Polymorphic olfactory receptor genes and HLA loci constitute extended haplotypes

Polymorphic olfactory receptor genes and HLA loci constitute extended haplotypes
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多态性嗅觉受体基因和HLA基因座构成扩展单倍型

DOI:
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发表时间:
2000
期刊:
影响因子:
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通讯作者:
S. Beck
S. Beck
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文献类型:
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作者:
A. Ziegler;A. Ehlers;S. Forbes;J. Trowsdale;B. Uchánska‐Ziegler;A. Volz;R. Younger;S. Beck

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嗅觉受体 (OR) 基因通常聚集在一起,并且已知位于大多数人类染色体上。在迄今为止在任何生物体中分析和测序的最大 OR 基因簇中,我们已经鉴定了 HLA-F 和 HFE 之间的 27 个 OR 基因,其中 23 个迄今为止位于 HLA-F 和 RFP 之间约 650 kilobasepairs 内。他们的产品可能涉及识别个体特异性、MHC 依赖性气味,并经过定制以执行此功能。在第一个系统的 OR 基因多态性研究中,对具有不同 HLA 单倍型的 10 个 HLA 纯合或半合子细胞系分析了 12 个 HLA 连锁 OR 基因。发现所有具有潜在功能的 HLA 连锁 OR 基因都表现出多态性,尽管程度差异很大。给定基因内的核苷酸变化发生在确定的位置,并且可能是推定的跨膜结构域的一部分或发生在其他残基处。到目前为止,已经可以在分析的 18 条染色体 6 上定义 12 种 HLA 连锁 OR 基因的单倍型。已知从 HLA-A 延伸到 HFE 的强连锁不平衡预计会保留这些扩展的 HLA/OR 单倍型。如果 HLA 和 HLA 连锁的多态性 OR 基因也被证明在功能上是相连的(我们对这些 OR 基因多态性的发现支持了这一观点),那么整个区域可能被认为构成了一个扩展的基因复合体,正如我们已经建议的那样,它可以被指定为“免疫嗅觉超级复合体”(IOS)。
Olfactory receptor (OR) genes are often clustered and are known to be located on most human chromosomes. In the largest OR gene cluster so far analyzed and sequenced in any organism, we have identified 27 OR genes between HLA-F and HFE, of which so far 23 are located within about 650 kilobasepairs between HLA-F and RFP. Their products could be involved in the recognition of individual-specific, MHC-dependent odours and be tailored to perform this function. In this first systematic OR gene polymorphism study, twelve HLA-linked OR genes were analyzed on ten HLA-homozygous or — hemizygous cell lines with different HLA haplotypes. All potentially functional HLA-linked OR genes were found to exhibit polymorphism, although the degree differed considerably. The nucleotide changes within a given gene occur at defined positions, and may be part of putative transmembrane domains or occur at other residues. It has been possible so far to define 12 haplotypes for the HLAlinked OR genes on the 18 chromosomes 6 analyzed. The strong linkage disequilibrium, which is known to extend from HLA-A to HFE, is expected to conserve these extended HLA/OR haplotypes. If HLA and HLA-linked polymorphic OR genes also turn out to be functionally connected, a view supported by our finding of polymorphism of these OR genes, the entire region might be considered to constitute an extended gene complex which could, as we have already suggested, be designated “Immuno-Olfactory Supercomplex” (IOS).
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