| 陆佳涛,徐福意,胡世贤,陈 科,朱豆豆,李 凯,周宇荀,肖君华.应用1号染色体替换系小鼠优选血脂QTLs内功能基因[J].,2018,(17):3218-3223 |
| 应用1号染色体替换系小鼠优选血脂QTLs内功能基因 |
| Prioritize Functional Genes in Blood Lipid QTLs Using Chromosome 1 Substitution Mice |
| 投稿时间：2017-10-28 修订日期：2017-11-24 |
| DOI：10.13241/j.cnki.pmb.2018.17.004 |
| 中文关键词: 血脂QTLs 染色体替换系 表达差异蛋白编码基因 功能突变基因 GWAS |
| 英文关键词: Blood lipid QTL Chromosome substitution strains Differentially expressed protein coding genes Functional annotation genes GWAS |
| 基金项目:国家自然科学基金面上项目（31371257）；上海市科委创新基金项目（15140900500；16140901300） |
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| 中文摘要: |
| 摘要 目的：利用野生小鼠来源1号染色体替换系B6-Chr1SJ和受体品系C57BL/6J (B6)筛选已知相关数量性状基因座( quantita- tive trait loci, QTL)内表达差异蛋白编码基因和功能突变基因，再结合人类全基因组关联分析（genome wide association study, GWAS）数据和相关文献优选出候选基因。方法：采用表达谱芯片技术对B6-Chr1SJ和B6进行肝脏基因表达谱检测；运用Tran- scriptome Analysis Console软件从基因水平进行表达差异分析，鉴定出表达差异蛋白编码基因；运用Ensembl Variant Effect Pre- dictor软件对B6-Chr1SJ小鼠1号染色体上的遗传变异进行功能注释，鉴定功能突变基因；利用小鼠系统遗传学资源数据库,筛选出已鉴定的血脂相关QTLs；利用bedtools中的intersectbed将鉴定的表达差异蛋白编码基因及功能突变基因与已鉴定的QTLs区段进行比较，并结合人类GWAS数据和相关文献优选出血脂相关候选基因。结果：在血脂相关QTLs内，共筛选出34个差异表达蛋白编码基因，分别有32、11和20个位于胆固醇（cholesterol, CHOL）、高密度脂蛋白胆固醇（High-density lipoprotein choles- terol, HDL-C）、低密度脂蛋白胆固醇（Low-density lipoprotein cholesterol, LDL-C）相关的QTLs内；共筛选出47个功能突变基因，分别有21、41和14个位于CHOL、HDL-C、LDL-C相关的QTLs内。在上述基因中，共优选出两个候选基因。其中，Marc1在人类GWAS研究中为阳性位点，Soat1已有报道与小鼠血脂代谢有关。结论：Marc1和Soat1可能是引起B6-Chr1SJ血脂异常的功能基因，其中Marc1未明确报道与血脂代谢相关，可作为候选基因进行进一步的功能验证。 |
| 英文摘要: |
| ABSTRACT Objective: Using chromosome 1 substitution strain derived from wild mice B6-Chr1SJ and recipent strainC57BL/6J(B6) to identify both differentially expressed protein coding genes and protein coding genes with deleterious mutation in blood lipids related quantitative trait loci(QTL), then potentially functional genes were further prioritized by analyzing human genome wide association study (GWAS) data and related literatures. Methods: First, gene expression profiles in liver tissue were assayed for B6-Chr1SJ and B6 with expression microarray technique and differentially expressed protein coding genes were determined using transcriptome analysis console software. Second, Functional annotation of the genetic variants identified in B6-Chr1SJ was performed using Ensembl Variant Ef- fect Predictor software. Third, the identified blood lipid related QTLs was screened out using the Systematic Genetics Resource Database of mice. Lastly, Both differentially expressed protein coding genes and functional mutation genes were compared with the identified QTLs using intersectbed in bedtools, then joint analysis of the human GWAS data and related literature to select candidate genes. Results: There are 34 differentially expressed protein encoding genes in blood lipids related QTLs. Among them, 32, 11, and 20 are in CHOL, HDL-C, and LDL-C related QTLs, respectively. We also identified 47 genes with functional mutations in which 21, 41, and 14 are in CHOL, HDL-C and LDL-C related QTLs. In these genes, Marc1 was a candidate genes in the blood lipid related human GWAS data, Soat1 has been reported to be a regulatory gene in blood lipid metabolism. Conclusion: Marc1 and Soat1 are likely to be the genes caus- ing dyslipidemia in B6-Chr1SJ, where Marc1 has not been specifically reported to be related to lipid metabolism and may be used as a candidate for further functional validation. |
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