Ward T L, Valberg S J, Lear T L, Guérin G, Milenkovic D, Swinburne J E, Binns M M, Raudsepp T, Skow L, Chowdhary B P, Mickelson J R
Department of Veterinary PathoBiology, University of Minnesota, St Paul, MN 55108, USA.
Cytogenet Genome Res. 2003;102(1-4):201-6. doi: 10.1159/000075749.
Comparative biochemical and histopathological data suggest that a deficiency in the glycogen branching enzyme (GBE) is responsible for a fatal neonatal disease in Quarter Horse foals that closely resembles human glycogen storage disease type IV (GSD IV). Identification of DNA markers closely linked to the equine GBE1 gene would assist us in determining whether a mutation in this gene leads to the GSD IV-like condition. FISH using BAC clones as probes assigned the equine GBE1 gene to a marker deficient region of ECA26q12-->q13. Four other genes, ROBO2, ROBO1, POU1F1, and HTR1F, that flank GBE1 within a 10-Mb segment of HSA3p12-->p11, were tightly linked to equine GBE1 when analyzed on the Texas A&M University 5000 rad equine radiation hybrid panel, while the GLB1, MITF, RYBP, and PROS1 genes that flank this 10-Mb interval were not linked with markers in the GBE1 group. A polymorphic microsatellite (GBEms1) in a GBE1 BAC clone was then identified and genetically mapped to ECA26 on the Animal Health Trust full-sibling equine reference family. All Quarter Horse foals affected with GSD IV were homozygous for an allele of GBEms1, as well as an allele of the most closely linked microsatellite marker, while a control horse population showed significant allelic variation with these markers. This data provides strong molecular genetic support for the candidacy of the GBE1 locus in equine GSD IV.
比较生物化学和组织病理学数据表明，糖原分支酶（GBE）缺乏是四分之一马驹致命性新生儿疾病的病因，该疾病与人类IV型糖原贮积病（GSD IV）极为相似。鉴定与马GBE1基因紧密连锁的DNA标记将有助于我们确定该基因的突变是否导致类似GSD IV的病症。使用BAC克隆作为探针进行荧光原位杂交（FISH），将马GBE1基因定位到ECA26q12→q13的一个标记缺失区域。在德克萨斯农工大学5000拉德马辐射杂种板上进行分析时，位于人3号染色体短臂12区→11区10 Mb片段内与GBE1侧翼的其他四个基因ROBO2、ROBO1、POU1F1和HTR1F与马GBE1紧密连锁，而位于这个10 Mb区间侧翼的GLB1、MITF、RYBP和PROS1基因与GBE1组中的标记不连锁。随后在一个GBE1 BAC克隆中鉴定出一个多态性微卫星（GBEms1），并在动物卫生信托全同胞马参考家系中将其遗传定位到ECA26。所有患GSD IV的四分之一马驹对于GBEms1的一个等位基因以及最紧密连锁的微卫星标记的一个等位基因均为纯合子，而对照马群体在这些标记上显示出显著的等位基因变异。这些数据为GBE1基因座作为马GSD IV候选基因提供了强有力的分子遗传学支持。
