Yang Kuo-Liang, Lin Py-Yu
Laboratory of Immunogenetics, Tzu Chi Cord Blood Bank, and Buddhist Tzu Chi Bone Marrow Donor Registry, Buddhist Tzu Chi Stem Cells Centre, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan.
Department of Laboratory Medicine and Biotechnology, Tzu Chi University, Hualien, Taiwan.
Tzu Chi Med J. 2024 Mar 26;36(2):166-174. doi: 10.4103/tcmj.tcmj_288_23. eCollection 2024 Apr-Jun.
It is thought that Taiwanese indigenous people were the "first people" to populate Taiwan (Formosa) having been there for over 5000 years, preceding the Dutch colonization (from 1624 to 1662) and Spanish colonization (from 1626 to 1642). Taiwan's indigenes, represented by Austronesian language speakers, currently constitute approximately 2% of the total population in Taiwan. It is unknown whether they evolved from Taiwan's Paleolithic or Neolithic cultures, arrived during or after the Neolithic period from China or Southeast Asia or both. HLA studies on the Taiwanese indigenous population have found several intriguing genetic information showing one or two relatively frequently observed alleles and a small number of relatively less frequently observed ones. We report here a relatively frequently observed HLA-C07:359 allele in the Taiwanese indigenous population, its linkage with HLA-B39:01, and its probable associated HLA haplotype in two Taiwanese indigenous families. HLA-C07:359 is a rarely observed allele in the HLA-C locus in the world populations. The objective of this study is to report the allele HLA-C07:359 that is more frequently found in the Taiwanese population, especially in the Taiwanese indigenous people, to demonstrate that it has a close linkage with HLA-B39:01 allele in the HLA-B locus and to show the plausible deduced HLA-A-C-B-DRB1-DQB1 haplotypes in association with HLA-C07:359 in two families of Taiwanese indigenous unrelated individuals.
The samples were peripheral whole blood, with dipotassium ethylenediaminetetraacetic acid and/or acid citrate dextrose anticoagulation additives. The sequence-based typing method was employed to confirm the low incidence of the allele of HLA-C*07:359 observed in Taiwanese. Polymerase chain reaction was carried out to amplify exons 2, 3, and 4 of the HLA-A,-B,-C,-DRB1 and-DQB1 loci with group-specific primer sets. Amplicons were sequenced using the BigDye Terminator Cycle Sequencing Ready Reaction Kit in both directions according to the manufacturer's protocol.
C07:359 is an uncommon allele in the HLA-C locus in the world general population, according to our literature review. However, in this study, it is observed in the general Taiwanese population (frequency 0.41%), especially in the Taiwanese indigenous people at a frequency of 0.23%. In addition, we deduced two probable HLA haplotypes in association with C07:359 in two indigenous families: A24:02-C07:359-B39:01-DRB104:36 and A24:02-C07:359-B39:01-DRB104:04.
The two deduced HLA haplotypes associated with the uncommon C07:359 allele that we report here are valuable for HLA tissue typing laboratories for reference purposes and for stem cell transplantation donor search coordinators to determine the likelihood of finding compatible donors in unrelated bone marrow donor registries for patients bearing the uncommon HLA allele. Since C07:359 was found mostly in the Taiwanese indigenous population, we think the allele and its haplotypes we report here are important in population and anthropological studies.
人们认为台湾原住民是最早在台湾(福尔摩沙)定居的“第一批人”,他们已在那里生活了5000多年,早于荷兰殖民统治时期(1624年至1662年)和西班牙殖民统治时期(1626年至1642年)。以说南岛语系语言的人为代表的台湾原住民,目前约占台湾总人口的2%。尚不清楚他们是由台湾的旧石器时代或新石器时代文化演变而来,还是在新石器时代期间或之后从中国或东南亚抵达,亦或是两者皆有。对台湾原住民群体的HLA研究发现了一些有趣的基因信息,显示出一两个相对常见的等位基因以及少数相对不那么常见的等位基因。我们在此报告在两个台湾原住民家庭中相对常见的HLA - C07:359等位基因、其与HLA - B39:01的连锁关系以及可能相关的HLA单倍型。HLA - C07:359是世界人群中HLA - C基因座中罕见的等位基因。本研究的目的是报告在台湾人群中,尤其是在台湾原住民中更常见的HLA - C07:359等位基因,证明其与HLA - B基因座中的HLA - B39:01等位基因紧密连锁,并展示在两个台湾原住民无关个体家庭中与HLA - C07:359相关的可能推导的HLA - A - C - B - DRB1 - DQB1单倍型。
样本为外周全血,使用乙二胺四乙酸二钾和/或酸性枸橼酸盐葡萄糖抗凝添加剂。采用基于序列的分型方法来确认在台湾观察到的HLA - C*07:359等位基因的低发生率。使用组特异性引物对进行聚合酶链反应,以扩增HLA - A、-B、-C、-DRB1和 - DQB1基因座的第2、3和4外显子。根据制造商的方案,使用BigDye Terminator循环测序预混试剂盒对扩增产物进行双向测序。
根据我们的文献综述,C07:359在世界普通人群的HLA - C基因座中是一个不常见的等位基因。然而,在本研究中,它在台湾普通人群中被观察到(频率为0.41%),尤其是在台湾原住民中频率为0.23%。此外,我们在两个原住民家庭中推导了与C07:359相关的两种可能的HLA单倍型:A24:02 - C07:359 - B39:01 - DRB104:36和A24:02 - C07:359 - B39:01 - DRB104:04。
我们在此报告的与不常见的C07:359等位基因相关的两种推导的HLA单倍型,对于HLA组织分型实验室具有参考价值,对于干细胞移植供体搜索协调员确定在无关骨髓供体登记处为携带不常见HLA等位基因的患者找到匹配供体的可能性也具有参考价值。由于C07:3主要在台湾原住民群体中被发现,我们认为我们在此报告的等位基因及其单倍型在群体和人类学研究中很重要。