Abstract
Red blood cells are essential for oxygen transport and other physiologic processes. Red cell characteristics are typically determined by complete blood counts which measure parameters such as hemoglobin levels and mean corpuscular volumes; these parameters reflect the quality and quantity of red cells in the circulation at any particular moment. To identify the genetic determinants of red cell parameters, we performed genome-wide association analysis on LG/J × SM/J F2 and F34 advanced intercross lines using single nucleotide polymorphism genotyping and a novel algorithm for mapping in the combined populations. We identified significant quantitative trait loci for red cell parameters on chromosomes 6, 7, 8, 10, 12, and 17; our use of advanced intercross lines reduced the quantitative trait loci interval width from 1.6- to 9.4-fold. Using the genomic sequences of LG/J and SM/J mice, we identified nonsynonymous coding single nucleotide polymorphisms in candidate genes residing within quantitative trait loci and performed sequence alignments and molecular modeling to gauge the potential impact of amino acid substitutions. These results should aid in the identification of genes critical for red cell physiology and metabolism and demonstrate the utility of advanced intercross lines in uncovering genetic determinants of inherited traits.
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Acknowledgments
The authors thank Kaitlin Samocha, Sherika Blevins, Wen Chen, Barry Paw, Rakina Yaneva, Peter Cresswell, Lihua Huang, Chester Brown, Corey Hoehn, and Carlo Brugnara for assistance and advice and James Cheverud for providing AIL lines and LG/J and SM/J genomic sequence data. This work was supported by NIH grants R01DA021336, R21DA024845, and R01MH079103 and a grant from the Schweppe Foundation to AAP, NIH grant T32DA007255 to CCP, NIH grant K99DK084122 to TBB, NIH grant R01DK080011 to MDF, and NIH T32MH020065 to JEL.
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T. B. Bartnikas and C. C. Parker contributed equally to this work.
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Bartnikas, T.B., Parker, C.C., Cheng, R. et al. QTLs for murine red blood cell parameters in LG/J and SM/J F2 and advanced intercross lines. Mamm Genome 23, 356–366 (2012). https://doi.org/10.1007/s00335-012-9393-3
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DOI: https://doi.org/10.1007/s00335-012-9393-3