Lin L, Jin L, Lin X, Voros A, Underhill P, Mignot E
Center for Narcolepsy, Department of Psychiatry, Stanford University Medical Center, Palo Alto, California 94304-5485, USA.
Tissue Antigens. 1998 Jul;52(1):9-18. doi: 10.1111/j.1399-0039.1998.tb03018.x.
Sequencing studies were performed in three previously described microsatellite and minisatellite markers located within the HLA-DQ region, DQCAR, DQCARII and G51152. Multiple nucleotide substitutions that did not change size polymorphisms were observed in all three markers. In all loci, the number of core repeats did not correlate with neighboring DQ allele sequence motifs while single nucleotide changes within or flanking the microsatellite sequence did. This result indicates higher mutation rates for microsatellite expansions/contractions than for nucleotide substitutions in these loci. Further analysis indicated an almost complete phylogenetic correspondence between DQCAR single nucleotide polymorphisms (SNPs) and DQB1 sequences on one side (1.0-1.5 kb apart) and a complete relationship between DQCARII and DQA1 sequences on the other (4.5 kb apart). In contrast, G51152 sequences did not correspond perfectly with DQB1 allelic sequences, thus suggesting the existence of several ancestral crossovers between this marker and DQB1 (20-25 kb). Sequencing microsatellites might be useful in disease mapping studies by increasing marker informativeness and by helping in the interpretation of association study results. It is also proposed that SNPs within the flanking region of CA repeats could be used to develop biallelic markers from already available mapped microsatellite markers.
对位于HLA - DQ区域内的三个先前描述的微卫星和小卫星标记DQCAR、DQCARII和G51152进行了测序研究。在所有三个标记中均观察到了不改变大小多态性的多个核苷酸替换。在所有位点，核心重复序列的数量与相邻的DQ等位基因序列基序不相关，而微卫星序列内部或侧翼的单核苷酸变化则相关。这一结果表明，在这些位点，微卫星扩增/收缩的突变率高于核苷酸替换的突变率。进一步分析表明，一方面，DQCAR单核苷酸多态性（SNP）与DQB1序列（相距1.0 - 1.5 kb）之间几乎完全存在系统发育对应关系，另一方面，DQCARII与DQA1序列（相距4.5 kb）之间存在完全对应关系。相比之下，G51152序列与DQB1等位基因序列并不完全对应，因此表明该标记与DQB1之间存在几个祖先交叉（20 - 25 kb）。对微卫星进行测序可能有助于疾病定位研究，可增加标记信息含量并有助于解释关联研究结果。还提出，CA重复序列侧翼区域内的SNP可用于从已有的定位微卫星标记开发双等位基因标记。
