McGinnis M D, Lebo R V, Quinn D L, Simons M J
GeneType Corporation, Fort Collins, Colorado.
Am J Med Genet. 1994 Oct 1;52(4):438-44. doi: 10.1002/ajmg.1320520409.
A 438 basepair intron 1 sequence adjacent to exon 2 in the human major histocompatibility complex DQA1 gene defined 16 allelic variants in 69 individuals from wide ethnic backgrounds. In contrast, the most variable coding region spanned by the 247 basepair exon 2 defined 11 allelic variants. Our phylogenetic human intron 1 tree derived by the Bootstrap algorithm reflects the same relative allelic relationships as the reported DQA1 exon 2 tree [Gyllensten and Erlich, Hum Immunol 36:1-10, 1989]. Thus 3' DQA1 intron 1 and exon 2 have cosegregated since divergence of the human races. Comparison of human alleles to a Rhesus monkey DQA1 first intron sequence found only 10 nucleotide substitutions unique to Rhesus, with the other 428 positions (98%) found in at least one human allele. This high degree of homology reflects the evolutionary stability of intron sequences since these two species diverged over 20 million years ago. Because more intron 1 alleles exist than exon 2 alleles, these polymorphic introns can be used to improve tissue typing for transplantation, paternity testing, and forensics and to derive more complete phylogenetic trees. These results suggest that introns represent a previously underutilized polymorphic resource.
人类主要组织相容性复合体DQA1基因中外显子2相邻的一段438个碱基对的内含子1序列，在来自广泛种族背景的69个人中定义了16个等位基因变体。相比之下，由247个碱基对的外显子2跨越的变化最大的编码区域定义了11个等位基因变体。我们通过Bootstrap算法得出的人类内含子1系统发育树反映出与已报道的DQA1外显子2树相同的相对等位基因关系[Gyllensten和Erlich，《人类免疫学》36:1 - 10，1989]。因此，自人类种族分化以来，DQA1内含子1和外显子2 3'端一直是共分离的。将人类等位基因与恒河猴DQA1第一内含子序列进行比较，发现只有10个核苷酸替换是恒河猴特有的，其他428个位置（98%）在至少一个人类等位基因中也能找到。这种高度的同源性反映了自这两个物种在2000多万年前分化以来内含子序列的进化稳定性。由于内含子1等位基因比外显子2等位基因更多，这些多态性内含子可用于改进移植、亲子鉴定和法医鉴定的组织分型，并得出更完整的系统发育树。这些结果表明，内含子代表了一种以前未得到充分利用的多态性资源。
