title: Consomic mouse strain selection based on effect size measurement, statistical significance testing and integrated behavioral z-scoring: focus on anxiety-related behavior and locomotion.
abstract: Selecting chromosome substitution strains (CSSs, also called consomic strains/lines) used in the search for quantitative trait loci (QTLs) consistently requires the identification of the respective phenotypic trait of interest and is simply based on a significant difference between a consomic and host strain. However, statistical significance as represented by P values does not necessarily predicate practical importance. We therefore propose a method that pays attention to both the statistical significance and the actual size of the observed effect. The present paper extends on this approach and describes in more detail the use of effect size measures (Cohen's d, partial eta squared - η p (2) ) together with the P value as statistical selection parameters for the chromosomal assignment of QTLs influencing anxiety-related behavior and locomotion in laboratory mice.
  
  
  
  The effect size measures were based on integrated behavioral z-scoring and were calculated in three experiments: (A) a complete consomic male mouse panel with A/J as the donor strain and C57BL/6J as the host strain. This panel, including host and donor strains, was analyzed in the modified Hole Board (mHB). The consomic line with chromosome 19 from A/J (CSS-19A) was selected since it showed increased anxiety-related behavior, but similar locomotion compared to its host. (B) Following experiment A, female CSS-19A mice were compared with their C57BL/6J counterparts; however no significant differences and effect sizes close to zero were found. (C) A different consomic mouse strain (CSS-19PWD), with chromosome 19 from PWD/PhJ transferred on the genetic background of C57BL/6J, was compared with its host strain. Here, in contrast with CSS-19A, there was a decreased overall anxiety in CSS-19PWD compared to C57BL/6J males, but not locomotion.
  
  
  
  This new method shows an improved way to identify CSSs for QTL analysis for anxiety-related behavior using a combination of statistical significance testing and effect sizes. In addition, an intercross between CSS-19A and CSS-19PWD may be of interest for future studies on the genetic background of anxiety-related behavior.
authors.affiliation: Division of Animal Welfare & Laboratory Animal Science, Department of Animals in Science and Society, Faculty of Veterinary Medicine, Utrecht University, P.O. Box 80166, 3508 TD, Utrecht, The Netherlands. m.labots@uu.nl.|Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands. m.labots@uu.nl.
authors.forename: M
authors.initials: M
authors.lastname: Labots
authors.affiliation: Division of Animal Welfare & Laboratory Animal Science, Department of Animals in Science and Society, Faculty of Veterinary Medicine, Utrecht University, P.O. Box 80166, 3508 TD, Utrecht, The Netherlands.|Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.|Present Address: Boston Scientific Nederland B.V., Nieuwegein, The Netherlands.
authors.forename: M C
authors.initials: MC
authors.lastname: Laarakker
authors.affiliation: Division of Animal Welfare & Laboratory Animal Science, Department of Animals in Science and Society, Faculty of Veterinary Medicine, Utrecht University, P.O. Box 80166, 3508 TD, Utrecht, The Netherlands.|Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: F
authors.initials: F
authors.lastname: Ohl
authors.affiliation: Division of Animal Welfare & Laboratory Animal Science, Department of Animals in Science and Society, Faculty of Veterinary Medicine, Utrecht University, P.O. Box 80166, 3508 TD, Utrecht, The Netherlands.|Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: H A
authors.initials: HA
authors.lastname: van Lith
mesh_terms: D000818:Animals; D001007:Anxiety / Q000235:genetics / Q000503:physiopathology*; D001522:Behavior, Animal; D005260:Female; D008124:Locomotion; D008297:Male; D051379:Mice; D040641:Quantitative Trait Loci / Q000235:genetics; D013045:Species Specificity; D013223:Statistics as Topic
keywords: Anxiety-related behavior; Cohen’s d; Consomic mouse strain; Effect size; Integrated z-score; Locomotion; Partial eta squared (η p 2 )