Abstract

Disturbances of iron homeostasis can have significant clinical consequences. Iron deficiency is the world's most prominent nutritional deficiency and anemia of chronic disease (ACD) from decreased intestinal iron absorption and impaired iron release from macrophages is common in hospitalized patients. The overall aim of this study is to help us understand the genetic basis of variation in iron metabolism between people. Inbred mice show significant variation in multiple traits including iron metabolism. We propose to identify loci underlying strain specific differences in iron metabolism through a combination of in silico SNP association and gene expression profiling. We will test candidate genes for iron related function in Zebrafish, a complementary vertebrate model. Finally, we will assess candidate genes for a role in human iron metabolism through population based studies. We have assembled a multi- disciplinary research team of iron metabolism biologists, geneticists and computational biologists to carry out the proposed study.

Public Health Relevance

Anemias from iron deficiency or chronic disease are common disorders. The overall aim of this study is to improve our understanding of iron metabolism and its variation between people in order to develop more effective therapies for these diseases.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM083198-03
Application #
8669002
Study Section
Macromolecular Structure and Function A Study Section (MSFA)
Program Officer
Krasnewich, Donna M
Project Start
2012-07-01
Project End
2016-05-31
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
3
Fiscal Year
2014
Total Cost
Indirect Cost

  Institution

Name
University of California Berkeley
Department
Nutrition
Type
Earth Sciences/Resources
DUNS #
City
Berkeley
State
CA
Country
United States
Zip Code
94704

  Publications

Fuqua, Brie K; Lu, Yan; Frazer, David M et al. (2018) Severe Iron Metabolism Defects in Mice With Double Knockout of the Multicopper Ferroxidases Hephaestin and Ceruloplasmin. Cell Mol Gastroenterol Hepatol 6:405-427
Olde Loohuis, Loes M; Mangul, Serghei; Ori, Anil P S et al. (2018) Transcriptome analysis in whole blood reveals increased microbial diversity in schizophrenia. Transl Psychiatry 8:96
Mangul, Serghei; Yang, Harry Taegyun; Strauli, Nicolas et al. (2018) ROP: dumpster diving in RNA-sequencing to find the source of 1 trillion reads across diverse adult human tissues. Genome Biol 19:36
Rahmani, Elior; Schweiger, Regev; Shenhav, Liat et al. (2018) BayesCCE: a Bayesian framework for estimating cell-type composition from DNA methylation without the need for methylation reference. Genome Biol 19:141
Kang, Eun Yong; Lee, Cue Hyunkyu; Furlotte, Nicholas A et al. (2018) An Association Mapping Framework To Account for Potential Sex Difference in Genetic Architectures. Genetics 209:685-698
Koppe, Tiago; Patchen, Bonnie; Cheng, Aaron et al. (2017) Nicotinamide N-methyltransferase expression decreases in iron overload, exacerbating toxicity in mouse hepatocytes. Hepatol Commun 1:803-815
Hormozdiari, Farhad; Zhu, Anthony; Kichaev, Gleb et al. (2017) Widespread Allelic Heterogeneity in Complex Traits. Am J Hum Genet 100:789-802
Bilow, Michael; Crespo, Fernando; Pan, Zhicheng et al. (2017) Simultaneous Modeling of Disease Status and Clinical Phenotypes To Increase Power in Genome-Wide Association Studies. Genetics 205:1041-1047
McLachlan, Stela; Page, Kathryn E; Lee, Seung-Min et al. (2017) Hamp1 mRNA and plasma hepcidin levels are influenced by sex and strain but do not predict tissue iron levels in inbred mice. Am J Physiol Gastrointest Liver Physiol 313:G511-G523
Fraenkel, Paula G (2017) Anemia of Inflammation: A Review. Med Clin North Am 101:285-296

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