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Objective:To analyze the results of the joint screening of newborn hearing and deafness genes in Dalian to provide a reference for the prevention and control of hereditary deafness.Methods:Eight hundred and forty-two neonates born in Dalian Women and Children′s Medical Group from January 1, 2022 to May 30, 2022 were screened retrospectively, using AABR (automatic brainstem evoked potential). And 20 mutation sites of common genetic deafness 4 genes , including GJB2, GJB3, SLC26A4 (PDS) and mitochondrial genes associated with drug-induced deafness (MT-RNRI)(12SrRNA), were detected by high-throughput sequencing.Results:Among the 842 newborns, 840 passed hearing screening (99.8%); 36 cases (4.3%) passed the hearing screening but not the hearing loss gene screening; 804 cases passed through the both screening (95.5%); 2 cases (0.24%) failed in the both screening. 38 cases of deafness gene mutations were detected, with a total carrying rate of 4.51% (38/842). Among them, the carrying rates of heterozygous mutations in GJB2, GJB3, SLC26A4 (PDS), MT-RNRI (12SrRNA) were 1.90%, 0.24%, 1.30%, and 0.95%, respectively. The carrying rates of GJB2/GJB3 composite heterozygous mutations were 0.12%.Conclusions:The combined screening of neonatal hearing and deafness genes can reduce the missed rate of hearing screening. The carrier rate of neonatal deafness gene in Dalian is 4.51%, with the highest GJB 2 carrier rate, followed by SLC26A4 (PDS) carrier rate.
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Objective:To investigate the efficiency of biochemical screening and hotspot gene screening in the detection of neonatal inherited metabolic diseases.Methods:This was a prospective multi-center study.The study was carried out on 21 442 neonatal samples collected from 12 hospitals in 10 provinces from November 2020 to November 2021.The results of biochemical screening and hotspot gene screening were analyzed jointly.Biochemical screening methods included glucose-6-phosphate dehydrogenase deficiency enzyme activity assay and neonatal tandem mass spectrometry.Genetic screening analysis involved 135 genes associated with 75 neonatal diseases.Results:Of all the 21 442 neonates enrolled in the study, 21 205 were subject to biochemical screening.A total of 813 cases were positive in the initial screening, and 0.45% of them (95 cases) were diagnosed after recall.All the 21 442 neonates underwent gene screening.About 168 positive cases were detected in the initial screening, and 0.73% (156 cases) of them were confirmed finally.Biochemical and genetic screening improved the detection sensitivity of such diseases as primary carnitine deficiency, neonatal intrahepatic cholestasis caused by citrin deficiency, and 2-methylbutyrylglycinemia.Moreover, biochemical and genetic screening enabled the detection of more diseases, including the common single-gene genetic diseases such as thalassemia and Wilson disease.Conclusions:In neonatal screening, the combination of biochemical screening and gene screening expands the number of diseases detected and improve screening efficiency.
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INTRODUCTION@#Fragile X syndrome (FXS) is the most prevalent X-linked intellectual disability (ID) and a leading genetic cause of autism, characterised by cognitive and behavioural impairments. The hyperexpansion of a CGG repeat in the fragile X mental retardation 1 (FMR1) gene leads to abnormal hypermethylation, resulting in the lack or absence of its protein. Tools for establishing the diagnosis of FXS have been extensively developed, including assays based on triplet-primed polymerase chain reaction (TP-PCR) for detection and quantification of the CGG trinucleotide repeat expansion, as well as determination of the methylation status of the alleles. This study aimed to utilise a simple, quick and affordable method for high sensitivity and specificity screening and diagnosis of FXS in institutionalised individuals with ID.@*METHODS@#A total of 109 institutionalised individuals at the Center for Social Rehabilitation of Intellectual Disability Kartini, Temanggung, Central Java, Indonesia, were screened in a three-step process using FastFrax™ Identification, Sizing and Methylation Status Kits.@*RESULTS@#Two samples that were classified as indeterminate with respect to the 41-repeat control at the identification step were subsequently determined to be non-expanded by both sizing and methylation status analyses. Two samples classified as expanded at the identification step were determined to carry full mutation expansions > 200 repeats that were fully methylated using sizing and methylation status analyses, respectively, yielding a disease prevalence of 1.83%.@*CONCLUSION@#Repeat expansion and methylation-specific TP-PCR is practical, effective and inexpensive for the diagnosis of FXS, especially in high-risk populations of individuals with ID of undetermined aetiology.
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Squalene is widely used in pharmaceutical, nutraceutical, cosmetics and other fields because of its strong antioxidative, antibacterial and anti-tumor activities. In order to produce squalene, a gene ispA encoding farnesyl pyrophosphate synthase was overexpressed in a previously engineered Escherichia coli strain capable of efficiently producing terpenoids, resulting in a chassis strain that efficiently synthesizes triterpenoids. Through phylogenetic analysis, screening, cloning and expression of squalene synthase derived from different prokaryotes, engineered E. coli strains capable of efficiently producing squalene were obtained. Among them, squalene produced by strains harboring squalene synthase derived from Thermosynechococcus elongatus and Synechococcus lividus reached (16.5±1.4) mg/g DCW ((167.1±14.3) mg/L broth) and (12.0±1.9) mg/g DCW ((121.8±19.5) mg/L broth), respectively. Compared with the first-generation strains harboring the human-derived squalene synthase, the squalene synthase derived from T. elongatus and S. lividus remarkably increased the squalene production by 3.3 times and 2.4 times, respectively, making progress toward the cost-effective heterologous production of squalene.
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Humanos , Clonagem Molecular , Escherichia coli/genética , Filogenia , Esqualeno , SynechococcusRESUMO
Breast cancer is the most common malignant tumor in women. With the development of cell biology and molecular bio-technology, great progress has been made in the study of the pathogenesis of breast cancer. Familial breast cancer is closely related to the mutation of susceptible genes. Selected susceptible genes of breast cancer can be grouped into three categories: high-, medium-, and low-penetrance susceptible genes. The means of identifying the high-risk sites of pathogenic mutation and genetic polymorphism is the focus of research on the genetic predisposition of breast cancer.
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Objective To investigate the expression of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in endometriosis (EMS) and its diagnostic value.Methods The information of EMS gene expression was collected from Gene-Cloud of Biotechnology Information (GCBI) and analyzed,in which MALAT1 gene was screened out accordingly.The total RNAs were extracted from tissues and serum samples of the patients with ovarian endometriosis and non-endometriosis and the expression of MALAT1 was detected by real-time quantitative PCR.The correlation between MALAT1 expression level and menstrual cycle was analyzed.The differential diagnostic efficacy of serum MALAT1 levels was analyzed by receiver operating characteristic (ROC) curve.Results Compared with the non-EMS group the expression of MAL4T1 gene was down-regulated by 1.35-fold (t =-3.27,P ＜ 0.01) in EMS group according to gene information analysis of GCBI.The relative expression levels of MALAT1 in ectopic and eutopic endometrium of patients with ovary endometriosis (0.41 ±0.18 and 0.61 ± 0.12) were significantly lower than those in non-endometriosis patients (1.05 ±-0.34,t =5.87 and 4.48,P ＜ 0.01).However,the expression level of MALAT1 was not related with menstrual cycle of the patients with ovarian endometriosis and non-endometriosis (t =1.54 and 1.52,P ＞ 0.05).The expression of MALAT1 in ectopic ovarian cysts was significantly lower than that in eutopic endometrium of ovary endometriosis (t =3.77,P ＜ 0.01).The relative expression of serum MALAT1 in ovary endometriosis (0.60 ±0.18) was significantly lower than that in non-endometriosis (1.05 ± 0.32,t =5.18,P ＜ 0.01).The area under the curve (AUCsOc) was 0.88.When the cut-off value of serum MALAT1 level was set as 0.74,the sensitivity and specificity of expression level of MALAT1 were 82.4％ and 92％ respectively,and Youden's index was 74.4％.Conclusion Low expression of MALAT1 in endometriosis may be related with occurrence and development of endometriosis.Serum MALAT1 level may have certain differential diagnostic value for EMS.
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Since the fundamental breakthrough in human genomics,gene diagnosis and gene therapy have become a hotspot technology in disease diagnosis and treatment.Scientists in UK and USA have applied the technology of gene screening consecutively to give birth to babies knocked out certain virulence genes,which triggered heated and controversial debates on gene screening technology.How should we see this novel technology,a new hope for human life and health,or a misfortune disaster? What attitude should we hold towards gene screening,to ban it all round,or to take scientific advantage of it? This paper brings forward a series of issues related to the novel technology of gene screening.