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Co-inheritance of variants/mutations in Malaysian patients with Crohn's disease

Chua KH, Ng CC, Hilmi I, Goh KL

Genet. Mol. Res., 2012;11(3):3115-21.
PMID: 23007989

Crohn's disease is a chronic, relapsing inflammatory bowel disease; it affects the mucosa and deeper layers of the digestive wall. Two Crohn's disease patients who carried the JW1 variant and two patients who carried the SNP5 variant were investigated for other co-inherited polymorphisms that could influence Crohn's disease development. Based on the sequencing results, a homozygous 5'-UTR-59 G to A variant in exon 1 (SNP6) was observed in a patient who carried SNP5, while a heterozygous SNP6 variant was detected in the other patient who carried SNP5. No other associated mutations or polymorphisms were detected in the two patients who carried the JW1 variant of the CARD15/NOD2 gene.

Matched MeSH terms: 5' Untranslated Regions/genetics
Phylogenetic evidence for inter-typic recombination in the emergence of human enterovirus 71 subgenotypes

Yoke-Fun C, AbuBakar S

BMC Microbiol, 2006 Aug 30;6:74.
PMID: 16939656

BACKGROUND: Human enterovirus 71 (EV-71) is a common causative agent of hand, foot and mouth disease (HFMD). In recent years, the virus has caused several outbreaks with high numbers of deaths and severe neurological complications. Several new EV-71 subgenotypes were identified from these outbreaks. The mechanisms that contributed to the emergence of these subgenotypes are unknown.
RESULTS: Six EV-71 isolates from an outbreak in Malaysia, in 1997, were sequenced completely. These isolates were identified as EV-71 subgenotypes, B3, B4 and C2. A phylogenetic tree that correlated well with the present enterovirus classification scheme was established using these full genome sequences and all other available full genome sequences of EV-71 and human enterovirus A (HEV-A). Using the 5' UTR, P2 and P3 genomic regions, however, isolates of EV-71 subgenotypes B3 and C4 segregated away from other EV-71 subgenotypes into a cluster together with coxsackievirus A16 (CV-A16/G10) and EV-71 subgenotype C2 clustered with CV-A8. Results from the similarity plot analyses supported the clustering of these isolates with other HEV-A. In contrast, at the same genomic regions, a CV-A16 isolate, Tainan5079, clustered with EV-71. This suggests that amongst EV-71 and CV-A16, only the structural genes were conserved. The 3' end of the virus genome varied and consisted of sequences highly similar to various HEV-A viruses. Numerous recombination crossover breakpoints were identified within the non-structural genes of some of these newer EV-71 subgenotypes.
CONCLUSION: Phylogenetic evidence obtained from analyses of the full genome sequence supports the possible occurrence of inter-typic recombination involving EV-71 and various HEV-A, including CV-A16, the most common causal agent of HFMD. It is suggested that these recombination events played important roles in the emergence of the various EV-71 subgenotypes.

Matched MeSH terms: 5' Untranslated Regions/genetics
Cellular proteins bind to the 3' and 5' untranslated regions of dengue 2 virus genome

Ong CC, Lam SK, AbuBakar S

Malays J Pathol, 1998 Jun;20(1):11-7.
PMID: 10879258

In vitro generated cloned full length dengue 2 virus untranslated regions (UTRs) were used in RNA gel mobility shift assays to examine cellular factors binding to the virus genomes. Cellular factors in lysates of Vero (monkey) and C6/36 (mosquito) cells bound specifically and non-specifically to the dengue 2 virus 3' UTR. Non-specific interaction with the 5' UTR, resulting in formation of at least 4 band shift complexes was noted with lysate of the C6/36 cells only. Pre-treating the cell lysates with proteinase K affected binding of cellular factors to the dengue 2 virus UTRs, suggesting that the cellular factors were proteins. These findings suggest that cellular proteins could interact with specific sites on the dengue virus genomes.

Matched MeSH terms: 5' Untranslated Regions/genetics
Genetic polymorphisms of EGF 5'-UTR and NAT2 857G/A associated with glioma in a case control study of Malaysian patients

Muthusamy KA, Lian LH, Vairavan N, Chua KH, Waran V

Genet. Mol. Res., 2012;11(3):2939-45.
PMID: 22782629

Studies of genetic mutations that have been used in predicting glioma prognosis have revealed a complex relationship between clinical and genetic factors. Epidermal growth factor (EGF) and the NAT2 gene play a central role in carcinogenesis. An adenine (A) to guanine (G) single nucleotide polymorphism at position 61 in the 5'-untranslated region (5'-UTR) of the EGF gene has been found to be associated with levels of EGF production, and the mutations in the NAT2 gene have been postulated as a risk factor for cancer. We investigated EGF and the NAT2 gene in 13 glioma tissue samples and 12 normal controls. In the EGF 5'-UTR 61G polymorphism, the heterozygote GA was the most common genotype in the glioma patients. In the NAT2 polymorphism at nucleotide position 857G/A, the G allele and the GG genotype were the most prevalent forms in both the glioma and normal samples. We did not find any homozygous AA genotypes in the glioma patients. Based on this preliminary evidence, the EGF 5'-UTR at position 61 and the NAT2 SNP at position 857 polymorphisms are associated with increased risk for glioma.

Matched MeSH terms: 5' Untranslated Regions/genetics*
The oil palm metallothionein promoter contains a novel AGTTAGG motif conferring its fruit-specific expression and is inducible by abiotic factors

Omidvar V, Abdullah SN, Izadfard A, Ho CL, Mahmood M

Planta, 2010 Sep;232(4):925-36.
PMID: 20635097 DOI: 10.1007/s00425-010-1220-z

The 1,053-bp promoter of the oil palm metallothionein gene (so-called MSP1) and its 5' deletions were fused to the GUS reporter gene, and analysed in transiently transformed oil palm tissues. The full length promoter showed sevenfold higher activity in the mesocarp than in leaves and 1.5-fold more activity than the CaMV35S promoter in the mesocarp. The 1,053-bp region containing the 5' untranslated region (UTR) gave the highest activity in the mesocarp, while the 148-bp region was required for minimal promoter activity. Two positive regulatory regions were identified at nucleotides (nt) -953 to -619 and -420 to -256 regions. Fine-tune deletion of the -619 to -420 nt region led to the identification of a 21-bp negative regulatory sequence in the -598 to -577 nt region, which is involved in mesocarp-specific expression. Gel mobility shift assay revealed a strong interaction of the leaf nuclear extract with the 21-bp region. An AGTTAGG core-sequence within this region was identified as a novel negative regulatory element controlling fruit-specificity of the MSP1 promoter. Abscisic acid (ABA) and copper (Cu(2+)) induced the activity of the promoter and its 5' deletions more effectively than methyl jasmonate (MeJa) and ethylene. In the mesocarp, the full length promoter showed stronger inducibility in response to ABA and Cu(2+) than its 5' deletions, while in leaves, the -420 nt fragment was the most inducible by ABA and Cu(2+). These results suggest that the MSP1 promoter and its regulatory regions are potentially useful for engineering fruit-specific and inducible gene expression in oil palm.

Matched MeSH terms: 5' Untranslated Regions/genetics
Distinct haplotype profiles and strong linkage disequilibrium at the MDR1 multidrug transporter gene locus in three ethnic Asian populations

Tang K, Ngoi SM, Gwee PC, Chua JM, Lee EJ, Chong SS, et al.

Pharmacogenetics, 2002 Aug;12(6):437-50.
PMID: 12172212

The MDR1 multidrug transporter plays a key role in determining drug bioavailability, and differences in drug response exist amongst different ethnic groups. Numerous studies have identified an association between the MDR1 single nucleotide polymorphism (SNP) exon 26 3435C>T and differences in MDR1 function. We performed a haplotype analysis of the MDR1 gene in three major ethnic groups (Chinese, Malays and Indians) by examining 10 intragenic SNPs. Four were polymorphic in all three ethnic groups: one occurring in the non-coding region and three occurring in coding exons. All three coding SNPs (exon 12 1236C>T, exon 21 2677G>T/A and exon 26 3435C>T) were present in high frequency in each ethnic group, and the derived haplotype profiles exhibited distinct differences between the groups. Fewer haplotypes were observed in the Malays (n = 6) compared to the Chinese (n = 10) and Indians (n = 9). Three major haplotypes (> 10% frequency) were observed in the Malays and Chinese; of these, two were observed in the Indians. Strong linkage disequilibrium (LD) was detected between the three SNPs in all three ethnic groups. The strongest LD was present in the Chinese, followed by Indians and Malays, with the corresponding LD blocks estimated to be approximately 80 kb, 60 kb and 40 kb, respectively. These data strongly support the hypothesis that strong LD between the neutral SNP exon 26 3435C>T and a nearby unobserved causal SNP underlies the observed associations between the neutral SNP and MDR1 functional differences. Furthermore, strong LD between exon 26 3435T and different unobserved causal SNPs in different study populations may provide a plausible explanation for conflicting reports associating the same exon 26 3435T allele with different MDR1 functional changes.

Matched MeSH terms: 5' Untranslated Regions/genetics