Cancer Genetics Group, Children's Cancer Institute Australia for Medical Research, Lowy Cancer Research Centre, University of New South Wales, Sydney, Australia.
DNA Res. 2010 Apr;17(2):117-22. doi: 10.1093/dnares/dsq003. Epub 2010 Feb 12.
A newly described heterodimeric cytokine, interleukin-23 (IL-23) is emerging as a key player in both the innate and the adaptive T helper (Th)17 driven immune response as well as an initiator of several autoimmune diseases. The rate-limiting element of IL-23 production is believed to be driven by expression of the unique p19 subunit encoded by IL23A. We set out to perform comprehensive DNA sequencing of this previously under-studied gene in 96 individuals from two evolutionary distinct human population groups, Southern African Bantu and European. We observed a total of 33 different DNA variants within these two groups, 22 (67%) of which are currently not reported in any available database. We further demonstrate both inter-population and intra-species sequence conservation within the coding and known regulatory regions of IL23A, supporting a critical physiological role for IL-23. We conclude that IL23A may have undergone positive selection pressure directed towards conservation, suggesting that functional genetic variants within IL23A will have a significant impact on the host immune response.
一种新描述的异二聚体细胞因子白细胞介素-23（IL-23）在先天和适应性 T 辅助（Th）17 驱动的免疫反应中以及几种自身免疫性疾病的启动中都起着关键作用。IL-23 产生的限速元件被认为是由 IL23A 编码的独特 p19 亚基的表达所驱动。我们着手对来自两个进化上不同的人类群体（南非班图人和欧洲人）的 96 个人进行了这个以前研究不足的基因的全面 DNA 测序。我们在这两个群体中总共观察到 33 种不同的 DNA 变体，其中 22 种（67%）目前在任何可用数据库中都没有报道。我们进一步证明了在 IL23A 的编码和已知调节区域内存在种间和种内序列保守性，支持了 IL-23 的关键生理作用。我们得出结论，IL23A 可能经历了针对保守性的正选择压力，这表明 IL23A 内的功能性遗传变异将对宿主免疫反应产生重大影响。
