The current assembled maize genomes cannot represent the broad genetic diversity of maize germplasms.Acquiring more genome sequences is critical for constructing a pan-genome and elucidating the linkage between genoty...The current assembled maize genomes cannot represent the broad genetic diversity of maize germplasms.Acquiring more genome sequences is critical for constructing a pan-genome and elucidating the linkage between genotype and phenotype in maize.Here we describe the genome sequence and annotation of A188,a maize inbred line with high phenotypic variation relative to other lines,acquired by single-molecule sequencing and optical genome mapping.We assembled a 2210-Mb genome with a scaffold N50 size of 11.61 million bases(Mb),compared to 9.73 Mb for B73 and 10.2 Mb for Mo17.Based on the B73_Ref Gen_V4 genome,295 scaffolds(2084.35 Mb,94.30%of the final genome assembly)were anchored and oriented on ten chromosomes.Comparative analysis revealed that~30%of the predicted A188 genes showed large structural divergence from B73,Mo17,and W22 genomes,which causes high protein divergence and may lead to phenotypic variation among the four inbred lines.As a line with high embryonic callus(EC)induction capacity,A188 provides a convenient tool for elucidating the molecular mechanism underlying the formation of EC in maize.Combining our new A188 genome with previously reported QTL and RNA sequencing data revealed eight genes with large structural variation and two differentially expressed genes playing potential roles in maize EC induction.展开更多
Reliable and accurate pre-implantation genetic diagnosis （PGD） of patient＇s embryos by next-generation sequencing （NGS） is dependent on efficient whole genome amplification （WGA） of a representative biopsy samp...Reliable and accurate pre-implantation genetic diagnosis （PGD） of patient＇s embryos by next-generation sequencing （NGS） is dependent on efficient whole genome amplification （WGA） of a representative biopsy sample. However, the performance of the current state of the art WGA methods has not been evaluated for sequencing. Using low template DNA （15 pg） and single cells, we showed that the two PCR-based WGA systems SurePlex and MALBAC are superior to the REPLI-g WGA multiple displacement amplification （MDA） system in terms of consistent and reproducible genome coverage and sequence bias across the 24 chromosomes, allowing better normalization of test to reference sequencing data. When copy number variation sequencing （CNV-Seq） was applied to single cell WGA products derived by either SurePlex or MALBAC amplification, we showed that known disease CNVs in the range of 3-15 Mb could be reliably and accurately detected at the correct genomic positions. These findings indicate that our CNV-Seq pipeline incorporating either SurePlex or MALBAC as the key initial WGA step is a powerful methodology for clinical PGD to identify euploid embryos in a patient＇s cohort for uterine transplantation,展开更多
Aneuploidy rates in embryos produced by assisted reproduc- tive technologies commonly exceed 50%, particularly in couples where the woman is of advanced maternal age or has experienced repeated implantation failure （...Aneuploidy rates in embryos produced by assisted reproduc- tive technologies commonly exceed 50%, particularly in couples where the woman is of advanced maternal age or has experienced repeated implantation failure （Harper et al., 2012）. Pre-implantation genetic diagnosis （PGD） conducted at many fertility clinics worldwide is now a frontline treatment for infertile couples with a poor prognosis for pregnancy as well as couples where one partner is a carrier of a balanced translocation （Munne, 2012）.展开更多
Objective:Histology grade,subtypes and TNM stage of lung adenocarcinomas are useful predictors of prognosis and survival.The aim of the study was to investigate the relationship between chromosomal instability,morphol...Objective:Histology grade,subtypes and TNM stage of lung adenocarcinomas are useful predictors of prognosis and survival.The aim of the study was to investigate the relationship between chromosomal instability,morphological subtypes and the grading system used in lung non-mucinous adenocarcinoma(LNMA).Methods:We developed a whole genome copy number variation(WGCNV)scoring system and applied next generation sequencing to evaluate CNVs present in 91 LNMA tumor samples.Results:Higher histological grades,aggressive subtypes and more advanced TNM staging were associated with an increased WGCNV score,particularly in CNV regions enriched for tumor suppressor genes and oncogenes.In addition,we demonstrate that 24-chromosome CNV profiling can be performed reliably from specific cell types(<100 cells)isolated by sample laser capture microdissection.Conclusions:Our findings suggest that the WGCNV scoring system we developed may have potential value as an adjunct test for predicting the prognosis of patients diagnosed with LNMA.展开更多
Fetal hydrops is a rare but serious fetal developmental abnormality characterized by the abnormal accumulation of large amounts of fluid in the fetus resulting in generalized edema,and clinically manifested by abnorma...Fetal hydrops is a rare but serious fetal developmental abnormality characterized by the abnormal accumulation of large amounts of fluid in the fetus resulting in generalized edema,and clinically manifested by abnormal functioning of multiple organs and systems.1 The ryanodine receptor 1(RYR1)gene encodes the ryanodine receptor found in skeletal muscle and is expressed predominantly in cardiac and skeletal muscle.展开更多
Post-polyploid diploidization associated with descending dysploidy and interspecific introgression drives plant genome evolution by unclear mechanisms.Raphanus is an economically and ecologically important Brassiceae ...Post-polyploid diploidization associated with descending dysploidy and interspecific introgression drives plant genome evolution by unclear mechanisms.Raphanus is an economically and ecologically important Brassiceae genus and model system for studying post-polyploidization genome evolution and introgres-sion.Here,we report the de novo sequence assemblies for 11 genomes covering most of the typical sub-species and varieties of domesticated,wild and weedy radishes from East Asia,South Asia,Europe,and America.Divergence among the species,sub-species,and South/East Asian types coincided with Quaternary glaciations.A genus-level pan-genome was constructed with family-based,locus-based,and graph-based methods,and whole-genome comparisons revealed genetic variations ranging from single-nucleotide polymorphisms(SNPs)to inversions and translocations of whole ancestral karyotype(AK)blocks.Extensive gene flow occurred between wild,weedy,and domesticated radishes.High fre-quencies of genome reshuffling,biased retention,and large-fragment translocation have shaped the genomic diversity.Most variety-specific gene-rich blocks showed large structural variations.Extensive translocation and tandem duplication of dispensable genes were revealed in two large rearrangement-rich islands.Disease resistance genes mostly resided on specific and dispensable loci.Variations causing the loss of function of enzymes modulating gibberellin deactivation were identified and could play an important role in phenotype divergence and adaptive evolution.This study provides new insights into the genomic evolution underlying post-polyploid diploidization and lays the foundation for genetic improve-ment of radish crops,biological control of weeds,and protection of wild species'germplasms.展开更多
Soybean was domesticated in China and has become one of the most important oilseed crops. Due to bottlenecks in their introduction and dissemination, soybeans from different geographic areas exhibit extensive genetic ...Soybean was domesticated in China and has become one of the most important oilseed crops. Due to bottlenecks in their introduction and dissemination, soybeans from different geographic areas exhibit extensive genetic diversity. Asia is the largest soybean market; therefore, a high-quality soybean reference genome from this area is critical for soybean research and breeding.Here, we report the de novo assembly and sequence analysis of a Chinese soybean genome for "Zhonghuang 13" by a combination of SMRT, Hi-C and optical mapping data. The assembled genome size is 1.025 Gb with a contig N50 of 3.46 Mb and a scaffold N50 of 51.87 Mb. Comparisons between this genome and the previously reported reference genome(cv. Williams82) uncovered more than 250,000 structure variations. A total of 52,051 protein coding genes and 36,429 transposable elements were annotated for this genome, and a gene co-expression network including 39,967 genes was also established. This high quality Chinese soybean genome and its sequence analysis will provide valuable information for soybean improvement in the future.展开更多
Halophytes have evolved specialized strategies to cope with high salinity.The extreme halophyte sea lavender(Limonium bicolor)lacks trichomes but possesses salt glands on its epidermis that can excrete harmful ions,su...Halophytes have evolved specialized strategies to cope with high salinity.The extreme halophyte sea lavender(Limonium bicolor)lacks trichomes but possesses salt glands on its epidermis that can excrete harmful ions,such as sodium,to avoid salt damage.Here,we report a high-quality,2.92-Gb,chromosome-scale L.bicolor genome assembly based on a combination of Illumina short reads,single-molecule,real-time long reads,chromosome conformation capture(Hi-C)data,and Bionano genome maps,greatly enriching the genomic information on recretohalophytes with multicellular salt glands.Although the L.bicolor genome contains genes that show similarity to trichome fate genes from Arabidopsis thaliana,it lacks homologs of the decision fate genes GLABRA3,ENHANCER OF GLABRA3,GLABRA2,TRANSPARENT TESTA GLABRA2,and SIAMESE,providing a molecular explanation for the absence of trichomes in this species.We identified key genes(LbHLH and LbTTG1)controlling salt gland development among classical trichome homologous genes and confirmed their roles by showing that their mutations markedly disrupted salt gland initiation,salt secretion,and salt tolerance,thus offering genetic support for the long-standing hypothesis that salt glands and trichomes may share a common origin.In addition,a whole-genome duplication event occurred in the L.bicolor genome after its divergence from Tartary buckwheat and may have contributed to its adaptation to high salinity.The L.bicolor genome resource and genetic evidence reported in this study provide profound insights into plant salt tolerance mechanisms that may facilitate the engineering of salt-tolerant crops.展开更多
The cotton bollworm,Helicoverpa armigera,is set to become the most economically devastating crop pest in the world,threatening food security and biosafety as its range expands across the globe.Key to understanding the...The cotton bollworm,Helicoverpa armigera,is set to become the most economically devastating crop pest in the world,threatening food security and biosafety as its range expands across the globe.Key to understanding the eco-evolutionary dynamics of H.armigera,and thus its management,is an understanding of population connectivity and the adaptations that allow the pest to establish in unique environments.We assembled a chromosome-scale reference genome and re-sequenced 503 individuals spanning the species range to delineate global patterns of connectivity,uncovering a previously cryptic population structure.展开更多
基金supported by the National Natural Science Foundation of China(31871637,32072073,and 32001500)the Project of Transgenic New Variety Cultivation(2016ZX08003003)。
文摘The current assembled maize genomes cannot represent the broad genetic diversity of maize germplasms.Acquiring more genome sequences is critical for constructing a pan-genome and elucidating the linkage between genotype and phenotype in maize.Here we describe the genome sequence and annotation of A188,a maize inbred line with high phenotypic variation relative to other lines,acquired by single-molecule sequencing and optical genome mapping.We assembled a 2210-Mb genome with a scaffold N50 size of 11.61 million bases(Mb),compared to 9.73 Mb for B73 and 10.2 Mb for Mo17.Based on the B73_Ref Gen_V4 genome,295 scaffolds(2084.35 Mb,94.30%of the final genome assembly)were anchored and oriented on ten chromosomes.Comparative analysis revealed that~30%of the predicted A188 genes showed large structural divergence from B73,Mo17,and W22 genomes,which causes high protein divergence and may lead to phenotypic variation among the four inbred lines.As a line with high embryonic callus(EC)induction capacity,A188 provides a convenient tool for elucidating the molecular mechanism underlying the formation of EC in maize.Combining our new A188 genome with previously reported QTL and RNA sequencing data revealed eight genes with large structural variation and two differentially expressed genes playing potential roles in maize EC induction.
基金supported by grants awarded to Yuanqing Yao by the Key Program of the "Twelfth Five-year plan" of People’s liberation Army(No.BWS11J058)the National High Technology Research and Development Program(SS2015AA020402)
文摘Reliable and accurate pre-implantation genetic diagnosis （PGD） of patient＇s embryos by next-generation sequencing （NGS） is dependent on efficient whole genome amplification （WGA） of a representative biopsy sample. However, the performance of the current state of the art WGA methods has not been evaluated for sequencing. Using low template DNA （15 pg） and single cells, we showed that the two PCR-based WGA systems SurePlex and MALBAC are superior to the REPLI-g WGA multiple displacement amplification （MDA） system in terms of consistent and reproducible genome coverage and sequence bias across the 24 chromosomes, allowing better normalization of test to reference sequencing data. When copy number variation sequencing （CNV-Seq） was applied to single cell WGA products derived by either SurePlex or MALBAC amplification, we showed that known disease CNVs in the range of 3-15 Mb could be reliably and accurately detected at the correct genomic positions. These findings indicate that our CNV-Seq pipeline incorporating either SurePlex or MALBAC as the key initial WGA step is a powerful methodology for clinical PGD to identify euploid embryos in a patient＇s cohort for uterine transplantation,
文摘Aneuploidy rates in embryos produced by assisted reproduc- tive technologies commonly exceed 50%, particularly in couples where the woman is of advanced maternal age or has experienced repeated implantation failure （Harper et al., 2012）. Pre-implantation genetic diagnosis （PGD） conducted at many fertility clinics worldwide is now a frontline treatment for infertile couples with a poor prognosis for pregnancy as well as couples where one partner is a carrier of a balanced translocation （Munne, 2012）.
基金grants from Beijing Hospital Key Research Program(121 Research Program,No.BJ2019-195)。
文摘Objective:Histology grade,subtypes and TNM stage of lung adenocarcinomas are useful predictors of prognosis and survival.The aim of the study was to investigate the relationship between chromosomal instability,morphological subtypes and the grading system used in lung non-mucinous adenocarcinoma(LNMA).Methods:We developed a whole genome copy number variation(WGCNV)scoring system and applied next generation sequencing to evaluate CNVs present in 91 LNMA tumor samples.Results:Higher histological grades,aggressive subtypes and more advanced TNM staging were associated with an increased WGCNV score,particularly in CNV regions enriched for tumor suppressor genes and oncogenes.In addition,we demonstrate that 24-chromosome CNV profiling can be performed reliably from specific cell types(<100 cells)isolated by sample laser capture microdissection.Conclusions:Our findings suggest that the WGCNV scoring system we developed may have potential value as an adjunct test for predicting the prognosis of patients diagnosed with LNMA.
基金funded by the Guangxi Science and Technology Department (China) (No.Guike AD23026025).
文摘Fetal hydrops is a rare but serious fetal developmental abnormality characterized by the abnormal accumulation of large amounts of fluid in the fetus resulting in generalized edema,and clinically manifested by abnormal functioning of multiple organs and systems.1 The ryanodine receptor 1(RYR1)gene encodes the ryanodine receptor found in skeletal muscle and is expressed predominantly in cardiac and skeletal muscle.
基金supported by the National Key Research and Development Program of China(2016YFD0100204-02,2013BAD01B04-1)the National Natural Science Foundation of China(31772301,31772303,and 31801858)the Technology Innovation Program of the Chinese Academy of Agricultural Sciences(CAAS-ASTIP-2019-IVFCAAS,CAAS-XTCX2016016-4-4,and CAAS-XTCX2016001-5-2).
文摘Post-polyploid diploidization associated with descending dysploidy and interspecific introgression drives plant genome evolution by unclear mechanisms.Raphanus is an economically and ecologically important Brassiceae genus and model system for studying post-polyploidization genome evolution and introgres-sion.Here,we report the de novo sequence assemblies for 11 genomes covering most of the typical sub-species and varieties of domesticated,wild and weedy radishes from East Asia,South Asia,Europe,and America.Divergence among the species,sub-species,and South/East Asian types coincided with Quaternary glaciations.A genus-level pan-genome was constructed with family-based,locus-based,and graph-based methods,and whole-genome comparisons revealed genetic variations ranging from single-nucleotide polymorphisms(SNPs)to inversions and translocations of whole ancestral karyotype(AK)blocks.Extensive gene flow occurred between wild,weedy,and domesticated radishes.High fre-quencies of genome reshuffling,biased retention,and large-fragment translocation have shaped the genomic diversity.Most variety-specific gene-rich blocks showed large structural variations.Extensive translocation and tandem duplication of dispensable genes were revealed in two large rearrangement-rich islands.Disease resistance genes mostly resided on specific and dispensable loci.Variations causing the loss of function of enzymes modulating gibberellin deactivation were identified and could play an important role in phenotype divergence and adaptive evolution.This study provides new insights into the genomic evolution underlying post-polyploid diploidization and lays the foundation for genetic improve-ment of radish crops,biological control of weeds,and protection of wild species'germplasms.
基金supported by the National Natural Science Foundation of China (91531304, 31525018, 31370266, and 31788103)the “Strategic Priority Research Program” of the Chinese Academy of Sciences (XDA08000000)the State Key Laboratory of Plant Cell and Chromosome Engineering (PCCE-KF-2017-03)
文摘Soybean was domesticated in China and has become one of the most important oilseed crops. Due to bottlenecks in their introduction and dissemination, soybeans from different geographic areas exhibit extensive genetic diversity. Asia is the largest soybean market; therefore, a high-quality soybean reference genome from this area is critical for soybean research and breeding.Here, we report the de novo assembly and sequence analysis of a Chinese soybean genome for "Zhonghuang 13" by a combination of SMRT, Hi-C and optical mapping data. The assembled genome size is 1.025 Gb with a contig N50 of 3.46 Mb and a scaffold N50 of 51.87 Mb. Comparisons between this genome and the previously reported reference genome(cv. Williams82) uncovered more than 250,000 structure variations. A total of 52,051 protein coding genes and 36,429 transposable elements were annotated for this genome, and a gene co-expression network including 39,967 genes was also established. This high quality Chinese soybean genome and its sequence analysis will provide valuable information for soybean improvement in the future.
基金supported by the National Natural Science Research Foundation of China(NSFC)(project nos.3217030131770288.and 31600200)the MOE Layout Foundation of Humanities and Social Sciences(21YJAZH108)the Shandong Provincial Bohai Granary Science and Technology Demonstration Project(2019BHLC004)。
文摘Halophytes have evolved specialized strategies to cope with high salinity.The extreme halophyte sea lavender(Limonium bicolor)lacks trichomes but possesses salt glands on its epidermis that can excrete harmful ions,such as sodium,to avoid salt damage.Here,we report a high-quality,2.92-Gb,chromosome-scale L.bicolor genome assembly based on a combination of Illumina short reads,single-molecule,real-time long reads,chromosome conformation capture(Hi-C)data,and Bionano genome maps,greatly enriching the genomic information on recretohalophytes with multicellular salt glands.Although the L.bicolor genome contains genes that show similarity to trichome fate genes from Arabidopsis thaliana,it lacks homologs of the decision fate genes GLABRA3,ENHANCER OF GLABRA3,GLABRA2,TRANSPARENT TESTA GLABRA2,and SIAMESE,providing a molecular explanation for the absence of trichomes in this species.We identified key genes(LbHLH and LbTTG1)controlling salt gland development among classical trichome homologous genes and confirmed their roles by showing that their mutations markedly disrupted salt gland initiation,salt secretion,and salt tolerance,thus offering genetic support for the long-standing hypothesis that salt glands and trichomes may share a common origin.In addition,a whole-genome duplication event occurred in the L.bicolor genome after its divergence from Tartary buckwheat and may have contributed to its adaptation to high salinity.The L.bicolor genome resource and genetic evidence reported in this study provide profound insights into plant salt tolerance mechanisms that may facilitate the engineering of salt-tolerant crops.
基金funded by the Agricultural Science and Technology Innovation Programof the Chinese Academy of Agricultural Sciences andMajor Projects of Basic Research of Science,The Sci-Tech Innovation 2030 Agenda(2022ZD04021)the Technology and Innovation Commission of Shenzhen Municipality,the United Kingdom’s Biotechnology and Biological Sciences Research Council(BB/L026821/1)+4 种基金Research Councils UK(BB/P023444/1)(to K.W.)funded by BBSRC(BB/G105364/1)supported by the University of Cambridge Department of Zoologyfunded by EMBO fellowship ATSF-6889 and the CSIRO-Julius Award(R-91040-11)supported by the Lemann Brazil Research Fund from Harvard University.
文摘The cotton bollworm,Helicoverpa armigera,is set to become the most economically devastating crop pest in the world,threatening food security and biosafety as its range expands across the globe.Key to understanding the eco-evolutionary dynamics of H.armigera,and thus its management,is an understanding of population connectivity and the adaptations that allow the pest to establish in unique environments.We assembled a chromosome-scale reference genome and re-sequenced 503 individuals spanning the species range to delineate global patterns of connectivity,uncovering a previously cryptic population structure.
