Patients affected by monogenic diseases impose a substantial burden on both themselves and their families.The primary preventive measure,i.e.,invasive prenatal diagnosis,carries a risk of miscarriage and cannot be per...Patients affected by monogenic diseases impose a substantial burden on both themselves and their families.The primary preventive measure,i.e.,invasive prenatal diagnosis,carries a risk of miscarriage and cannot be performed early in pregnancy.Hence,there is a need for non-invasive prenatal testing(NIPT)for monogenic diseases.By utilizing enriched cell-free fetal DNA(cffDNA)from maternal plasma,we refine the NIPT method,which combines targeted region capture technology,haplotyping,and analysis of informative site frequency.We apply this method to 93 clinical families at genetic risk for thalassemia,encompassing various genetic variant types,to establish a workflow and evaluate its efficiency.Our approach requires only 3 ng of DNA input to generate 0.1 Gb informative target genomic data and leverages a minimum of 3%cffDNA.This method has a 98.16%success rate and 100%concordance with conventional invasive methods.Furthermore,we demonstrate the ability to analyze fetal genotypes as early as eight weeks of gestation.This study establishes an optimized NIPT method for the early detection of various thalassemia disorders during pregnancy.This technique demonstrates high accuracy and potential for clinical application in prenatal diagnosis.展开更多
Aims The two coexisting Leymus chinensis ecotypes exhibit remarkable divergences in adaptive strategies under drought and salinity in semi-humid meadows and semi-arid steppes.In order to detect the major genetic and e...Aims The two coexisting Leymus chinensis ecotypes exhibit remarkable divergences in adaptive strategies under drought and salinity in semi-humid meadows and semi-arid steppes.In order to detect the major genetic and environmental factors dominating the intraspecific phenotype variations and ecotype formation,the questions regarding the two distinct phenotypic forms(ecotypes)in L.chin-ensis were addressed:(i)did environments drive the L.chinensis ecotype formation?(ii)was there a molecular basis for the morphological divergence between the two ecotypes?(iii)which driving force dominated the intraspecies divergence,divergent natural selection,genetic drift or stabilizing selection?Methods We applied a series experiments on demographical,morphological and physiological traits of two Leymus chinensis ecotypes with gray green(GG)and yellow green(YG)leaf color in nine wild sites along a longitudinal gradient from 114°to 124°E in northeast China.The environmental data including mean annual precipitation,mean annual temperature,elevation and soil properties were collected.We compared the differences of morphological,physiological and genetic differentiations between the two ecotypes.Important FindingsThe GG type exhibited stronger fitness than YG type from the population densities,morphological traits(e.g.shoot height,leaf area,leaf and seed weights et al.),leaf mass per area(LMA)and physiological traits[relative water content(RWC),proline,soluble sugar contents].Most of above phenotypes(e.g.total shoot densities,spike length et al.)were significantly correlated with mean annual precipitation,mean annual temperature and soil water content(SWC),rarely a correlated with soil pH and soil nutrient.Transplanted populations showed convergence trend by their leaf chlorophyll contents and osmotic adjustments(proline and soluble sugar contents)in the greenhouse,but still exhibited their divergences between two ecotypes in the outdoor transplantation,suggesting that whether L.chinensis ecotype differentiated could be largely affected by the environmental conditions.Furthermore,by the comparison result of quantitative genetic variation(Q_(ST))values from phenotypes with theoretical neutral genetic differentiation(F_(ST)),differentiation in phenotypic traits greatly surpassed neutral predictions,implying that directional natural selection played a crucial role in L.chinen-sis ecotype differentiation.In addition,microsatellite analysis from Neighbor-joining tree and Bayesian assignment generated into two groups according to ecotypes,indicating molecular genetic differentiation also propelled the two ecotypes divergence.We conclude that L.chinensis population variations were driven by combing divergent natural selection(precipitation,temperature and SWCs)along the large-scale gradient and significantly intrinsic genetic differentiation.展开更多
基金supported by the National Key R&D Program of China(2024YFA1802300)the Major Science and Technology Program of Hainan Province(ZDKJ2021037)+4 种基金the Regional Innovation and Development Joint Fund of the National Natural Science Foundation of China(U24A20677)Hainan Province Science and Technology Special Fund(ZDYF2020117,ZDY2024SHFZ143)Hainan Province Science and TechnologyProject(LCXY202102,LCYX202203,LCYX202301,LCYx202502)Innovative research project for postgraduate students in Hainan Medical University(HYYB2021A05)the Hainan Province Clinical Medical Center,and the specific research fund of The Innovation Platform for Academicians of Hainan Province(YSPTZX202310).
文摘Patients affected by monogenic diseases impose a substantial burden on both themselves and their families.The primary preventive measure,i.e.,invasive prenatal diagnosis,carries a risk of miscarriage and cannot be performed early in pregnancy.Hence,there is a need for non-invasive prenatal testing(NIPT)for monogenic diseases.By utilizing enriched cell-free fetal DNA(cffDNA)from maternal plasma,we refine the NIPT method,which combines targeted region capture technology,haplotyping,and analysis of informative site frequency.We apply this method to 93 clinical families at genetic risk for thalassemia,encompassing various genetic variant types,to establish a workflow and evaluate its efficiency.Our approach requires only 3 ng of DNA input to generate 0.1 Gb informative target genomic data and leverages a minimum of 3%cffDNA.This method has a 98.16%success rate and 100%concordance with conventional invasive methods.Furthermore,we demonstrate the ability to analyze fetal genotypes as early as eight weeks of gestation.This study establishes an optimized NIPT method for the early detection of various thalassemia disorders during pregnancy.This technique demonstrates high accuracy and potential for clinical application in prenatal diagnosis.
基金National Scientific Foundation of China(31470404 and 31070228).
文摘Aims The two coexisting Leymus chinensis ecotypes exhibit remarkable divergences in adaptive strategies under drought and salinity in semi-humid meadows and semi-arid steppes.In order to detect the major genetic and environmental factors dominating the intraspecific phenotype variations and ecotype formation,the questions regarding the two distinct phenotypic forms(ecotypes)in L.chin-ensis were addressed:(i)did environments drive the L.chinensis ecotype formation?(ii)was there a molecular basis for the morphological divergence between the two ecotypes?(iii)which driving force dominated the intraspecies divergence,divergent natural selection,genetic drift or stabilizing selection?Methods We applied a series experiments on demographical,morphological and physiological traits of two Leymus chinensis ecotypes with gray green(GG)and yellow green(YG)leaf color in nine wild sites along a longitudinal gradient from 114°to 124°E in northeast China.The environmental data including mean annual precipitation,mean annual temperature,elevation and soil properties were collected.We compared the differences of morphological,physiological and genetic differentiations between the two ecotypes.Important FindingsThe GG type exhibited stronger fitness than YG type from the population densities,morphological traits(e.g.shoot height,leaf area,leaf and seed weights et al.),leaf mass per area(LMA)and physiological traits[relative water content(RWC),proline,soluble sugar contents].Most of above phenotypes(e.g.total shoot densities,spike length et al.)were significantly correlated with mean annual precipitation,mean annual temperature and soil water content(SWC),rarely a correlated with soil pH and soil nutrient.Transplanted populations showed convergence trend by their leaf chlorophyll contents and osmotic adjustments(proline and soluble sugar contents)in the greenhouse,but still exhibited their divergences between two ecotypes in the outdoor transplantation,suggesting that whether L.chinensis ecotype differentiated could be largely affected by the environmental conditions.Furthermore,by the comparison result of quantitative genetic variation(Q_(ST))values from phenotypes with theoretical neutral genetic differentiation(F_(ST)),differentiation in phenotypic traits greatly surpassed neutral predictions,implying that directional natural selection played a crucial role in L.chinen-sis ecotype differentiation.In addition,microsatellite analysis from Neighbor-joining tree and Bayesian assignment generated into two groups according to ecotypes,indicating molecular genetic differentiation also propelled the two ecotypes divergence.We conclude that L.chinensis population variations were driven by combing divergent natural selection(precipitation,temperature and SWCs)along the large-scale gradient and significantly intrinsic genetic differentiation.
