核型分析作为产前诊断常规项目应用于遗传学诊断和遗传咨询。染色体多态性在核型分析中很常见,但因缺乏以图示为参照的多态性判断标准,使各实验室对同一染色体变异是否应判断为多态性以及用什么符号表达多态性存在差异,从而影响核型分...核型分析作为产前诊断常规项目应用于遗传学诊断和遗传咨询。染色体多态性在核型分析中很常见,但因缺乏以图示为参照的多态性判断标准,使各实验室对同一染色体变异是否应判断为多态性以及用什么符号表达多态性存在差异,从而影响核型分析报告的互认及多态性的临床解读。本共识通过采集已确诊的各种多态性核型图,研究其在不同显带技术中的形态特征,比较各种多态性的G带、C带和N带的特征异同,确认多态性G带特征,并参照《人类细胞基因组学国际命名体系(ISCN 2024)》(An International System for Human Cytogenomic Nomenclature,ISCN 2024)进行多态性归类,提出判断标准、鉴别流程、知情告知和临床解读模式,以规范多态性判别,促进核型分析报告互认,确保遗传咨询结果一致,解决本行业长期困扰的多态性判断标准缺乏和同一多态性被不同解读的遗传咨询问题。展开更多
过去20年,全基因组关联研究(genome-wide association study,GWAS)已确定了诸多遗传性疾病相关的基因变异和遗传位点。随着GWAS方法的逐步成熟与饱和,全转录组关联研究(transcriptome-wide association study,TWAS)作为一种关联遗传表...过去20年,全基因组关联研究(genome-wide association study,GWAS)已确定了诸多遗传性疾病相关的基因变异和遗传位点。随着GWAS方法的逐步成熟与饱和,全转录组关联研究(transcriptome-wide association study,TWAS)作为一种关联遗传表型与基因表达水平的研究方法,为解析复杂疾病的遗传机制提供了新视角。TWAS与其他多组学分析联合应用,能使人们更好地理解和研究遗传性疾病。本文对近年来具有突破意义和代表性的TWAS方法和工具进行介绍,分析不同工具的优势与不足,并探讨TWAS未来发展趋势。展开更多
目的检测1例下切牙先天缺失家系的基因突变情况,确定突变位点并探究突变对蛋白结构和功能的潜在影响,为下切牙先天缺失的发生机制提供新的见解。方法通过全外显子组测序及Sanger测序筛选该家系可能的致病基因,并对验证后的基因进行功能...目的检测1例下切牙先天缺失家系的基因突变情况,确定突变位点并探究突变对蛋白结构和功能的潜在影响,为下切牙先天缺失的发生机制提供新的见解。方法通过全外显子组测序及Sanger测序筛选该家系可能的致病基因,并对验证后的基因进行功能预测及突变位点氨基酸保守性分析。利用AlphaFold和PyMOL预测该蛋白的三维结构。使用小鼠基因组信息学和时空转录组图谱对候选基因表达进行分析。使用单细胞RNA测序数据分析白细胞受体簇成员9(leukocyte receptor cluster member 9,LENG9)基因可能参与调控的下游通路。结果在临床诊疗过程中发现1例下切牙先天缺失的家系。先证者及先证者的弟弟存在先天缺失下切牙的表型,先证者两侧磨牙远中关系、尖牙远中关系、上前牙轻度拥挤、下颌散在间隙、深覆牙合、深覆盖,而先证者的父母无缺牙表型。通过全外显子组测序发现在LENG9基因外显子1上存在(c.392C>T:p.Arg131His)的突变,且第131号的精氨酸在各物种间具有高度保守性。生物信息学分析显示LENG9在颌骨和牙齿中有表达。GO和KEGG通路注释分析表明,LENG9可能通过调控氧化磷酸化相关通路参与先天缺牙的发生。结论本研究报道了1例下切牙先天缺失的家系和1个LENG9(c.392C>T:p.Arg131His)的新发突变,研究结果提示该突变可能是导致该家系下切牙先天缺失的致病基因。展开更多
The comorbidity of skin and gastrointestinal tract(GIT)diseases,primarily driven by the gut-skin axis(GSA),is well established.However,the genetic contribution to the GSA remains unclear.Here,using genome-wide associa...The comorbidity of skin and gastrointestinal tract(GIT)diseases,primarily driven by the gut-skin axis(GSA),is well established.However,the genetic contribution to the GSA remains unclear.Here,using genome-wide association study(GWAS)summary statistics from European populations,we performed a genome-wide pleiotropic analysis to investigate the shared genetic basis and causal associations between skin and GIT diseases.We observed extensive genetic correlations and overlaps between skin and GIT diseases.A total of 298 pleiotropic loci were identified,75 of which were colocalized,and 61 exhibited pleiotropic effects across multiple trait pairs,including 2p16.1(PUS10),6p21.32(HLA-DRB1),10q21.2(ZNF365),and 19q13.11(SLC7A10).Additionally,five novel loci were identified based on the pleiotropic analysis;among them,the 15q22.2 locus harboring RORA was validated by the latest inflammatory bowel disease GWAS.Gene-based analysis identified 394 unique pleiotropic genes,which were enriched in GSA-associated tissues and the immune system,and protein-protein interaction analysis further revealed that the GPCR-cAMP,chromatin remodeling,JAK-STAT,and HLA-mediated immunity pathways were involved in GSA comorbidity.Notably,the JAK-STAT pathway showed strong potential for drug repurposing,with adalimumab targeting tumor necrosis factor and ustekinumab targeting interleukin-12 subunit beta already being used to treat both skin and GIT diseases.Finally,Mendelian randomization analysis identified five significant causal associations,and subsequent mediation analysis identified three potential microbiota-GIT-skin pathways.Taken together,our study demonstrated that the shared genetic factors between skin and GIT diseases were widely distributed across the genome.These findings will enhance our understanding of the genetic mechanisms underlying GSA comorbidity.展开更多
文摘核型分析作为产前诊断常规项目应用于遗传学诊断和遗传咨询。染色体多态性在核型分析中很常见,但因缺乏以图示为参照的多态性判断标准,使各实验室对同一染色体变异是否应判断为多态性以及用什么符号表达多态性存在差异,从而影响核型分析报告的互认及多态性的临床解读。本共识通过采集已确诊的各种多态性核型图,研究其在不同显带技术中的形态特征,比较各种多态性的G带、C带和N带的特征异同,确认多态性G带特征,并参照《人类细胞基因组学国际命名体系(ISCN 2024)》(An International System for Human Cytogenomic Nomenclature,ISCN 2024)进行多态性归类,提出判断标准、鉴别流程、知情告知和临床解读模式,以规范多态性判别,促进核型分析报告互认,确保遗传咨询结果一致,解决本行业长期困扰的多态性判断标准缺乏和同一多态性被不同解读的遗传咨询问题。
文摘过去20年,全基因组关联研究(genome-wide association study,GWAS)已确定了诸多遗传性疾病相关的基因变异和遗传位点。随着GWAS方法的逐步成熟与饱和,全转录组关联研究(transcriptome-wide association study,TWAS)作为一种关联遗传表型与基因表达水平的研究方法,为解析复杂疾病的遗传机制提供了新视角。TWAS与其他多组学分析联合应用,能使人们更好地理解和研究遗传性疾病。本文对近年来具有突破意义和代表性的TWAS方法和工具进行介绍,分析不同工具的优势与不足,并探讨TWAS未来发展趋势。
文摘目的检测1例下切牙先天缺失家系的基因突变情况,确定突变位点并探究突变对蛋白结构和功能的潜在影响,为下切牙先天缺失的发生机制提供新的见解。方法通过全外显子组测序及Sanger测序筛选该家系可能的致病基因,并对验证后的基因进行功能预测及突变位点氨基酸保守性分析。利用AlphaFold和PyMOL预测该蛋白的三维结构。使用小鼠基因组信息学和时空转录组图谱对候选基因表达进行分析。使用单细胞RNA测序数据分析白细胞受体簇成员9(leukocyte receptor cluster member 9,LENG9)基因可能参与调控的下游通路。结果在临床诊疗过程中发现1例下切牙先天缺失的家系。先证者及先证者的弟弟存在先天缺失下切牙的表型,先证者两侧磨牙远中关系、尖牙远中关系、上前牙轻度拥挤、下颌散在间隙、深覆牙合、深覆盖,而先证者的父母无缺牙表型。通过全外显子组测序发现在LENG9基因外显子1上存在(c.392C>T:p.Arg131His)的突变,且第131号的精氨酸在各物种间具有高度保守性。生物信息学分析显示LENG9在颌骨和牙齿中有表达。GO和KEGG通路注释分析表明,LENG9可能通过调控氧化磷酸化相关通路参与先天缺牙的发生。结论本研究报道了1例下切牙先天缺失的家系和1个LENG9(c.392C>T:p.Arg131His)的新发突变,研究结果提示该突变可能是导致该家系下切牙先天缺失的致病基因。
基金supported by grants from the National Natural Science Foundation of China(Grant No.32470658)the National Key Research and Development Program of China(Grant Nos.2022YFC2502400 and 2022YFC2502402).
文摘The comorbidity of skin and gastrointestinal tract(GIT)diseases,primarily driven by the gut-skin axis(GSA),is well established.However,the genetic contribution to the GSA remains unclear.Here,using genome-wide association study(GWAS)summary statistics from European populations,we performed a genome-wide pleiotropic analysis to investigate the shared genetic basis and causal associations between skin and GIT diseases.We observed extensive genetic correlations and overlaps between skin and GIT diseases.A total of 298 pleiotropic loci were identified,75 of which were colocalized,and 61 exhibited pleiotropic effects across multiple trait pairs,including 2p16.1(PUS10),6p21.32(HLA-DRB1),10q21.2(ZNF365),and 19q13.11(SLC7A10).Additionally,five novel loci were identified based on the pleiotropic analysis;among them,the 15q22.2 locus harboring RORA was validated by the latest inflammatory bowel disease GWAS.Gene-based analysis identified 394 unique pleiotropic genes,which were enriched in GSA-associated tissues and the immune system,and protein-protein interaction analysis further revealed that the GPCR-cAMP,chromatin remodeling,JAK-STAT,and HLA-mediated immunity pathways were involved in GSA comorbidity.Notably,the JAK-STAT pathway showed strong potential for drug repurposing,with adalimumab targeting tumor necrosis factor and ustekinumab targeting interleukin-12 subunit beta already being used to treat both skin and GIT diseases.Finally,Mendelian randomization analysis identified five significant causal associations,and subsequent mediation analysis identified three potential microbiota-GIT-skin pathways.Taken together,our study demonstrated that the shared genetic factors between skin and GIT diseases were widely distributed across the genome.These findings will enhance our understanding of the genetic mechanisms underlying GSA comorbidity.
