AIM： To study the genes responsible for retinitis pigmentosa.METHODS： A total of 15 Chinese families with retinitis pigmentosa, containing 94 sporadically afflicted cases, were recruited. The targeted sequences were...AIM： To study the genes responsible for retinitis pigmentosa.METHODS： A total of 15 Chinese families with retinitis pigmentosa, containing 94 sporadically afflicted cases, were recruited. The targeted sequences were captured using the Target_Eye_365_V3 chip and sequenced using the BGISEQ-500 sequencer, according to the manufacturer＇s instructions. Data were aligned to UCSC Genome Browser build hg19, using the Burroughs Wheeler Aligner MEM algorithm. Local realignment was performed with the Genome Analysis Toolkit（GATK v.3.3.0） Indel Realigner, and variants were called with the Genome Analysis Toolkit Haplotypecaller, without any use of imputation. Variants were filtered against a panel derived from 1000 Genomes Project, 1000 G_ASN, ESP6500, Ex AC and db SNP138. In all members of Family ONE and Family TWO with available DNA samples, the genetic variant was validated using Sanger sequencing.RESULTS： A novel, pathogenic variant of retinitis pigmentosa, c.357_358 del AA（p.Ser119 Serfs X5） was identified in PRPF31 in 2 of 15 autosomal-dominant retinitis pigmentosa（ADRP） families, as well as in one, sporadic case. Sanger sequencing was performed uponprobands, as well as upon other family members. This novel, pathogenic genotype co-segregated with retinitis pigmentosa phenotype in these two families. CONCLUSION： ADRP is a subtype of retinitis pigmentosa, defined by its genotype, which accounts for 20%-40% of the retinitis pigmentosa patients. Our study thus expands the spectrum of PRPF31 mutations known to occur in ADRP, and provides further demonstration of the applicability of the BGISEQ500 sequencer for genomics research.展开更多
Modern land plants comprise two main lineages:tracheophytes and bryophytes.The latter include mosses,liverworts,and hornworts.Bryophytes are second only to angiosperms in diversity,with approximately 22,000 species(Sh...Modern land plants comprise two main lineages:tracheophytes and bryophytes.The latter include mosses,liverworts,and hornworts.Bryophytes are second only to angiosperms in diversity,with approximately 22,000 species(Shaw,2008).They are characterized by a life cycle dominated by haploid gametophytes,with unbranched diploid sporophytes attached to the gametophytes,producing spores for sexual reproduction(Shaw and Renzaglia,2004).Bryophytes have demonstrated great adaptability to modern ecosystems,thriving in environments ranging from deserts to wetlands and from tropical to polar regions(Degola et al.,2022).This adaptability suggests that bryophytes may have evolved an effective genetic toolkit for stress tolerance.Advances in genome sequencing and assembly technologies offer great opportunities to decipher the genetic toolkit and study the evolution of resistance and environmental adaptation in bryophytes.展开更多
Marchantia polymorpha,a model liverwort,provides a valuable system for investigating the evolution of plant sexual reproduction.To explore the cellular landscape of its reproductive structures,we generate a single-nuc...Marchantia polymorpha,a model liverwort,provides a valuable system for investigating the evolution of plant sexual reproduction.To explore the cellular landscape of its reproductive structures,we generate a single-nucleus transcriptomic atlas of the antheridiophore,archegoniophore,and sporophyte.Using singlenucleus RNA sequencing(snRNA-seq),we capture over 30,000 high-quality nuclei and identify distinct cel populations.In the male organ,we characterize stages of spermatogenesis from early antheridium cells to mature sperm,revealing dynamic transcriptional programs including cell cycle regulation,chromatin remodeling,and calcium signaling.In the female organ,we define cell types including archegonial layers and secondary central cells.Sporophyte clusters are annotated as spores,elaters,capsule wall,foot,and seta cells,with transcriptional signatures related to structural support,stress response,and reproductive functions.Cross-species analysis indicates that capsule wall cells in liverworts are similar to tapetum cells.Notably,foot cells exhibit high expression of genes involved in sporopollenin biosynthesis and signaling pathways,serving as a central hub that mediates communication between the maternal gametophyte and the developing sporophyte.This study provides a comprehensive cellular and molecular map of M.polymorpha reproductive organs and sporophyte,establishing a framework for investigating the development and evolution of sexual reproduction in early land plants.展开更多
The occurrence of severe thalassemia,an inherited blood disorder that is either blood-transfusiondependent or fatal,can be mitigated through carrier screening.Here,we aim to evaluate the effectiveness and outcomes of ...The occurrence of severe thalassemia,an inherited blood disorder that is either blood-transfusiondependent or fatal,can be mitigated through carrier screening.Here,we aim to evaluate the effectiveness and outcomes of pre-conceptional and early pregnancy screening initiatives for severe thalassemia prevention in a diverse population of 28,043 women.Using next-generation sequencing(NGS),we identify 4,226(15.07%)thalassemia carriers across 29 ethnic groups and categorize them into high-(0.75%),low-(25.86%),and unknown-risk(69.19%)groups based on their spouses'screening results.Post-screening follow-up reveals 59 fetuses with severe thalassemia exclusively in high-risk couples,underscoring the efficacy of risk classification.Among 25,053 live births over 6 months of age,two severe thalassemia infants were born to unknown-risk couples,which was attributed to incomplete screening and late NGS-based testing for a rare variant.Notably,64 rare variants are identified in 287 individuals,highlighting the genetic heterogeneity of thalassemia.We also observe that migrant flow significantly impacts carrier rates,with 93.90%of migrants to Chenzhou originating from high-prevalence regions in southern China.Our study demonstrates that NGS-based screening during pre-conception and early pregnancy is effective for severe thalassemia prevention,emphasizing the need for continuous screening efforts in areas with high and underestimated prevalence.展开更多
Handedness is a fundamental behavioral trait in humans,with the majority exhibiting right-hand dominance.While its origins remain elusive,it is considered an innate genetic trait.This study demonstrates pawedness in m...Handedness is a fundamental behavioral trait in humans,with the majority exhibiting right-hand dominance.While its origins remain elusive,it is considered an innate genetic trait.This study demonstrates pawedness in mice(n=473),comparable to human handedness,as an acquired trait rapidly emerging after limited unilateral paw training.Notably,acquired right-pawedness demonstrates greater conservativeness compared to left-pawedness,as evidenced by stronger stability and greater resistance to reversal.This results in a population right-paw dominance under random training conditions.Moreover,acquired pawedness also exhibits sex differences,with the initial preference proving more malleable in females.These findings unveil the acquired features of pawedness in mice.By illuminating possible behavioral laterality commonalities across species,the study proposes a postnatal hypothesis for the origins of human handedness:it is not an innate genetic trait as traditionally believed,but rather an environmentally acquired stable behavior whose development is actively guided by genetic predispositions.展开更多
目的 评估孕期居住地周边绿地暴露与低出生体重(low birth weight,LBW,出生体重<2 500 g)风险的关联。方法 本研究为回顾性队列研究,基于既有多中心母婴队列数据库(重庆、贵阳、成都、连云港)开展二次分析。回顾性纳入2023年12月—2...目的 评估孕期居住地周边绿地暴露与低出生体重(low birth weight,LBW,出生体重<2 500 g)风险的关联。方法 本研究为回顾性队列研究,基于既有多中心母婴队列数据库(重庆、贵阳、成都、连云港)开展二次分析。回顾性纳入2023年12月—2024年12月在四中心分娩并符合纳排标准的单胎妊娠孕妇,提取其孕期及分娩相关资料,并采用MODIS MOD13Q1估计居住地500 m缓冲区归一化植被指数均值(normalized difference vegetation index mean within 500 m buffer,NDVImean-500 m)与增强型植被指数均值(enhanced vegetation index mean within 500 m buffer,EVImean-500 m)。以LBW为二分类结局,采用Logistic回归评估NDVI/EVI(每增加0.1单位)与LBW风险的关联,并构建限制性立方样条(restricted cubic spline,RCS)评估剂量―反应关系。多因素模型(Model 2)调整高龄(≥35岁)、受教育程度、孕前体重指数(body mass index,BMI)分组与产次。另在Model 2基础上开展“附加调整孕周(<37周)”及“足月限制(≥37周)”敏感性分析。结果 共纳入单胎孕妇5 397例,其中LBW 147例,发生率为2.72%(95%CI:2.32%~3.19%)。在完全调整模型中,EVImean-500 m每增加0.1单位与LBW风险降低相关(OR=0.488,95%CI:0.405~0.587,P<0.001),NDVImean-500 m结果一致(OR=0.690,95%CI:0.587~0.810,P<0.001)。RCS分析显示,2个指标总体关联均显著(P<0.001);EVI提示非线性(P<0.001),NDVI未见显著非线性(P=0.095)。附加调整孕周及足月限制后,关联方向与主分析一致。结论 在单胎妊娠样本中,孕期居住地周边绿地暴露水平与LBW风险降低相关,并呈现剂量―反应特征。鉴于观察性研究可能存在残余混杂与暴露错分,结果应谨慎解释为相关性发现,尚需进一步研究验证其因果关系与作用路径。展开更多
文摘AIM： To study the genes responsible for retinitis pigmentosa.METHODS： A total of 15 Chinese families with retinitis pigmentosa, containing 94 sporadically afflicted cases, were recruited. The targeted sequences were captured using the Target_Eye_365_V3 chip and sequenced using the BGISEQ-500 sequencer, according to the manufacturer＇s instructions. Data were aligned to UCSC Genome Browser build hg19, using the Burroughs Wheeler Aligner MEM algorithm. Local realignment was performed with the Genome Analysis Toolkit（GATK v.3.3.0） Indel Realigner, and variants were called with the Genome Analysis Toolkit Haplotypecaller, without any use of imputation. Variants were filtered against a panel derived from 1000 Genomes Project, 1000 G_ASN, ESP6500, Ex AC and db SNP138. In all members of Family ONE and Family TWO with available DNA samples, the genetic variant was validated using Sanger sequencing.RESULTS： A novel, pathogenic variant of retinitis pigmentosa, c.357_358 del AA（p.Ser119 Serfs X5） was identified in PRPF31 in 2 of 15 autosomal-dominant retinitis pigmentosa（ADRP） families, as well as in one, sporadic case. Sanger sequencing was performed uponprobands, as well as upon other family members. This novel, pathogenic genotype co-segregated with retinitis pigmentosa phenotype in these two families. CONCLUSION： ADRP is a subtype of retinitis pigmentosa, defined by its genotype, which accounts for 20%-40% of the retinitis pigmentosa patients. Our study thus expands the spectrum of PRPF31 mutations known to occur in ADRP, and provides further demonstration of the applicability of the BGISEQ500 sequencer for genomics research.
基金funded by Scientific Foundation of the Urban Management Bureau of Shenzhen(202403 to YL and 202302 to SD)part of the 10KP project(https://db.cngb.org/10kp/)+1 种基金supported by China National GeneBank(CNGBhttps://www.cngb.org/).
文摘Modern land plants comprise two main lineages:tracheophytes and bryophytes.The latter include mosses,liverworts,and hornworts.Bryophytes are second only to angiosperms in diversity,with approximately 22,000 species(Shaw,2008).They are characterized by a life cycle dominated by haploid gametophytes,with unbranched diploid sporophytes attached to the gametophytes,producing spores for sexual reproduction(Shaw and Renzaglia,2004).Bryophytes have demonstrated great adaptability to modern ecosystems,thriving in environments ranging from deserts to wetlands and from tropical to polar regions(Degola et al.,2022).This adaptability suggests that bryophytes may have evolved an effective genetic toolkit for stress tolerance.Advances in genome sequencing and assembly technologies offer great opportunities to decipher the genetic toolkit and study the evolution of resistance and environmental adaptation in bryophytes.
基金supported by the 10 KP project(https://db.cngb.org/1Okp/)and the Scientific Foundation of the Urban Management Bureau of Shenzhen(202403).
文摘Marchantia polymorpha,a model liverwort,provides a valuable system for investigating the evolution of plant sexual reproduction.To explore the cellular landscape of its reproductive structures,we generate a single-nucleus transcriptomic atlas of the antheridiophore,archegoniophore,and sporophyte.Using singlenucleus RNA sequencing(snRNA-seq),we capture over 30,000 high-quality nuclei and identify distinct cel populations.In the male organ,we characterize stages of spermatogenesis from early antheridium cells to mature sperm,revealing dynamic transcriptional programs including cell cycle regulation,chromatin remodeling,and calcium signaling.In the female organ,we define cell types including archegonial layers and secondary central cells.Sporophyte clusters are annotated as spores,elaters,capsule wall,foot,and seta cells,with transcriptional signatures related to structural support,stress response,and reproductive functions.Cross-species analysis indicates that capsule wall cells in liverworts are similar to tapetum cells.Notably,foot cells exhibit high expression of genes involved in sporopollenin biosynthesis and signaling pathways,serving as a central hub that mediates communication between the maternal gametophyte and the developing sporophyte.This study provides a comprehensive cellular and molecular map of M.polymorpha reproductive organs and sporophyte,establishing a framework for investigating the development and evolution of sexual reproduction in early land plants.
基金supported by the National Natural Science Foundation of China(81760037)Yunling Scholar Project of Yunnan Province(YNWR-YLXZ-2019-0005)+1 种基金Hunan Provincial Innovation Platform and Talent Program(2018SK4004)Hunan Provincial Natural Science Foundation(2019JJ80048).
文摘The occurrence of severe thalassemia,an inherited blood disorder that is either blood-transfusiondependent or fatal,can be mitigated through carrier screening.Here,we aim to evaluate the effectiveness and outcomes of pre-conceptional and early pregnancy screening initiatives for severe thalassemia prevention in a diverse population of 28,043 women.Using next-generation sequencing(NGS),we identify 4,226(15.07%)thalassemia carriers across 29 ethnic groups and categorize them into high-(0.75%),low-(25.86%),and unknown-risk(69.19%)groups based on their spouses'screening results.Post-screening follow-up reveals 59 fetuses with severe thalassemia exclusively in high-risk couples,underscoring the efficacy of risk classification.Among 25,053 live births over 6 months of age,two severe thalassemia infants were born to unknown-risk couples,which was attributed to incomplete screening and late NGS-based testing for a rare variant.Notably,64 rare variants are identified in 287 individuals,highlighting the genetic heterogeneity of thalassemia.We also observe that migrant flow significantly impacts carrier rates,with 93.90%of migrants to Chenzhou originating from high-prevalence regions in southern China.Our study demonstrates that NGS-based screening during pre-conception and early pregnancy is effective for severe thalassemia prevention,emphasizing the need for continuous screening efforts in areas with high and underestimated prevalence.
基金supported by grants from the National Natural Science Foundation of China,China(32470630 to Z.S.)the Scientific Foundation of the Institute of Psychology,Chinese Academy of Sciences,China(E2CX4115CX to J.W.)State Key Laboratory of Animal Biodiversity Conservation and Integrated Pest Management,China(SKLA2508 to Y.W.).
文摘Handedness is a fundamental behavioral trait in humans,with the majority exhibiting right-hand dominance.While its origins remain elusive,it is considered an innate genetic trait.This study demonstrates pawedness in mice(n=473),comparable to human handedness,as an acquired trait rapidly emerging after limited unilateral paw training.Notably,acquired right-pawedness demonstrates greater conservativeness compared to left-pawedness,as evidenced by stronger stability and greater resistance to reversal.This results in a population right-paw dominance under random training conditions.Moreover,acquired pawedness also exhibits sex differences,with the initial preference proving more malleable in females.These findings unveil the acquired features of pawedness in mice.By illuminating possible behavioral laterality commonalities across species,the study proposes a postnatal hypothesis for the origins of human handedness:it is not an innate genetic trait as traditionally believed,but rather an environmentally acquired stable behavior whose development is actively guided by genetic predispositions.
文摘目的 评估孕期居住地周边绿地暴露与低出生体重(low birth weight,LBW,出生体重<2 500 g)风险的关联。方法 本研究为回顾性队列研究,基于既有多中心母婴队列数据库(重庆、贵阳、成都、连云港)开展二次分析。回顾性纳入2023年12月—2024年12月在四中心分娩并符合纳排标准的单胎妊娠孕妇,提取其孕期及分娩相关资料,并采用MODIS MOD13Q1估计居住地500 m缓冲区归一化植被指数均值(normalized difference vegetation index mean within 500 m buffer,NDVImean-500 m)与增强型植被指数均值(enhanced vegetation index mean within 500 m buffer,EVImean-500 m)。以LBW为二分类结局,采用Logistic回归评估NDVI/EVI(每增加0.1单位)与LBW风险的关联,并构建限制性立方样条(restricted cubic spline,RCS)评估剂量―反应关系。多因素模型(Model 2)调整高龄(≥35岁)、受教育程度、孕前体重指数(body mass index,BMI)分组与产次。另在Model 2基础上开展“附加调整孕周(<37周)”及“足月限制(≥37周)”敏感性分析。结果 共纳入单胎孕妇5 397例,其中LBW 147例,发生率为2.72%(95%CI:2.32%~3.19%)。在完全调整模型中,EVImean-500 m每增加0.1单位与LBW风险降低相关(OR=0.488,95%CI:0.405~0.587,P<0.001),NDVImean-500 m结果一致(OR=0.690,95%CI:0.587~0.810,P<0.001)。RCS分析显示,2个指标总体关联均显著(P<0.001);EVI提示非线性(P<0.001),NDVI未见显著非线性(P=0.095)。附加调整孕周及足月限制后,关联方向与主分析一致。结论 在单胎妊娠样本中,孕期居住地周边绿地暴露水平与LBW风险降低相关,并呈现剂量―反应特征。鉴于观察性研究可能存在残余混杂与暴露错分,结果应谨慎解释为相关性发现,尚需进一步研究验证其因果关系与作用路径。
