QTL influencing baseline hematocrit in the C57BL/6J and DBA/2J lineage: age-related effects

Frank Johannes, David A Blizard, Arimantas Lionikas, Dena H Lang, David J Vandenbergh, Joseph T Stout, James A Strauss, Gerald E McClearn, George P Vogler

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Abstract

Baseline serum hematocrit varies substantially in the population. While additive genetic factors account for a large part of this variability, little is known about the genetic architecture underlying the trait. Because hematocrit levels vary with age, it is plausible that quantitative trait loci (QTL) that influence the phenotype also show an age-specific profile. To investigate this possibility, hematocrit was measured in three different age cohorts of mice (150, 450, and 750 days) of the C57BL/6J (B6) and the DBA2/J (D2) lineage. QTL were searched in the B6D2F(2) intercross and the BXD recombinant inbred (RI) strains. The effects of these QTL were explored across the different age groups. On the phenotypic level, baseline serum hematocrit declines with age in a sex-specific manner. In the B6D2F(2) intercross, suggestive QTL that influence the phenotype were located on Chromosomes (Chr) 1, 2, 7, 11, 13, and 16. With the exception of the QTL on Chr 2, all of these QTL exerted their largest effect at 750 days. The QTL on Chr 1, 2, 7, 11 and 16 were confirmed in the BXD RIs in a sex- and age-specific manner. Linkage analysis in the BXD RIs revealed an additional significant QTL on Chr 19. Baseline serum hematocrit is influenced by several QTL that appear to vary with the age and sex of the animal. These QTL primarily overlap with QTL that have been shown to regulate hematopoietic stem cell phenotypes.
Original languageEnglish
Pages (from-to)689-699
Number of pages11
JournalMammalian Genome
Volume17
Issue number6
DOIs
Publication statusPublished - 2006

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Keywords

  • Age Factors
  • Aging
  • Animals
  • Female
  • Hematocrit
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Quantitative Trait Loci

Cite this

Johannes, F., Blizard, D. A., Lionikas, A., Lang, D. H., Vandenbergh, D. J., Stout, J. T., ... Vogler, G. P. (2006). QTL influencing baseline hematocrit in the C57BL/6J and DBA/2J lineage: age-related effects. Mammalian Genome, 17(6), 689-699. https://doi.org/10.1007/s00335-006-0009-7