DQCAR microsatellite polymorphisms in three selected HLA class II-associated diseases.
DQCAR microsatellite polymorphisms in three selected HLA class II-associated diseases.
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三种选定的 HLA II 类相关疾病中的 DQCAR 微卫星多态性。
DOI：
10.1111/j.1399-0039.1995.tb02496.x
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Cambon-Thomsen,A
中科院分区：
文献类型：
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作者：
Mignot,E;Kimura,A;Abbal,M;Thorsby,E;Lin,X;Voros,A;Macaubas,C;Bouissou,F;Sollid,LM;Cambon-Thomsen,A
DQCAR 是位于 HLA DQA1 和 DQB1 基因之间的高度多态性 CA 重复微卫星。先前的研究表明，特定的 DQCAR 等位基因与已知的 HLA DR-DQ 单倍型处于紧密连锁不平衡状态。特别令人感兴趣的是，包含长 CA 重复等位基因 (DQCAR > 111) 的单倍型通常在种族群体内和种族群体之间具有更多的多态性。在后一种情况下，甚至在包含相同侧翼 DQA1 和 DQB1 等位基因的单倍型中也发现了多个 DQCAR 等位基因。在这项工作中，使用 DQCAR 微卫星研究了三种 HLA II 类相关疾病。本研究的目的是测试 DQCAR 分型是否可以区分对照个体和受影响个体中具有相同 DRB1、DQA1 和 DQB1 等位基因的单倍型。为此，将具有选定 HLA DR-DQ 易感性单倍型的患者与 HLA DR 和 DQ 匹配的对照进行比较。其中包括：患有乳糜泻和 HLA DRB1*0301、DQA1*05011、DQB1*02 单倍型的挪威受试者；患有 1 型（胰岛素依赖性）糖尿病且 HLA DRB1*0405、DQA 1*0302、DQB 1*0401 单倍型的日本受试者；患有皮质敏感性特发性肾病综合征且 HLA DRB 1*0701、DQA 1*0201、DQB1*0202 单倍型的法国患者。这些特定的单倍型是从我们早期的工作中选择的，包括带有短 DQCAR 等位基因的一种单倍型（乳糜泻和 DR3，DQ2-DQCAR99）和带有长 DQCAR 等位基因的两种单倍型（糖尿病和 DR4，DQ4-DQCAR 113 或 115 特发性肾病综合征和 DR7，DQ2-DQCAR） 111-121）。在携带具有长 CA 重复等位基因的单倍型的对照和患者中都发现了额外的 DQCAR 多样性。结果表明，DQCAR 分型与高分辨率 DNA HLA 分型结合作为这三种疾病的标记并没有提高特异性。
DQCAR is a very polymorphic CA repeat microsatellite located between the HLA DQA1 and DQB1 gene. Previous studies have shown that specific DQCAR alleles are in tight linkage disequilibrium with known HLA DR‐DQ haplotypes. Of special interest was the fact that haplotypes containing long CA repeat alleles (DQCAR > 111) were generally more polymorphic within and across ethnic groups. In these latter cases, several DQCAR alleles were found even in haplotypes containing the same flanking DQA1 and DQB1 alleles. In this work, three HLA class II associated diseases were studied using the DQCAR microsatellite. The aim of this study was to test if DQCAR typing could distinguish haplotypes with the same DRB1, DQA1 and DQB1 alleles in control and affected individuals. To do so, patients with selected HLA DR‐DQ susceptibility haplotypes were compared with HLA DR and DQ matched controls. This included: Norwegian subjects with Celiac disease and the HLA DRB1*0301, DQA1*05011, DQB1*02 haplotype; Japanese subjects with Type 1 (insulin‐dependent) Diabetes Mellitus and the HLA DRB1*0405, DQA 1*0302, DQB 1*0401 haplotype; and French patients with corticosensitive Idiopathic Nephrotic Syndrome and the HLA DRB 1*0701, DQA 1*0201, DQB1*0202 haplotype. These specific haplotypes were selected from our earlier work to include one haplotype bearing a short DQCAR allele (celiac disease and DR3, DQ2‐DQCAR99) and two haplotypes bearing long DQCAR alleles (Diabetes Mellitus and DR4, DQ4‐DQCAR 113 or 115 Idiopathic Nephrotic syndrome and DR7, DQ2‐DQCAR 111–121). Additional DQCAR diversity was found in both control and patients bearing haplotypes with long CA repeat alleles. The results indicate that DQCAR typing did not improve specificity in combination with high resolution DNA HLA typing as a marker for these three disorders.