Person: Zong, Chenghang
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Zong
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Chenghang
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Zong, Chenghang
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Publication Rare event of histone demethylation can initiate singular gene expression of olfactory receptors(Proceedings of the National Academy of Sciences, 2013) Tan, Longzhi; Zong, Chenghang; Xie, XiaoliangIn mammals, the sense of odors relies on the peculiar expression pattern of olfactory receptors (ORs). Each single neuron chooses one, and only one, from all ∼1,400 OR genes that are present in a mouse genome. In neurobiology, a long-standing mystery is how such singularity can be achieved. We show theoretically that a simple kinetic scheme of OR activation followed by feedback can be solely responsible for the observed singularity, as long as the two timescales—slow activation by epigenetic modification and fast feedback by transcriptional regulation—are well separated. Our work provides the theoretical underpinning behind the choice of ORs, and demonstrates how the nervous system utilizes the kinetics of epigenetic changes to direct neurogenesis.Publication Reproducible copy number variation patterns among single circulating tumor cells of lung cancer patients(Proceedings of the National Academy of Sciences, 2013) Ni, Xiaohui; Zhuo, Minglei; Su, Zhe; Duan, J.; Gao, Yan; Wang, Z.; Zong, Chenghang; Bai, H.; Chapman, Alec; Zhao, J.; Xu, L.; An, T.; Ma, Q.; Wang, Y.; Wu, M.; Sun, Y.; Wang, S.; Li, Z.; Yang, X.; Yong, Jun; Su, X.-D.; Lu, Y.; Bai, F.; Xie, Xiaoliang; Wang, J.Circulating tumor cells (CTCs) enter peripheral blood from primary tumors and seed metastases. The genome sequencing of CTCs could offer noninvasive prognosis or even diagnosis, but has been hampered by low single-cell genome coverage of scarce CTCs. Here, we report the use of the recently developed multiple annealing and looping-based amplification cycles for whole-genome amplification of single CTCs from lung cancer patients. We observed characteristic cancer-associated single-nucleotide variations and insertions/deletions in exomes of CTCs. These mutations provided information needed for individualized therapy, such as drug resistance and phenotypic transition, but were heterogeneous from cell to cell. In contrast, every CTC from an individual patient, regardless of the cancer subtypes, exhibited reproducible copy number variation (CNV) patterns, similar to those of the metastatic tumor of the same patient. Interestingly, different patients with the same lung cancer adenocarcinoma (ADC) shared similar CNV patterns in their CTCs. Even more interestingly, patients of small-cell lung cancer have CNV patterns distinctly different from those of ADC patients. Our finding suggests that CNVs at certain genomic loci are selected for the metastasis of cancer. The reproducibility of cancer-specific CNVs offers potential for CTC-based cancer diagnostics.Publication Genome-Wide Detection of Single-Nucleotide and Copy-Number Variations of a Single Human Cell(American Association for the Advancement of Science, 2012) Zong, Chenghang; Chapman, Alec; Xie, XiaoliangKindred cells can have different genomes because of dynamic changes in DNA. Single cell sequencing is needed to characterize these genomic differences but has been hindered by whole-genome amplification bias, resulting in low genome coverage. Here we report a new amplification method: Multiple Annealing and Looping Based Amplification Cycles (MALBAC) that offer high uniformity across the genome. Sequencing MALBAC amplified DNA achieves 93% genome coverage ≥1x for a single human cell at 25x mean sequencing depth. We detected digitized copy number variations (CNVs) of a single cancer cell. By sequencing three kindred cells, we were able to call individual single nucleotide variations (SNVs) with no false positives observed. We directly measured the genome-wide mutation rate of a cancer cell line and found that purine-pyrimidine exchanges occurred unusually frequently among the newly acquired SNVs.Publication Probing Meiotic Recombination and Aneuploidy of Single Sperm Cells by Whole-Genome Sequencing(American Association for the Advancement of Science, 2012) Lu, Sijia; Zong, Chenghang; Fan, Wei; Yang, Mingyu; Li, Jinsen; Chapman, Alec; Zhu, Ping; Hu, Xuesong; Xu, Liya; Yan, Liying; Bai, Fan; Qiao, Jie; Tang, Fuchou; Li, Ruiqiang; Xie, XiaoliangMeiotic recombination creates genetic diversity and ensures segregation of homologous chromosomes. Previous population analyses yielded results averaged among individuals and affected by evolutionary pressures. We sequenced 99 sperm from an Asian male by using the newly developed amplification method—multiple annealing and looping-based amplification cycles—to phase the personal genome and map recombination events at high resolution, which are nonuniformly distributed across the genome in the absence of selection pressure. The paucity of recombination near transcription start sites observed in individual sperm indicates that such a phenomenon is intrinsic to the molecular mechanism of meiosis. Interestingly, a decreased crossover frequency combined with an increase of autosomal aneuploidy is observable on a global per-sperm basis.