Systems genetics analysis of iron regulation in the brain

Leslie C. Jellen, John L. Beard, Byron Jones

Research output: Contribution to journalShort survey

26 Citations (Scopus)

Abstract

Iron imbalances in the brain, including excess accumulation and deficiency, are associated with neurological disease and dysfunction; yet, their origins are poorly understood. Using systems genetics analysis, we have learned that large individual differences exist in brain iron concentrations, even in the absence of neurological disease. Much of the individual differences can be tied to the genetic makeup of the individual. This genetic-based differential regulation can be modeled in genetic reference populations of rodents. The work in our laboratory centers on iron regulation in the brain and our animal model consists of 25 BXD/Ty recombinant inbred mouse strains. By studying naturally occurring variation in iron phenotypes, such as tissue iron concentration, we can tie that variability to one or more genes by way of quantitative trait loci (QTL) analysis. Moreover, we can conduct genetic correlation analyses between our phenotypes and others previously measured in the BXD/Ty strains. We have observed several suggestive QTL related to ventral midbrain iron content, including one on chromosome 17 that contains btbd9, a gene that in humans has been associated with restless legs syndrome and serum ferritin. We have also observed gene expression correlations with ventral midbrain iron, including btbd9 expression and dopamine receptor expression. In addition, we have observed significant correlations between ventral midbrain iron content and dopamine-related phenotypes. The following is a discussion of iron regulation in the brain and the contributions a systems genetics approach can make toward understanding the genetic underpinnings and relation to neurological disease.

Original languageEnglish (US)
Pages (from-to)1255-1259
Number of pages5
JournalBiochimie
Volume91
Issue number10
DOIs
StatePublished - Oct 1 2009

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Brain
Iron
Mesencephalon
Quantitative Trait Loci
Phenotype
Individuality
Genes
Genetics
Restless Legs Syndrome
Chromosomes, Human, Pair 17
Inbred Strains Mice
Dopamine Receptors
Population Genetics
Ferritins
Chromosomes
Gene expression
Rodentia
Dopamine
Animals
Animal Models

All Science Journal Classification (ASJC) codes

  • Biochemistry

Cite this

Systems genetics analysis of iron regulation in the brain. / Jellen, Leslie C.; Beard, John L.; Jones, Byron.

In: Biochimie, Vol. 91, No. 10, 01.10.2009, p. 1255-1259.

Research output: Contribution to journalShort survey

Jellen, Leslie C. ; Beard, John L. ; Jones, Byron. / Systems genetics analysis of iron regulation in the brain. In: Biochimie. 2009 ; Vol. 91, No. 10. pp. 1255-1259.
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