Analyses of polymorphisms in the FUT2 and FUT3 and mechanism of synthesis of Lewis blood group antigens

FUT2和FUT3多态性分析及Lewis血型抗原合成机制

基本信息

批准号：
18590647
负责人：
SOEJIMA Mikiko
金额：
$ 2.57万
依托单位：
Kurume University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590647/
关键词：
FUT2 FUT3 Lewis blood groups glycosyltransferase 細胞内局在

项目摘要

We identified 24 SNPs containing seven novel SNPs (three of them are inactivating mutations) in the coding region of the FUT2 in Ovambos, Turks, and Mongolian populations. The genetic variations observed in these populations were similar to that of neighboring ones and seemed to reflect the geographic background and history of human migration. During screening of the se^<fus>, a Sec1-FUT2-Sec1 hybrid allele was identified in a Mongolian sample. This result implies that we need to be careful in choosing PCR primers otherwise make false-positive typing of se^<fus> because of recombinant alleles, while this allele is rare. By analysis the promoter region of the FUT2, we found African-specific SNPs with high incidence that affected transcriptional activity in culture cells. It is possible that long linkage disequilibrium (LD) block containing this region in African populations and the upstream region is also under balancing selection as an independent block of coding region.To elucidate the location of the Lewis and Se enzymes that regulate the synthesis of Lewis antigens in Golgi apparatus, we constructed chimeric genes, FUT23 and FUT32 that exchanged the N-terminal cytoplasmic regions of the FUT2 and FUT3. We observed higher expression of the Le^a than that of Le^b antigens on the COS-7 transfectants of FUT23 and FUT32 comparing to which of FUT2 and FUT3. This observation suggests that the localization of two enzymes is important for the expression of the Lewis antigens and the cytoplasmic domains contain the signal of that. We are under investigation of subcellular localization of the enzymes encoded by the fusion proteins with fluorescent proteins and the variations of the coding region of the FUT3 in several human populations.

我们在Ovambos，Turks和Mongolian人群的FUT2编码区域中确定了24个SNP，其中包含七个新型SNP（其中三个是灭活突变）。在这些人群中观察到的遗传变异与相邻的差异相似，似乎反映了人类迁移的地理背景和历史。在筛选SE^<FUS>期间，在蒙古样品中鉴定出SEC1-FUT2-SEC1混合等位基因。该结果意味着我们需要谨慎选择PCR引物，否则由于重组等位基因而进行se^<fus>的假阳性键入，而该等位基因很少。通过分析，FUT2的启动子区域，我们发现非洲特异性SNP具有很高的发病率，从而影响了培养细胞中的转录活性。 It is possible that long linkage disequilibrium (LD) block containing this region in African populations and the upstream region is also under balancing selection as an independent block of coding region.To elucidate the location of the Lewis and Se enzymes that regulate the synthesis of Lewis antigens in Golgi apparatus, we constructed chimeric genes, FUT23 and FUT32 that exchanged the N-terminal cytoplasmic FUT2和FUT3的区域。我们观察到Le^a的表达高于fut23和fut32的cos-7转染剂，与fut2和fut3的cos-7转染剂的表达更高。该观察结果表明，两种酶的定位对于刘易斯抗原的表达和细胞质结构域的表达很重要。我们正在研究由融合蛋白与荧光蛋白编码的酶的亚细胞定位，以及在几个人类种群中FUT3的编码区域的变化。