title: The phenotypic impact of the male-specific region of chromosome-Y in inbred mating: the role of genetic variants and gene duplications in multiple inbred rat strains.
abstract: BACKGROUND
  The male-specific region of chromosome-Y (MSY) contributes to phenotypes outside of testis development and has a high rate of evolution between mammalian species. With a lack of genomic crossover, MSY is one of the few genomic areas under similar variation and evolutionary selection in inbred and outbred animal populations, allowing for an assessment of evolutionary mechanisms to translate between the populations.
  
  
  METHODS
  Using next-generation sequencing, MSY consomic strains, molecular characterization, and large-scale phenotyping, we present here regions of MSY that contribute to inbred strain phenotypes.
  
  
  RESULTS
  We have shown that (1) MSY of rat has nine autosomal gene transposition events with strain-specific selection; (2) sequence variants in MSY occur with a 1.98-fold higher number of variants than other chromosomes in seven sequenced rat strains; (3) Sry, the most studied MSY gene, has undergone extensive gene duplications, driving ubiquitous expression not seen in human or mouse; (4) the expression profile of Sry in the rat is driven by the insertion of the Sry2 copy into an intron of the ubiquitously expressed Kdm5d gene in antisense orientation, but due to several loss of function mutations in the Sry2 protein, nuclear localization and transcriptional control are decreased; (5) expression of Sry copies other than Sry2 in the rat overlaps with the expression profile for human SRY; (6) gene duplications and sequence variants (P76T) of Sry can be selected for phenotypes such as high blood pressure and androgen receptor signaling within inbred mating; and most importantly, (7) per chromosome size, MSY contributes to higher strain-specific phenotypic variation relative to all other chromosomes, with 53 phenotypes showing both a male to female and consomic cross significance.
  
  
  CONCLUSIONS
  The data presented supports a high probability of MSY genetic variation altering a broad range of inbred rat phenotypes.
authors: HudsonAlpha Institute for Biotechnology, 601 Genome Way, Huntsville, AL 35806 USA ; Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, WI 53226 USA ; Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226 USA.
authors: Jeremy W
authors: JW
authors: Prokop
authors: Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, WI 53226 USA.
authors: Shirng-Wern
authors: SW
authors: Tsaih
authors: Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, WI 53226 USA ; Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226 USA.
authors: Allison B
authors: AB
authors: Faber
authors: Department of Biology, The University of Akron, Akron, OH 44325 USA.
authors: Shannon
authors: S
authors: Boehme
authors: Department of Mathematics and Science, Walsh University, North Canton, OH 44720 USA.
authors: Adam C
authors: AC
authors: Underwood
authors: Department of Biology, The University of Akron, Akron, OH 44325 USA.
authors: Samuel
authors: S
authors: Troyer
authors: Department of Biology, The University of Akron, Akron, OH 44325 USA.
authors: Lauren
authors: L
authors: Playl
authors: Department of Biology, The University of Akron, Akron, OH 44325 USA.
authors: Amy
authors: A
authors: Milsted
authors: Department of Biology, The University of Akron, Akron, OH 44325 USA.
authors: Monte E
authors: ME
authors: Turner
authors: Department of Biology, The University of Akron, Akron, OH 44325 USA.
authors: Daniel
authors: D
authors: Ely
authors: Núcleo de Fisiologia Geral e Genômica Funcional-ICB-Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais Brazil.
authors: Almir S
authors: AS
authors: Martins
authors: Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, WI 53226 USA.
authors: Marek
authors: M
authors: Tutaj
authors: HudsonAlpha Institute for Biotechnology, 601 Genome Way, Huntsville, AL 35806 USA ; Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, WI 53226 USA ; Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226 USA.
authors: Jozef
authors: J
authors: Lazar
authors: Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, WI 53226 USA ; Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226 USA.
authors: Melinda R
authors: MR
authors: Dwinell
authors: HudsonAlpha Institute for Biotechnology, 601 Genome Way, Huntsville, AL 35806 USA ; Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, WI 53226 USA ; Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226 USA.
authors: Howard J
authors: HJ
authors: Jacob
keywords: Gene duplications; Inbred mating; MSY; Med14y; Phenotypic variation; Rattus norvegicus; Sry; Ube2q2y