Identification of genomic regions controlling experimental autoimmune uveoretinitis in rats.
Identification of genomic regions controlling experimental autoimmune uveoretinitis in rats.
复制标题
鉴定控制大鼠实验性自身免疫性葡萄膜视网膜炎的基因组区域。
DOI：
10.1093/intimm/11.4.529
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发表时间：
1999
影响因子：
4.4
通讯作者：
Remmers,EF
中科院分区：
文献类型：
--
作者：
Sun,SH;Silver,PB;Caspi,RR;Du,Y;Chan,CC;Wilder,RL;Remmers,EF
本研究试图在耐药Fischer(F344/N)和易感Lewis(LOW/N)近交系大鼠的F2代中确定影响实验性自身免疫性葡萄膜视网膜炎(EAU)易感性的特定遗传位点。用光感受器间视黄醇结合蛋白(IRBP)R16肽免疫F344/N×LEW/N近交系大鼠F2代。使用125个简单序列长度多态标记对患严重眼病或未受影响的F2动物进行全基因组扫描，以确定表型：基因共分离。F2人群(n=1287)显示了广泛的组织学评估的EAU评分(评分范围为0-4)。疾病的发病率和严重程度不符合简单的孟德尔遗传模型。在F2代大鼠中，60%的大鼠发生了EAU，这意味着存在与LEW基因组相关的不完全外显的有效易感基因或更复杂的多基因遗传模式。4号和12号染色体上的两个基因组区域与EAU表型(P<；0.0016)有很强的遗传连锁，表明在这些染色体区域存在易感基因座。总之，我们已经确定了4号染色体上从D4Arb8到D4Mit17和从染色体末端到12号染色体上D12Arb8的两个基因组候选区间，它们似乎影响了LEW/F344大鼠的EAU易感性。对这些基因组区域的进一步分析可能导致对易感基因的识别和对其功能的描述。
The present study attempts to identify specific genetic loci contributing to experimental autoimmune uveoretinitis (EAU) susceptibility in F2progeny of resistant Fischer (F344/N) and susceptible Lewis (LEW/N) inbred rats. F2progeny of F344/N × LEW/N inbred rats were immunized with the R16 peptide of interphotoreceptor retinoid-binding protein (IRBP). A genome-wide scan was conducted using 125 simple sequence length polymorphism markers in selected F2animals that developed severe eye disease or remained unaffected to identify phenotype:genotype co-segregation. The F2population (n= 1287) demonstrated a wide range of histologically assessed EAU scores (assessed on a scale of 0–4). The disease incidence and severity were not consistent with a simple Mendelian inheritance model. Of the F2hybrid rats, 60% developed EAU, implying the existence of a potent susceptibility locus with incomplete penetrance associated with the LEW genome or a more complex polygenic model of inheritance. Two genomic regions, on chromosomes 4 and 12, showed strong genetic linkage to the EAU phenotype (P< 0.0016), suggesting the presence of susceptibility loci in these chromosomal regions. In conclusion, we have identified two genomic candidate intervals fromD4Arb8toD4Mit17on chromosome 4 and from the chromosome end toD12Arb8on chromosome 12, that appear to influence EAU susceptibility in LEW/F344 rats. Further analysis of these genomic regions may lead to identification of the susceptibility genes and to characterization of their function.