Adult-onset alopecia areata is a complex polygenic trait in the C3H/HeJ mouse model
Adult-onset alopecia areata is a complex polygenic trait in the C3H/HeJ mouse model
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DOI：
10.1111/j.0022-202x.2004.23222.x
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发表时间：
2004-08-01
影响因子：
6.5
通讯作者：
King, LE
中科院分区：
文献类型：
--
作者：
Sundberg, JP;Silva, KA;King, LE
斑秃（AA）是一种自身免疫性疾病，其靶向人类和其他哺乳动物的活跃生长（生长期）毛囊。C3 H/HeJ，而不是C57 BL/6 J，小鼠自发地发展成一个成年发病形式的AA。C3 HB 6 F2雌性小鼠（n=1096）的分离群体，从这两个菌株杂交产生的，用于全基因组连锁分析，以确定AA遗传易感性。先前的分析确定了17号染色体（Alaa 1）和9号染色体（Alaa 2）上的易感区间。使用额外的标记在这些区间和饱和映射声称的染色体8和15上的区间，两个额外的区域被确定（分别为Alaa 3和Alaa 4）。人类基因关联研究确定了特定的人类白细胞抗原的间隔与那些（主要组织相容性复合体）在小鼠中发现的Alaa 1。其他人类研究确定了在该连锁研究中未发现的基因，但这些人类转录因子直接受Alaa 1内的基因调控。这些结果表明，有必要在小鼠和人类中整合基因关联和全基因组连锁研究，以了解这些和其他多基因疾病的复杂性。
Alopecia areata (AA) is an autoimmune disease that targets actively growing (anagen) hair follicles in humans and other mammals. C3H/HeJ, but not C57BL/6J, mice spontaneously develop an adult-onset form of AA. A segregating population of C3HB6F2 female mice (n=1096), generated from crossing these two strains, was used for genome-wide linkage analysis to identify AA genetic susceptibility. Previous analysis identified susceptibility intervals on chromosomes 17 (Alaa1) and 9 (Alaa2). Using additional markers in these intervals and saturation mapping purported intervals on chromosomes 8 and 15, two additional regions were identified (Alaa3 and Alaa4, respectively). Human gene association studies identified specific human leukocyte antigen intervals comparable with those (major histocompatibility complex) found in Alaa1 in the mouse. Other human studies identified genes not found in this linkage study, but these human transcription factors are directly regulated by genes within Alaa1. These results indicate the necessity of integrating both gene association and genome-wide linkage studies in both mice and humans to understand the complex nature of these and other polygenic diseases.