Biomedical subjects

Guo-Yin Feng

Publications and source records attributed to Guo-Yin Feng.

14 recordsLinked to original sources

PubMed2006

Population-based and family-based association studies of an (AC)n dinucleotide repeat in alpha-7 nicotinic receptor subunit gene and schizophrenia.

The human alpha-7 neuronal nicotinic receptor subunit (CHRNA7) gene, located at chromosome 15q13.2, represents a strong candidate gene for schizophrenia. We have examined an (AC)n dinucleotide repeat in intron 2 of the CHRNA7 gene, which was previously shown to be strongly linked with schizophrenia, using both population-based and family-based association studies. In the population-based study, no significant differences between the genotype and allele frequency distributions in schizophrenia patients and control subjects were observed after correction for multiple testing, although a nominally significant association between the most common allele and schizophrenia was observed (P = 0.023, uncorrected for multiple testing). In the family-based study, there is no significant over-transmission (Transmitted/Non-transmitted: 61/50) of the same allele in 160 family trios. Overall, our results do not support a major role for the (AC)n dinucleotide repeat in schizophrenia susceptibility in Han Chinese. Further large-scale genetic studies based on a set of single nucleotide polymorphisms (SNPs) that fully characterize the linkage disequilibrium patterns at the CHRNA7 gene are necessary to determine the relevance of this gene as a risk factor for schizophrenia susceptibility.

Adult↗

PubMed2006

Case-control association study of Disrupted-in-Schizophrenia-1 (DISC1) gene and schizophrenia in the Chinese population.

Disrupted-in-Schizophrenia-1 (DISC1) has first been identified as a candidate gene for schizophrenia through study of a Scottish family with a balanced (1; 11) (q42.1; q14.3) translocation. Lots of linkage and association studies supported DISC1 as a risk factor for schizophrenia. In this study, we genotyped three SNPs in DISC1 using a set of Han Chinese samples of 560 schizophrenics and 576 controls. No positive association was detected in the whole samples but analysis of allele frequencies in female samples showed weak association between SNP rs2295959 and the disease (chi(2)=6.188, P=0.0135, OR=0.728, 95% CI=0.567-0.935). Our results provide further evidence for sex difference for the effect of the gene on the aetiology of schizophrenia. Our findings also would encourage further studies, particularly family-based association studies with larger samples, to analyze the association between DISC1 and schizophrenia.

Adult↗

PubMed2006

Association between the brain-derived neurotrophic factor (BDNF) gene and schizophrenia in the Chinese population.

Brain-derived neurotrophic factor (BDNF) belongs to a family of the neurotrophin which plays important roles in the development of the brain. BDNF has been suggested as a factor that increases the risk of schizophrenia. In this study, we genotyped three single nucleotide polymorphisms (SNPs) in the BDNF gene using a set sample of Han Chinese subjects consisting of 560 schizophrenes and 576 controls. No significant differences were found for either the genotype or allele distribution of analyzed polymorphisms, nor was any gender-specific association found. Thus, our data suggest that the BDNF gene may not be an important factor in susceptibility to schizophrenia.

Adult↗

PubMed2006

A novel deletion mutation in CCM1 gene (krit1) is detected in a Chinese family with cerebral cavernous malformations.

Cerebral Cavernous Malformations (CCM) are vascular malformations that are mostly located in the central nervous system (CNS) and occasionally within the skin and retina, which are classified into three types (CCM1, CCM2 and CCM3) by being located at different loci on chromosomes. At present, CCM1 (7q21), CCM2 (7p13-p15) and CCM3 (3q25.2-q27) are respectively linked to krit1 (Krev interaction trapped gene 1), MGC4607 and PDCD10 (programmed cell death 10). In this work, we identified a novel "GTA" deletion mutation at the acceptor splicing site of intron9/exon10 on krit1. The mutation results in an abnormally spliced protein by creating a premature termination code at the 23rd amino acid downstream from the sequence alteration. Our results are consistent with previous research on krit1 mutations and confirm the conclusion that KRIT1 haploinsufficiency may be the underlying mechanism of CCM1.

Adult↗

PubMed2006

A gene locus responsible for reticulate pigmented anomaly of the flexures maps to chromosome 17p13.3.

Reticulate pigmented anomaly of the flexures (RPAF), also called Dowling-Degos disease, is a rare autosomal-dominant cutaneous disorder characterized by spotted and reticulate pigmentation of the flexures. The gene, or even the chromosomal location, for RPAF has not yet been identified. In this study, one Chinese family with RPAF was identified and subjected to a genomewide screen for linkage analysis. We identified a locus at chromosome 17p13.3 with a maximum two-point limit of detection score of 3.61 at markers D17S831and D17S1866 (at recombination fraction theta=0.00). Haplotype analyses indicated that the disease gene is located within the 6.8 cM region distal to D17S1798. It is the first locus identified for RPAF. This study provides a map location for isolation of a disease gene causing RPAF.

Acanthosis Nigricans↗

PubMed2006

Association of DRD2 polymorphisms and chlorpromazine-induced extrapyramidal syndrome in Chinese schizophrenic patients.

AIM: Extrapyramidal syndrome (EPS) is most commonly affected by typical antipsychotic drugs that have a high affinity with the D2 receptor. Recently, many research groups have reported on the positive relationship between the genetic variations in the DRD2 gene and the therapeutic response in schizophrenia patients as a result of the role of variations in the receptor in modulating receptor expression. In this study, we evaluate the role DRD2 plays in chlorpromazine-induced EPS in schizophrenic patients. METHODS: We identified seven SNP(single nucleotide polymorphism) (-141Cins>del, TaqIB, TaqID, Ser311Cys, rs6275, rs6277 and TaqIA) in the DRD2 gene in 146 schizophrenic inpatients (59 with EPS and 87 without EPS according to the Simpson-Angus Scale) treated with chlorpromazine after 8 weeks. The alleles of all loci were determined by PCR (polymerase chain reaction). RESULTS: Polymorphisms TaqID, Ser311Cys and rs6277 were not polymorphic in the population recruited in the present study. No statistical significance was found in the allele distribution of -141Cins>del, TaqIB, rs6275 and TaqIA or in the estimated haplotypes (constituted by TaqIB, rs6275 and TaqIA) in linkage disequilibrium between the two groups. CONCLUSION: Our results did not lend strong support to the view that the genetic variation of the DRD2 gene plays a major role in the individually variable adverse effect induced by chlorpromazine, at least in Chinese patients with schizophrenia. Our results confirmed a previous study on the relationship between DRD2 and EPS in Caucasians.

Adult↗

PubMed2005

An association study between the transthyretin (TTR) gene and mental retardation.

It is known that in the pathogenesis of mental retardation (MR), both genetic and environmental factors (particularly iodine deficiency) appear to play a critical role. Transthyretin (TTR) transports between 20% and 30% of serum thyroxine in normal individuals and it is the main T(4)-binding protein in CSF. Variability in the TTR gene may influence risk for iodine-deficiency-based MR. The SNPs we selected from dbSNP were detected and identified using ARMS-PCR and sequencing methods, and we identified five novel sequence variants. Singular-locus association analysis indicated no association between the TTR gene and MR. In haplotype analysis, however, we found a haplotype CGTG+ (rs723744/G+6649C/T+6690C/rs2276382/del9) showed a weak positive association with MR (chi(2) = 6.699, p = 0.035). Finally, we concluded that the weak positive result is more likely to be due to sampling error and the small size of this haplotype resulting from its relative low frequency. Our negative results provide no evidence that variants of TTR gene influence susceptibility to MR in the iodine-deficient areas of China and suggest that there may be a compensatory mechanism(s) in humans and mice, which work(s) to compensate the effect of mutation in the TTR gene on MR.

Child↗

PubMed2005

Case-control association study of the close homologue of L1 (CHL1) gene and schizophrenia in the Chinese population.

The close homolog of L1 (CHL1), located on human chromosome 3p26.1, is a newly identified member of the L1 family of cell adhesion molecules which play important roles in cell migration, axonal growth, and synaptic remodeling. A positive association has been reported between a missense polymorphism in CHL1 gene and schizophrenia in the Japanese population [Sakurai, K., Migita, O., Toru, M., Arinami, T., 2002. An association between a missense polymorphism in the close homologue of L1 (CHL1, CALL) gene and schizophrenia. Mol. Psychiatry 7, 412-415]. An association between a missense polymorphism in the close homologue of L1 (CHL1, CALL) gene and schizophrenia. In order to test this finding, we genotyped four SNPs in the gene in the Han Chinese population using a sample of 560 cases and 576 controls. Analysis of allele frequencies in both samples also showed strong association between SNP rs2272522 (the same marker studied by K. Sakurai) and the disease (X2=31.591, P<0.000001, OR=1.745, 95% CI=1.435-2.121). Our results confirm the positive association between CHL1 gene and schizophrenia and indicate that CHL1 may be involved in the etiology of schizophrenia.

Adult↗

PubMed2005

Catechol-O-methyltransferase gene Val/Met functional polymorphism and risk of schizophrenia: a large-scale association study plus meta-analysis.

BACKGROUND: A common functional polymorphism (Val/Met) in the catechol-O-methyltransferase gene (COMT) that markedly affects enzyme activity has been shown to affect executive cognition and the physiology of the prefrontal cortex in humans. It is hypothesized that the high activity Val allele slightly increases risk for schizophrenia through its effect on dopamine-mediated prefrontal information processing. METHODS: We compared the allele/genotype frequencies of the Val/Met polymorphism in a large independent patient-control sample (862 patient and 928 healthy control subjects) from Han Chinese population, and an update meta-analysis was performed to assess the collective evidence across individual studies. RESULTS: No statistically significant differences were found in allele or genotype frequencies between patient and normal control subjects, although a nonsignificant overrepresentation of the Val allele in schizophrenia patients (odds ratio [OR] = 1.09, 95% confidence interval [CI] = .94-1.26) was suggested. Comparatively, the meta-analysis of all published population-based association studies showed statistically significant evidence for heterogeneity among the group of studies. Stratification of the studies by ethnicity of the samples yielded no significant evidence for an association with the Val allele in Asian population (OR = .96, 95% CI = .85-1.09), nor in European population (OR = 1.06, 95% CI = .95-1.19). CONCLUSIONS: Our data provide minimal evidence that the Val allele is a susceptibility factor for schizophrenia in either European or Asian populations.

Amino Acid Substitution↗

PubMed2005

Predicting protein subcellular location using digital signal processing.

The biological functions of a protein are closely related to its attributes in a cell. With the rapid accumulation of newly found protein sequence data in databanks, it is highly desirable to develop an automated method for predicting the subcellular location of proteins. The establishment of such a predictor will expedite the functional determination of newly found proteins and the process of prioritizing genes and proteins identified by genomic efforts as potential molecular targets for drug design. The traditional algorithms for predicting these attributes were based solely on amino acid composition in which no sequence order effect was taken into account. To improve the prediction quality, it is necessary to incorporate such an effect. However, the number of possible patterns in protein sequences is extremely large, posing a formidable difficulty for realizing this goal. To deal with such difficulty, a well-developed tool in digital signal processing named digital Fourier transform (DFT) [1] was introduced. After being translated to a digital signal according to the hydrophobicity of each amino acid, a protein was analyzed by DFT within the frequency domain. A set of frequency spectrum parameters, thus obtained, were regarded as the factors to represent the sequence order effect. A significant improvement in prediction quality was observed by incorporating the frequency spectrum parameters with the conventional amino acid composition. One of the crucial merits of this approach is that many existing tools in mathematics and engineering can be easily applied in the predicting process. It is anticipated that digital signal processing may serve as a useful vehicle for many other protein science areas.

Algorithms↗

PubMed2005

[Association study between NPY and YWHAH gene polymorphisms and schizophrenia].

A case-control study was carried out on a sample of 583 cases vs. 372 controls in the Chinese Han population, investigating several published polymorphisms in the YWHAH and NPY genes, which reported to be associated with schizophrenia. The polymorphism -134 (GCCTGCA)2-4, in the YWHAH was not analyzed for the failure of amplification, and the polymorphism T1128C in the NPY is not existent in the samples. The analysis was then emphasized on the variants -485C > T(NPY) and G753A(YWHAH). However, no significant differences of allele frequencies (with P values of 0.696 and 0.743, OR values of 1.041 and 0.962 respectively) or genotype frequencies (with P value of 0.45 and 0.75, chi2 = 1.51 and 0.58 respectively) among the matched groups were found. No sex-dependent effect was found either. Also,the analysis of the relative risk between the genotypes of the two genes indicates that the two genes could not cooperate with each other to add the risk of disease (P > 0.05). The results suggest that the polymorphisms - 485C > T (NPY) and G753A (YWHAH) are unlikely to be linked with genetic susceptibility to schizophrenia in the Chinese Han population.

14-3-3 Proteins↗

PubMed2004

Polymorphism of Prodynorphin promoter is associated with schizophrenia in Chinese population.

AIM: To investigate the correlation between single nucleotide polymorphisms (SNPs) of functional candidate gene Prodynorphin (PDYN) and schizophrenia. METHODS: SNPs in the promoter and exon regions of PDYN were screened and genotyped for association study in a cohort of Chinese Han schizophrenia cases and controls. RESULTS: Two SNPs PDYN-1576C>T and PDYN-946C>G were identified in the promoter region but PDYN-946C>G showed significant differences of allele distribution (x2=6.15, P=0.013) and genotype distribution (x2=6.87, P=0.032) between schizophrenic and control subjects. CONCLUSION: PDYN-946C>G polymorphism demonstrated an association with population susceptibility to schizophrenia.

Adult↗

PubMed2003

Application of pseudo amino acid composition for predicting protein subcellular location: stochastic signal processing approach.

The function of a protein is closely correlated with its subcellular location. With the success of human genome project and the rapid increase in the number of newly found protein sequences entering into data banks, it is highly desirable to develop an automated method for predicting the subcellular location of proteins. The establishment of such a predictor will no doubt expedite the functionality determination of newly found proteins and the process of prioritizing genes and proteins identified by genomics efforts as potential molecular targets for drug design. Based on the concept of pseudo amino acid composition originally proposed by K. C. Chou (Proteins: Struct. Funct. Genet. 43: 246-255, 2001), the digital signal processing approach has been introduced to partially incorporate the sequence order effect. One of the remarkable merits by doing so is that many existing tools in mathematics and engineering can be straightforwardly used in predicting protein subcellular location. The results thus obtained are quite encouraging. It is anticipated that the digital signal processing may serve as a useful vehicle for many other protein science areas as well.

Algorithms↗

PubMed2003

[Genetic analysis of a Chinese pedigree with congenital synpolydactyly].

Syndactyly is a limb malformation that shows a characteristic manifestation in both hands and feet. This condition is inherited as an autosomal dominant trait with reduced penetrance. Clinical presentation, in general, is complete or partial webbing between 3rd and 4th fingers. Syndactyly type I, II and III were mapped to 2q34-36, 2q31-q32 and 6q21-23.2 respectively. Syndactyly type II is named as synpolydactyly (SPD). Expansion of a polyalanine tract in the HOXD13 gene is known to cause synpolydactyly. HOXD13 gene locates in the HoxD complex. Nine homologous genes (HOXD1, -D3, -D4, -D8, -D9, -D10, -D11, -D12, -D13) of HoxD complex locate on chromosome 2 in the order of HOXD1 to HOXD13, among which HOXD13 is closest to the centromere. Deletions and duplications in HoxD complex or its upstream regulator factors have been identified to cause hand heteroplasia and consequently lead to abnormity of finger number or abnormity of configuration. We performed linkage analysis in a kindred with autosomal dominant hereditary syndactyly. Tight linkage to markers on chromosome 2q31-q32 (maximum two-point lod score: 6.78 at recombination fraction theta = 0.00) was observed. Multipoint linkage analysis produced a maximum LOD score of 7.02. Haplotype construction and analysis of recombination events narrowed this locus to a 20.61 cM region between markers D2S2302 and D2S315. No mutation was found in the coding region, the intro-exon boundaries, or part of the promoter region of HOXD13. Our result demonstrates that synpolydactyly locus in the Chinese Han Population is in the region of chromosome 2q31-q32 but a different causal gene can be involved.

China↗