Klein Andrés D
Telethon Institute of Genetics and Medicine, Pozzuoli (NA), Italy
Physiol Genomics. 2017 Mar 1;49(3):177-179. doi: 10.1152/physiolgenomics.00123.2016. Epub 2017 Jan 27.
The genetic basis of the phenotypic variability observed in patients can be studied in mice by generating disease models through genetic or chemical interventions in many genetic backgrounds where the clinical phenotypes can be assessed and used for genome-wide association studies (GWAS). This is particularly relevant for rare disorders, where patients sharing identical mutations can present with a wide variety of symptoms, but there are not enough number of patients to ensure statistical power of GWAS. Inbred strains are homozygous for each loci, and their single nucleotide polymorphisms catalogs are known and freely available, facilitating the bioinformatics and reducing the costs of the study, since it is not required to genotype every mouse. This kind of approach can be applied to pharmacogenomics studies as well.
通过在多种遗传背景下进行基因或化学干预来建立疾病模型,从而在小鼠中研究患者所观察到的表型变异性的遗传基础。在这些遗传背景中,可以评估临床表型并将其用于全基因组关联研究(GWAS)。这对于罕见疾病尤为重要,因为携带相同突变的患者可能会表现出各种各样的症状,但患者数量不足以确保GWAS的统计效力。近交系在每个位点都是纯合的,其单核苷酸多态性目录是已知的且可免费获取,这有利于生物信息学研究并降低研究成本,因为无需对每只小鼠进行基因分型。这种方法也可应用于药物基因组学研究。