Haplotypic information in diploid organisms provides valuable information on human evolutionary history and plays an important role in identifying a candidate gene in the etiology of complex genetic diseases. However,...Haplotypic information in diploid organisms provides valuable information on human evolutionary history and plays an important role in identifying a candidate gene in the etiology of complex genetic diseases. However, haplotypes of diploid individuals cannot be acquired easily. Molecular haplotyping methods are very costly and have low throughput, and current genotyping and sequenc- ing methods do not provide information on the linkage phase in diploid organisms. The application of statistical methods to infer the haplotype phase in samples of diploid sequences is a very cost-effective approach.展开更多
In multiloci-based genetic association studies of complex diseases, a powerful and high efficient tool for analyses oflinkage disequilibrium (LD) between markers, haplotype distributions and many chi-square/p values w...In multiloci-based genetic association studies of complex diseases, a powerful and high efficient tool for analyses oflinkage disequilibrium (LD) between markers, haplotype distributions and many chi-square/p values with a large numberof samples has been sought for long. In order to achieve the goal of obtaining meaningful results directly from raw data,we developed a robust and user-friendly software platform with a series of tools for analysis in association study withhigh efficiency. The platform has been well evaluated by several sets of real data.展开更多
Microsporogenesis and male gametogenesis are essential for the alternating life cycle of flowering plants between diploid sporophyte and haploid gametophyte generations. Rice （Oryza sativa） is the world＇s major sta...Microsporogenesis and male gametogenesis are essential for the alternating life cycle of flowering plants between diploid sporophyte and haploid gametophyte generations. Rice （Oryza sativa） is the world＇s major staple food, and manipulation of pollen fertility is particularly important for the demands to increase rice grain yield. Towards a better understanding of the mechanisms controlling rice male reproductive development, we describe here the cytological changes of anther development through 14 stages, including cell division, differentiation and degeneration of somatic tissues consisting of four concentric cell layers surrounding and supporting reproductive cells as they form mature pollen grains through meiosis and mitosis. Furthermore, we compare the morphological difference of anthers and pollen grains in both monocot rice and eudicot Arabidopsis thaliana. Additionally, we describe the key genes identified to date critical for rice anther development and pollen formation.展开更多
Dear Editor, Identification of Drosophila melanogaster as a model organism for cancer research has facilitated the exploration of human tumor malignancy. In Drosophila, loss- of-function mutations in the neoplastic t...Dear Editor, Identification of Drosophila melanogaster as a model organism for cancer research has facilitated the exploration of human tumor malignancy. In Drosophila, loss- of-function mutations in the neoplastic tumor suppressor genes （nYSGs） lethal（2）giant larvae （lgl）, discs large （dlg） or scribble （scrib） cause a malignant tumor-like phenotype characteristic of disrupted cell polarity and overgrowth in epithelial tissues such as imaginal discs [1 ].展开更多
The Hedgehog （Hh） family of secreted signaling proteins plays a critical role in regulating the development of several tissues and organ systems. The ability of Hh proteins to exert their biological effects is regul...The Hedgehog （Hh） family of secreted signaling proteins plays a critical role in regulating the development of several tissues and organ systems. The ability of Hh proteins to exert their biological effects is regulated by a series of post-translational processes. These processes include an intramolecular cleavage, covalent addition of cholesterol and/or palmitate, and conversion into a multimeric freely diffusible form. The processing of Hh proteins affects their trafficking, potency, and ability to signal over several cell diameters. Here we review the current understanding of the Hh signaling mechanisms that govern the establishment of the Hh gradient and the transduction of the Hh signal in the light of recent data.展开更多
Single-nucleotide polymorphisms （SNPs） of ADIPOQ, ADIPOR1, and ADIPOR2 have been associated with type 2 diabetes mellitus （T2DM）, but there are many conflicting results especially in Chinese populations. To invest...Single-nucleotide polymorphisms （SNPs） of ADIPOQ, ADIPOR1, and ADIPOR2 have been associated with type 2 diabetes mellitus （T2DM）, but there are many conflicting results especially in Chinese populations. To investigate the contribution of the adiponectin genes and their receptors to T2DM, a case-control study was performed and 11 SNPs ofADIPOQ, ADIPOR1, and ADIPOR2 were genotyped in 985 T2DM and 1,050 control subjects, rs 16861194 （-11426 A〉G） in the putative promoter of ADIPOQ was associated with T2DM （P = 0.007; OR = 1.29, 95% CI 1.08-1.55）. None of the other 10 SNPs were associated with T2DM in this study, although rs2241766 and rs1501299 were reported to be associated with T2DM in previous Chinese studies. There was also no significant difference found from the ADIPOQ haplotype analysis, which contains rs 16861194. In addition, we also assessed potential gene-gene interactions in three genes and no interactions were found. In conclusion, our results supported the ADIPOQ gene as a possible risk factor for type 2 diabetes in Han Chinese population.展开更多
Although AGAMOUS-LIKE6 (AGL6) MADS-box genes are ancient with wide distributions in gymnosperms and angiosperms, their functions remain poorly understood. Here, we show the biological role of the AGL6-1ike gene, OsMAD...Although AGAMOUS-LIKE6 (AGL6) MADS-box genes are ancient with wide distributions in gymnosperms and angiosperms, their functions remain poorly understood. Here, we show the biological role of the AGL6-1ike gene, OsMADS6, in specifying floral organ and meristem identities in rice (Oryza sativa L.). OsMADS6 was strongly ex- pressed in the floral meristem at early stages. Subsequently, OsMADS6 transcripts were mainly detectable in paleas, lodicules, carpels and the integument of ovule, as well as in the receptacle. Compared to wild type plants, osmads6 mutants displayed altered palea identity, extra glume-like or mosaic organs, abnormal carpel development and loss of floral meristem determinacy. Strikingly, mutation of a SEPALLATA (SEP)-like gene, OsMADS1 (LHS1), enhanced the defect of osmads6 flowers, and no inner floral organs or glume-like structures were observed in whorls 2 and 3 of osmadsl-z osmads6-1 flowers. Furthermore, the osmadsl-z osmads6-1 double mutants developed severely indetermi- nate floral meristems. Our finding, therefore, suggests that the ancient OsMADS6 gene is able to specify "floral state" by determining floral organ and meristem identities in monocot crop rice together with OsMADS1.展开更多
To understand the molecular mechanism of male reproductive development in the model crop rice,we isolated a complete male sterile mutant post-meiotic deficient anther1 （pda1） from a γ-ray-treated rice mutant librar...To understand the molecular mechanism of male reproductive development in the model crop rice,we isolated a complete male sterile mutant post-meiotic deficient anther1 （pda1） from a γ-ray-treated rice mutant library.Genetic analysis revealed that the pda1 mutant was controlled by a recessive nucleus gene.The pda1 mutant anther seemed smaller with white appearance.Histological analysis demonstrated that the pda1 mutant anther undergoes normal early tapetum development without obvious altered meiosis.However,the pda1 mutant displayed obvious defects in postmeiotic tapetal development,abnormal degeneration occurred in the tapetal cells at stage 9 of anther development.Also we observed abnormal lipidic Ubisch bodies from the tapetal layer of the pda1 mutant,causing no obvious pollen exine formation.RT-PCR analysis indicated that the expression of genes involved in anther development including GAMYB,OsC4 and Wax-deficient anther1 （WDA1） was greatly reduced in the pda1 mutant anther.Using map-based cloning approach,the PDA1 gene was finely mapped between two markers HLF610 and HLF627 on chromosome 6 using 3,883 individuals of F2 population.The physical distance between HLF610 and HLF627 was about 194 kb.This work suggests that PDA1 is required for post-meiotic tapetal development and pollen/microspore formation in rice.展开更多
Vertebrate digits are essential structures for movement, feeding and communication. Specialized regions of the developing limb bud including the zone of polarizing activity （ZPA）, the apical ectodermal ridge （AER）...Vertebrate digits are essential structures for movement, feeding and communication. Specialized regions of the developing limb bud including the zone of polarizing activity （ZPA）, the apical ectodermal ridge （AER）, and the non-ridge ectoderm regulate the patterning of digits. Although a series of signaling molecules have been characterized as patterning signals from the organizing centers, the delicate cellular and molecular mechanisms that interpret how these patterning signals control the detailed digit anatomy remain unclear, Recent studies from model organisms and human hand malformations provide new insights into the mechanisms regulating this process. Here, we review the current understanding of the genetic networks governing digit morphogenesis展开更多
Dear Editor, We developed a GPU-based analytical method, named as SHEsisEpi, which purely focuses on risk epistasis in a genome-wide association study （GWAS） of complex traits, excluding the contamination of margin...Dear Editor, We developed a GPU-based analytical method, named as SHEsisEpi, which purely focuses on risk epistasis in a genome-wide association study （GWAS） of complex traits, excluding the contamination of marginal effects caused by single-locus association. We analyzed the Wellcome Trust Case Control Consortium＇s （WTCCC） GWAS data of bipolar disorder （BPD） with 500K SNPs.展开更多
N-ethyl-N-nitrosourea （ENU） mutagenesis has led to the elucidation of several regulator genes for melanocyte and skin development. Here we characterized a mutant from ENU mutagenesis with similar phenotype as that o...N-ethyl-N-nitrosourea （ENU） mutagenesis has led to the elucidation of several regulator genes for melanocyte and skin development. Here we characterized a mutant from ENU mutagenesis with similar phenotype as that of Splotch mutant, including exencephaly, spina bifida and abnormal limbs in homozygotes as well as white belly spotting and occasionally loop-tail in heterozygotes. This novel mutant was named as SpxG. Through genome-wide linkage analysis in backcross progenies with microsatellite markers, the SpxG was confined to a region between DIMIT415 and DIMIT7 on chromosome 1, where notable Pax3 gene was located. Direct sequencing revealed that SpxG carried a nucleotide A894G missense transition in exon 6 of Pax3 gene that resulted in Asn to Asp substitution at amino acid 269 within the highly-conserved homeodomain （HD） DNA recognition module, which was the first point mutation found in this domain in mice. This N269D mutation impaired the transactivation capacity of Pax3 protein, but exerted no effect on Pax3 protein translation. The characterization of the new mutation expanded our understanding the transactivation and DNA-binding structure of Pax3 protein.展开更多
Objective Thyroid hormones(THs)regulate multiple physiological activities in the liver,including cellular metabolism,differentiation,and cell growth,and play important roles in the pathogenesis of hepatocellular carci...Objective Thyroid hormones(THs)regulate multiple physiological activities in the liver,including cellular metabolism,differentiation,and cell growth,and play important roles in the pathogenesis of hepatocellular carcinoma(HCC).Thyroid peroxidase(TPO)is a key molecule involved in the THs synthesis and signaling pathway.As an epigenetic modification,DNA methylation has a critical role in tumorigenesis with diagnostic potential.However,the connection between THs and DNA methylation has been rarely investigated.Methods The methylation of key TH-related genes was analyzed by in-house epigenome-wide scanning,and we further analyzed the methylation levels of the TPO promotor in 164 sample pairs of HCC and adjacent non-cancerous tissues by Sequenom EpiTYPER assays,and evaluated their clinical implications.Results We identified that the methylation of the TPO promoter was downregulated in the HCC tissues(P<0.0001)with a mean difference ranging from 18.5%to 22.3%.This methylation pattern correlated with several clinical factors,including a multi-satellite tumor,fibrous capsule,and the presence of tumor thrombus.The receiver operator characteristic(ROC)curve analysis further confirmed that the percent methylated reference(PMR)values for TPO were predictive of the tumor[the area under the curve(AUC)ranged from 0.755 to 0.818]and the thrombosis in the HCC patients(the AUC ranged from 0.706 to 0.777).Conclusion These findings demonstrated that epigenetic alterations of TPO,as indicated by the PMR values,were a potential biomarker for HCC patients with tumor thrombosis.展开更多
Objeelive To prepare and characterize polyelectrolyte multilayer film coated microbubbles for use as ultrasound contrast agent （UCA） and evaluate its effects in ultrasonic imaging on normal rabbit＇s fiver parenchym...Objeelive To prepare and characterize polyelectrolyte multilayer film coated microbubbles for use as ultrasound contrast agent （UCA） and evaluate its effects in ultrasonic imaging on normal rabbit＇s fiver parenchyma. Methods Perfluorocarbon （PFC）-containing microbubbles （ST68-PFC） were prepared by sonication based on suffactant （ Span 60 and Tween 80）. Subsequently, the resulting ST68-PFC microbubbles were coated using oppositely charged polyelectrolytes by microbubble-templated layer-by-layer self-assembly technique via electrostatic interaction. The enhancement effects in ultrasonic imaging on normal rabbit＇s liver parenchyma were assessed. Results The obtained microbubbles exhibited a narrow size distribution. The polyelectrolytes were successfully assembled onto the surface of ST68-PFC microbubbles. In vivo experiment showed that polyelectrolyte multilayer film coated UCA effectively enhanced the imaging of rabbit＇s liver parenchyma. Conclusions The novel microbubbles UCA coated with polyelectrolyte multilayer, when enabled more function, has no obvious difference in enhancement effects compared with the pre-modified microbubbles. The polymers with chemically active groups （ such as amino group and carboxyl group） can be used as the outermost layer for attachment of targeting ligands onto microbubbles, allowing selective targeting of the microbubbles to combine with desired sites.展开更多
AIM: To search candidate tumor suppressor genes (TSGs) on chromosome 4q through detecting high loss of heterozygosity (LOH) regions in sporadic colorectal carcinoma in Chinese patients. METHODS: Thirteen fluorescent l...AIM: To search candidate tumor suppressor genes (TSGs) on chromosome 4q through detecting high loss of heterozygosity (LOH) regions in sporadic colorectal carcinoma in Chinese patients. METHODS: Thirteen fluorescent labeled polymorphic microsatellite markers were analyzed in 83 cases of colorectal carcinoma and matched normal tissue DNA by polymerase chain reaction (PCR). PCR products were eletrophoresed on an ABI 377 DNA sequencer. Genescan 3.7 and Genotype 3.7 software were used for LOH scanning and analysis. Comparison between LOH frequency and clinicopathological factors were performed by χ2 test. RESULTS: Data were collected on all informative loci. The average LOH frequency on 4q was 28.56%. The D4S2915 locus showed highest LOH frequency (36.17%). Two obvious deletion regions were detected: one between D4S3000 and D4S2915 locus (4q12-21.1), another flanked by D4S407 and D4S2939 locus (4q25-31.1). None case showed complete deletion of 4q, most cases displayed interstitial deletion pattern solely. Furthermore, compared with clinicopathological features, a significant relationship was observed between LOH frequencies on D4S3018locus. In tumors larger than 5 cm in diameter, LOH frequency was significantly higher than tumors that were less than 5 cm (56% vs 13.79%, P = 0.01). On D4S1534 locus, LOH was significantly associated with liver metastasis (80% vs 17.25%, P = 0.012). No relationship was detected on other locus compared with clinicopathologial features. CONCLUSION: By high resolution deletion mapping, two high frequency regions of LOH (4q12-21.1 and 4q25-31.1) were detected, which may contribute to locate TSGs on chromosome 4q involved in carcinogenesis and progression of sporadic colorectal carcinoma.展开更多
AIM: To study the candidate tumor suppressor genes (TSG) on chromosome 4p by detecting the high frequency of loss of heterozygosity (LOH) in sporadic colorectal carcinoma in Chinese patients.METHODS: Seven fluorescent...AIM: To study the candidate tumor suppressor genes (TSG) on chromosome 4p by detecting the high frequency of loss of heterozygosity (LOH) in sporadic colorectal carcinoma in Chinese patients.METHODS: Seven fluorescent labeled polymorphic microsatellite markers were analyzed in 83 cases of colorectal carcinoma and matched normal tissue DNA by PCR. PCR products were eletrophoresed on an ABI 377 DNA sequencer. Genescan 3.7 and Genotype 3.7 software were used for LOH scanning and analysis. The same procedure was performed by the other six microsatellite markers spanning D4S3013 locus to make further detailed deletion mapping. Comparison between LOH frequency and clinicopathological factors was performed by χ2 test.RESULTS: Data were collected from all informative loci. The average LOH frequency on 4p was 24.25%, and 42.3% and 35.62% on D4S405 and D4S3013 locus, respectively. Adjacent markers of D4S3013 displayed a low LOH frequency (< 30%) by detailed deletion mapping. Significant opposite difference was observed between LOH frequency and tumor diameter on D4S412 and D4S1546 locus (0% vs 16.67%, P = 0.041; 54.55% vs 11.11%, P = 0.034, respectively). On D4S403 locus, LOH was significantly associated with tumor gross pattern (11.11%, 0, 33.33%, P = 0.030). No relationship was detected on other loci compared with clinicopathologial features.CONCLUSION: By deletion mapping, two obvious high frequency LOH regions spanning D4S3013 (4p15.2) and D4S405 (4p14) locus are detected. Candidate TSG, which is involved in carcinogenesis and progression of sporadic colorectal carcinoma on chromosome 4p, may be located between D4S3017 and D4S2933 (about 1.7 cm).展开更多
文摘Haplotypic information in diploid organisms provides valuable information on human evolutionary history and plays an important role in identifying a candidate gene in the etiology of complex genetic diseases. However, haplotypes of diploid individuals cannot be acquired easily. Molecular haplotyping methods are very costly and have low throughput, and current genotyping and sequenc- ing methods do not provide information on the linkage phase in diploid organisms. The application of statistical methods to infer the haplotype phase in samples of diploid sequences is a very cost-effective approach.
基金This work was supported by the Major State Basic Research Development program of Chinathe National High Technology Research and Development Program of China.
文摘In multiloci-based genetic association studies of complex diseases, a powerful and high efficient tool for analyses oflinkage disequilibrium (LD) between markers, haplotype distributions and many chi-square/p values with a large numberof samples has been sought for long. In order to achieve the goal of obtaining meaningful results directly from raw data,we developed a robust and user-friendly software platform with a series of tools for analysis in association study withhigh efficiency. The platform has been well evaluated by several sets of real data.
基金supported by the funds from the National Basic Research Program of China(Nos.2009CB941500 and 2007CB108700)the National Natural Science Foundation of China(No.30725022)+1 种基金the Chinese Transgenic Project(No. 2009ZX08009-108B)the National 863 High-Tech Project (No.2011AA10A101)
文摘Microsporogenesis and male gametogenesis are essential for the alternating life cycle of flowering plants between diploid sporophyte and haploid gametophyte generations. Rice （Oryza sativa） is the world＇s major staple food, and manipulation of pollen fertility is particularly important for the demands to increase rice grain yield. Towards a better understanding of the mechanisms controlling rice male reproductive development, we describe here the cytological changes of anther development through 14 stages, including cell division, differentiation and degeneration of somatic tissues consisting of four concentric cell layers surrounding and supporting reproductive cells as they form mature pollen grains through meiosis and mitosis. Furthermore, we compare the morphological difference of anthers and pollen grains in both monocot rice and eudicot Arabidopsis thaliana. Additionally, we describe the key genes identified to date critical for rice anther development and pollen formation.
基金Supplementary information is linked to the online version of the paper on the Cell Research website.Acknowledgments We thank Michel S6m6riva （IBDML, France）, Fumio Matsuzaki （RIKEN CDB, Japan）, Michael J Galko （UT MD Anderson Cancer Center, USA）, Enrique Martin-Blanco （Instituto de Biologia Molecular de Barcelona, Spain）, Dirk Bohmann （University of Rochester, USA）, Kyung-Ok Cho （Baylor College of Medicine, USA）, the Bloomington Drosophila Stock Center, NIGFLY （Japan）, and the Developmental Studies Hybridoma Bank for providing fly strains and antibodies. We also thank Wenjuan Xiang and Wentian Gu in ML＇s Lab for the technical assistance.This work was supported by National Natural Science Foundation of China （30470890）, National Basic Research Program of China （2007CB914504, 2007CB947301）, the Shanghai Pujiang Program （05PJ14075） and Shanghai Leading Academic Discipline Project （B205）.
文摘Dear Editor, Identification of Drosophila melanogaster as a model organism for cancer research has facilitated the exploration of human tumor malignancy. In Drosophila, loss- of-function mutations in the neoplastic tumor suppressor genes （nYSGs） lethal（2）giant larvae （lgl）, discs large （dlg） or scribble （scrib） cause a malignant tumor-like phenotype characteristic of disrupted cell polarity and overgrowth in epithelial tissues such as imaginal discs [1 ].
文摘The Hedgehog （Hh） family of secreted signaling proteins plays a critical role in regulating the development of several tissues and organ systems. The ability of Hh proteins to exert their biological effects is regulated by a series of post-translational processes. These processes include an intramolecular cleavage, covalent addition of cholesterol and/or palmitate, and conversion into a multimeric freely diffusible form. The processing of Hh proteins affects their trafficking, potency, and ability to signal over several cell diameters. Here we review the current understanding of the Hh signaling mechanisms that govern the establishment of the Hh gradient and the transduction of the Hh signal in the light of recent data.
基金supported by the National Natural Science Foundation of ChinaNational Basic Research Pro-gram of China (973 Program)+5 种基金National High-tech R&D Program (863 Program)the Chinese Nutrition Soci-ety (No. 05015)the Dannon Institute, the Shanghai-Unilever Research and Development Fund (No. 06SU07007)the Shanghai Municipality Science & Tech-nology Commission (No. 05JC14090)the Shanghai Leading Academic Discipline Project (No. B205)the Knowledge Innovation Program of the Chinese Academy of Sciences (No. KSCX2-YW-R-01)
文摘Single-nucleotide polymorphisms （SNPs） of ADIPOQ, ADIPOR1, and ADIPOR2 have been associated with type 2 diabetes mellitus （T2DM）, but there are many conflicting results especially in Chinese populations. To investigate the contribution of the adiponectin genes and their receptors to T2DM, a case-control study was performed and 11 SNPs ofADIPOQ, ADIPOR1, and ADIPOR2 were genotyped in 985 T2DM and 1,050 control subjects, rs 16861194 （-11426 A〉G） in the putative promoter of ADIPOQ was associated with T2DM （P = 0.007; OR = 1.29, 95% CI 1.08-1.55）. None of the other 10 SNPs were associated with T2DM in this study, although rs2241766 and rs1501299 were reported to be associated with T2DM in previous Chinese studies. There was also no significant difference found from the ADIPOQ haplotype analysis, which contains rs 16861194. In addition, we also assessed potential gene-gene interactions in three genes and no interactions were found. In conclusion, our results supported the ADIPOQ gene as a possible risk factor for type 2 diabetes in Han Chinese population.
基金We gratefully acknowledge B Han from National Center for Gene Research, Chinese Academy of Sciences (CAS) and Rice Genome Resource Center (RGRC) for providing BAC clone, cDNA clone and Tosl7 insertion line. We thank Z-J Luo and M-J Chen from Shanghai Jiao Tong University for mutant screening and generation of F2 populations, X-Y Gao from Institute of Plant Physiology and Ecology, SIBS, CAS, for SEM, H Yu from Nation- al University Of Singapore for critical reading of this manuscript and H Ma from Fudan University for helpful discussion. This work was supported by funds from the National Basic Research Program of China (2009CB941500, 2006CB 101700), the National Natural Science Foundation of China (30725022, 30830014 and 90717109) and the Shanghai Leading Academic Discipline Project (B205).
文摘Although AGAMOUS-LIKE6 (AGL6) MADS-box genes are ancient with wide distributions in gymnosperms and angiosperms, their functions remain poorly understood. Here, we show the biological role of the AGL6-1ike gene, OsMADS6, in specifying floral organ and meristem identities in rice (Oryza sativa L.). OsMADS6 was strongly ex- pressed in the floral meristem at early stages. Subsequently, OsMADS6 transcripts were mainly detectable in paleas, lodicules, carpels and the integument of ovule, as well as in the receptacle. Compared to wild type plants, osmads6 mutants displayed altered palea identity, extra glume-like or mosaic organs, abnormal carpel development and loss of floral meristem determinacy. Strikingly, mutation of a SEPALLATA (SEP)-like gene, OsMADS1 (LHS1), enhanced the defect of osmads6 flowers, and no inner floral organs or glume-like structures were observed in whorls 2 and 3 of osmadsl-z osmads6-1 flowers. Furthermore, the osmadsl-z osmads6-1 double mutants developed severely indetermi- nate floral meristems. Our finding, therefore, suggests that the ancient OsMADS6 gene is able to specify "floral state" by determining floral organ and meristem identities in monocot crop rice together with OsMADS1.
基金supported by the Funds from the National Key Basic Research Developments Program of the Ministry of Science and Technology, China (No. 2009CB941500)Shanghai Leading Academic Discipline Project (No. B205)
文摘To understand the molecular mechanism of male reproductive development in the model crop rice,we isolated a complete male sterile mutant post-meiotic deficient anther1 （pda1） from a γ-ray-treated rice mutant library.Genetic analysis revealed that the pda1 mutant was controlled by a recessive nucleus gene.The pda1 mutant anther seemed smaller with white appearance.Histological analysis demonstrated that the pda1 mutant anther undergoes normal early tapetum development without obvious altered meiosis.However,the pda1 mutant displayed obvious defects in postmeiotic tapetal development,abnormal degeneration occurred in the tapetal cells at stage 9 of anther development.Also we observed abnormal lipidic Ubisch bodies from the tapetal layer of the pda1 mutant,causing no obvious pollen exine formation.RT-PCR analysis indicated that the expression of genes involved in anther development including GAMYB,OsC4 and Wax-deficient anther1 （WDA1） was greatly reduced in the pda1 mutant anther.Using map-based cloning approach,the PDA1 gene was finely mapped between two markers HLF610 and HLF627 on chromosome 6 using 3,883 individuals of F2 population.The physical distance between HLF610 and HLF627 was about 194 kb.This work suggests that PDA1 is required for post-meiotic tapetal development and pollen/microspore formation in rice.
基金the National Basic Research Program of China (973 Program) (No. 2007CB947301).
文摘Vertebrate digits are essential structures for movement, feeding and communication. Specialized regions of the developing limb bud including the zone of polarizing activity （ZPA）, the apical ectodermal ridge （AER）, and the non-ridge ectoderm regulate the patterning of digits. Although a series of signaling molecules have been characterized as patterning signals from the organizing centers, the delicate cellular and molecular mechanisms that interpret how these patterning signals control the detailed digit anatomy remain unclear, Recent studies from model organisms and human hand malformations provide new insights into the mechanisms regulating this process. Here, we review the current understanding of the genetic networks governing digit morphogenesis
文摘Dear Editor, We developed a GPU-based analytical method, named as SHEsisEpi, which purely focuses on risk epistasis in a genome-wide association study （GWAS） of complex traits, excluding the contamination of marginal effects caused by single-locus association. We analyzed the Wellcome Trust Case Control Consortium＇s （WTCCC） GWAS data of bipolar disorder （BPD） with 500K SNPs.
基金supported by the National Basic Research Program of China(No.2007CB947301)the National Natural Science Foundation of China(No.30800613)Pujiang Talent(No.08PJ1407200)
文摘N-ethyl-N-nitrosourea （ENU） mutagenesis has led to the elucidation of several regulator genes for melanocyte and skin development. Here we characterized a mutant from ENU mutagenesis with similar phenotype as that of Splotch mutant, including exencephaly, spina bifida and abnormal limbs in homozygotes as well as white belly spotting and occasionally loop-tail in heterozygotes. This novel mutant was named as SpxG. Through genome-wide linkage analysis in backcross progenies with microsatellite markers, the SpxG was confined to a region between DIMIT415 and DIMIT7 on chromosome 1, where notable Pax3 gene was located. Direct sequencing revealed that SpxG carried a nucleotide A894G missense transition in exon 6 of Pax3 gene that resulted in Asn to Asp substitution at amino acid 269 within the highly-conserved homeodomain （HD） DNA recognition module, which was the first point mutation found in this domain in mice. This N269D mutation impaired the transactivation capacity of Pax3 protein, but exerted no effect on Pax3 protein translation. The characterization of the new mutation expanded our understanding the transactivation and DNA-binding structure of Pax3 protein.
文摘Objective Thyroid hormones(THs)regulate multiple physiological activities in the liver,including cellular metabolism,differentiation,and cell growth,and play important roles in the pathogenesis of hepatocellular carcinoma(HCC).Thyroid peroxidase(TPO)is a key molecule involved in the THs synthesis and signaling pathway.As an epigenetic modification,DNA methylation has a critical role in tumorigenesis with diagnostic potential.However,the connection between THs and DNA methylation has been rarely investigated.Methods The methylation of key TH-related genes was analyzed by in-house epigenome-wide scanning,and we further analyzed the methylation levels of the TPO promotor in 164 sample pairs of HCC and adjacent non-cancerous tissues by Sequenom EpiTYPER assays,and evaluated their clinical implications.Results We identified that the methylation of the TPO promoter was downregulated in the HCC tissues(P<0.0001)with a mean difference ranging from 18.5%to 22.3%.This methylation pattern correlated with several clinical factors,including a multi-satellite tumor,fibrous capsule,and the presence of tumor thrombus.The receiver operator characteristic(ROC)curve analysis further confirmed that the percent methylated reference(PMR)values for TPO were predictive of the tumor[the area under the curve(AUC)ranged from 0.755 to 0.818]and the thrombosis in the HCC patients(the AUC ranged from 0.706 to 0.777).Conclusion These findings demonstrated that epigenetic alterations of TPO,as indicated by the PMR values,were a potential biomarker for HCC patients with tumor thrombosis.
基金Supported by the Program for New Century Excellent in University of China(30740061)the National Natural Science Foundation of China(30672001)
文摘Objeelive To prepare and characterize polyelectrolyte multilayer film coated microbubbles for use as ultrasound contrast agent （UCA） and evaluate its effects in ultrasonic imaging on normal rabbit＇s fiver parenchyma. Methods Perfluorocarbon （PFC）-containing microbubbles （ST68-PFC） were prepared by sonication based on suffactant （ Span 60 and Tween 80）. Subsequently, the resulting ST68-PFC microbubbles were coated using oppositely charged polyelectrolytes by microbubble-templated layer-by-layer self-assembly technique via electrostatic interaction. The enhancement effects in ultrasonic imaging on normal rabbit＇s liver parenchyma were assessed. Results The obtained microbubbles exhibited a narrow size distribution. The polyelectrolytes were successfully assembled onto the surface of ST68-PFC microbubbles. In vivo experiment showed that polyelectrolyte multilayer film coated UCA effectively enhanced the imaging of rabbit＇s liver parenchyma. Conclusions The novel microbubbles UCA coated with polyelectrolyte multilayer, when enabled more function, has no obvious difference in enhancement effects compared with the pre-modified microbubbles. The polymers with chemically active groups （ such as amino group and carboxyl group） can be used as the outermost layer for attachment of targeting ligands onto microbubbles, allowing selective targeting of the microbubbles to combine with desired sites.
基金The National Natural Science Foundation of China, No. 30080016 and No. 30470977
文摘AIM: To search candidate tumor suppressor genes (TSGs) on chromosome 4q through detecting high loss of heterozygosity (LOH) regions in sporadic colorectal carcinoma in Chinese patients. METHODS: Thirteen fluorescent labeled polymorphic microsatellite markers were analyzed in 83 cases of colorectal carcinoma and matched normal tissue DNA by polymerase chain reaction (PCR). PCR products were eletrophoresed on an ABI 377 DNA sequencer. Genescan 3.7 and Genotype 3.7 software were used for LOH scanning and analysis. Comparison between LOH frequency and clinicopathological factors were performed by χ2 test. RESULTS: Data were collected on all informative loci. The average LOH frequency on 4q was 28.56%. The D4S2915 locus showed highest LOH frequency (36.17%). Two obvious deletion regions were detected: one between D4S3000 and D4S2915 locus (4q12-21.1), another flanked by D4S407 and D4S2939 locus (4q25-31.1). None case showed complete deletion of 4q, most cases displayed interstitial deletion pattern solely. Furthermore, compared with clinicopathological features, a significant relationship was observed between LOH frequencies on D4S3018locus. In tumors larger than 5 cm in diameter, LOH frequency was significantly higher than tumors that were less than 5 cm (56% vs 13.79%, P = 0.01). On D4S1534 locus, LOH was significantly associated with liver metastasis (80% vs 17.25%, P = 0.012). No relationship was detected on other locus compared with clinicopathologial features. CONCLUSION: By high resolution deletion mapping, two high frequency regions of LOH (4q12-21.1 and 4q25-31.1) were detected, which may contribute to locate TSGs on chromosome 4q involved in carcinogenesis and progression of sporadic colorectal carcinoma.
基金Supported by The National Natural Science Foundation of China, No. 30080016 and No. 30470977
文摘AIM: To study the candidate tumor suppressor genes (TSG) on chromosome 4p by detecting the high frequency of loss of heterozygosity (LOH) in sporadic colorectal carcinoma in Chinese patients.METHODS: Seven fluorescent labeled polymorphic microsatellite markers were analyzed in 83 cases of colorectal carcinoma and matched normal tissue DNA by PCR. PCR products were eletrophoresed on an ABI 377 DNA sequencer. Genescan 3.7 and Genotype 3.7 software were used for LOH scanning and analysis. The same procedure was performed by the other six microsatellite markers spanning D4S3013 locus to make further detailed deletion mapping. Comparison between LOH frequency and clinicopathological factors was performed by χ2 test.RESULTS: Data were collected from all informative loci. The average LOH frequency on 4p was 24.25%, and 42.3% and 35.62% on D4S405 and D4S3013 locus, respectively. Adjacent markers of D4S3013 displayed a low LOH frequency (< 30%) by detailed deletion mapping. Significant opposite difference was observed between LOH frequency and tumor diameter on D4S412 and D4S1546 locus (0% vs 16.67%, P = 0.041; 54.55% vs 11.11%, P = 0.034, respectively). On D4S403 locus, LOH was significantly associated with tumor gross pattern (11.11%, 0, 33.33%, P = 0.030). No relationship was detected on other loci compared with clinicopathologial features.CONCLUSION: By deletion mapping, two obvious high frequency LOH regions spanning D4S3013 (4p15.2) and D4S405 (4p14) locus are detected. Candidate TSG, which is involved in carcinogenesis and progression of sporadic colorectal carcinoma on chromosome 4p, may be located between D4S3017 and D4S2933 (about 1.7 cm).
