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英文摘要
DESCRIPTION (provided by applicant): CpG islands, clusters of CpG dinucleotides in GC-rich regions, are often located in the 5' end of genes and are considered gene markers in mammalian genomes. Experiments have shown that methylation of promoter CpG islands plays an important role in gene silencing, genomic imprinting, X-chromosome inactivation, and carcinogenesis. Although many studies have been performed to identify CpG islands, to estimate the CpG mutation rates, and to examine the methylation modulation on disease genes, little is known about the distribution of CpG islands in the specific genomic regions across mammalian genomes or the pattern of genetic variation in CpG islands or in promoter-associated CpG islands. In addition, how CpG islands in mammalian genomes evolved and which kind of genes tend to gain or lose CpG islands remains largely unknown to us. The recent releases of several mammalian genomes, the discovery of millions of single nucleotide polymorphisms (SNPs) in these genomes, and large-scale methylation status data in the human genome provide us with an unprecedented opportunity to examine these issues in details. In this project, we will first perform a comprehensive survey of the distribution of CpG islands in five mammalian genomes (human, chimpanzee, mouse, rat, and dog) and their genomic regions. We will compare the features of CpG islands in the housekeeping genes with those in tissue-specific genes and compare the distribution and features of CpG islands in different categories of Gene Ontology (GO). Second, we will examine mutation patterns in CpG islands in four genomes (human, chimpanzee, mouse, and dog), each of which has more than 1 million SNPs. Third, we will investigate the mechanisms of CpG island evolution in mammalian genomes and to infer its effect on gene function. One approach is to examine the mutation pattern (e.g., CpG??TpG/CpA) and sequence features in each segment of CpG islands. Using the HapMap SNPs with their allele frequencies, we will test the possible natural selection in CpG islands. Finally, we will test the hypothesis that there is a relationship between CpG island loss and methylation status in CpG islands. Our comparative genomics and biomedical informatics analyses will provide a detailed view of the CpG island distribution in mammalian genomes, the mechanisms of CpG island evolution, and the relationship of the mutation pattern in CpG islands with functional categories of genes, especially cancer-related genes.
期刊论文(5)
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DOI: 10.1002/cbdv.201100354
发表时间: 2012-05
期刊: CHEMISTRY & BIODIVERSITY
影响因子: 2.9
作者: [Zheng, Siyuan, Zhao, Zhongming]
通讯作者: Zhao, Zhongming
DOI: 10.1080/03014460802558522
发表时间: 2009-01
期刊: Annals of human biology
影响因子: 1.7
作者: [Zhao Z, Khan F, Borkar M, Herrera R, Agrawal S]
通讯作者: Agrawal S
CpG islands or CpG clusters: how to identify functional GC-rich regions in a genome?
CpG 岛或 CpG 簇:如何识别基因组中功能性富含 GC 的区域?
DOI: 10.1186/1471-2105-10-65
发表时间: 2009-02-20
期刊: BMC bioinformatics
影响因子: 3
作者: [Han L, Zhao Z]
通讯作者: Zhao Z
DOI: 10.1371/journal.pone.0004995
发表时间: 2009
期刊: PloS one
影响因子: 3.7
作者: [Clarke RA, Zhao Z, Guo AY, Roper K, Teng L, Fang ZM, Samaratunga H, Lavin MF, Gardiner RA]
通讯作者: Gardiner RA
Constructing A Transcriptomic Atlas of Retrotransposon in Alzheimer's Disease
Deep learning methods to predict the function of genetic variants in orofacial clefts
Predicting Phenotype by Deep Learning Heterogeneous Multi-Omics Data
Predicting Phenotype by Deep Learning Heterogeneous Multi-Omics Data
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