Healing quantitative trait loci in a combined cross analysis using related mouse strain crosses

J. M. Cheverud, H. A. Lawson, R. Funk, J. Zhou, E. P. Blankenhorn, E. Heber-Katz

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Inbred mouse strains MRL and LG share the ability to fully heal ear hole punches with the full range of appropriate tissues without scarring. They also share a common ancestry, MRL being formed from a multi-strain cross with two final backcrosses to LG before being inbred by brother-sister mating. Many gene-mapping studies for healing ability have been performed using these two strains, resulting in the location of about 20 quantitative trait loci (QTLs). Here, we combine two of these crosses (N638), MRL/lpr × C57BL/6NTac and LG/J × SM/J, in a single combined cross analysis to increase the mapping power, decrease QTL support intervals, separate multiple QTLs and establish allelic states at individual QTL. The combined cross analysis located 11 QTLs, 6 affecting only one cross (5 LG × SM and 1 MRL × B6) and 5 affecting both crosses, approximately the number of common QTLs expected given strain SNP similarity. Amongst the five QTLs mapped in both crosses, three had significantly different genetic effects, additive in one cross and over or underdominant in the other. It is possible that allelic states at these three loci are different in SM and B6 because they lead to differences in dominance interactions with the LG and MRL alleles. QTL support intervals are 40% smaller in the combined cross analysis than in either of the single crosses. Combined cross analysis was successful in enhancing the interpretation of earlier QTL results for these strains.

Original languageEnglish
Pages (from-to)441-446
Number of pages6
JournalHeredity
Volume108
Issue number4
DOIs
StatePublished - Apr 1 2012

Keywords

  • combined cross
  • mouse
  • quantitative trait loci
  • tissue regeneration
  • wound healing

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    Cheverud, J. M., Lawson, H. A., Funk, R., Zhou, J., Blankenhorn, E. P., & Heber-Katz, E. (2012). Healing quantitative trait loci in a combined cross analysis using related mouse strain crosses. Heredity, 108(4), 441-446. https://doi.org/10.1038/hdy.2011.94