TY - JOUR
T1 - Positional identification of variants of Adamts16 linked to inherited hypertension
AU - Joe, Bina
AU - Saad, Yasser
AU - Lee, Norman H.
AU - Frank, Bryan C.
AU - Achinike, Ovokeraye H.
AU - Luu, Truong V.
AU - Gopalakrishnan, Kathirvel
AU - Toland, Edward J.
AU - Farms, Phyllis
AU - Yerga-Woolwine, Shane
AU - Manickavasagam, Ezhilarasi
AU - Rapp, John P.
AU - Garrett, Michael R.
AU - Coe, David
AU - Apte, Suneel S.
AU - Rankinen, Tuomo
AU - Pérusse, Louis
AU - Ehret, Georg B.
AU - Ganesh, Santhi K.
AU - Cooper, Richard S.
AU - O'Connor, Ashley
AU - Rice, Treva
AU - Weder, Alan B.
AU - Chakravarti, Aravinda
AU - Rao, Dabeeru C.
AU - Bouchard, Claude
N1 - Funding Information:
This work was supported by funding from the National Institutes of Health (HL076709 to B.J., HL075414 to B.J., N.H.L., HL45670 to C.B., HL054512 to A.W., AR049930 to S.A.). C.B. is partially funded by the George A. Bray Chair in Nutrition. C.D.M. is supported by a post-doctoral fellowship from the National Institute for Arthritis, Musculoskeletal and Skin Diseases training award (1T32 AR050959; awarded to P.R. Cavanagh and J. Iannotti). Funding to pay the Open Access charge was provided by the Department of physiology and pharmacology, University of Toledo College of Medicine.
PY - 2009
Y1 - 2009
N2 - A previously reported blood pressure (BP) quantitative trait locus on rat Chromosome 1 was isolated in a short congenic segment spanning 804.6 kb. The 804.6 kb region contained only two genes, LOC306664 and LOC306665. LOC306664 is predicted to translate into A Disintegrin-like and Metalloproteinase with Thrombospondin Motifs-16 (Adamts16). LOC306665 is a novel gene. All predicted exons of both LOC306664 and LOC306665 were sequenced. Non-synonymous variants were identified in only one of these genes, LOC306664. These variants were naturally existing polymorphisms among inbred, outbred and wild rats. The full-length rat transcript of Adamts16 was detected in multiple tissues. Similar to ADAMTS16 in humans, expression of Adamts16 was prominent in the kidney. Renal transcriptome analysis suggested that a network of genes related to BP was differential between congenic and S rats. These genes were also differentially expressed between kidney cell lines with or without knock-down of Adamts16. Adamts16 is conserved between rats and humans. It is a candidate gene within the homologous region on human Chromosome 5, which is linked to systolic and diastolic BP in the Quebec Family Study. Multiple variants, including an Ala to Pro variant in codon 90 (rs2086310) of human ADAMTS16, were associated with human resting systolic BP (SBP). Replication study in GenNet confirmed the association of two variants of ADAMTS16 with SBP, including rs2086310. Overall, our report represents a high resolution positional cloning and translational study for Adamts16 as a candidate gene controlling BP.
AB - A previously reported blood pressure (BP) quantitative trait locus on rat Chromosome 1 was isolated in a short congenic segment spanning 804.6 kb. The 804.6 kb region contained only two genes, LOC306664 and LOC306665. LOC306664 is predicted to translate into A Disintegrin-like and Metalloproteinase with Thrombospondin Motifs-16 (Adamts16). LOC306665 is a novel gene. All predicted exons of both LOC306664 and LOC306665 were sequenced. Non-synonymous variants were identified in only one of these genes, LOC306664. These variants were naturally existing polymorphisms among inbred, outbred and wild rats. The full-length rat transcript of Adamts16 was detected in multiple tissues. Similar to ADAMTS16 in humans, expression of Adamts16 was prominent in the kidney. Renal transcriptome analysis suggested that a network of genes related to BP was differential between congenic and S rats. These genes were also differentially expressed between kidney cell lines with or without knock-down of Adamts16. Adamts16 is conserved between rats and humans. It is a candidate gene within the homologous region on human Chromosome 5, which is linked to systolic and diastolic BP in the Quebec Family Study. Multiple variants, including an Ala to Pro variant in codon 90 (rs2086310) of human ADAMTS16, were associated with human resting systolic BP (SBP). Replication study in GenNet confirmed the association of two variants of ADAMTS16 with SBP, including rs2086310. Overall, our report represents a high resolution positional cloning and translational study for Adamts16 as a candidate gene controlling BP.
UR - http://www.scopus.com/inward/record.url?scp=67650718354&partnerID=8YFLogxK
U2 - 10.1093/hmg/ddp218
DO - 10.1093/hmg/ddp218
M3 - Article
C2 - 19423552
AN - SCOPUS:67650718354
SN - 0964-6906
VL - 18
SP - 2825
EP - 2838
JO - Human molecular genetics
JF - Human molecular genetics
IS - 15
ER -