Mutational Screening of FGFR1, CER1, and CDON in a Large Cohort of Trigonocephalic Patients

2006 ◽  
Vol 43 (2) ◽  
pp. 148-151 ◽  
Author(s):  
Fernanda Sarquis Jehee ◽  
Luis G. Alonso ◽  
Denise P. Cavalcanti ◽  
Chong Kim ◽  
Steven A. Wall ◽  
...  
Keyword(s):  
High Performance ◽  
Direct Sequencing ◽  
Nucleotide Polymorphisms ◽  
Related Gene ◽  
Inclusion Criteria ◽  
Coding Region ◽  
Single Nucleotide ◽  
Metopic Synostosis ◽  
Mutational Screening ◽  
Johns Hopkins University

Objective Screen the known craniosynostotic related gene, FGFR1 (exon 7), and two new identified potential candidates, CER1 and CDON, in patients with syndromic and nonsyndromic metopic craniosynostosis to determine if they might be causative genes. Design Using single-strand conformational polymorphisms (SSCPs), denaturing high-performance liquid chromatography, and/or direct sequencing, we analyzed a total of 81 patients for FGFR1 (exon 7), 70 for CER1, and 44 for CDON. Patients Patients were ascertained in the Centro de Estudos do Genoma Humano in São Paulo, Brazil (n = 39), the Craniofacial Unit, Oxford, U.K. (n = 23), and the Johns Hopkins University, Baltimore, Maryland (n = 31). Clinical inclusion criteria included a triangular head and/or forehead, with or without a metopic ridge, and a radiographic documentation of metopic synostosis. Both syndromic and nonsyndromic patients were studied. Results No sequence alterations were found for FGFR1 (exon 7). Different patterns of SSCP migration for CER1 compatible with the segregation of single nucleotide polymorphisms reported in the region were identified. Seventeen sequence alterations were detected in the coding region of CDON, seven of which are new, but segregation analysis in parents and homology studies did not indicate a pathological role. Conclusions: FGFR1 (exon 7), CER1, and CDON are not related to trigonocephaly in our sample and should not be considered as causative genes for metopic synostosis. Screening of FGFR1 (exon 7) for diagnostic purposes should not be performed in trigonocephalic patients.

Pharmacokinetics of Gemcitabine in Japanese Cancer Patients: The Impact of a Cytidine Deaminase Polymorphism

2007 ◽  
Vol 26 (1) ◽  
pp. 32-42 ◽  
Author(s):  
Emiko Sugiyama ◽  
Nahoko Kaniwa ◽  
Su-Ryang Kim ◽  
Ruri Kikura-Hanajiri ◽  
Ryuichi Hasegawa ◽  
...  
Keyword(s):  
Cancer Patients ◽  
High Performance ◽  
Cytidine Deaminase ◽  
Direct Sequencing ◽  
Pharmacokinetic Parameters ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Inactive Metabolite ◽  
Grade 3 ◽  
The Impact

PurposeGemcitabine is rapidly metabolized to its inactive metabolite, 2′,2′-difluorodeoxyuridine (dFdU), by cytidine deaminase (CDA). We previously reported that a patient with homozygous 208A alleles of CDA showed severe adverse reactions with an increase in gemcitabine plasma level. This study extended the investigation of the effects of CDA genetic polymorphisms on gemcitabine pharmacokinetics and toxicities.Patients and MethodsGenotyping of CDA was performed by a direct sequencing of DNA obtained from the peripheral blood of Japanese gemcitabine-naïve cancer patients (n = 256). The patients recruited to the association study received a 30-minute intravenous infusion of gemcitabine at a dose of either 800 or 1,000 mg/m2, and eight blood samples were periodically collected (n = 250). Plasma levels of gemcitabine and dFdU were measured by high-performance liquid chromatography. Plasma CDA activities toward cytidine and gemcitabine were also measured (n = 121).ResultsTwenty-six genetic variations, including 14 novel ones and two known nonsynonymous single nucleotide polymorphisms (SNPs), were detected. Haplotypes harboring the nonsynonymous SNPs 79A>C (Lys27Gln) and 208G>A (Ala70Thr) were designated *2 and *3, respectively. The allelic frequencies of the two SNPs were 0.207 and 0.037, respectively. Pharmacokinetic parameters of gemcitabine and plasma CDA activities significantly depended on the number of haplotype *3. Haplotype *3 was also associated with increased incidences of grade 3 or higher neutropenia in the patients who were coadministered fluorouracil, cisplatin, or carboplatin. Haplotype *2 showed no significant effect on gemcitabine pharmacokinetics.ConclusionHaplotype *3 harboring a nonsynonymous SNP, 208G>A (Ala70Thr), decreased clearance of gemcitabine, and increased incidences of neutropenia when patients were coadministered platinum-containing drugs or fluorouracil.

scholarly journals Pathogenesis and characteristics of large ameloblastoma of the jaw: a report of two rare cases

2021 ◽  
Vol 49 (5) ◽  
pp. 030006052110148
Author(s):  
Xue Qiao ◽  
Xing Niu ◽  
Jiayi Liu ◽  
Lijie Chen ◽  
Yan Guo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Epithelial Mesenchymal Transition ◽  
Morphological Changes ◽  
Molecular Evidence ◽  
Nucleotide Polymorphisms ◽  
Related Gene ◽  
Epithelial Tumor ◽  
Single Nucleotide ◽  
Mesenchymal Transition ◽  
Hras Gene

Ameloblastoma is a common odontogenic epithelial tumor that exhibits various biological behaviors, ranging from simple cystic expansion to aggressive solid masses characterized by local invasiveness, a high risk of recurrence, and even malignant transformation. We report on two cases of unusually large solid ameloblastomas. We detected epithelial–mesenchymal transition-related gene expression and HRAS gene single nucleotide polymorphisms, providing possible molecular evidence of mesenchymal morphological changes in ameloblastoma. The detailed analysis of the pathogenesis of these two cases of ameloblastoma may deepen our understanding of this rare disease and offer promising targets for future targeted therapy.

scholarly journals Effect of P450 Oxidoreductase Polymorphisms on the Metabolic Activities of Ten Cytochrome P450s Varied by Polymorphic CYP Genotypes in Human Liver Microsomes

2018 ◽  
Vol 47 (4) ◽  
pp. 1604-1616 ◽  
Author(s):  
Yan Fang ◽  
Na Gao ◽  
Xin Tian ◽  
Jun Zhou ◽  
Hai-Feng Zhang ◽  
...  
Keyword(s):  
Gene Polymorphisms ◽  
High Performance ◽  
Liver Microsomes ◽  
Nucleotide Polymorphisms ◽  
Liquid Chromatograph ◽  
Single Nucleotide ◽  
P450 Oxidoreductase ◽  
Human Livers ◽  
Metabolic Activities ◽  
The Impact

Background/ Aims: Little is known about the effect of P450 oxidoreductase (POR) gene polymorphisms on the activities of CYPs with multiple genotypes. Methods: We genotyped 102 human livers for 18 known POR single nucleotide polymorphisms (SNPs) with allelic frequencies greater than 1% as well as for 27 known SNPs in 10 CYPs. CYP enzyme activities in microsomes prepared from these livers were determined by measuring probe substrate metabolism by high performance liquid chromatograph. Results: We found that the effects of the 18 POR SNPs on 10 CYP activities were CYP genotype-dependent. The POR mutations were significantly associated with decreased overall Km for CYP2B6 and 2E1, and specific genotypes within CYP1A2, 2A6, 2B6, 2C8, 2D6 and 2E1 were identified as being affected by these POR SNPs. Notably, the effect of a specific POR mutation on the activity of a CYP genotype could not be predicted from other CYP genotypes of even the same CYP. When combining one POR SNP with other POR SNPs, a hitherto unrecognized effect of multiple-site POR gene polymorphisms (MSGP) on CYP activity was uncovered, which was not necessarily consistent with the effect of either single POR SNP. Conclusions: The effects of POR SNPs on CYP activities were not only CYP-dependent, but more importantly, CYP genotype-dependent. Moreover, the effect of a POR SNP alone and in combination with other POR SNPs (MSGP) was not always consistent, nor predictable. Understanding the impact of POR gene polymorphisms on drug metabolism necessitates knowing the complete SNP complement of POR and the genotype of the relevant CYPs.

Single nucleotide polymorphisms of CBF4 locus region of Arabidopsis thaliana correspond to drought tolerance

2004 ◽  
Vol 1 (3) ◽  
pp. 181-190 ◽  
Author(s):  
Hao Gang-Ping ◽  
Wu Zhong-Yi ◽  
Chen Mao-Sheng ◽  
Cao Ming-Qing ◽  
Dominique Brunel ◽  
...  
Keyword(s):  
Arabidopsis Thaliana ◽  
Drought Tolerance ◽  
World Wide ◽  
Nucleotide Variation ◽  
Nucleotide Polymorphisms ◽  
Water Deficiency ◽  
Coding Region ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Adaptation To Drought

AbstractThe levels of drought tolerance and nucleotide polymorphism at the CBF4 locus were examined in a world-wide sample of 17 core accessions of Arabidopsis thaliana. The results showed that different accessions exhibited considerable differences in adaptation to drought stress. Compared with Columbia accession, the frequency of nucleotide polymorphism at the CBF4 locus of 25av, 203av and 244av accessions, including single nucleotide polymorphism (SNP) and insertion/deletion (Indel), was high, on average 1 SNP per 35.8 bp and 1 Indel per 143 bp. No significance in all regions of Tajima's D test indicated that the neutral mutation hypothesis could explain the nucleotide polymorphism in this CBF4 gene region. The higher polymorphism was the result of purification selection. Nucleotide polymorphism in the non-coding region was three times higher than in the coding region. This might indicate a recent relaxation of selection pressures on the non-coding region of CBF4 gene. In the coding region of CBF4, SNP frequency was 1 SNP per 96.4 bp and one non-synonymous mutation was detected from 25av, 203av and 244av accessions: the amino acid variation gly↔val at position 205, caused by the nucleotide variation G↔T at position 1034 (corresponding to the nucleotide at position 19 696 of GenBank accession no. AB015478 as 1). Furthermore, four differential SNPs were discovered in haplotype 6 constituted by 203av, one of them located in the 3′ non-coding region (A↔C at position 1106) and the others in the 5′ non-coding region (A↔G, A↔C and G↔A at positions 27, 129 and 171, respectively). The drought tolerance assay indicated that accession 203av was the best at tolerating water deficiency. We propose that haplotype 6 is consistent with its drought tolerance.

scholarly journals Screening of Three Different Alleles of mtDNA (G709A, G3496T, A3537G) in Subpopulation of UKM Students

2018 ◽  
Vol 5 (1) ◽  
pp. 37-40
Author(s):  
Seri Mirianti Ishar ◽  
Jeyaganesan Pillay a/l Balaraman ◽  
Muhammad Jefri Mohd Yusof ◽  
Khairul Osman ◽  
Lee Loong Chuen
Keyword(s):  
Uv Light ◽  
Forensic Genetics ◽  
Nucleotide Polymorphisms ◽  
Coding Region ◽  
Documentation System ◽  
Single Nucleotide ◽  
National University ◽  
Pcr Products ◽  
Malay Population ◽  
Mutation Allele

Human DNA consists of nucleus DNA (nDNA) and mitochondrial DNA (mtDNA). Both are valuable in medicine and forensic genetics but in this project, single nucleotide polymorphisms (SNPs) in mtDNA are used to trace the mutation occurred. Mutations in the sequence of alleles can lead to haplogroup variation and also certain diseases. The purpose of this study is to screen of mutations on alleles G709A, G3496T, and A3537G in Malay population of The National University of Malaysia (UKM) students. These SNPs lie in the ND1 (nitrogen dehydrogenase subunit 1) coding region, and the reports state that these three alleles are prone to mutate. From MitoMap Web site, the mutations of these alleles are reported to have potential in causing several diseases with the collaboration of other SNPs mutation. Allele G709A is reported to have an association with hearing loss and Leber Hereditary Optic Neuropathy (LHON) while allele G3496T is associated to LHON only. Allele A3537G is related to diabetes. A total of 100 DNA samples were collected from Malay students of UKM and preserved on FTA card to be purified later. The concentration of the DNA on the purified FTA card was between 10μM to 20μM. An attempt was made by amplifying those three loci from the genomic DNA. The amplified product was detected and separated using 1% gel electrophoresis. Before sequencing, the PCR products were visualized under UV light using gel documentation system. All PCR products were sequenced to detect the mutation on every single position chosen. From the alignment of sequencing results, allele G709A and allele G3496T showed no mutation. Meanwhile four samples from alleles A3537G has the mutation. From the results obtained, it seems that mutations are rare in all selected alleles. It is recommended to increase the sample size and alleles selected in the future to increase the strength of the study. This study also should be applied to other populations in Malaysia such as Chinese and Indian.  

scholarly journals Melanocortin-4 Receptor (MC4R) gene polymorphism and its effect on growth traits in Madura cattle

2019 ◽  
Vol 44 (1) ◽  
pp. 38
Author(s):  
P. W. Prihandini ◽  
S. Sumadi ◽  
G. Suparta ◽  
D. Maharani
Keyword(s):  
Growth Traits ◽  
Balance Control ◽  
Direct Sequencing ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Mc4r Gene ◽  
Melanocortin 4 Receptor ◽  
Pcr Rflp ◽  
Reverse Primer ◽  
Selection For

Melanocortin-4 receptor (MC4R) gene has an important role in the regulation of feed intake and energy balance control. The objective of this study was to identify the single nucleotide polymorphisms (SNPs) of MC4R gene and their association with growth traits in Madura cattle. A total of 198 calves were used in this study.Forward primer: 5’-GTCGGGCGTCTTGTTCATC-3’and reverse primer: 5’-GCTTGTGTTTAGCATCGCGT-3’ were used to amplify approximately 493 bp of MC4R gene. The results showed that two SNPs, g.1133C>G and g.1108C>T were identified by direct sequencing. The PCR-RFLP method was performed to genotype all individuals studied based on SNP g.1133C>G, and its SNP was significantly associated with shoulder height (SH) at yearling age (P<0.05). Animals with GG genotype had a higher SH (110.35±6.40cm) than those with CC (102.00±8.00 cm) and CG genotype (105.96±6.23 cm). The SNP g.1133 C>G changed amino acid from valine to leucine. In conclusion, the SNP g.1133C>G of the MC4R gene may be used as a marker-assisted selection for SH trait in Madura cattle.

scholarly journals Association Analysis of Single Nucleotide Polymorphisms in the 5′ Regulatory Region of the IL-6 Gene with Eimeria tenella Resistance in Jinghai Yellow Chickens

Genes ◽  
2019 ◽  
Vol 10 (11) ◽  
pp. 890 ◽  
Author(s):  
Hailiang Yu ◽  
Wenbin Zou ◽  
Shijie Xin ◽  
Xiaohui Wang ◽  
Changhao Mi ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Association Analysis ◽  
Direct Sequencing ◽  
Regulatory Region ◽  
Eimeria Tenella ◽  
Least Square ◽  
Bursa Of Fabricius ◽  
Control Group ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide

Interleukin 6 (IL-6) is an immunoregulatory cytokine involved in various inflammatory and immune responses. To investigate the effects of single nucleotide polymorphisms (SNPs) and haplotypes of IL-6 on resistance to Eimeria tenella (E. tenella), SNPs in the 5′ regulatory region of IL-6 were detected with direct sequencing, and the effects of SNPs and haplotypes on resistance to E. tenella were analyzed by the least square model in Jinghai yellow chickens. Nineteen SNPs were identified in the 5′ regulation region of IL-6, among which three SNPs were newly discovered. The SNP association analysis results showed that nine of the SNPs were significantly associated with E. tenella resistance indexes; the A-483G locus was significantly associated with the GSH-Px, IL-2, and IL-17 indexes (p < 0.05); the C-447G locus was significantly associated with the SOD, GSH-Px, IL-17, and IL-2 indexes (p < 0.05); and the G-357A locus had significant effects on the CAT and IL-16 indexes (p < 0.05). Haplotype analysis showed that H2H3 and H2H5 were favorable haplotype combinations with good coccidium resistance. Furthermore, we used qRT-PCR and observed that the expression of IL-6 in the infection group was higher than that in the control group in the liver, proventriculus, small intestine, thymus, kidney, and bursa of Fabricius and extremely significantly different than that in the cecum especially (p < 0.01). In summary, SNPs and haplotypes in the 5′ regulatory region of IL-6 have important effects on E. tenella resistance, and the results will provide a reference for molecular marker selection of E. tenella resistance in Jinghai yellow chickens.

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