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The identity of the chromosome 12 and 16 genes remains unknown. To identify whole body phenotypes associated with the chromosome 12 and 16 linkage regions, we generated and characterised new congenic strains, with WKY donor segments introgressed onto an SHR genetic background, for the chromosome 12 and 16 linkage regions. We found a &amp;gt;50% increase in insulin sensitivity in both the chromosome 12 and 16 strains. Blood pressure and left ventricular weight were reduced in the two congenic strains consistent with the congenic segments harboring SHR genes for insulin resistance, hypertension and cardiac hypertrophy. Integrated genomic analysis, using physiological and whole genome sequence data across 42 rat strains, identified variants within the congenic regions in Upk3bl, RGD1565131 and AABR06087018.1 that were associated with blood pressure, cardiac mass and insulin sensitivity. Quantitative trait transcript analysis across 29 recombinant inbred strains showed correlation between expression of Hspb1, Zkscan5 and Pdgfrl respectively with adipocyte volume, systolic blood pressure and cardiac mass. Comparative genome analysis showed marked enrichment of orthologues for human GWAS-associated genes for insulin resistance within the syntenic regions of both the chromosome 12 and 16 congenic intervals. Our study defines whole body phenotypes associated with the SHR chromosome 12 and 16 insulin resistance QTLs, identifies candidate genes for these SHR QTLs and finds human orthologues of rat genes in these regions that associate with related human traits. Further study of these genes in the congenic strains will lead to robust identification of the underlying genes and cellular mechanisms.<\/jats:p>","DOI":"10.1242\/dmm.026716","type":"journal-article","created":{"date-parts":[[2017,1,27]],"date-time":"2017-01-27T01:20:13Z","timestamp":1485480013000},"source":"Crossref","is-referenced-by-count":8,"title":["Genetic, physiological and comparative genomic studies of hypertension and insulin resistance in the spontaneously hypertensive rat"],"prefix":"10.1242","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6158-380X","authenticated-orcid":false,"given":"Philip M.","family":"Coan","sequence":"first","affiliation":[{"name":"Centre for Genomic and Experimental Medicine & Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oliver","family":"Hummel","sequence":"additional","affiliation":[{"name":"Cardiovascular and Metabolic Sciences, Max-Delbr\u00fcck-Center for Molecular Medicine (MDC), Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana Isabel Garcia","family":"Diaz","sequence":"additional","affiliation":[{"name":"Department of Medicine, Imperial College London, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marjorie","family":"Barrier","sequence":"additional","affiliation":[{"name":"Centre for Genomic and Experimental Medicine & Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neza","family":"Alfazema","sequence":"additional","affiliation":[{"name":"Centre for Genomic and Experimental Medicine & Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Penny J.","family":"Norsworthy","sequence":"additional","affiliation":[{"name":"MRC Clinical Sciences Centre, Imperial College London, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michal","family":"Pravenec","sequence":"additional","affiliation":[{"name":"Department of Model Diseases, Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enrico","family":"Petretto","sequence":"additional","affiliation":[{"name":"MRC Clinical Sciences Centre, Imperial College London, London, UK"},{"name":"Duke-NUS Medical School, Singapore, Republic of Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norbert","family":"Huebner","sequence":"additional","affiliation":[{"name":"Cardiovascular and Metabolic Sciences, Max-Delbr\u00fcck-Center for Molecular Medicine (MDC), Berlin, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), partner site Berlin, Germany"},{"name":"Charit\u00e9-Universit\u00e4tsmedizin, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7875-4502","authenticated-orcid":false,"given":"Timothy J.","family":"Aitman","sequence":"additional","affiliation":[{"name":"Centre for Genomic and Experimental Medicine & Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, UK"},{"name":"Department of Medicine, Imperial College London, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[2017,1,1]]},"reference":[{"key":"2021042500054385500_DMM026716C1","doi-asserted-by":"publisher","first-page":"1622","DOI":"10.1016\/j.biocel.2012.04.002","article-title":"Small heat shock proteins HSP27 (HspB1), alphaB-crystallin (HspB5) and HSP22 (HspB8) as regulators of cell death","volume":"44","author":"Acunzo","year":"2012","journal-title":"Int. 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