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Defining the spectrum of alleles that contribute to blood lipid concentrations in humans.

机译:定义有助于人类血脂浓度的等位基因谱。

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PURPOSE OF REVIEW: Recently, genome-wide genetic screening of common DNA sequence variants has proven a successful approach to identify novel genetic contributors to complex traits. This review summarizes recent genome-wide association studies for lipid phenotypes, and evaluates the next steps needed to obtain a full picture of genotype-phenotype correlation and apply these findings to inform clinical practice. RECENT FINDINGS: So far, genome-wide association studies have defined at least 19 genomic regions that contain common DNA single nucleotide polymorphisms associated with LDL cholesterol, HDL cholesterol and/or triglycerides. Of these, eight represent novel loci in humans, whereas 11 genes have been previously implicated in lipoprotein metabolism. Many of the same loci with common variants have already been shown to lead to monogenic lipid disorders in humans and/or mice, suggesting that a spectrum of common and rare alleles at each validated locus contributes to blood lipid concentrations. SUMMARY: At least 19 loci harbor common variations that contribute to blood lipid concentrations in humans. Larger scale genome-wide association studies should identify additional loci, and sequencing of these loci should pinpoint all relevant alleles. With a full catalog of DNA polymorphisms in hand, a panel of lipid-related variants can be studied to provide clinical risk stratification and targeting of therapeutic interventions.
机译:审查目的:最近,对常见DNA序列变异进行全基因组遗传筛选已被证明是鉴定复杂性状的新遗传贡献者的成功方法。这篇综述总结了脂质表型的最新全基因组关联研究,并评估了获得基因型-表型相关全貌并将这些发现应用于临床实践所需的下一步。最近的发现:到目前为止,全基因组关联研究已经定义了至少19个基因组区域,其中包含与LDL胆固醇,HDL胆固醇和/或甘油三酸酯相关的常见DNA单核苷酸多态性。其中,八个代表人类中的新基因座,而先前已有11个基因与脂蛋白代谢有关。已经显示出许多具有共同变异体的相同基因座会导致人类和/或小鼠的单基因脂质失调,这表明在每个经过验证的基因座处的共同和稀有等位基因的频谱都有助于血脂浓度的升高。摘要:至少有19个基因座包含有助于人类血脂浓度变化的常见变异。大规模的全基因组关联研究应确定其他基因座,这些基因座的测序应查明所有相关等位基因。拥有完整的DNA多态性目录,可以研究一组与脂质相关的变体,以提供临床风险分层和靶向治疗干预措施。

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