High resolution HLA-C typing by PCR-SSP: Identification of allelic frequencies and linkage disequilibria in 604 unrelated random UK Caucasoids and a comparison with serology (Corrected and reprinted from Tissue Antigens Vol. 48 (6): 1996, 680-691)

High resolution HLA-C typing by PCR-SSP: Identification of allelic frequencies and linkage disequilibria in 604 unrelated random UK Caucasoids and a comparison with serology (Corrected and reprinted from Tissue Antigens Vol. 48 (6): 1996, 680-691)
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DOI:
10.1111/j.1399-0039.1997.tb02847.x
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发表时间:
1997-01-01
期刊:
影响因子:
--
通讯作者:
Welsh, K. I.
Welsh, K. I.
中科院分区:
医学4区
文献类型:
--
作者:
Bunce, M.;Barnardo, M. C. N. M.;Welsh, K. I.

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最近的证据表明,HLA-C分子通过诱导t细胞反应和控制NK细胞功能而具有生物学相关性。此外,HLA-C与多种疾病的易感性有关,特别是寻常型牛皮癣。然而,阐明HLA-C的全部生物学作用被证明是困难的,因为使用同种抗血清补体介导的细胞毒性检测HLA-C抗原是低效的。由于相对较低的表达、缺乏血清学试剂和缺乏关于HLA-C空白等位基因分布的信息,每个种族中高达50%的个体血清学上无法检测到HLA-C位点抗原。近年来,利用序列特异性引物(PCR-SSP)扩增DNA已被证明是一种可靠、准确和快速的中分辨率HLA-C分型方法。我们现在利用等位基因和群体特异性PCR-SSP反应开发了高分辨率HLA-C分型,可以识别大多数杂合组合中的所有HLA-C等位基因(非编码变化等位基因除外)。使用该系统,我们输入了604个不相关的英国高加索人种,以产生准确的频率和连锁不平衡数据。为了评估血清学对HLA-C的有效性,604个人中有527人的PCR-SSP分型与血清学进行了比较。我们发现许多HLA-C抗原的频率被血清学低估了,一些抗原如Cw6一直被血清学错误地分配。血清学和SSP之间的总体差异率高达37%(195/527)。还对112个国际组织相容性研讨会细胞系进行了高分辨率HLA-C分型。
Recent evidence indicates that HLA-C molecules are biologically relevant by eliciting T-cell responses and exerting control over NK cell function. In addition, HLA-C is associated with susceptibility to various diseases, notably psoriasis vulgaris. Clarification of the full biological roles for HLA-C has however proved difficult because detection of HLA-C antigens by complement mediated cytotoxicity using alloantisera is inefficient. Up to 50% of individuals in every race have serologically undetectable HLA-C locus antigens due to a combination of relatively low expression, lack of serological reagents and a lack of information about the distribution of the HLA-C blank alleles. Recently, amplification of DNA using sequence-specific primers (PCR-SSP) has proved a reliable, accurate and rapid method for medium resolution HLA-C typing. We have now developed high resolution HLA-C typing by PCR-SSP utilizing allele and group-specific PCR-SSP reactions which can identify all HLA-C alleles (except non-coding change alleles) in most heterozygous combinations. Using this system we have typed 604 unrelated United Kingdom Caucasoids to generate accurate frequency and linkage disequilibrium data. To assess the validity of serology for HLA-C, PCR-SSP typings for 527 out of the 604 individuals were compared to serology. We find that the frequency of many HLA-C antigens has been underestimated by serology and some antigens such as Cw6 are consistently assigned incorrectly by serology. The overall discrepancy rate between serology and SSP was high at 37% (195/527). High-resolution HLA-C typing of 112 International Histocompatibility Workshop cell lines has also been performed.