title: Systems genetics of metabolism: the use of the BXD murine reference panel for multiscalar integration of traits.
abstract: Metabolic homeostasis is achieved by complex molecular and cellular networks that differ significantly among individuals and are difficult to model with genetically engineered lines of mice optimized to study single gene function. Here, we systematically acquired metabolic phenotypes by using the EUMODIC EMPReSS protocols across a large panel of isogenic but diverse strains of mice (BXD type) to study the genetic control of metabolism. We generated and analyzed 140 classical phenotypes and deposited these in an open-access web service for systems genetics (www.genenetwork.org). Heritability, influence of sex, and genetic modifiers of traits were examined singly and jointly by using quantitative-trait locus (QTL) and expression QTL-mapping methods. Traits and networks were linked to loci encompassing both known variants and novel candidate genes, including alkaline phosphatase (ALPL), here linked to hypophosphatasia. The assembled and curated phenotypes provide key resources and exemplars that can be used to dissect complex metabolic traits and disorders.
authors.affiliation: Laboratory of Integrative and Systems Physiology, School of Life Sciences, École Polytechnique Fédérale de Lausanne 1015, Switzerland.
authors.forename: Pénélope A
authors.initials: PA
authors.lastname: Andreux
authors.forename: Evan G
authors.initials: EG
authors.lastname: Williams
authors.forename: Hana
authors.initials: H
authors.lastname: Koutnikova
authors.forename: Riekelt H
authors.initials: RH
authors.lastname: Houtkooper
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Champy
authors.forename: Hugues
authors.initials: H
authors.lastname: Henry
authors.forename: Kristina
authors.initials: K
authors.lastname: Schoonjans
authors.forename: Robert W
authors.initials: RW
authors.lastname: Williams
authors.forename: Johan
authors.initials: J
authors.lastname: Auwerx
mesh_terms: D000469:Alkaline Phosphatase / Q000737:chemistry / Q000235:genetics; D000818:Animals; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D005260:Female; D006706:Homeostasis; D006801:Humans; D007014:Hypophosphatasia / Q000235:genetics; D008297:Male; D008659:Metabolic Diseases / Q000235:genetics*; D051379:Mice / Q000235:genetics*; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D011110:Polymorphism, Genetic; D040641:Quantitative Trait Loci; D012015:Reference Standards; D025101:Vitamin B 6 / Q000378:metabolism
chemical_list: D025101:Vitamin B 6; D000469:Alkaline Phosphatase