title: A Chromosome 13 locus is associated with male-specific mortality in mice.
abstract: OBJECTIVE
  Mortality is a highly complex trait influenced by a wide array of genetic factors.
  
  
  METHODS
  We examined a population of 1200 mice that were F2 generation offspring of a 4-way reciprocal cross between C57BL6/J and DBA2/J strains. Animals were sacrificed at age 200, 500, or 800 days and genotyped at 96 markers. The 800 days old cohort, which were the survivors of a much larger breeding group, were examined for enriched frequency of alleles that benefit survival and depletion of alleles that reduce survival.
  
  
  RESULTS
  Loci on Chr 13 in males and on Chr X in females were significantly distorted from Mendelian expectations, even after conservative correction for multiple testing. DBA2/J alleles between 35 and 80 Mb on Chr 13 were underrepresented in the age 800 male animals. D2 genotypes in this region were also associated with premature death during behavioral testing. Furthermore, confirmatory analysis showed BXD recombinant inbred strains carrying the D2 alleles in this region had shorter median survival. Exploration of available pathology data indicated that a syndrome involving dental malocclusions, pancreatic islet hypertrophy, and kidney lipidosis may have mediated the effects of DBA alleles on mortality specifically in male mice. The heterozygote advantage locus on the X Chr was not found to be associated with any pathology.
  
  
  CONCLUSIONS
  These results suggest a novel locus influencing survival in the B6/D2 genetic background, perhaps via a metabolic disorder that emerges by 200 days of age in male animals.
authors.affiliation: Department of Biobehavioral Health, Pennsylvania State University, University Park, PA, 16802, USA. jgyekis@psu.edu.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Gyekis
authors.affiliation: Department of Kinesiology and School of Engineering Design, Technology, and Professional Programs, Penn State University, University Park, PA, 16802, USA.
authors.forename: Dean H
authors.initials: DH
authors.lastname: Lang
authors.affiliation: Department of Biobehavioral Health, Pennsylvania State University, University Park, PA, 16802, USA.|Penn State Institute for the Neurosciences, Pennsylvania State University, University Park, PA, 16802, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Vandenbergh
authors.affiliation: Department of Medical Genetics and Molecular Biochemistry, Temple University School of Medicine, Philadelphia, PA, 19140, USA.
authors.forename: Glenn S
authors.initials: GS
authors.lastname: Gerhard
authors.affiliation: Institute of Comparative Medicine, Pennsylvania State University, Hershey, PA, 17033, USA.
authors.forename: James W
authors.initials: JW
authors.lastname: Griffith
authors.affiliation: Animal Resource Program, Pennsylvania State University, University Park, PA, 16802, USA.
authors.forename: Jeffery W
authors.initials: JW
authors.lastname: Dodds
authors.affiliation: Department of Pathology, Wake Forest University Medical Center, Winston-Salem, NC, 27103, USA.
authors.forename: Zakaria K
authors.initials: ZK
authors.lastname: Shihabi
authors.affiliation: Department of Biobehavioral Health, Pennsylvania State University, University Park, PA, 16802, USA.
authors.forename: Mera K
authors.initials: MK
authors.lastname: Tilley
authors.affiliation: Department of Biobehavioral Health, Pennsylvania State University, University Park, PA, 16802, USA. dab22@psu.edu.
authors.forename: David A
authors.initials: DA
authors.lastname: Blizard
mesh_terms: D000483:Alleles; D000818:Animals; D033481:Chromosomes, Mammalian / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D008136:Longevity / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA
keywords: Lifespan; Linkage; Longevity; Mouse; Pathology