Haplotype analysis of the human α2‐HS glycoprotein (fetuin) gene
Haplotype analysis of the human α2‐HS glycoprotein (fetuin) gene
复制标题
人类α2-HS糖蛋白（胎球蛋白）基因的单倍型分析
DOI：
10.1046/j.1469-1809.2001.6510027.x
复制
发表时间：
2001
影响因子：
1.9
通讯作者：
Kazuo Umetsu
中科院分区：
文献类型：
--
作者：
Motoki Osawa;Isao Yuasa;Takashi Kitano;Jürgen Henke;Mika Kaneko;T. Udono;Naruya Saitou;Kazuo Umetsu
Alpha 2-HS糖蛋白（AHSG），相当于其他物种中的胎球蛋白，是一种在人血浆中发现的蛋白质。AHSG具有多态性，有两个常见的等位基因和许多变体。为了检查基因内单倍型及其在该位点的多样性，分析了20个样本（40条染色体）中的连续基因组DNA序列（10·3 kb），并确定了309名受试者的单倍型。从比对的核苷酸序列和保守的氨基酸残基比较人类和黑猩猩AHSG，可以得出结论，1型等位基因可能是更古老的，并已演变成四个主要的亚等位基因。2型等位基因由1型等位基因的一个分支产生。发现AHSG*3和 *5变体均在外显子7中具有单核苷酸变化，分别导致氨基酸残基从Arg 299变为Cys和从Asp 258变为Asn。注意到AHSG*3突变产生额外的半胱氨酸残基，这可能影响蛋白质的构象。AHSG基因突变率低，无明显重组事件。此外，检测到的取代是非均匀分布在这个位点。特别是，四个非同义取代集中在羧基末端结构域。
Alpha2‐HS glycoprotein (AHSG), which is equivalent to fetuin in other species, is a protein found in human plasma. AHSG is polymorphic with two common alleles and many variants. To examine the intragenic haplotypes and their diversity at this locus, a contiguous genomic DNA sequence (10·3 kb) was analyzed in 20 samples (40 chromosomes), and haplotypes were determined for 309 subjects. Judging from the aligned nucleotide sequences and the conserved amino acid residues comparing human and chimpanzee AHSG, it was concluded that the type 1 allele is probably older and has evolved into four major suballeles. The type 2 allele was generated from one branch of the type 1 allele. AHSG*3 and *5 variants were each found to have a single nucleotide change in exon 7, resulting in the change of an amino acid residue from Arg299 to Cys and from Asp258 to Asn, respectively. It was noted that the AHSG*3 mutation gives rise to an additional cysteine residue, which possibly affects the conformation of the protein. The AHSG gene was found to have a low mutation rate and no apparent recombination events. Furthermore, the detected substitutions were nonhomogeneously distributed at this locus. In particular, four nonsynonymous substitutions were concentrated in the carboxyl‐terminal domain.