Vitamin K epoxide reductase complex subunit 1 (Vkorc1) haplotype diversity in mouse priority strains.
Vitamin K epoxide reductase complex subunit 1 (Vkorc1) haplotype diversity in mouse priority strains.
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DOI：
10.1186/1756-0500-1-125
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发表时间：
2008-12-01
影响因子：
1.8
通讯作者：
Kohn, Michael H
中科院分区：
文献类型：
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作者：
Song, Ying;Vera, Nicole;Kohn, Michael H
背景：维生素 K-环氧化物还原酶复合物亚基 1 基因 Vkorc1 的多态性可能影响凝血和其他维生素 K 依赖性蛋白，例如骨钙素（骨 Gla 蛋白，BGP）。在这里，我们对 40 种小鼠优先品系的 Vkorc1 基因进行了测序。我们分析了 Vkorc1 单倍型的凝血酶原时间 (PT) 和骨矿物质密度和成分（BMD 和 BMC）；表型预计是维生素 K 依赖性的，并由小鼠表型组数据库 (MPD) 中的数据表示。研究结果：在常用的家小家鼠实验室菌株中，我们仅鉴定出四种单倍型，其内含子或 Vkorc1 的 5' 区域序列不同。在小鼠的其他亚种中鉴定出了编码和非编码多态性不同的六种单倍型。我们检测到 Vkorc1 单倍型与 Mus 每个亚种内的 PT、BMD 和 BMC 没有显着关联。亚种间 Vkorc1 单倍型序列差异与 PT、BMD 和 BMC 相关。结论：Mus 亚种内 PT、BMD 和 BMC 的表型变异虽然很大，但似乎主要是由 Vkorc1 以外的基因的遗传变异主导。这对于 M. m 来说尤其明显。家鼠，其中观察到单个单倍型与本研究中包括的所有 5 个鼠亚种的几乎整个 PT、BMD 和 BMC 值范围相结合。亚种之间这些表型的差异也不应归因于 Vkorc1 变异，而应被视为全基因组遗传差异的结果。
BACKGROUND: Polymorphisms in the vitamin K-epoxide reductase complex subunit 1 gene, Vkorc1, could affect blood coagulation and other vitamin K-dependent proteins, such as osteocalcin (bone Gla protein, BGP). Here we sequenced the Vkorc1 gene in 40 mouse priority strains. We analyzed Vkorc1 haplotypes with respect to prothrombin time (PT) and bone mineral density and composition (BMD and BMC); phenotypes expected to be vitamin K-dependent and represented by data in the Mouse Phenome Database (MPD).FINDINGS: In the commonly used laboratory strains of Mus musculus domesticus we identified only four haplotypes differing in the intron or 5' region sequence of the Vkorc1. Six haplotypes differing by coding and non-coding polymorphisms were identified in the other subspecies of Mus. We detected no significant association of Vkorc1 haplotypes with PT, BMD and BMC within each subspecies of Mus. Vkorc1 haplotype sequences divergence between subspecies was associated with PT, BMD and BMC.CONCLUSION: Phenotypic variation in PT, BMD and BMC within subspecies of Mus, while substantial, appears to be dominated by genetic variation in genes other than the Vkorc1. This was particularly evident for M. m. domesticus, where a single haplotype was observed in conjunction with virtually the entire range of PT, BMD and BMC values of all 5 subspecies of Mus included in this study. Differences in these phenotypes between subspecies also should not be attributed to Vkorc1 variants, but should be viewed as a result of genome wide genetic divergence.