Cell and Developmental Biology | Open Access Articles

Identification Of Susceptibility Pathways For The Role Of Chromosome 15q25.1 In Modifying Lung Cancer Risk, Xuemei Ji, Yohan Bossé, Maria Teresa Landi, Jiang Gui, Xiangjun Xiao, David Qian, Philippe Joubert Joubert, Maxime Lamontagne, Yafang Li, Ivan Gorlov, Mariella De Biasi, Younghun Han, Olga Gorlova, Rayjean J. Hung, Xifeng Wu, James Mckay, Xuchen Zong, Robert Carreras-Torres, David C. Christiani, Neil Caporaso, Mattias Johansson, Geoffrey Liu, Stig E. Bojesen, Loic Le Marchand, Demetrios Albanes, Heike Bickeböller, Melinda C. Aldrich, William S. Bush, Adonina Tardon, Gad Rennert, Susanne M. Arnold

Markey Cancer Center Faculty Publications

Genome-wide association studies (GWAS) identified the chromosome 15q25.1 locus as a leading susceptibility region for lung cancer. However, the pathogenic pathways, through which susceptibility SNPs within chromosome 15q25.1 affects lung cancer risk, have not been explored. We analyzed three cohorts with GWAS data consisting 42,901 individuals and lung expression quantitative trait loci (eQTL) data on 409 individuals to identify and validate the underlying pathways and to investigate the combined effect of genes from the identified susceptibility pathways. The KEGG neuroactive ligand receptor interaction pathway, two Reactome pathways, and 22 Gene Ontology terms were identified and replicated to be significantly associated …

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Kruppel-Like Factor 4-Dependent Staufen1-Mediated Mrna Decay Regulates Cortical Neurogenesis, Byoung-San Moon, Jinlun Bai, Mingyang Cai, Chunming Liu, Jiandang Shi, Wange Lu

Molecular and Cellular Biochemistry Faculty Publications

Kruppel-like factor 4 (Klf4) is a zinc-finger-containing protein that plays a critical role in diverse cellular physiology. While most of these functions attribute to its role as a transcription factor, it is postulated that Klf4 may play a role other than transcriptional regulation. Here we demonstrate that Klf4 loss in neural progenitor cells (NPCs) leads to increased neurogenesis and reduced self-renewal in mice. In addition, Klf4 interacts with RNA-binding protein Staufen1 (Stau1) and RNA helicase Ddx5/17. They function together as a complex to maintain NPC self-renewal. We report that Klf4 promotes Stau1 recruitment to the 3′-untranslated region of neurogenesis-associated mRNAs, …

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Pleiotropy Of Genetic Variants On Obesity And Smoking Phenotypes: Results From The Oncoarray Project Of The International Lung Cancer Consortium, Tao Wang, Jee-Young Moon, Yiqun Wu, Christopher I. Amos, Rayjean J. Hung, Adonina Tardon, Angeline Andrew, Chu Chen, David C. Christiani, Demetrios Albanes, Erik H. F. M. Van Der Heijden, Eric Duell, Gadi Rennert, Gary Goodman, Geoffrey Liu, James D. Mckay, Jian-Min Yuan, John K. Field, Jonas Manjer, Kjell Grankvist, Lambertus A. Kiemeney, Loic Le Marchand, M. Dawn Teare, Matthew B. Schabath, Mattias Johansson, Melinda C. Aldrich, Michael Davies, Mikael Johansson, Ming-Sound Tsao, Neil Caporaso, Susanne Arnold

Internal Medicine Faculty Publications

Obesity and cigarette smoking are correlated through complex relationships. Common genetic causes may contribute to these correlations. In this study, we selected 241 loci potentially associated with body mass index (BMI) based on the Genetic Investigation of ANthropometric Traits (GIANT) consortium data and calculated a BMI genetic risk score (BMI-GRS) for 17,037 individuals of European descent from the Oncoarray Project of the International Lung Cancer Consortium (ILCCO). Smokers had a significantly higher BMI-GRS than never-smokers (p = 0.016 and 0.010 before and after adjustment for BMI, respectively). The BMI-GRS was also positively correlated with pack-years of smoking (p < 0.001) in smokers. Based on causal network inference analyses, seven and five of 241 SNPs were classified to pleiotropic models for BMI/smoking status and BMI/pack-years, respectively. Among them, three and four SNPs associated with smoking status and pack-years (p < 0.05), respectively, were followed up in the ever-smoking data of the Tobacco, Alcohol and Genetics (TAG) consortium. Among these seven candidate SNPs, one SNP (rs11030104, BDNF) …

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A Linkage Map For The Newt Notophthalmus Viridescens: Insights In Vertebrate Genome And Chromosome Evolution, Melissa C. Keinath, S. Randal Voss, Panagiotis A. Tsonis, Jeramiah J. Smith

Biology Faculty Publications

Genetic linkage maps are fundamental resources that enable diverse genetic and genomic approaches, including quantitative trait locus (QTL) analyses and comparative studies of genome evolution. It is straightforward to build linkage maps for species that are amenable to laboratory culture and genetic crossing designs, and that have relatively small genomes and few chromosomes. It is more difficult to generate linkage maps for species that do not meet these criteria. Here, we introduce a method to rapidly build linkage maps for salamanders, which are known for their enormous genome sizes. As proof of principle, we developed a linkage map with thousands …

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Full-Text Articles in Cell and Developmental Biology

Markey Cancer Center Faculty Publications

Kruppel-Like Factor 4-Dependent Staufen1-Mediated Mrna Decay Regulates Cortical Neurogenesis, Byoung-San Moon, Jinlun Bai, Mingyang Cai, Chunming Liu, Jiandang Shi, Wange Lu

Molecular and Cellular Biochemistry Faculty Publications

Internal Medicine Faculty Publications

A Linkage Map For The Newt Notophthalmus Viridescens: Insights In Vertebrate Genome And Chromosome Evolution, Melissa C. Keinath, S. Randal Voss, Panagiotis A. Tsonis, Jeramiah J. Smith

Biology Faculty Publications