中国彝族人群p表型家系分析及新A4GALT等位基因鉴定  

Pedigree Analysis of P-Phenotype and the Identification of a Novel A4GALT Allele in Chinese Yi Population

作　　者：贺坤华 苏品璨[2] 许先国[3] 林裕翔 徐路琼 徐银霞 赵瑜 马丽琼[1] HE Kun-hua;SU Pin-can;XU Xian-guo(Department of Blood Transfusion,Qujing First People's Hospital,Yunnan 655000)

机构地区：[1]云南省曲靖市第一人民医院输血科,655000 [2]云南昆明血液中心 [3]浙江省血液中心 [4]江苏中济万泰生物医药有限公司

出　　处：《临床输血与检验》2021年第1期45-49,共5页Journal of Clinical Transfusion and Laboratory Medicine

基　　金：云南省科技厅-昆明医科大学应用基础研究联合专项[No.2019FE001(-105)]资助。

摘　　要：目的研究一个彝族家系P1Pk血型系统中罕见p表型的分子遗传机制。方法对34例家系成员样本进行血型血清学鉴定;红细胞稀有血型基因分型采用荧光定量PCR法;同时采用Sanger测序法分析α1,4-半乳糖基转移酶(α-1,4-galactosyltransferase,A4GALT)基因和β1,3-N乙酰半乳糖胺转移酶(β-1,3-N-acetylgalactosyltransferase,B3GALNT1)基因的多态性。结果先证者及其哥哥均为罕见的p表型,血清中均含有能与所有非p表型红细胞凝集并致其溶血的抗-PP1P~K抗体,其他家系成员为正常的P1或P2表型。基因测序发现,34例彝族家系成员中有2例A4GALT基因编码区存在456-457insACACCCC(Bank IT:MG812384)纯合突变,6例456-457insACACCCC杂合突变,7例109A>G和987G>A杂合突变,3例IVS+228C>T杂合突变;所有家系成员B3GALNT1序列均与参考序列一致。456-457insACACCCC突变导致开放阅读框移码,并提前形成终止密码子,产生无效等位基因。结论在一个彝族家系中发现2例p表型,并首次鉴定A4GALT新等位基因456-457insACACCCC,是p表型的分子遗传基础。Objective Explore the molecular mechanism of the rare p phenotype in the P1Pk blood group system of the Yi family.Methods Blood groups of the proband and 33 family members were identified by serologic test.Rare blood group genotyping was determined by qRT-PCR,theα-1,4-galactosyltransferase gene andβ-1,3-N-acetylgalactosyltransferase were analyzed by Sanger sequencing.Results The proband and his brother are both rare p phenotypes and the serum contains anti-PP1PK antibody that can reacts with all non-p phenotype erythrocytes and causes hemolysis,other pedigree members are the normal P1 or P2 phenotype.The gene sequencing revealed that 2 of the 34 Yi family members were homozygous 456-457 ins ACACCCC(Bank IT:MG812384)in the A4GALT gene coding region,while 6 of them were 456-457ins ACACCCC heterozygous,7 of them were 109A>G and 987G>A heterozygous,and 3 of them were IVS+228C>T heterozygous.The 7 bp insertion caused the frame shift in reading frame to form a premature termination codon,thus generate an invalid alleles.All the family members showed the consensus B3GALNT1 genes with the standard sequence.Conclusion In Yi family,we identified two cases of p phenotype with a novel A4GALT 456-457 ins ACACCCC alleles.The homozygous mutation is the molecular basis of the p phenotype.

关 键 词：彝族 p表型 抗-PP1P~K A4GALT 新等位基因 家系分析 

分 类 号：R457.1[医药卫生—治疗学]