In the early 1990s,shortly after we identified the genetic defect in FMR1 that results in fragile X syndrome（Verkerk et al.,1991）,I attended a conference sponsored by the US National Fragile X Foundation.This biannu...In the early 1990s,shortly after we identified the genetic defect in FMR1 that results in fragile X syndrome（Verkerk et al.,1991）,I attended a conference sponsored by the US National Fragile X Foundation.This biannual meeting mixes families and scientists in a very productive and enlightening way.展开更多
1 Introduction Advances in human genetics have facilitated the investigation of the genetic architecture underlying numerous complex traits.In particular,studies of quantitative expression trait loci(eQTL)have played ...1 Introduction Advances in human genetics have facilitated the investigation of the genetic architecture underlying numerous complex traits.In particular,studies of quantitative expression trait loci(eQTL)have played a pivotal role in elucidating how genetic variants influence gene expression across cell types.This progress has enabled the quantification of effect size for disease genetic risk loci and the construction of binary relational datasets linking diseases to their respective disease genes,such as Fantom5[1]and DisGeNET[2].展开更多
Recent studies have decoded the human Y chromosome sequencing with predominant precision and coverage,offering promising prospects in human genetics and clinical translation.Such an achievement is facilitated by third...Recent studies have decoded the human Y chromosome sequencing with predominant precision and coverage,offering promising prospects in human genetics and clinical translation.Such an achievement is facilitated by third-generation sequencing technologies including Oxford Nanopore Technology and Pacific Biosciences,which can overcome the limitations of next-generation sequencing.In the context of digestive diseases,these advancements hold significant potential as they can help address the‘missing heritability’problem and detect various genomic variants in genetic association analyses,beyond single nucleotide polymorphisms,hoping to reveal‘major’genes for complex diseases.Besides,the completion of the Y chromosome enables research into sex-specific genetic effects on diseases and this knowledge can lead to sex-specific therapeutic targets and a better understanding of molecular mechanisms behind gender disparities.In summary,the recent decoding of the Y chromosome,coupled with third-generation sequencing,offers new opportunities to address heritability gaps,discover major disease genes and investigate sex-specific effects in digestive diseases,providing valuable insights for clinicians in delivering precise healthcare services.展开更多
The stability and evolution of human genetics depend on chromosomes and chromosome-chromosome interactions.We wish to understand the spatial location of chromosomes in dividing cells in order to understand the relatio...The stability and evolution of human genetics depend on chromosomes and chromosome-chromosome interactions.We wish to understand the spatial location of chromosomes in dividing cells in order to understand the relationship between chromosome-chromosome interactions and to further investigate the role of chromosomes and their impact on cell biological behavior.In this study,we explored the relative spatial positional relationships of chromosomes[t(9;22)and t(15;17)]in B-ALL cells by using the three-dimensional DNA fluorescent in situ hybridization(3D-FISH)method.The results showed that chromosomes[t(9;22)and t(15;17)]showed relatively stable spatial relationships.The relative stability of the spatial location of chromosomes in dividing cells may be relevant to disease.展开更多
Spinal cord injury （SCI） continues to be a pressing health and social problem. The injury leads to neuronal and glial cell death accompanied by degeneration of nerve fibers. There are currently no particularly effec...Spinal cord injury （SCI） continues to be a pressing health and social problem. The injury leads to neuronal and glial cell death accompanied by degeneration of nerve fibers. There are currently no particularly effective treatments. SCI causes profound disabil- ity of people affected and has attracted increased attention in the international field of neuroregeneration. For the past two decades, much hope has been placed in cell therapies for the restoration of both structure and function of the injured spinal cord. Embryonic and neural stem cells, olfactory ensheathing cells, microglia-like cells, Schwann cells, mesenchymal stem cells.展开更多
The highest-level interference essence against virus and turnour genetic engineering medicine is a new type created in the 1980s. Compared with chemical medicines, the interference essence has a special effect in the ...The highest-level interference essence against virus and turnour genetic engineering medicine is a new type created in the 1980s. Compared with chemical medicines, the interference essence has a special effect in the treatment of viruses and tumours. The human a, type genetic engineering interference essense is prepared by the Institute of Viruses of the Chinese Academy of Preventive Medical Sciences, the Shanghai Vaccine展开更多
Male infertility is a major public health issue predominantly caused by defects in germ cell development. In the past, studies on the genetic regulation of spermatogenesis as well as on negative environmental impacts ...Male infertility is a major public health issue predominantly caused by defects in germ cell development. In the past, studies on the genetic regulation of spermatogenesis as well as on negative environmental impacts have been hampered by the fact that human germ cell development is intractable to direct analysis in vivo. Compared with model organisms including mice, there are fundamental differences in the molecular processes of human germ cell development. Therefore, an in vitro model mimicking human sperm formation would be an extremely valuable research tool. In the recent past, both human embryonic stem （ES） cells and induced pluripotent stem （iPS） cells have been reported to harbour the potential to differentiate into primordial germ cells and gametes. We here discuss the possibility to use human amniotic fluid stem （AFS） ceils as a biological model. Since their discovery in 2003, AFS cells have been characterized to differentiate into cells of all three germ layers, to be genomically stable, to have a high proliferative potential and to be non-tumourigenic. In addition, AFS cells are not subject of ethical concerns. In contrast to iPS cells, AFSs cells do not need ectopic induction of pluripotency, which is often associated with only imperfectly cleared epigenetic memory of the source cells. Since AFS cells can be derived from amniocentesis with disease-causing mutations and can be transfected with high efficiency, they could be used in probing gene functions for spermatogenesis and in screening for male reproductive toxicity.展开更多
Ⅰ. INTRODUCTION Alpha-1-antitrypsin (A1AT; locus symbol, PI) is one of the main protease inhibitors in serum. Up to now there are at least 50 A1AT variants that have been found in human populations (Cox, D. W., priva...Ⅰ. INTRODUCTION Alpha-1-antitrypsin (A1AT; locus symbol, PI) is one of the main protease inhibitors in serum. Up to now there are at least 50 A1AT variants that have been found in human populations (Cox, D. W., private communication). The distribution of A1AT variants appears highly racial specificity and geographical variability. This展开更多
There have been controversies over differing opinions in the source of the American Indians. In this paper, the writer criticized the so-called classical theory that the remote ancestors of the American Indians entere...There have been controversies over differing opinions in the source of the American Indians. In this paper, the writer criticized the so-called classical theory that the remote ancestors of the American Indians entered America from Asia through the Bering Straits 14,000 ~ 20,000 years ago, worn their “clothes” and carried kindling during the late Paleolithic, no matter how by “boat” across the Bering Sea or by foot through a “Bering Land Bridge” which might once link up Asia and North America during glacial period;and independently proposed a new hypothesis that American Indians might be originated from the Western Rift Valley of North America. On the basis of locus distribution of American ancient human’s remnants, the writer pointed out that American ancient humans might be first originated at Yukon Territory of Canada within the Western Rift Valley of North America (the Basin & Range Province), and then migrated south ward (Yukon Territory → Mojave Desert → Mexico → Peru → Chile). Moreover, American Indians would have long been a presence for 40,000 years, or even 100,000 ~ 200,000 years in the American continents. So far, the logical basis which American Indians came from Asia 14,000 ~ 20,000 years ago was crushed, and derived two inferences: 1) American Indians might be originated from the Western Rift Valley of North America;2) Only the Eskimo might be the mover eastward from Asia, because of their gene B.展开更多
To investigate the HLA-A, -B allele polymorphism in Han population of Shandong province and to explore the possibility to find out the HLA-A,-B-matehed cord blood donors for stem cell transplantation to be used in oth...To investigate the HLA-A, -B allele polymorphism in Han population of Shandong province and to explore the possibility to find out the HLA-A,-B-matehed cord blood donors for stem cell transplantation to be used in other area in China, 5844 umbilical cord blood samples were taken from Han population donors of Shandong province, and assayed with PCR-sequence-oligonucleotide （PCR-SSO） assay. In Shandong Hart donors, 20 alleles at HLA-A locus and 46 alleles at HLA-B locus could be detected as revealed in the present study. Among the 20 alleles at HLA-A locus, the most prevalent five alleles included A ＊ 02（0.3041）, A ＊ 11（0. 1443）, A ＊ 24（0. 1434）, A ＊ 30（0.0975） and A 33（0.0859）, while, the alleles with lower gene frequencies included A ＊ 34（0.0006）, A ＊ 25 （0.0005）, A ＊ 66（0.0005）, A ＊ 74（0.0004） and A ＊ （0.0001）. Of the 46 HLA-B alleles detected, the most prevalent five alleles were B ＊ 13（0.1348）, B ＊ 51（0.0713）, B ＊ 62（0.0712）, B ＊ 61 （0.0676） and B ＊ 60（0.0642）; while alleles with lower gene frequencies included B ＊ 77（0.0001）, B ＊ 76（0.0002）, B ＊ 47（0.0003）, B ＊ 42（0.0003） and B ＊ 72（0.0004）. In comparison with those of the other Han population in China, the HLA-A, -B gene frequencies in the umbilical cord blood of Shandong province possess unique distribution features among the investigated populations from various regions of the same race origin, and the differences in various regions of the same race were less than those among the different race. It is evident that the HLA-A,-B alleles of the umbilical cord blood taken in Shangdong province show high degree of polymorphism, and it might be part of those of Northem Han population in China. So, it is reasonable for patients of Northern Chinese to receive HLA class Ⅰ -match transplant of cord blood stem ceils for tissue and organ transplantation from Shangdong umbilical cord blood bank.展开更多
Background Human urate anion exchanger (hURAT1) as a major urate transporter expressed on renal tubular epithelial cells regulates blood urate level by reabsorbing uric acid. Antibody is an important tool to study h...Background Human urate anion exchanger (hURAT1) as a major urate transporter expressed on renal tubular epithelial cells regulates blood urate level by reabsorbing uric acid. Antibody is an important tool to study hURAT1. This study aimed, by genetic immunization, to produce mouse anti-hURAT1 polyclonal antibody with high throughput and high specificity and to detect the location of hURAT1 in human kidney.Methods Human renal total RNA was isolated and the entire cDNA of hURAT1 was amplified by RT-PCR. The sequence of intracellular high antigenicity fragment (A280 to R349) was chosen by prediction software of protein antigenicity, and its cDNA was amplified from cDNA of hURAT1, and then cloned into pBQAP-TT vector to construct recombinant plasmid pBQAP-TT-hURAT1-210 for genetic immunization. Mice were inoculated with this recombinant plasmid and two other adjuvant plasmids, pCMVi-GMCSF and pCMVi-Flt3L, which helped to enhance the antibody’s generation. After four weeks, the mice were sacrificed to obtain the anti-hURAT1 antibody from serum. The antibody was identified by western blot analysis and immunohistochemistry. At the same time, rabbit anti-hURAT1 antibody was produced by protein immunization. The specificity and efficiency between the rabbit and mouse anti-hURAT1 antibody were compared by western blot analysis and immunohistochemistry. Results The entire cDNA of hURAT1 and cDNA of its intracellular high immunogenic fragment were amplified successfully. Recombinant plasmid pBQAP-TT-hURAT1-210 for genetic immunization was confirmed by restriction digestion and sequencing. Both!the mouse anti-hURAT1 antibody and rabbit anti-hURAT1 antibody recognized 58kD hURAT1 and 64kD glycosylated hURAT1 protein bands in western blot. Immunohistochemically, hURAT1 was located at the brush border membrane of renal proximal tubular cells. In addition, the throughput and specificity of the mouse anti-hURAT1 antibody were higher than those of the rabbit anti-hURAT1 antibody.Conclusion Genetic immunization can generate anti-hURAT1 polyclonal antibody of high throughput and specificity.展开更多
Metabolic dysfunction-associated steatotic liver disease(MASLD)has emerged as the most prevalent cause of chronic liver disease worldwide affecting over one-third of the adult population.Despite the recent evolution o...Metabolic dysfunction-associated steatotic liver disease(MASLD)has emerged as the most prevalent cause of chronic liver disease worldwide affecting over one-third of the adult population.Despite the recent evolution of new nomenclature and diagnostic criteria for MASLD,progress in drug development for this condition remains limited.This review highlights the potential of drug-target Mendelian randomisation(MR),a study design that leverages human genetics and genomics,for the discovery,repositioning and safety assessment of drug targets in MASLD.We summarised key aspects of designing and appraising a drug-target MR study,discussing its inherent assumptions and considerations for instrument selection.Furthermore,we presented real-world examples from studies in MASLD which focused on opportunities and challenges in identifying novel drug targets,repositing existing drug targets,informing adjunctive treatments and addressing issues in paediatric MASLD.展开更多
We propose a computational workflow(I3)for intuitive integrative interpretation of complex genetic data mainly building on the self-organising principle.We illustrate the use in interpreting genetics of gene expressio...We propose a computational workflow(I3)for intuitive integrative interpretation of complex genetic data mainly building on the self-organising principle.We illustrate the use in interpreting genetics of gene expression and understanding genetic regulators of protein phenotypes,particularly in conjunction with information from human population genetics and/or evolutionary history of human genes.We reveal that loss-of-function intolerant genes tend to be depleted of tissue-sharing genetics of gene expression in brains,and if highly expressed,have broad effects on the protein phenotypes studied.We suggest that this workflow presents a general solution to the challenge of complex genetic data interpretation.I3 is available at http://suprahex.r-forge.r-project.org/I3.html.展开更多
Background: Rare mutations in surfactant-associatedgenes contribute to neonatal respiratory distress syndrome.The frequency of mutations in these genes in the Chinesepopulation is unknown.Methods: We obtained blood sp...Background: Rare mutations in surfactant-associatedgenes contribute to neonatal respiratory distress syndrome.The frequency of mutations in these genes in the Chinesepopulation is unknown.Methods: We obtained blood spots from the GuangxiNeonatal Screening Center in Nanning, China thatincluded Han (n=443) and Zhuang (n=313) ethnic groups.We resequenced all exons of the surfactant proteins-B(SFTPB), -C (SFTPC), and the ATP-binding cassettemember A3 (ABCA3) genes and compared the frequenciesof 5 common and all rare variants.Results: We found minor differences in thefrequencies of the common variants in the Han andZhuang cohorts. We did not find any rare mutations inSFTPB or SFTPC, but we found three ABCA3 mutationsin the Han [minor allele frequency (MAF)=0.003] and 7 inthe Zhuang (MAF=0.011) cohorts (P=0.10). The ABCA3mutations were unique to each cohort;five were novel.The collapsed carrier rate of rare ABCA3 mutations inthe Han and Zhuang populations combined was 1.3%,which is signifi cantly lower than that in the United States(P<0.001).Conclusions: The population-based frequency ofmutations in ABCA3 in south China newborns is signifi cantlylower than that in United States. The contribution of theserare ABCA3 mutations to disease burden in the south Chinapopulation is still unknown.展开更多
基金support and guidance of colleagues andcoworkers across the genetics community and for the contributions to my own research from the Cullen Foundation, the FRAXA foundation, the Azrieli Foundation(Brain Canada), and the US NIH (HD084802, HD083092 and NS051630)
文摘In the early 1990s,shortly after we identified the genetic defect in FMR1 that results in fragile X syndrome（Verkerk et al.,1991）,I attended a conference sponsored by the US National Fragile X Foundation.This biannual meeting mixes families and scientists in a very productive and enlightening way.
基金supported by the National Natural Science Foundation of China(Grant Nos.62172318,62372349,62132015).
文摘1 Introduction Advances in human genetics have facilitated the investigation of the genetic architecture underlying numerous complex traits.In particular,studies of quantitative expression trait loci(eQTL)have played a pivotal role in elucidating how genetic variants influence gene expression across cell types.This progress has enabled the quantification of effect size for disease genetic risk loci and the construction of binary relational datasets linking diseases to their respective disease genes,such as Fantom5[1]and DisGeNET[2].
文摘Recent studies have decoded the human Y chromosome sequencing with predominant precision and coverage,offering promising prospects in human genetics and clinical translation.Such an achievement is facilitated by third-generation sequencing technologies including Oxford Nanopore Technology and Pacific Biosciences,which can overcome the limitations of next-generation sequencing.In the context of digestive diseases,these advancements hold significant potential as they can help address the‘missing heritability’problem and detect various genomic variants in genetic association analyses,beyond single nucleotide polymorphisms,hoping to reveal‘major’genes for complex diseases.Besides,the completion of the Y chromosome enables research into sex-specific genetic effects on diseases and this knowledge can lead to sex-specific therapeutic targets and a better understanding of molecular mechanisms behind gender disparities.In summary,the recent decoding of the Y chromosome,coupled with third-generation sequencing,offers new opportunities to address heritability gaps,discover major disease genes and investigate sex-specific effects in digestive diseases,providing valuable insights for clinicians in delivering precise healthcare services.
文摘The stability and evolution of human genetics depend on chromosomes and chromosome-chromosome interactions.We wish to understand the spatial location of chromosomes in dividing cells in order to understand the relationship between chromosome-chromosome interactions and to further investigate the role of chromosomes and their impact on cell biological behavior.In this study,we explored the relative spatial positional relationships of chromosomes[t(9;22)and t(15;17)]in B-ALL cells by using the three-dimensional DNA fluorescent in situ hybridization(3D-FISH)method.The results showed that chromosomes[t(9;22)and t(15;17)]showed relatively stable spatial relationships.The relative stability of the spatial location of chromosomes in dividing cells may be relevant to disease.
基金supported by grants 15-04-07527(AAR) and 16-34-60101(YOM) from Russian Foundation for Basic Researchsupported by a Presidential Grant for government support of young scientists(PhD) from the Russian Federation(MK-4020.2015.7)+1 种基金performed in accordance with Program of Competitive Growth of Kazan Federal Universitya subsidy allocated to Kazan Federal University for the state assignment in the sphere of scientific activities
文摘Spinal cord injury （SCI） continues to be a pressing health and social problem. The injury leads to neuronal and glial cell death accompanied by degeneration of nerve fibers. There are currently no particularly effective treatments. SCI causes profound disabil- ity of people affected and has attracted increased attention in the international field of neuroregeneration. For the past two decades, much hope has been placed in cell therapies for the restoration of both structure and function of the injured spinal cord. Embryonic and neural stem cells, olfactory ensheathing cells, microglia-like cells, Schwann cells, mesenchymal stem cells.
文摘The highest-level interference essence against virus and turnour genetic engineering medicine is a new type created in the 1980s. Compared with chemical medicines, the interference essence has a special effect in the treatment of viruses and tumours. The human a, type genetic engineering interference essense is prepared by the Institute of Viruses of the Chinese Academy of Preventive Medical Sciences, the Shanghai Vaccine
文摘Male infertility is a major public health issue predominantly caused by defects in germ cell development. In the past, studies on the genetic regulation of spermatogenesis as well as on negative environmental impacts have been hampered by the fact that human germ cell development is intractable to direct analysis in vivo. Compared with model organisms including mice, there are fundamental differences in the molecular processes of human germ cell development. Therefore, an in vitro model mimicking human sperm formation would be an extremely valuable research tool. In the recent past, both human embryonic stem （ES） cells and induced pluripotent stem （iPS） cells have been reported to harbour the potential to differentiate into primordial germ cells and gametes. We here discuss the possibility to use human amniotic fluid stem （AFS） ceils as a biological model. Since their discovery in 2003, AFS cells have been characterized to differentiate into cells of all three germ layers, to be genomically stable, to have a high proliferative potential and to be non-tumourigenic. In addition, AFS cells are not subject of ethical concerns. In contrast to iPS cells, AFSs cells do not need ectopic induction of pluripotency, which is often associated with only imperfectly cleared epigenetic memory of the source cells. Since AFS cells can be derived from amniocentesis with disease-causing mutations and can be transfected with high efficiency, they could be used in probing gene functions for spermatogenesis and in screening for male reproductive toxicity.
基金Project supported by the Science Fund of Academia Sinica
文摘Ⅰ. INTRODUCTION Alpha-1-antitrypsin (A1AT; locus symbol, PI) is one of the main protease inhibitors in serum. Up to now there are at least 50 A1AT variants that have been found in human populations (Cox, D. W., private communication). The distribution of A1AT variants appears highly racial specificity and geographical variability. This
文摘There have been controversies over differing opinions in the source of the American Indians. In this paper, the writer criticized the so-called classical theory that the remote ancestors of the American Indians entered America from Asia through the Bering Straits 14,000 ~ 20,000 years ago, worn their “clothes” and carried kindling during the late Paleolithic, no matter how by “boat” across the Bering Sea or by foot through a “Bering Land Bridge” which might once link up Asia and North America during glacial period;and independently proposed a new hypothesis that American Indians might be originated from the Western Rift Valley of North America. On the basis of locus distribution of American ancient human’s remnants, the writer pointed out that American ancient humans might be first originated at Yukon Territory of Canada within the Western Rift Valley of North America (the Basin & Range Province), and then migrated south ward (Yukon Territory → Mojave Desert → Mexico → Peru → Chile). Moreover, American Indians would have long been a presence for 40,000 years, or even 100,000 ~ 200,000 years in the American continents. So far, the logical basis which American Indians came from Asia 14,000 ~ 20,000 years ago was crushed, and derived two inferences: 1) American Indians might be originated from the Western Rift Valley of North America;2) Only the Eskimo might be the mover eastward from Asia, because of their gene B.
文摘To investigate the HLA-A, -B allele polymorphism in Han population of Shandong province and to explore the possibility to find out the HLA-A,-B-matehed cord blood donors for stem cell transplantation to be used in other area in China, 5844 umbilical cord blood samples were taken from Han population donors of Shandong province, and assayed with PCR-sequence-oligonucleotide （PCR-SSO） assay. In Shandong Hart donors, 20 alleles at HLA-A locus and 46 alleles at HLA-B locus could be detected as revealed in the present study. Among the 20 alleles at HLA-A locus, the most prevalent five alleles included A ＊ 02（0.3041）, A ＊ 11（0. 1443）, A ＊ 24（0. 1434）, A ＊ 30（0.0975） and A 33（0.0859）, while, the alleles with lower gene frequencies included A ＊ 34（0.0006）, A ＊ 25 （0.0005）, A ＊ 66（0.0005）, A ＊ 74（0.0004） and A ＊ （0.0001）. Of the 46 HLA-B alleles detected, the most prevalent five alleles were B ＊ 13（0.1348）, B ＊ 51（0.0713）, B ＊ 62（0.0712）, B ＊ 61 （0.0676） and B ＊ 60（0.0642）; while alleles with lower gene frequencies included B ＊ 77（0.0001）, B ＊ 76（0.0002）, B ＊ 47（0.0003）, B ＊ 42（0.0003） and B ＊ 72（0.0004）. In comparison with those of the other Han population in China, the HLA-A, -B gene frequencies in the umbilical cord blood of Shandong province possess unique distribution features among the investigated populations from various regions of the same race origin, and the differences in various regions of the same race were less than those among the different race. It is evident that the HLA-A,-B alleles of the umbilical cord blood taken in Shangdong province show high degree of polymorphism, and it might be part of those of Northem Han population in China. So, it is reasonable for patients of Northern Chinese to receive HLA class Ⅰ -match transplant of cord blood stem ceils for tissue and organ transplantation from Shangdong umbilical cord blood bank.
文摘Background Human urate anion exchanger (hURAT1) as a major urate transporter expressed on renal tubular epithelial cells regulates blood urate level by reabsorbing uric acid. Antibody is an important tool to study hURAT1. This study aimed, by genetic immunization, to produce mouse anti-hURAT1 polyclonal antibody with high throughput and high specificity and to detect the location of hURAT1 in human kidney.Methods Human renal total RNA was isolated and the entire cDNA of hURAT1 was amplified by RT-PCR. The sequence of intracellular high antigenicity fragment (A280 to R349) was chosen by prediction software of protein antigenicity, and its cDNA was amplified from cDNA of hURAT1, and then cloned into pBQAP-TT vector to construct recombinant plasmid pBQAP-TT-hURAT1-210 for genetic immunization. Mice were inoculated with this recombinant plasmid and two other adjuvant plasmids, pCMVi-GMCSF and pCMVi-Flt3L, which helped to enhance the antibody’s generation. After four weeks, the mice were sacrificed to obtain the anti-hURAT1 antibody from serum. The antibody was identified by western blot analysis and immunohistochemistry. At the same time, rabbit anti-hURAT1 antibody was produced by protein immunization. The specificity and efficiency between the rabbit and mouse anti-hURAT1 antibody were compared by western blot analysis and immunohistochemistry. Results The entire cDNA of hURAT1 and cDNA of its intracellular high immunogenic fragment were amplified successfully. Recombinant plasmid pBQAP-TT-hURAT1-210 for genetic immunization was confirmed by restriction digestion and sequencing. Both!the mouse anti-hURAT1 antibody and rabbit anti-hURAT1 antibody recognized 58kD hURAT1 and 64kD glycosylated hURAT1 protein bands in western blot. Immunohistochemically, hURAT1 was located at the brush border membrane of renal proximal tubular cells. In addition, the throughput and specificity of the mouse anti-hURAT1 antibody were higher than those of the rabbit anti-hURAT1 antibody.Conclusion Genetic immunization can generate anti-hURAT1 polyclonal antibody of high throughput and specificity.
基金supported by Seed Fund for Basic Science(2302101604),the University of Hong Kong.
文摘Metabolic dysfunction-associated steatotic liver disease(MASLD)has emerged as the most prevalent cause of chronic liver disease worldwide affecting over one-third of the adult population.Despite the recent evolution of new nomenclature and diagnostic criteria for MASLD,progress in drug development for this condition remains limited.This review highlights the potential of drug-target Mendelian randomisation(MR),a study design that leverages human genetics and genomics,for the discovery,repositioning and safety assessment of drug targets in MASLD.We summarised key aspects of designing and appraising a drug-target MR study,discussing its inherent assumptions and considerations for instrument selection.Furthermore,we presented real-world examples from studies in MASLD which focused on opportunities and challenges in identifying novel drug targets,repositing existing drug targets,informing adjunctive treatments and addressing issues in paediatric MASLD.
基金the National Natural Science Foundation of China(Grant No.31301041 awarded to HF,and Grant Nos.81530003 and 81770153 awarded to KW).
文摘We propose a computational workflow(I3)for intuitive integrative interpretation of complex genetic data mainly building on the self-organising principle.We illustrate the use in interpreting genetics of gene expression and understanding genetic regulators of protein phenotypes,particularly in conjunction with information from human population genetics and/or evolutionary history of human genes.We reveal that loss-of-function intolerant genes tend to be depleted of tissue-sharing genetics of gene expression in brains,and if highly expressed,have broad effects on the protein phenotypes studied.We suggest that this workflow presents a general solution to the challenge of complex genetic data interpretation.I3 is available at http://suprahex.r-forge.r-project.org/I3.html.
基金supported by the National Natural Science Foundation of China 81260094(Chen YJ)National Institutes of Health R01 HL065174(Cole FS,Hamvas A),R01 HL082747(Cole FS,Hamvas A),K12 HL089968(Wambach JA,Cole FS),K08 HL105891(Wambach JA)Foundation of Health Department of Guangxi Zhuang Autonomous Region 2012059(Chen YJ).
文摘Background: Rare mutations in surfactant-associatedgenes contribute to neonatal respiratory distress syndrome.The frequency of mutations in these genes in the Chinesepopulation is unknown.Methods: We obtained blood spots from the GuangxiNeonatal Screening Center in Nanning, China thatincluded Han (n=443) and Zhuang (n=313) ethnic groups.We resequenced all exons of the surfactant proteins-B(SFTPB), -C (SFTPC), and the ATP-binding cassettemember A3 (ABCA3) genes and compared the frequenciesof 5 common and all rare variants.Results: We found minor differences in thefrequencies of the common variants in the Han andZhuang cohorts. We did not find any rare mutations inSFTPB or SFTPC, but we found three ABCA3 mutationsin the Han [minor allele frequency (MAF)=0.003] and 7 inthe Zhuang (MAF=0.011) cohorts (P=0.10). The ABCA3mutations were unique to each cohort;five were novel.The collapsed carrier rate of rare ABCA3 mutations inthe Han and Zhuang populations combined was 1.3%,which is signifi cantly lower than that in the United States(P<0.001).Conclusions: The population-based frequency ofmutations in ABCA3 in south China newborns is signifi cantlylower than that in United States. The contribution of theserare ABCA3 mutations to disease burden in the south Chinapopulation is still unknown.
