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QTL Analysis of a Trade‐off in Bone Length within the Mouse Zygomatic Arch
Author(s) -
Percival Christopher J.,
Green Rebecca,
Gatti Daniel M.,
Pomp Daniel,
Roseman Charles C.,
Marcucio Ralph,
Hallgrímsson Benedikt
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.387.3
Subject(s) - zygomatic arch , skull , biology , anatomy , zygomatic bone , evolutionary biology
We use a powerful mouse resource to identify candidate genes associated with a negative correlation in the length of bones that contribute to the zygomatic arch. Because system‐wide growth factors contribute to all skeletal dimensions, most skull linear distances are positively correlated with each other. However, the lengths of two adjacent zygomatic arch bones are negatively correlated in our Diversity Outbred (DO) mice. This is evidence for an opposite pleiotropic effect or developmental constraint during zygomatic arch formation, which appears to limit variation in total zygomatic arch length. Determining the basis for this negative correlation will help us understand developmental mechanisms that limit phenotypic variation and underlie variation in how individual bones contribute to overall skull form. We completed high‐resolution genetic mapping with 563 DO mice to identify genomic regions and candidate genes associated with this negative correlation. DO mice are ideal for this, because each mouse carries a high degree of heterozygosity and a unique combination of alleles. We separately mapped 1) jugal bone length, 2) jugal process of maxilla length, and 3) total zygomatic arch length. Analysis was completed on raw linear distances without scaling or removing the allometric component of variation, because these procedures remove variation associated with overall size and artificially create negative associations between linear distance measurements. A genomic interval between 85 and 86 Mb on chromosome 17 was significantly associated with variation in jugal bone length and jugal process length, but not total zygomatic arch length. In addition, founder haplotypes under this peak displayed opposite phenotypic effects on individual bone lengths, suggesting it includes a genetic factor driving relative length of these zygomatic bones, but not total arch length. This interval includes Six2 , Six3 , and Six3os1 , which are expressed in the pharyngeal arches or forebrain during facial development, as well as Camkmt , which is pivotal for calmodulin methylation. Ongoing real‐time PCR will show whether expression of these genes within the maxillary arch at E10.5 in three founder strains is correlated with measured founder haplotype effects. Understanding the genetic and developmental basis for this negative correlation is important because it results in a developmental constraint on total zygomatic arch length, which will act to limit evolvability of this structure. Support or Funding Information Funding graciously provided by the NIH (U01DE020054, 2R01DE019638, R01DE021708, R01GM070683), NSERC (238992‐12), and to CJP by the Alberta Innovates Health Solutions.