Systems genetic analysis of multivariate response to iron deficiency in mice

Lina Yin, Erica L. Unger, Leslie C. Jellen, Christopher J. Earley, Richard P. Allen, Ann Tomaszewicz, James C. Fleet, Byron C. Jones

Research output: Contribution to journalArticlepeer-review


The aim of this study was to identify genes that influence iron regulation under varying dietary iron availability. Male and female mice from 20+ BXD recombinant inbred strains were fed iron-poor or iron-adequate diets from weaning until 4 mo of age. At death, the spleen, liver, and blood were harvested for the measurement of hemoglobin, hematocrit, total iron binding capacity, transferrin saturation, and liver, spleen and plasma iron concentration. For each measure and diet, we found large, strainrelated variability. A principal-components analysis (PCA) was performed on the strain means for the seven parameters under each dietary condition for each sex, followed by quantitative trait loci (QTL) analysis on the factors. Compared with the iron-adequate diet, iron deficiency altered the factor structure of the principal components. QTL analysis, combined with PosMed (a candidate gene searching system) published gene expression data and literature citations, identified seven candidate genes, Ptprd, Mdm1, Picalm, lip1, Tcerg1, Skp2, and Frzb based on PCA factor, diet, and sex. Expression of each of these is cis-regulated, significantly correlated with the corresponding PCA factor, and previously reported to regulate iron, directly or indirectly. We propose that polymorphisms in multiple genes underlie individual differences in iron regulation, especially in response to dietary iron challenge. This research shows that iron management is a highly complex trait, influenced by multiple genes. Systems genetics analysis of iron homeostasis holds promise for developing new methods for prevention and treatment of iron deficiency anemia and related diseases.

Original languageEnglish (US)
Pages (from-to)R1282-R1296
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Issue number11
StatePublished - Jun 1 2012


  • BXD mice
  • Complex traits
  • Quantitative trait loci analysis

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


Dive into the research topics of 'Systems genetic analysis of multivariate response to iron deficiency in mice'. Together they form a unique fingerprint.

Cite this