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Co-localizing Quantitative Trait Loci for Bone Mineral Density and HDL in Mice

小鼠骨矿物质密度和 HDL 的定量性状基因座的共定位

基本信息

批准号：
8894967
负责人：
Cheryl Lynne Ackert-Bicknell
金额：
$ 25.99万
依托单位：
UNIVERSITY OF ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-01 至 2016-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8894967
关键词：
Co localizing Quantitative Trait Loci

项目摘要

Project Summary/Abstract: Half of all Americans either have or are at serious risk for developing osteoporosis. Bone mineral density (BMD) can be readily measured in a clinical setting, and low BMD is associated with increased risk of osteoporotic fracture. Cardiovascular disease (CVD) a major cause of death in industrialized societies, and it is well established that raising HDL cholesterol reduces the risk of cardiovascular disease. Studies have shown that low BMD can be used as an independent predictor of CVD, and patients with CVD are more likely to have low BMD. Smoking, lack of exercise and eating a high fat “Western” diet increases the risk of developing both CVD and osteoporosis. Together these suggest that there may be shared causes for these two diseases. Both BMD and serum HDL levels have been shown to be genetically regulated. Preliminary studies in humans have suggested the existence of shared genetic causes for both of these phenotypes, but, as environmental and lifestyle factors influence both BMD and serum HDL levels, identifying the genetic link between CVD and osteoporosis has been difficult. The mouse is an excellent model for mapping genes that underlie complex traits, and unlike in human studies, environment can be controlled and modulated as needed in studies using the mouse. Two quantitative trait loci (QTL) for BMD have been identified on mouse Chromosome 1 and 8 that are coincident for QTL for serum HDL. Furthermore, both of these BMD QTL interact with dietary cholesterol intake. The Chr 1 QTL has been narrowed down to two genes and the Chr 8 QTL has been narrowed down to 4 candidate genes. In this application, transgenic mice for the candidate genes on Chr 1 will be used to confirm that: 1) that these genes impact BMD; 2) this QTL interacts with dietary cholesterol intake to affect BMD; and 3) this same genes do or do not regulates serum HDL levels. In the second Aim, the gene underlying the BMD QTL on Chr 8 will be identified and the hypothesis that a single gene at this locus regulates both the BMD and HDL QTL will be confirmed.

项目摘要/摘要：一半的美国人要么有严重的骨质疏松症风险，要么有严重的风险。骨密度 (BMD)可以在临床环境中很容易地测量，低BMD与增加患骨质疏松性骨折。心血管疾病(CVD)是工业化社会的主要死亡原因，众所周知，提高高密度脂蛋白可以降低心血管疾病的风险。研究研究表明，低骨密度可作为心血管疾病的独立预测因子，而心血管疾病患者更有可能有低骨密度。吸烟、缺乏锻炼和吃高脂肪的“西式”饮食会增加患心血管疾病和骨质疏松症的风险。总而言之，这些都表明可能会有共享的这两种疾病的病因。 BMD和血清高密度脂蛋白水平都被证明是受基因控制的。中国的初步研究人类已经提出，这两种表型存在共同的遗传原因，但正如环境和生活方式因素同时影响BMD和血清高密度脂蛋白水平，确定遗传联系心血管疾病和骨质疏松症之间的关系一直很难确定。小鼠是定位基因的极佳模型。这是复杂特征的基础，与人类研究不同，环境可以被控制和调节在使用鼠标的研究中根据需要。在小鼠1号和8号染色体上发现了两个影响骨密度的数量性状基因座(QTL)，分别是血清高密度脂蛋白的QTL符合。此外，这两个BMD QTL都与饮食胆固醇相互作用入口处。Chr 1 QTL已缩小为两个基因，而Chr 8 QTL已被缩小只剩下4个候选基因。在这个应用中，Chr1上候选基因的转基因小鼠将是用来证实：1)这些基因影响骨密度；2)这个QTL与饮食中的胆固醇相互作用摄入量影响BMD；3)这些基因调节或不调节血清高密度脂蛋白水平。在第二个目的：确定中国人骨质疏松症8号染色体上BMD QTL的基因，并假设单个基因在这个基因座上，骨密度和高密度脂蛋白的QTL都将得到确认。

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Passenger Gene Mutations: Unwanted Guests in Genetically Modified Mice.

DOI：
10.1002/jbmr.2772
发表时间：
2016-02
期刊：
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
影响因子：
0
作者：
Ackert-Bicknell CL;Rosen CJ
通讯作者：
Rosen CJ

Genetics of aging bone.

DOI：
10.1007/s00335-016-9650-y
发表时间：
2016-08
期刊：
Mammalian genome : official journal of the International Mammalian Genome Society
影响因子：
0
作者：
Adams DJ;Rowe DW;Ackert-Bicknell CL
通讯作者：
Ackert-Bicknell CL

Mapping of Craniofacial Traits in Outbred Mice Identifies Major Developmental Genes Involved in Shape Determination.

远交小鼠颅面特征图谱鉴定了参与形状决定的主要发育基因。

DOI：
10.1371/journal.pgen.1005607
发表时间：
2015
期刊：
PLoS genetics
影响因子：
4.5
作者：
Pallares,LuisaF;Carbonetto,Peter;Gopalakrishnan,Shyam;Parker,ClarissaC;Ackert-Bicknell,CherylL;Palmer,AbrahamA;Tautz,Diethard
通讯作者：
Tautz,Diethard

HDL cholesterol and bone mineral density: is there a genetic link?