Experimental Cardiovascular Biology Research Unit, Institut de Recherches Cliniques de Montréal, Montréal, Quebec, Canada.
Hypertension. 2010 Feb;55(2):453-8. doi: 10.1161/HYPERTENSIONAHA.109.145235. Epub 2009 Dec 14.
Most common diseases and/or their consequences, including hypertension and susceptibility to end-organ damage, have genetic components. Contrary to hereditary Mendelian diseases (where the existence of a rare mutation within a single gene usually dictates whether signs of the disease are present), the manifestations of common diseases correspond to what is defined in genetics as “quantitative complex traits”. Such traits show within populations continuous variation from low to high values, and are shaped by the interactions of a great number of genes (each typically having small effects on their own) with environmental factors. Consequently, identification of genetic variants contributing to complex traits must rely on methods that are different than those used for the identification of Mendelian genetic mutations (which can be performed by following within pedigrees the hereditary transmission of markers linked to the mutated gene). Among several available tools, genetic animal models have proved particularly useful to identify the effects of naturally occurring genetic variants and their effects within mammalian organisms. Indeed, inbred strains are organisms that carry identical copies of each gene. Accordingly, it is possible by performing crosses between them to reduce the complexity of the problem, since the progeny of crosses will carry only 2 possible variants of any gene and experimental and environmental conditions can be controlled.
大多数常见疾病及其后果，包括高血压和易发生靶器官损伤，都有遗传成分。与遗传性孟德尔疾病（在这种疾病中，单个基因内罕见突变的存在通常决定疾病是否存在）相反，常见疾病的表现符合遗传学中定义的“数量复杂特征”。这些特征在人群中表现为从低到高值的连续变化，并且受到大量基因（每个基因通常对自身的影响都很小）与环境因素相互作用的影响。因此，确定导致复杂特征的遗传变异必须依赖于不同于用于识别孟德尔基因突变的方法（可以通过在谱系中跟踪与突变基因相关的标记的遗传传递来完成）。在几种可用的工具中，遗传动物模型已被证明特别有助于确定自然发生的遗传变异及其在哺乳动物中的作用。事实上，近交系是携带每个基因相同拷贝的生物体。因此，可以通过它们之间的杂交来降低问题的复杂性，因为杂交的后代只携带任何基因的 2 种可能的变异，并且可以控制实验和环境条件。
