Genes on Chromosome 17 Regulating % Body Fat in the Mouse

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• 批准号: 7988175
• 负责人: David Brian West
• 金额: $ 40.13万
• 依托单位: CHILDREN'S HOSPITAL & RES CTR AT OAKLAND
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-10 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7988175
• 关键词: Accounting; Adipose tissue; Affect; Agreement; Alleles; Bioinformatics; Body Composition; Body fat; Candidate Disease Gene; Chromosomes, Human, Pair 17; Complex; Computer software; Data; Development; Diet; Disease; Fatty acid glycerol esters; Female; Functional disorder; Gene Physical Location; Genes; Genetic; Genetic Complementation Test; Genetic Crosses; Genomics; Haplotypes; Human; Inbred Strain; Individual; Knockout Mice; Lead; Link; Maps; Measures; Medical; Methods; Mitogen-Activated Protein Kinases; Molecular; Mouse Strains; Mus; North America; Obesity; Obesity associated disease; Pathway interactions; Patients; Phenotype; Phosphoric Monoester Hydrolases; Predisposition; Process; Proteins; Quantitative Trait Loci; Recombinants; Regulation; Risk; Role; Surveys; Systems Biology; Techniques; Technology; Testing; Transgenic Mice; base; disorder risk; feeding; gene environment interaction; insulin signaling; lipid metabolism; mouse model; novel; obesity risk; obesity treatment; public health relevance; salt-inducible kinase; tool; trait

DESCRIPTION (provided by applicant): The long-term objective of this project is to identify and characterize the quantitative trait genes (QTGs) located on proximal mouse chromosome 17 (Chr17) that confer susceptibility and risk for the development of obesity. We have identified significant linkage for % body fat content on Chr17 using a mouse cross between C57BL/6N and 129P2 mouse strains. At this locus it is the C57BL allele that is associated with increased body fat. Linkage in this region on proximal Chr17 has been identified in numerous other mouse genetic crosses using different substrains of C57 mice, and the C57 allele is always the allele conferring increased risk for obesity. The physical location of the genes underlying this Chr17 QTL has been significantly narrowed by haplotype-based association analysis and bioinformatics. The best candidates for this trait on proximal Chr17 will be identified using a variety of molecular techniques including tiling arrays, sequencing, and expression analyses. Finally the role of specific candidates will be validated using phenotypes measured in null/null mice and the recombinant Quantitative Complementation (rQC) test. The functional role of validated QTGs will then be tested in wildtype, null/null and the mice produced in the rQC test by characterizing the molecular function, as well as the cellular and systems biology of the candidate QTG. PUBLIC HEALTH RELEVANCE: Identification of the genetic basis of disease risk will lead to the development of better treatments for obesity and obesity-related diseases and will lead to methods for tailoring treatment to individual patients based upon their genetic background.

描述（由申请人提供）：该项目的长期目标是确定和表征小鼠近端17号染色体（Chr17）上与肥胖易感性和发展风险相关的数量性状基因（qtg）。我们利用C57BL/6N和129P2小鼠品系的杂交，发现了Chr17上%体脂含量的显著连锁关系。在这个位点上，C57BL等位基因与体脂增加有关。在使用C57小鼠的不同亚株的许多其他小鼠遗传杂交中，已经发现了该区域在近端Chr17上的连锁，并且C57等位基因总是导致肥胖风险增加的等位基因。通过基于单倍型的关联分析和生物信息学，该Chr17 QTL的基因物理位置已显著缩小。将使用各种分子技术，包括平铺阵列、测序和表达分析，来确定近端Chr17上该性状的最佳候选者。最后，将通过在null/null小鼠中测量的表型和重组定量互补（rQC）测试来验证特定候选物的作用。然后通过表征候选QTG的分子功能以及细胞和系统生物学特性，在野生型、null/null和rQC测试中产生的小鼠中测试验证QTG的功能作用。