Positional identification of variants of Adamts16 linked to inherited hypertension.
Positional identification of variants of Adamts16 linked to inherited hypertension.
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DOI：
10.1093/hmg/ddp218
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发表时间：
2009-08-01
影响因子：
3.5
通讯作者：
Bouchard C
中科院分区：
文献类型：
--
作者：
Joe B;Saad Y;Dhindaw S;Lee NH;Frank BC;Achinike OH;Luu TV;Gopalakrishnan K;Toland EJ;Farms P;Yerga-Woolwine S;Manickavasagam E;Rapp JP;Garrett MR;Coe D;Apte SS;Rankinen T;Pérusse L;Ehret GB;Ganesh SK;Cooper RS;O'Connor A;Rice T;Weder AB;Chakravarti A;Rao DC;Bouchard C
在大鼠1号染色体上分离到一个804.6kb的血压数量性状基因座。804.6kb的区域仅包含两个基因，LOC 306664和LOC 306665。预计LOC 306664可翻译为具有血小板反应蛋白基序-16（Adamts 16）的解联蛋白样金属蛋白酶。LOC 306665是一个新基因。对LOC 306664和LOC 306665的所有预测外显子进行测序。仅在这些基因之一LOC 306664中鉴定出非同义变体。这些变异是近交系、远交系和野生大鼠中自然存在的多态性。在多个组织中检测到Adamts 16的全长大鼠转录本。与人类中的ADAMTS 16类似，Adamts 16在肾脏中的表达显著。肾转录组分析表明，BP相关的基因网络是同源和S大鼠之间的差异。这些基因在敲除或未敲除Adamts的肾细胞系之间也差异表达16。Adamts 16在大鼠和人类之间是保守的。在魁北克家族研究中，它是人类5号染色体同源区域内的候选基因，与收缩压和舒张压相关。多个变体，包括人ADAMTS 16密码子90（rs 2086310）中的Ala至Pro变体，与人静息收缩压（SBP）相关。GenNet中的复制研究证实了ADAMTS 16的两种变体与SBP的相关性，包括rs 2086310。总之，我们的报告代表了一个高分辨率的位置克隆和翻译研究Adamts 16作为一个候选基因控制BP。
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.
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影响因子：
3.8
作者：
HALEY, CS;KNOTT, SA
通讯作者：
KNOTT, SA
影响因子：
4.8
作者：
Longpré, JM;Leduc, R
通讯作者：
Leduc, R
影响因子：
4.6
作者：
Garrett, MR;Rapp, JP
通讯作者：
Rapp, JP
影响因子：
30.8
作者：
HANSSON, JH;NELSONWILLIAMS, C;LIFTON, RP
通讯作者：
LIFTON, RP
影响因子：
3.9
作者：
Kutz, Wendy E.;Wang, Lauren W.;Apte, Suneel S.
通讯作者：
Apte, Suneel S.