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Preliminary structural and functional study on a novel gene HSPCSET.

Ju WEI ; Xiao-jian SUN ; Xin-yan WU ; Sai-juan CHEN ; Zhu CHEN ; Chun WANG ; Qiu-hua HUANG

Chinese Journal of Medical Genetics.2009;26(1):35-39. doi:10.3760/cma.j.issn.1003-9406.2009.01.008

OBJECTIVETo characterize the structural and the functional feature of a novel gene HSPCSET isolated from human CD34+ hematopoietic stem/progenitor cells (HS/PCs).

METHODSBioinformatic technology was used to identify the structural features of the HSPCSET protein and perform the multiple sequence alignment. Yeast-two-hybrid system was used to identify the proteins interacting with the HSPCSET protein. After sequencing, we selected out the positive clones which had clear functions, and carried out beta-gal experiment and GST pull down assay to confirm the results. The cellular location of the HSPCSET was checked by immunofluorescence assay.

RESULTSThe HSPCSET protein belongs to a SET domain family, which is evolutionarily conserved across species. It implied that HSPCSET may have biologically important function. Using yeast-two-hybrid system, we showed that the protein sequence with SET domain might bind to 13 proteins, which involved in signaling transduction, transcriptional regulation, apoptosis, tumorigenesis, development, etc. And 4 proteins (GADD34, SIVA, DNAJ and PHF1) were confirmed by one-on-one back of the hybrid experiment, beta-gal test and GST pull down assay. When GADD34 and HSPCSET were co-transfected, they co-localized in the nucleus, suggesting a strong interaction.

CONCLUSIONThe novel gene HSPCSET is likely to have biologically important function. This study provides the basis for further studies of its function in hematopoiesis and tumorigenesis.

Amino Acid Sequence ; Animals ; Antigens, Differentiation ; metabolism ; Cell Cycle Proteins ; metabolism ; Computational Biology ; Conserved Sequence ; Hematopoietic Stem Cells ; metabolism ; Humans ; Molecular Sequence Data ; Protein Phosphatase 1 ; Protein Structure, Tertiary ; Proteins ; chemistry ; genetics ; metabolism ; Sequence Homology, Amino Acid ; Two-Hybrid System Techniques

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Association of serotonin transporter gene linked polymorphic region polymorphism with early onset myocardial infarction and platelet membrane glycoprotein I b.

Da-sheng XIA ; Qian-yu GUO ; Yan-qiang LIU ; Chao LI ; Feng ZHANG ; Min-xin WEI

Chinese Journal of Medical Genetics.2009;26(1):31-34. doi:10.3760/cma.j.issn.1003-9406.2009.01.007

OBJECTIVETo investigate the association of serotonin transporter gene linked polymorphic region (5-HTTLPR) insertion/deletion polymorphism with early onset myocardial infarction(MI) and platelet membrane glycoprotein I b(GP I b) in Northern Han population of China.

METHODSA total of 150 patients with early onset MI and 150 age- and sex-matched controls with negative coronary arteriography were genotyped for the 5-HTTLPR polymorphism by using a polymerase chain reaction-based technique. The percentage of positive platelet membrane GP I b and the average fluorescence intensity were quantified by flow cytometry.

RESULTSThe genotype frequencies of LL, LS and SS in the 5-HTTLPR were 32%, 47% and 21% in the MI patients, 17%, 43% and 39% in the controls respectively(P<0.01). The L allele frequency in the MI patients was significantly higher than that of the control group (56% vs 39%, P<0.01). The percentage of positive platelet membrane GP I b and the fluorescence intensity in subjects with LL homozygote were markedly lower than that of LS and SS genotypes in the MI and control groups (all P<0.01). Multivariate logistic regression analysis showed that the 5-HTTLPR LL genotype was independently related to the occurrence of early onset MI(OR was 1.961, P was 0.037).

CONCLUSIONThe LL genotype of the 5-HTTLPR might be associated with the susceptibility to developing early MI in Northern Han population of China. The platelet activation is increased in individuals of LL genotype.

Adult ; Age of Onset ; Alleles ; Asian Continental Ancestry Group ; genetics ; Case-Control Studies ; Ethnic Groups ; genetics ; Female ; Gene Frequency ; Homozygote ; Humans ; INDEL Mutation ; Logistic Models ; Male ; Middle Aged ; Myocardial Infarction ; genetics ; metabolism ; pathology ; Platelet Glycoprotein GPIb-IX Complex ; metabolism ; Polymorphism, Genetic ; Serotonin Plasma Membrane Transport Proteins ; genetics

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Characteristics of the PAH gene mutation in Chinese patients with phenylketonuria in Xinjiang.

Wu-zhong YU ; Dong-hui QIU ; Fang SONG ; Li LIU ; Shao-ming LIU ; Xin-jian HE ; Yu-wei JIN ; Yan-ling ZHANG ; Hong-yun ZOU ; Jiang HE ; Quan LEI ; Xing-wen LIU

Chinese Journal of Medical Genetics.2009;26(1):26-30. doi:10.3760/cma.j.issn.1003-9406.2009.01.006

OBJECTIVETo study the characteristics of the PAH gene mutation in patients with phenylketonuria (PKU) in Xinjiang area.

METHODSThe mutations in exons 3, 5, 6, 7, 11 and 12 and the flanking intronic sequence of the PAH gene were detected by PCR/SSCP analysis and direct DNA sequencing in 46 PKU patients.

RESULTSTwenty different mutations were found in 68/92 alleles (73.9%). The prevalent mutations of R243Q, EX6 96A>G, R111X, Y356X and V399V were similar to that of Northern China populations. The mutations F161S, L255S, P281L, and R413P were significantly different from that in other Chinese populations. It was the second time that E280G and A434D mutations were reported in the world, that L255S, P281L, R261Q, and I65T mutations were found in China. Thirteen different mutations were first found in Chinese Uygur, which showed a distinct ethnic characteristics.

CONCLUSIONThe study showed not only a distinct and conservative, but also a crossed and syncretic genetic characteristics in Xinjiang Uygur population. The results suggest that Xinjiang could be an ideal genetic resource repertoire for studying diversity of gene mutations, heterogeneity of PAH gene, human origins and migration.

Adolescent ; Adult ; Alleles ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; Child ; Child, Preschool ; China ; DNA Mutational Analysis ; Ethnic Groups ; genetics ; Exons ; genetics ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Mutation ; Phenylalanine Hydroxylase ; genetics ; Phenylketonurias ; enzymology ; genetics

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Mutational screening of the SLC26A4 gene in patients with nonsyndromic hearing loss by denaturing high-performance liquid chromatography.

Juan ZHAO ; Ling-qian WU ; Yong FENG ; Qian PAN ; Kai ZHAO ; Hong-yan LI ; De-sheng LIANG

Chinese Journal of Medical Genetics.2009;26(1):21-25. doi:10.3760/cma.j.issn.1003-9406.2009.01.005

OBJECTIVETo study the SLC26A4 gene mutations in patients with nonsyndromic hearing loss (NSHL) and provide the clinical guidance of gene diagnosis.

METHODSPCR and denaturing high-performance liquid chromatography (DHPLC) were used to screen the 21 exons and their flanking regions of the SLC26A4 gene. Samples with abnormal DHPLC wave patterns were sequenced to identify the variations.

RESULTSAmong the 30 unrelated NSHL patients in whom no deafness-causing mutations of the GJB2 gene were identified, 10 types of variations were detected, including 7 known mutations, 2 novel mutations (F572L and D87Y), and 1 known polymorphism (Ivs11+47T>C). The Ivs7-2A>G is the most common type of variation, accounting for 40% of all the mutations.

CONCLUSIONSLC26A4 mutation is a major cause of NSHL, just next to the GJB2 mutations. For NSHL patients without deafness-causing GJB2 mutations, the SLC26A4 mutation rate was 23.3%, and the Ivs7-2A>G was the most common mutation.

Adolescent ; Adult ; Base Sequence ; Child ; Child, Preschool ; Chromatography, High Pressure Liquid ; Connexins ; DNA Mutational Analysis ; methods ; Genetic Testing ; Genotype ; Hearing Loss ; diagnosis ; genetics ; pathology ; Humans ; Infant ; Membrane Transport Proteins ; genetics ; Mutation ; Phenotype ; Polymorphism, Genetic

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Association analysis of neuregulin 1 gene polymorphism with schizophrenia in Chinese Han population.

Hong-xing ZHANG ; Wen-qiang LI ; Yan ZHANG ; Jing-ping ZHAO ; Lu-xian LV ; Ge YANG

Chinese Journal of Medical Genetics.2009;26(1):16-20. doi:10.3760/cma.j.issn.1003-9406.2009.01.004

OBJECTIVETo investigate the association of the Neuregulin 1(NRG1) gene polymorphism with schizophrenia by analyzing allele transmission in schizophrenic parent-proband trios.

METHODSQuantitative real-time PCR was used to check the genotypes of four SNPs-rs221533(C/T), rs7820838(C/T), 433E1006(A/G) and rs3924999(C/T), located at the 5o terminus of the Nrg1 gene, in 258 Chinese Han schizophrenic parent-proband trios. The transmission disequilibrium test (TDT) program (Genehunter software 2.0) was used to evaluate the association of the NRG1 gene with schizophrenia.

RESULTSFor all the subjects, the genotypes of the 4 SNPs were in Hardy-Weinberg equilibrium. In all the 258 parent-proband trios, there were significant transmission disequilibrium in allelic transmission of C, A, T from rs221533, 433E1006, rs3924999 loci respectively (rs221533: chi-square was 27.45, P was 0.000; 433E1006: chi-square was 56.08, P was 0.000; rs3924999: chi-square was 10.53, P was 0.001). Haplotype was analyzed at frequency exceeding 1%. In three-marker-haplotype, C/C/G and C/C/A (marker order: rs221533, rs7820838, 433E1006) transmitted predominantly(C/C/G: chi-square was 5.26, P was 45.08; C/C/A: chi-square was 0.026, P was 0.000). In four-marker-haplotype (marker order: rs221533, rs7820838, 433E1006, rs3924999), C/C/G/T, C/C/A/C and C/C/A/T showed transmission disequilibrium (C/C/G/T: chi-square was 10.71, P was 0.001; C/C/A/C: chi-square was 8.83, P was 0.006, C/C/A/T: chi-square was 27.00, P was 0.000). In the positive subtype of parent-proband trios, C/T/G/C hapoltype transmission was not observed.

CONCLUSIONThe NRG1 gene polymorphism is significantly associated with schizophrenia in Chinese Han, especially in the positive subtype of schizophrenia.

Adolescent ; Adult ; Alleles ; Asian Continental Ancestry Group ; genetics ; China ; Ethnic Groups ; genetics ; Female ; Haplotypes ; genetics ; Humans ; Linkage Disequilibrium ; Male ; Neuregulin-1 ; genetics ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide ; Schizophrenia ; genetics

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A novel mutation of 428delG in DAX-1 gene causing X-linked adrenal congenital hypoplasia.

Min XU ; You-min WANG ; Xue-nong XING ; Xiao-hui ZHOU

Chinese Journal of Medical Genetics.2009;26(1):11-15. doi:10.3760/cma.j.issn.1003-9406.2009.01.003

OBJECTIVETo investigate the clinical features and to identify the DAX-1 gene mutation in a Chinese kindred with X-linked adrenal hypoplasia congenital(AHC).

METHODSClinical data and peripheral blood samples were obtained from the affected individuals and their relatives. The genomic DNA was isolated from whole blood. Four pairs of primers were used to amplify the two exons of the DAX-1 gene, and PCR products were purified and sequenced directly. Sequencing results were compared to the human DAX-1 sequence in the public database.

RESULTSA novel hemizygous frameshift mutation (428delG) in exon 1 of the DAX-1 gene was found in both patients (the index case and his cousin). Some clinical features such as the age of onset were different although these 2 patients carried the same mutation. Three females in the family, including the mothers of the 2 patients and their grandmother were carriers of this mutation. No such mutation was detected in other healthy persons in the family.

CONCLUSIONThe result suggested that X-linked AHC in the kindred was caused by a novel mutation of 428delG in the DAX-1 gene, and the same mutation can give rise to variable phenotypes.

Adolescent ; Adrenal Hyperplasia, Congenital ; genetics ; pathology ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; Child ; DAX-1 Orphan Nuclear Receptor ; DNA-Binding Proteins ; genetics ; Female ; Genetic Diseases, X-Linked ; genetics ; pathology ; Humans ; Male ; Mutation ; Pedigree ; Phenotype ; Receptors, Retinoic Acid ; genetics ; Repressor Proteins ; genetics ; Sequence Analysis, DNA

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Study on the mitochondrial DNA mutations in familial diabetes mellitus in Chinese population.

Sui-jun WANG ; Song-hua WU ; Tai-shan ZHENG ; Ling WANG ; Hui-juan LU ; Kun-san XIANG

Chinese Journal of Medical Genetics.2009;26(1):6-10. doi:10.3760/cma.j.issn.1003-9406.2009.01.002

OBJECTIVETo assess the prevalence of mutations or variants of the mitochondrial DNA (mtDNA) in familial diabetes mellitus in Chinese population, and to explore the relationship between mtDNA mutations or variants and diabetes.

METHODSSeven hundred and seventy randomly selected, unrelated probands of diabetes pedigrees and 309 controls over 60 years of age with normal glucose tolerance were recruited. PCR-RFLP and PCR-direct sequencing were applied to the screening of mtDNA mutations or variants, including the mutations at nucleotides 3243, 3256 in tRNALeu region, 12258 in tRNASer region, 14709 in tRNAGlu region, 8296, 8344, 8363 in tRNALys region, 3316, 3394, 3426 in ND1 region and 12026 in ND4 region.

RESULTSIn the diabetic group, 13 (1.69%) had mt3243 A>G mutation, 9(1.17%) had tRNAGlu 14709 T>C variant, 17 (2.21%) carried mt3316 G>A variant, 18 (2.34%) had mt3394 T>C variant, and 28 (3.63%) harbored the 12026 A>G variant. In the control group, the 14709, 3316, 3394, 12026 variants were detected in 5(1.62%), 5(1.62%), 6(1.94%), and 9(2.91%) subjects respectively. The 3256, 8296, 8344, 8363, 3426 and 12258 point mutations were not detected both in the diabetic patients and the controls. In the diabetic group, we found two double mutations, one was A3243G and T3394C, the other was A3243G and A12026G. Except that the A3243G mutation was only observed in the diabetic group, the frequencies of the other variants mentioned above were not statistically different between the diabetic and control groups. Moreover, clinical characteristics such as age of onset, BMI, and insulin resistance index were not different between diabetic patients with and without the variants.

CONCLUSIONThe tRNA (LeuUUR) 3243 A>G mutation may be the major cause of diabetes, representing 1.69% of the familial diabetes mellitus in Chinese. The other variants may be polymorphisms in this population, and the mutations not detected in our studied population may not be common contributors to diabetes mellitus in Chinese.

Adult ; Age of Onset ; Alleles ; Asian Continental Ancestry Group ; genetics ; Body Mass Index ; Case-Control Studies ; China ; DNA Mutational Analysis ; DNA, Mitochondrial ; genetics ; Diabetes Mellitus ; genetics ; pathology ; physiopathology ; Female ; Humans ; Insulin Resistance ; genetics ; Male ; Middle Aged ; Mutation ; Polymorphism, Genetic

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Fine mapping of a pure paroxysmal kinesigenic dyskinesia family.

Ding LIU ; Guo-liang LI ; Chan-juan CHEN ; Jin-xia ZHOU ; Bei ZHANG ; Zhi-guo WU ; Bo XIAO

Chinese Journal of Medical Genetics.2009;26(1):1-5. doi:10.3760/cma.j.issn.1003-9406.2009.01.001

OBJECTIVETo fine map the gene responsible for pure paroxysmal kinesigenic dyskinesia in a Chinese family.

METHODSSix additional markers flanking the tightly linked markers were chosen in the candidate region resulting from a whole genome-wide scanning and tested by parameter and nonparameter analysis using Linkage and Genehunter softwares to fine map the candidate region.

RESULTSEvidence for linkage of the pure paroxysmal kinesigenic dyskinesia to chromosome 3 was further confirmed. A maximum two-lod score of 2.82 at theta=0 was obtained with D3S3669. Critical recombinants place the PKD gene between D3S1314 and D3S1265.

CONCLUSIONA new locus of pure paroxysmal kinesigenic dyskinesia (PKD) is localized within a 10.2 cM interval on 3q28-29, between markers D3S1314 and D3S1265.

Adolescent ; Asian Continental Ancestry Group ; genetics ; Child ; Child, Preschool ; Chorea ; genetics ; Chromosome Mapping ; methods ; Female ; Genetic Linkage ; Genetic Markers ; genetics ; Genome, Human ; genetics ; Genomics ; Haplotypes ; Humans ; Male ; Pedigree

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Analysis of the genetic polymorphisms of 15 autosomal short tandem repeat in a Han population of Shandong.

Jianpin TANG ; Jian ZHANG ; Bo HU ; Fenghui JIANG ; Xiaojun YU

Chinese Journal of Medical Genetics.2008;25(6):715-717.

OBJECTIVETo obtain population genetic data at 15 short tandem repeat(STRs) in Shandong Han population.

METHODSFifteen STRs were genotyped in 200 unrelated individuals from Shandong Han population using Identifiler(TM) Kit.

RESULTSIn this Shandong Han population, the observed heterozygosities of the 15 loci ranged from 0.605 to 0.882, and the expected heterozygosities were 0.625-0.862, the polymorphic information contents ranged from 0.57 to 0.85, the discrimination powers ranged from 0.795 to 0.958, and the exclusion probabilities ranged from 0.297 to 0.758. The non-differentiation exact P values at TPOX loci were more than 0.05 between Shandong and Han population of Henan, Jilin, and Jiangsu. The non-differentiation exact P values between Shandong Han population and others populations were more than 0.05 at others loci. The P value at D13S317 was more than 0.05 between Shandong Han population and Ewenki population.

CONCLUSIONThese loci are polymorphic in Shandong Han population, and the discrimination powers and exclusion probabilities were high in the 15 STRs except TPOX and TH01.

Asian Continental Ancestry Group ; genetics ; Chromosomes, Human ; genetics ; Ethnic Groups ; genetics ; Female ; Forensic Genetics ; Gene Frequency ; Genome, Human ; genetics ; Genomics ; Heterozygote ; Humans ; Male ; Microsatellite Repeats ; genetics ; Polymorphism, Genetic

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Simultaneous presence of ins (15;17),t(2;17;20) and trisomy 8 in a patient with acute promyelocytic leukemia.

Shuxiao BAI ; Yongquan XUE ; Yafang WU ; Jinlan PAN ; Jun ZHANG ; Juan SHEN ; Yong WANG ; Huiying QIU

Chinese Journal of Medical Genetics.2008;25(6):712-714.

OBJECTIVETo report a rare complex karyotypic abnormalities including ins (15;17),t(2;17;20) and trisomy 8 in a patient with acute promyelocytic leukemia (APL).

METHODSChromosomes were prepared after 24 h culture of bone marrow cells. R-banding technique was used to analyze the karyotype. Multiplex fluorescence in situ hybridization (M-FISH), chromosome painting using whole chromosome parint (WCP) 2, 15, 17 and 20 and interphase-FISH (I-FISH) using PML-RARa dual-colour dual-fusion translocation probe were performed to ascertain the essence and origin of the abnormal chromosomes detected by conventional karyotypic analysis.

RESULTSKaryotypic analysis revealed a karyotype of 47, XY, 2q-, + 8, 17q+ , 20p+ . M-FISH analysis showed a karyotype of 47, XY, t(2;17;20) (q24;q21;p13), + 8, which was confirmed by chromosome painting. PML-RARa fusion gene which lied in the derivative chromosome 15 was detected by I-FISH suggesting a cryptic insertion (15;17)(q22;q21.1q21.3).

CONCLUSIONFISH is a reliable method for characterization of cryptic ins (15;17) and other complex translocations. It should be used in all suspected APL patients lacking t(15;17) by conventional karyotypic analysis.

Chromosomes, Human ; genetics ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Leukemia, Promyelocytic, Acute ; genetics ; Male ; Middle Aged ; Time Factors ; Translocation, Genetic ; genetics ; Trisomy ; genetics

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