Dunn David S, Inoko Hiditoshi, Kulski Jerzy K
Centre for Bioinformatics and Biological Computing, School of Information Technology, Murdoch University, Murdoch, Western Australia, Australia 6150.
Electrophoresis. 2003 Aug;24(16):2740-8. doi: 10.1002/elps.200305524.
Most Alu members of the large SINE family are fixed within the human genome but some younger mobile members are dimorphic, that is, they are either present or absent in the genome. Four different dimorphic Alu insertions have been identified and characterized previously within the class I region of the major histocompatibility complex (MHC). Here we report on (i) the identification and characterization of a new dimorphic Alu insertion, AluyTF, located between the transcription factor II H (TFIIH) and corneodesmosin (CDSN) genes within a region of the MHC that is telomeric of the human leukocyte antigen type B (HLA-B) locus and centromeric of the HLA-A locus, (ii) the haplotypic relationships between the AluyTF dimorphism and the HLA-A and -B loci within a panel of 48 IHW cell-lines representing at least 36 different HLA class I haplotypes, (iii) the AluyTF genotype, allele and haplotype frequencies present in the Australian caucasian and Japanese populations, and (iv) the frequency of association between the AluTF dimorphisms and HLA-A and -B alleles in 108 Australian caucasians and 99 Japanese. The AluyTF insertion was present at 27% in the IHW cell lines, and the gene frequency was 0.107 and 0.083 in the Australian caucasian and Japanese population, respectively. The Alu haplotype frequencies constructed from four different dimorphic Alu loci including AluyTF within the MHC were not significantly different (p > 0.05) between the two populations. There were no significant associations between the Alu insertion and either the HLA-A or -B alleles except for a moderately strong association with HLA-A29 in the Australians (71.7%). This polymorphic AluyTF element, along with the four other previously described polymorphic Alu elements within the class I region of the MHC, will be useful lineage and linkage markers in human population studies and for elucidating the evolution of HLA class I haplotypes.
大SINE家族的大多数Alu成员在人类基因组中是固定的，但一些较新的可移动成员是二态性的，也就是说，它们在基因组中要么存在，要么不存在。先前已在主要组织相容性复合体（MHC）的I类区域内鉴定并表征了四种不同的二态性Alu插入。在此，我们报告：（i）在MHC区域中位于转录因子II H（TFIIH）和角质桥粒蛋白（CDSN）基因之间鉴定并表征了一种新的二态性Alu插入AluyTF，该区域位于人类白细胞抗原B型（HLA - B）基因座的端粒侧且在HLA - A基因座的着丝粒侧；（ii）在一组代表至少36种不同HLA I类单倍型的48个IHW细胞系中，AluyTF二态性与HLA - A和 - B基因座之间的单倍型关系；（iii）澳大利亚白种人和日本人群中存在的AluyTF基因型、等位基因和单倍型频率；以及（iv）108名澳大利亚白种人和99名日本人中AluTF二态性与HLA - A和 - B等位基因之间的关联频率。AluyTF插入在IHW细胞系中的出现率为27%，在澳大利亚白种人和日本人群中的基因频率分别为0.107和0.083。由包括MHC内AluyTF在内的四个不同二态性Alu位点构建的Alu单倍型频率在两个人群之间无显著差异（p>0.05）。除了在澳大利亚人中与HLA - A29有中等强度的关联（71.7%）外，Alu插入与HLA - A或 - B等位基因之间均无显著关联。这种多态性AluyTF元件，连同先前描述的MHC I类区域内的其他四种多态性Alu元件，将成为人类群体研究中有用的谱系和连锁标记，有助于阐明HLA I类单倍型的进化。
