In silico QTL mapping of basal liver iron levels in inbred mouse strains

Stela McLachlan, Seung Min Lee, Teresa M. Steele, Paula L. Hawthorne, Matthew A. Zapala, Eleazar Eskin, Nicholas J. Schork, Gregory J. Anderson, Chris D. Vulpe

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Both iron deficiency and iron excess are detrimental in many organisms, and previous studies in both mice and humans suggest that genetic variation may influence iron status in mammals. However, these genetic factors are not well defined. To address this issue, we measured basal liver iron levels in 18 inbred strains of mice of both sexes on a defined iron diet and found ∼4-fold variation in liver iron in males (lowest 153 μg/g, highest 661 μg/g) and ∼3-fold variation in females (lowest 222 μg/g, highest 658 μg/g). We carried out a genome-wide association mapping to identify haplotypes underlying differences in liver iron and three other related traits (copper and zinc liver levels, and plasma diferric transferrin levels) in a subset of 14 inbred strains for which genotype information was available. We identified two putative quantitative trait loci (QTL) that contain genes with a known role in iron metabolism: Eif2ak1 and Igf2r. We also identified four putative QTL that reside in previously identified iron-related QTL and 22 novel putative QTL. The most promising putative QTL include a 0.22 Mb region on Chromosome 7 and a 0.32 Mb region on Chromosome 11 that both contain only one candidate gene, Adam12 and Gria1, respectively. Identified putative QTL are good candidates for further refinement and subsequent functional studies.

Original languageEnglish
Pages (from-to)136-147
Number of pages12
JournalPhysiological Genomics
Volume43
Issue number3
DOIs
Publication statusPublished - 2011 Feb 1

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Inbred Strains Mice
Quantitative Trait Loci
Computer Simulation
Iron
Liver
Chromosomes, Human, Pair 11
Chromosomes, Human, Pair 7
Medical Genetics
Haplotypes
Zinc
Copper
Mammals
Genotype
Genome
Diet

All Science Journal Classification (ASJC) codes

  • Physiology
  • Genetics

Cite this

McLachlan, S., Lee, S. M., Steele, T. M., Hawthorne, P. L., Zapala, M. A., Eskin, E., ... Vulpe, C. D. (2011). In silico QTL mapping of basal liver iron levels in inbred mouse strains. Physiological Genomics, 43(3), 136-147. https://doi.org/10.1152/physiolgenomics.00025.2010
McLachlan, Stela ; Lee, Seung Min ; Steele, Teresa M. ; Hawthorne, Paula L. ; Zapala, Matthew A. ; Eskin, Eleazar ; Schork, Nicholas J. ; Anderson, Gregory J. ; Vulpe, Chris D. / In silico QTL mapping of basal liver iron levels in inbred mouse strains. In: Physiological Genomics. 2011 ; Vol. 43, No. 3. pp. 136-147.
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McLachlan, S, Lee, SM, Steele, TM, Hawthorne, PL, Zapala, MA, Eskin, E, Schork, NJ, Anderson, GJ & Vulpe, CD 2011, 'In silico QTL mapping of basal liver iron levels in inbred mouse strains', Physiological Genomics, vol. 43, no. 3, pp. 136-147. https://doi.org/10.1152/physiolgenomics.00025.2010

In silico QTL mapping of basal liver iron levels in inbred mouse strains. / McLachlan, Stela; Lee, Seung Min; Steele, Teresa M.; Hawthorne, Paula L.; Zapala, Matthew A.; Eskin, Eleazar; Schork, Nicholas J.; Anderson, Gregory J.; Vulpe, Chris D.

In: Physiological Genomics, Vol. 43, No. 3, 01.02.2011, p. 136-147.

Research output: Contribution to journalArticle

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