Objective: To further refine the extent of deletion on chromosome 9p21-22 in nasopharyngeal carcinoma (NPC) and provide evidence for discovering new tumor suppressor gene. Methods: Loss of heterozygosity (LOH) on chro...Objective: To further refine the extent of deletion on chromosome 9p21-22 in nasopharyngeal carcinoma (NPC) and provide evidence for discovering new tumor suppressor gene. Methods: Loss of heterozygosity (LOH) on chromosome 9p21-22 was analyzed in 25 paired blood and tumor samples by using 11 high-density microsatellite polymorphic markers. Results: 17 of 25 cases (68.0%) showed LOH at one or more loci. Higher frequencies of LOH were found at four loci: D9S161 (35.0%), D9S1678 (31.5%), D9S263 (33.3%) and D9S1853 (33.3%), where 6 cases had a contiguous stretch of allelic loss. Conclusion: The minimal common region of deletion might be defined between D9S161 and D9S1853 (estimated about 2.7 cM in extent) at 9p21.1, suggesting that inactivation of one or more tumor suppressor genes located in this region may be an important step in NPC.展开更多
The chromosomal polymorphism defined by variations of some chromosomal regions of a person (the constitutive heterochromatin and the short arms of the acrocentric chromosomes (13 to 15 and 21 - 22)) sometimes highligh...The chromosomal polymorphism defined by variations of some chromosomal regions of a person (the constitutive heterochromatin and the short arms of the acrocentric chromosomes (13 to 15 and 21 - 22)) sometimes highlighted problems with regard to their safety and their pathogenicity. Polymorphisms are usually found in the same family and transmitted in the dominant Mendelian. Chromosome 9 inversion is a frequent phenomenon that some cytogeneticists consider as a variant of normal. Despite its classification as a minor chromosome rearrangement which does not correspond to abnormal phenotypes, many reports have raised conflicting opinions as well, and its complete safety is controversial. 27 cases of inversion of chromosome 9 were identified in our laboratory. The main indications for karyotype of the case of inv (9) were congenital cardiopathy (18.5%), sex development disorders of (18.5%), down syndrome (18.5%), and infertility (14.8%). This study stood out the observations of many authors who highlighted the involvement of inv (9) in the genesis of several pathologies.展开更多
Pericentric inversion of chromosome 9(inv[9])is a common chromosomal structural variant,but its impact on clinical outcomesremains debated.The screening criteria of sperm banks are rarely mentioned to individuals with...Pericentric inversion of chromosome 9(inv[9])is a common chromosomal structural variant,but its impact on clinical outcomesremains debated.The screening criteria of sperm banks are rarely mentioned to individuals with inv(9).In this study,we evaluatedthe fertility of sperm donors with inv(9)who met eligibility criteria for sperm banks(inv[9]-eligible donors).From March 2004 toMay 2022,chromosomal analysis of 16124 sperm donors at CITIC-Xiangya Human Sperm Bank in Hunan Province(Changsha,China)found that 251(1.6%)had chromosome variations,with inv(9)being the most prevalent at 1.1%.All 169 inv(9)-eligibledonors were contacted to collect fertility outcome data,along with 206 eligible donors without inv(9)as controls.In addition,semen samples from inv(9)-eligible donors and eligible donors underwent assessments of sperm fluorescence in situ hybridization(FISH),mitochondrial membrane potential,DNA fragmentation index,acrosome integrity,reactive oxygen species(ROS),andsperm morphology.Results showed that inv(9)did not significantly increase reproductive risks overall.Despite detecting ROSlevel differences,the clinical impact may be insignificant.This study provides new data on the inv(9)population that can serveas a valuable reference for decision-making by sperm banks as well as for genetic counseling and clinical guidance for individualscarrying inv(9)variant.展开更多
Background Susceptibility to coronary artery disease （CAD） and diabetes is encoded by distinct, tightly-linked single nucleotide polymorphisms on chromosome 9p21. This study aimed to examine the association of varia...Background Susceptibility to coronary artery disease （CAD） and diabetes is encoded by distinct, tightly-linked single nucleotide polymorphisms on chromosome 9p21. This study aimed to examine the association of variant rs1333049 on chromosome 9p21.3 with early-onset and severity of CAD in Chinese patients with and without type 2 diabetes, and to determine the possible impact of rs1333049 on glucose metabolism and inflammation pathways. Methods Genotyping of variant rs1333049 on chromosome 9p21.3 was performed in 2387 patients with and without diabetes who were undergoing coronary angiography to evaluate suspected or established CAD. Serum levels of glucose, glycosylated hemoglobin Alc （HbAlo）, insulin, high-sensitivity C-reactive protein, tumor necrosis factor-a, and interleukin-6 were also measured, and compared with each patient＇s genotype. Results The homozygous CC genotype of rs1333049 was significantly associated with CAD in diabetic （OR： 1.270, P=-0.044） and non-diabetic （OR： 1.369, P=0.011） patients after adjusting for traditional risk factors. There was an association between CC genotype and number of diseased vessels in diabetics （P=0.019）, but not in non-diabetics （P=0.126）. Among diabetic patients, CC genotype carriers had an increased risk of early-onset CAD （OR：. 2.367, ,~=-0.008） and greater cumulative atherosclerotic burden compared with non-CC genotype carriers （Gensini score： 31.80＋17.20 vs. 23.09＋_21.63, P=-0.039）. No significant differences were observed between genotypes of rs1333049 in serum levels of glucose, insulin, HbAlc, or inflammatory cytokines for diabetic or non-diabetic patients with CAD. Conclusions This study demonstrated a significant association of rs1333049 polymorphism on chromosome 9p21.3 with CAD in Chinese diabetic and non-diabetic patients. The homozygous CC genotype of rs1333049 confers a magnified risk of early-onset and more severe CAD in diabetic patients through a novel biological pathway unrelated to glucose metabolism or inflammation.展开更多
Deciphering the biological functions of each gene in the genome is fundamental for understanding the molecular mechanisms underlying normal development, physiology,and behavior, as well as diseases. One common approac...Deciphering the biological functions of each gene in the genome is fundamental for understanding the molecular mechanisms underlying normal development, physiology,and behavior, as well as diseases. One common approach to determine gene function is to disrupt individual genes and assess the consequences. Zebrafish (Danio rerio) has been gaining popularity as a model organism to analyze gene function. This is particularly true in China.展开更多
The GGGGCC(G_(4)C_(2))hexanucleotide repeat expansion in the C9ORF72 gene is a major cause of both hereditary amyotrophic lateral sclerosis and familial frontotemporal dementia.Recent studies have shown that G_(4)C_(2...The GGGGCC(G_(4)C_(2))hexanucleotide repeat expansion in the C9ORF72 gene is a major cause of both hereditary amyotrophic lateral sclerosis and familial frontotemporal dementia.Recent studies have shown that G_(4)C_(2)hexanucleotide repeat-containing RNA transcripts((G_(4)C_(2))_(n)RNA)could go through liquid-liquid phase separation to form RNA foci,which may elicit neurodegeneration.However,the direct causality between these abnormal RNA foci and neuronal toxicity remains to be demonstrated.Here we introduce an optogenetic control system that can induce the assembly and phase separation of(G_(4)C_(2))_(n)RNA foci with blue light illumination in human cells,by fusing a specific(G_(4)C_(2))_(n)RNA binding protein as the linker domain to Cry2,a protein that oligomerizes in response to blue light.Our results demonstrate that a higher number of G_(4)C_(2)repeats have the potential to be induced into more RNA foci in the cells.Both spontaneous and induced RNA foci display liquid-like properties according to FRAP measurements.Computational simulation shows strong consistency with the experimental results and supports the effect of our system to promote the propensity of(G_(4)C_(2))_(n)RNA towards phase separation.This system can thus be used to investigate whether(G_(4)C_(2))_(n)RNA foci would disrupt normal cellular processes and lead to pathological phenotypes relevant to repeat expansion disorders.展开更多
基金a grant from the National "863" Project of China (No. 102-10-01-05).
文摘Objective: To further refine the extent of deletion on chromosome 9p21-22 in nasopharyngeal carcinoma (NPC) and provide evidence for discovering new tumor suppressor gene. Methods: Loss of heterozygosity (LOH) on chromosome 9p21-22 was analyzed in 25 paired blood and tumor samples by using 11 high-density microsatellite polymorphic markers. Results: 17 of 25 cases (68.0%) showed LOH at one or more loci. Higher frequencies of LOH were found at four loci: D9S161 (35.0%), D9S1678 (31.5%), D9S263 (33.3%) and D9S1853 (33.3%), where 6 cases had a contiguous stretch of allelic loss. Conclusion: The minimal common region of deletion might be defined between D9S161 and D9S1853 (estimated about 2.7 cM in extent) at 9p21.1, suggesting that inactivation of one or more tumor suppressor genes located in this region may be an important step in NPC.
文摘The chromosomal polymorphism defined by variations of some chromosomal regions of a person (the constitutive heterochromatin and the short arms of the acrocentric chromosomes (13 to 15 and 21 - 22)) sometimes highlighted problems with regard to their safety and their pathogenicity. Polymorphisms are usually found in the same family and transmitted in the dominant Mendelian. Chromosome 9 inversion is a frequent phenomenon that some cytogeneticists consider as a variant of normal. Despite its classification as a minor chromosome rearrangement which does not correspond to abnormal phenotypes, many reports have raised conflicting opinions as well, and its complete safety is controversial. 27 cases of inversion of chromosome 9 were identified in our laboratory. The main indications for karyotype of the case of inv (9) were congenital cardiopathy (18.5%), sex development disorders of (18.5%), down syndrome (18.5%), and infertility (14.8%). This study stood out the observations of many authors who highlighted the involvement of inv (9) in the genesis of several pathologies.
基金financial supported by National Natural Science Foundationof China(No.82001634)the China Postdoctoral Science Foundation(No.2019M661521).
文摘Pericentric inversion of chromosome 9(inv[9])is a common chromosomal structural variant,but its impact on clinical outcomesremains debated.The screening criteria of sperm banks are rarely mentioned to individuals with inv(9).In this study,we evaluatedthe fertility of sperm donors with inv(9)who met eligibility criteria for sperm banks(inv[9]-eligible donors).From March 2004 toMay 2022,chromosomal analysis of 16124 sperm donors at CITIC-Xiangya Human Sperm Bank in Hunan Province(Changsha,China)found that 251(1.6%)had chromosome variations,with inv(9)being the most prevalent at 1.1%.All 169 inv(9)-eligibledonors were contacted to collect fertility outcome data,along with 206 eligible donors without inv(9)as controls.In addition,semen samples from inv(9)-eligible donors and eligible donors underwent assessments of sperm fluorescence in situ hybridization(FISH),mitochondrial membrane potential,DNA fragmentation index,acrosome integrity,reactive oxygen species(ROS),andsperm morphology.Results showed that inv(9)did not significantly increase reproductive risks overall.Despite detecting ROSlevel differences,the clinical impact may be insignificant.This study provides new data on the inv(9)population that can serveas a valuable reference for decision-making by sperm banks as well as for genetic counseling and clinical guidance for individualscarrying inv(9)variant.
文摘Background Susceptibility to coronary artery disease （CAD） and diabetes is encoded by distinct, tightly-linked single nucleotide polymorphisms on chromosome 9p21. This study aimed to examine the association of variant rs1333049 on chromosome 9p21.3 with early-onset and severity of CAD in Chinese patients with and without type 2 diabetes, and to determine the possible impact of rs1333049 on glucose metabolism and inflammation pathways. Methods Genotyping of variant rs1333049 on chromosome 9p21.3 was performed in 2387 patients with and without diabetes who were undergoing coronary angiography to evaluate suspected or established CAD. Serum levels of glucose, glycosylated hemoglobin Alc （HbAlo）, insulin, high-sensitivity C-reactive protein, tumor necrosis factor-a, and interleukin-6 were also measured, and compared with each patient＇s genotype. Results The homozygous CC genotype of rs1333049 was significantly associated with CAD in diabetic （OR： 1.270, P=-0.044） and non-diabetic （OR： 1.369, P=0.011） patients after adjusting for traditional risk factors. There was an association between CC genotype and number of diseased vessels in diabetics （P=0.019）, but not in non-diabetics （P=0.126）. Among diabetic patients, CC genotype carriers had an increased risk of early-onset CAD （OR：. 2.367, ,~=-0.008） and greater cumulative atherosclerotic burden compared with non-CC genotype carriers （Gensini score： 31.80＋17.20 vs. 23.09＋_21.63, P=-0.039）. No significant differences were observed between genotypes of rs1333049 in serum levels of glucose, insulin, HbAlc, or inflammatory cytokines for diabetic or non-diabetic patients with CAD. Conclusions This study demonstrated a significant association of rs1333049 polymorphism on chromosome 9p21.3 with CAD in Chinese diabetic and non-diabetic patients. The homozygous CC genotype of rs1333049 confers a magnified risk of early-onset and more severe CAD in diabetic patients through a novel biological pathway unrelated to glucose metabolism or inflammation.
基金Research in the Chen laboratory is supported by NIH(DK117147 and DK109407)supported by China Scholarship Council(#201904910575)。
文摘Deciphering the biological functions of each gene in the genome is fundamental for understanding the molecular mechanisms underlying normal development, physiology,and behavior, as well as diseases. One common approach to determine gene function is to disrupt individual genes and assess the consequences. Zebrafish (Danio rerio) has been gaining popularity as a model organism to analyze gene function. This is particularly true in China.
基金the National Natural Science Foundation of China(31970747 to X.S.,82050008 to B.L.).
文摘The GGGGCC(G_(4)C_(2))hexanucleotide repeat expansion in the C9ORF72 gene is a major cause of both hereditary amyotrophic lateral sclerosis and familial frontotemporal dementia.Recent studies have shown that G_(4)C_(2)hexanucleotide repeat-containing RNA transcripts((G_(4)C_(2))_(n)RNA)could go through liquid-liquid phase separation to form RNA foci,which may elicit neurodegeneration.However,the direct causality between these abnormal RNA foci and neuronal toxicity remains to be demonstrated.Here we introduce an optogenetic control system that can induce the assembly and phase separation of(G_(4)C_(2))_(n)RNA foci with blue light illumination in human cells,by fusing a specific(G_(4)C_(2))_(n)RNA binding protein as the linker domain to Cry2,a protein that oligomerizes in response to blue light.Our results demonstrate that a higher number of G_(4)C_(2)repeats have the potential to be induced into more RNA foci in the cells.Both spontaneous and induced RNA foci display liquid-like properties according to FRAP measurements.Computational simulation shows strong consistency with the experimental results and supports the effect of our system to promote the propensity of(G_(4)C_(2))_(n)RNA towards phase separation.This system can thus be used to investigate whether(G_(4)C_(2))_(n)RNA foci would disrupt normal cellular processes and lead to pathological phenotypes relevant to repeat expansion disorders.
