Minghui Zhao

The University of Hong Kong, Hong Kong, Hong Kong

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Publications (3)12.09 Total impact

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    ABSTRACT: ITGAM was recently found to be associated with systemic lupus erythematosus (SLE) in populations of not only European ancestry, but also in Hispanic- and African-Americans, Mexicans and Colombians. The risk alleles in the gene, however, were found to be monomorphic in two Asian populations examined: Japanese and Korean. In this study, using a collection of 910 SLE patients and 2360 controls from Chinese living in Hong Kong, analyzed by both genome-wide association and direct sequencing, we confirmed the association of the same risk alleles in ITGAM with the disease. These findings were further replicated in the Thai population with 278 patients and 383 ethnicity- and geography-matched controls. Subphenotype stratification analyses showed significantly more involvement of the gene in patients with renal nephritis and neurological disorders. Although our results support a pivotal role by rs1143679 (R77H) in disease association, our data also suggests an additional contribution from rs1143683, another non-synonymous polymorphism in this gene (A858V). Therefore, despite the low-allele frequencies of the risk alleles of the gene in our two Asian populations, ITGAM was confirmed to be a risk factor related to disease susceptibility and probably severe manifestations of SLE.
    Human Molecular Genetics 04/2009; 18(11):2063-70. · 7.69 Impact Factor
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    ABSTRACT: Regulation of gene expression plays important role in cellular functions. Co-regulation of different genes may indicate functional connection or even physical interaction between gene products. Thus analysis on genomic structures that may affect gene expression regulation could shed light on the functions of genes. In a whole genome analysis of alternative splicing events, we found that two distinct genes, copine I (CPNE1) and RNA binding motif protein 12 (RBM12), share the most 5' exons and therefore the promoter region in human. Further analysis identified many gene pairs in human genome that share the same promoters and 5' exons but have totally different coding sequences. Analysis of genomic and expressed sequences, either cDNAs or expressed sequence tags (ESTs) for CPNE1 and RBM12, confirmed the conservation of this phenomenon during evolutionary courses. The co-expression of the two genes initiated from the same promoter is confirmed by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) in different tissues in both human and mouse. High degrees of sequence conservation among multiple species in the 5'UTR region common to CPNE1 and RBM12 were also identified. Promoter and 5'UTR sharing between CPNE1 and RBM12 is observed in human, mouse and zebrafish. Conservation of this genomic structure in evolutionary courses indicates potential functional interaction between the two genes. More than 20 other gene pairs in human genome were found to have the similar genomic structure in a genome-wide analysis, and it may represent a unique pattern of genomic arrangement that may affect expression regulation of the corresponding genes.
    BMC Genomics 11/2008; 9:456. · 4.40 Impact Factor
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    ABSTRACT: Early detection of cancer is key to prompt treatment and patient's long term survival. Designing noninvasive and simple methodologies that can be used in large scale screening for early tumor detection is an important research area that could have profound impact on cancer prevention and treatment. Taking advantage of available gene expression databases, we have performed extensive analysis on differentially expressed (DE) genes and alternatively spliced (AS) forms of genes in cancer tissues. In this study we detected genes that are potentially up-regulated in tumor tissues comparing to normal tissues. We also aligned the 8 million human EST sequences in dbEST with human genomic sequences, and found several hundreds AS variants that have a potential to be specific to or over expressed in tumor tissues comparing to normal tissues. Our results showed the possibility of using gene expression databases to detect potential "cancer genes ", and to use those DS genes and AS variants of genes as markers for early cancer detection.
    BioMedical Engineering and Informatics, 2008. BMEI 2008. International Conference on; 06/2008