Without known analogous sex-determining factors like SRY(sex determining region Y)in mammals,the chicken(Gallus gallus)sex determination mechanism still remains unclear,which highly restricts the biological research o...Without known analogous sex-determining factors like SRY(sex determining region Y)in mammals,the chicken(Gallus gallus)sex determination mechanism still remains unclear,which highly restricts the biological research on chicken development and poultry single-sex reproduction.Here we not only characterized a new female-biased gene UBE2I and identified the expression pattern by qRT-PCR,but also described the functional role of UBE2I in the gonadal development of chicken embryos.Results showed that UBE2I exhibited a female-biased expression pattern in the early stage of PGCs(primordial germ cells)in embryonic gonads and robust expression in ovaries of newborn chickens.Most importantly,we successfully developed an effective method to interfere or overexpress UBE2I in chicken embryos through the intravascular injection.The qRT-PCR analysis showed that the sex-related genes(FOXL2,CYP19A1 and HINTW)in females were upregulated(P<0.05)under the overexpression of UBE2I and the sex-related genes(SOX9,DMRT1 and WT1)in females were downregulated(P<0.05)after interfering UBE2I.Furthermore,the change of UBE2I expression was associated with the level of estradiol and its receptors(AR and ESR),which suggests that UBE2I is necessary to initiate the female-specific development in chickens.In conclusion,this work demonstrates that UBE2I is a crucial sex differentiation-related gene in the embryonic development of chickens,which provides insights for further understanding the mechanism of sex determination in chickens.展开更多
Background Understanding the genetic basis of male reproduction in mammals remains challenging.Commercial pig populations offer a unique model for studying fertility,as semen traits are routinely recorded using high-t...Background Understanding the genetic basis of male reproduction in mammals remains challenging.Commercial pig populations offer a unique model for studying fertility,as semen traits are routinely recorded using high-throughput systems.Results In a large-scale GWAS of 15 semen traits based on 286,314 ejaculates collected from 2,954 boars of a purebred pig line,we identified 10 QTL,including four loci with recessive deleterious alleles.Several lead SNPs affected multiple semen traits.For example,a SNP on SSC6 was significantly associated with distal cytoplasmic droplets and with effects on tail abnormalities and sperm motility in a follow up analysis.The allele frequencies of some loci were different in older boar's,most likely due to culling based on poor semen quality.Using WGS,we identified six missense variants in high linkage disequilibrium(LD)with lead SNPs in genes related to sperm production(e.g.,MEIOB,CFAP74 and UBE2B).Remarkably,the frequency of some alleles with predicted deleterious effects on semen traits increased between 2013 and 2019.Conclusions Our results highlight loci with major effects on semen quality,some of which are linked to functional variants in key genes involved in spermatogenesis.The information from this study can be used to select against deleterious alleles affecting semen characteristics in pigs and provides valuable insight into the genetics of mammalian male fertility.展开更多
该文报道1个累及3代共9人的Nascimento型X连锁智力障碍(Nascimento form of syndromic X-linked intellectual developmental disorder,MRXSN)大家系的临床特点及基因突变类型并进行文献复习。家系中共9人有相似的智力障碍、特殊面容等...该文报道1个累及3代共9人的Nascimento型X连锁智力障碍(Nascimento form of syndromic X-linked intellectual developmental disorder,MRXSN)大家系的临床特点及基因突变类型并进行文献复习。家系中共9人有相似的智力障碍、特殊面容等,其中4人已去世。基因检测提示先证者UBE2A基因存在2~3号外显子缺失,来自母亲。荧光定量聚合酶链反应显示,先证者和表舅UBE2A基因存在2~3号外显子缺失,先证者之母亲、外婆及表姨奶UBE2A基因存在2~3号外显子杂合缺失;先证者之父亲、姐姐、表姨UBE2A基因2~3号外显子拷贝数均正常。文献报道的34例患者临床表型多样,UBE2A基因突变(22/34,65%)和大片段缺失(12/34,35%)为主要突变类型。中重度智力障碍(34/34,100%)、言语障碍(33/34,97%)、特殊面容(32/34,94%)等是MRXSN患者主要的临床表现。该病具有明显的表型异质性,尽早明确诊断有利于优生优育。展开更多
UBE2O is a distinctive ubiquitin-conjugating enzyme characterized by its large size(1292 residues)and dual E2/E3 enzymatic activities,enabling diverse ubiquitylation types.Unlike typical E2 enzymes(150~200 residues),U...UBE2O is a distinctive ubiquitin-conjugating enzyme characterized by its large size(1292 residues)and dual E2/E3 enzymatic activities,enabling diverse ubiquitylation types.Unlike typical E2 enzymes(150~200 residues),UBE2O’s multifunctionality allows it to regulate substrate degradation,subcellular localization,and functional modulation.Emerging studies highlight its critical roles in protein quality control,erythroid differentiation,metabolic regulation,and maintenance of circadian rhythm.Dysregulation of UBE2O is implicated in various diseases,including cancers,neurodegenerative disorders,and metabolic diseases.This review extensively discusses the unique structural features,diverse biological functions,and pathological roles of UBE2O,as well as its therapeutic potential for associated diseases.展开更多
基金funded by the National Natural Science Foundation of China(31772582 and 31972547)the National Key R&D Program of China(2017YFE0108000)+2 种基金the High Level Talents Support Program of Yangzhou University,Postgraduate Research&Practice Innovation Program of Jiangsu Province,China(KYCX182376)the Jiangsu Science and Technology Project,China(Youth Fund,BK20180918)the Natural Science Research Project of Jiangsu Higher Education Institutions,China(18KJB230008)。
文摘Without known analogous sex-determining factors like SRY(sex determining region Y)in mammals,the chicken(Gallus gallus)sex determination mechanism still remains unclear,which highly restricts the biological research on chicken development and poultry single-sex reproduction.Here we not only characterized a new female-biased gene UBE2I and identified the expression pattern by qRT-PCR,but also described the functional role of UBE2I in the gonadal development of chicken embryos.Results showed that UBE2I exhibited a female-biased expression pattern in the early stage of PGCs(primordial germ cells)in embryonic gonads and robust expression in ovaries of newborn chickens.Most importantly,we successfully developed an effective method to interfere or overexpress UBE2I in chicken embryos through the intravascular injection.The qRT-PCR analysis showed that the sex-related genes(FOXL2,CYP19A1 and HINTW)in females were upregulated(P<0.05)under the overexpression of UBE2I and the sex-related genes(SOX9,DMRT1 and WT1)in females were downregulated(P<0.05)after interfering UBE2I.Furthermore,the change of UBE2I expression was associated with the level of estradiol and its receptors(AR and ESR),which suggests that UBE2I is necessary to initiate the female-specific development in chickens.In conclusion,this work demonstrates that UBE2I is a crucial sex differentiation-related gene in the embryonic development of chickens,which provides insights for further understanding the mechanism of sex determination in chickens.
基金the GEroNIMO(Genome and Epigenome Enabled Breeding in Monogastics)project.The GEroNIMO project has received funding from the European Union’s Horizon 2020 research and innovation program under Grant Agreement No 101000236。
文摘Background Understanding the genetic basis of male reproduction in mammals remains challenging.Commercial pig populations offer a unique model for studying fertility,as semen traits are routinely recorded using high-throughput systems.Results In a large-scale GWAS of 15 semen traits based on 286,314 ejaculates collected from 2,954 boars of a purebred pig line,we identified 10 QTL,including four loci with recessive deleterious alleles.Several lead SNPs affected multiple semen traits.For example,a SNP on SSC6 was significantly associated with distal cytoplasmic droplets and with effects on tail abnormalities and sperm motility in a follow up analysis.The allele frequencies of some loci were different in older boar's,most likely due to culling based on poor semen quality.Using WGS,we identified six missense variants in high linkage disequilibrium(LD)with lead SNPs in genes related to sperm production(e.g.,MEIOB,CFAP74 and UBE2B).Remarkably,the frequency of some alleles with predicted deleterious effects on semen traits increased between 2013 and 2019.Conclusions Our results highlight loci with major effects on semen quality,some of which are linked to functional variants in key genes involved in spermatogenesis.The information from this study can be used to select against deleterious alleles affecting semen characteristics in pigs and provides valuable insight into the genetics of mammalian male fertility.
文摘该文报道1个累及3代共9人的Nascimento型X连锁智力障碍(Nascimento form of syndromic X-linked intellectual developmental disorder,MRXSN)大家系的临床特点及基因突变类型并进行文献复习。家系中共9人有相似的智力障碍、特殊面容等,其中4人已去世。基因检测提示先证者UBE2A基因存在2~3号外显子缺失,来自母亲。荧光定量聚合酶链反应显示,先证者和表舅UBE2A基因存在2~3号外显子缺失,先证者之母亲、外婆及表姨奶UBE2A基因存在2~3号外显子杂合缺失;先证者之父亲、姐姐、表姨UBE2A基因2~3号外显子拷贝数均正常。文献报道的34例患者临床表型多样,UBE2A基因突变(22/34,65%)和大片段缺失(12/34,35%)为主要突变类型。中重度智力障碍(34/34,100%)、言语障碍(33/34,97%)、特殊面容(32/34,94%)等是MRXSN患者主要的临床表现。该病具有明显的表型异质性,尽早明确诊断有利于优生优育。
基金Supported by Special Projects in Key Areas for Guangdong Provincial Colleges and Universities (No.2021ZDZX2009)Guangzhou Medical University Discipline Construction Funds (Basic Medicine)(No.JCXKJS2022A05)。
文摘UBE2O is a distinctive ubiquitin-conjugating enzyme characterized by its large size(1292 residues)and dual E2/E3 enzymatic activities,enabling diverse ubiquitylation types.Unlike typical E2 enzymes(150~200 residues),UBE2O’s multifunctionality allows it to regulate substrate degradation,subcellular localization,and functional modulation.Emerging studies highlight its critical roles in protein quality control,erythroid differentiation,metabolic regulation,and maintenance of circadian rhythm.Dysregulation of UBE2O is implicated in various diseases,including cancers,neurodegenerative disorders,and metabolic diseases.This review extensively discusses the unique structural features,diverse biological functions,and pathological roles of UBE2O,as well as its therapeutic potential for associated diseases.
