3-fold depth) and the coupling of genome-wide association study(GWAS) and selection signatures(FST(fixation index) and θπ(nucleotide diversity)) was carried out to pinpoint the associated loci and genes that contribute to pectoral muscle weight(PMW) and thigh muscle weight(TMW). A total of 7 890 258 single nucleotide polymorphisms(SNPs) remained to be analyzed after quality control and imputation. The integration of GWAS and selection signature analyses revealed that genetic determinants responsible for skeletal muscle production traits were mainly localized on chromosomes 1(168.95–172.43 Mb) and 4(74.37–75.23 Mb). A total of 17 positional candidate genes(PCGs)(LRCH1, CDADC1, CAB39 L, LOC112531568, LOC112531569, FAM124 A, FOXO1, NBEA, GPALPP1, RUBCNL, ARL11, KPNA3, LHFP, GBA3, LOC112532426, KCNIP4, and SLIT2) were identified in these regions. In particular, KPNA3 and FOXO1 were the most promising candidates for meat production in chickens. These findings will help enhance our understanding of the genetic architecture of chicken muscle production traits, and the significant SNPs identified could be promising candidates for integration into practical breeding programs such as genome-wide selection(GS) to improve the meat yield of chickens.
