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

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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 B6D2F2 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 B6D2F2 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.

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Acknowledgments

This work was supported by the National Institute on Aging (grant AG14731) of the National Institutes of Health.

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Authors and Affiliations

  1. Center for Developmental and Health Genetics, The Pennsylvania State University, University Park, Pennsylvania, 16803, USA

    Frank Johannes, David A. Blizard, Arimantas Lionikas, David J. Vandenbergh, Joseph T. Stout, Gerald E. McClearn & George P. Vogler

  2. Department of Biobehavioral Health, The Pennsylvania State University, University Park, Pennsylvania, 16803, USA

    Frank Johannes, David J. Vandenbergh, Gerald E. McClearn & George P. Vogler

  3. Center for Locomotion Studies, The Pennsylvania State University, University Park, Pennsylvania, 16803, USA

    Dena H. Lang

  4. Department of Biology, The Pennsylvania State University, University Park, Pennsylvania, 16803, USA

    James A. Strauss

  5. Department of Biobehavioral Health, Center for Developmental and Health Genetics, The Pennsylvania State University, 101 Amy Gardner House, University Park, PA, 16803, USA

    Frank Johannes

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  1. Frank Johannes
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  2. David A. Blizard
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  3. Arimantas Lionikas
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  9. George P. Vogler
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Correspondence to Frank Johannes.

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Johannes, F., Blizard, D.A., Lionikas, A. et al. QTL influencing baseline hematocrit in the C57BL/6J and DBA/2J lineage: age-related effects. Mamm Genome 17, 689–699 (2006). https://doi.org/10.1007/s00335-006-0009-7

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  • DOI: https://doi.org/10.1007/s00335-006-0009-7

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