Identification of a critical gene involved in the pathogenesis of systemic lupus erythematosus by linkage analysis and exome resequencing

全基因组关联研究未能识别出与系统性红斑狼疮（SLE）发病机制密切相关的基因，因为SLE是一种多因素疾病。我们发现了一个日本近亲SLE家族，包括3个患病兄弟姐妹和1个未患病兄弟姐妹。为了确定潜在基因，我们进行了定位克隆分析，发现了一个纯合区（FSLE-2; 1.1Mb）。接下来，我们对FSLE-2区域进行了外显子组重测序，并确定了一个候选基因。我们正在建立候选基因的转基因小鼠，以了解该基因与SLE发病机制的关联。

Genome wide association studies have failed to identify genesthat strongly contribute to the pathogenesis of systemic lupus erythematosus (SLE) because SLE is a multifactorial disease. We found one Japanese consanguineous SLE family which consists of 3 affected and 1 unaffected sibling. To identify the underlying gene, we performed a positional cloning analysis and revealed one homozygous region (FSLE-2; 1.1Mb). Next we carried out exome resequencing in FSLE-2 region and identified a candidate gene. We are establishing a genetically modified mouse of the candidate gene to know the association of this gene with the pathogenesis of SLE.