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首页> 外文期刊>Nature clinical practice. Rheumatology >Primer: comparative genetics of animal models of arthritis--a tool to resolve complexity.
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Primer: comparative genetics of animal models of arthritis--a tool to resolve complexity.

机译：入门：关节炎动物模型的比较遗传学-解决复杂性的工具。

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Complex traits, including inflammatory rheumatic diseases, have important genetic features, but most of the responsible genes have not been conclusively identified. Genetic analysis of inbred animal models and comparative genetics--the comparison of genes between different species--might help to identify the crucial genes and to investigate more directly the biology involved. Genome-wide linkage analysis of particular genes can be assessed by genetic segregation studies, whereas disease pathways can be delineated by the use of congenic strains. To clone disease genes, the traits need to be transformed so that they are inherited in a more Mendelian manner: achieving this pattern requires isolation of the locus on a genetic background that allows high penetrance by minimization of the size of congenic fragments, genetic manipulations without associated artifacts, or identification of highly penetrant mutations by phenotypic selection. Although almost one hundred quantitative trait loci for arthritis havebeen identified, only a few genes have so far been positionally cloned. In this Review we highlight the possibilities of using animal models to identify genes associated with complex diseases like arthritis, illustrated with available findings for genes such as those encoding major histocompatibility complex class II, neutrophil cytosolic factor 1 (Ncf1/p47(phox)) and ZAP70.
机译：复杂的性状，包括炎性风湿病，具有重要的遗传特征，但大多数负责任的基因尚未最终确定。近交动物模型的遗传分析和比较遗传学-不同物种之间基因的比较-可能有助于鉴定关键基因并更直接地调查所涉及的生物学。特定基因的全基因组连锁分析可以通过遗传隔离研究进行评估，而疾病途径可以通过使用同系菌株来描绘。要克隆疾病基因，需要对其特性进行转化，以便以更孟德尔的方式遗传：要实现这种模式，就需要在遗传背景上分离基因座，从而通过最小化同基因片段的大小实现高渗透率，而无需进行遗传操作相关文物，或通过表型选择鉴定高度渗透性突变。尽管已经确定了将近一百个关节炎的定量性状基因座，但是到目前为止，只有少数基因被定位克隆。在本综述中，我们重点介绍了使用动物模型鉴定与关节炎等复杂疾病相关的基因的可能性，并举例说明了编码主要组织相容性复合物II类，嗜中性粒细胞胞浆因子1（Ncf1 / p47（phox））和ZAP70。

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