Gould T D, Pfeifer K
Laboratory of Mammalian Genes and Development, National Institute of Child Health and Human Development, Building 6B, Room 2B206, 9000 Rockville Pike, Bethesda, MD 20892, USA.
Hum Mol Genet. 1998 Mar;7(3):483-7. doi: 10.1093/hmg/7.3.483.
Mouse distal chromosome 7 contains a cluster of at least five imprinted genes. The syntenic region in humans, at 11p15.5, has been implicated in several genetic disorders. Consistent with the imprinted status of the genes in the region, Beckwith-Wiedemann syndrome (BWS) and Wilms tumor are each associated with loss of maternal information. Also mapping to 11p15.5 are long QT and Jervell and Lange-Nielsen (JLN) syndromes. In contrast to BWS and Wilms tumor, these syndromes do not show any parent of origin bias. Recently positional cloning has identified KVLQT1 as the 11p15.5 gene responsible for increased susceptibility to long QT and JLN syndromes. Other studies associate KVLQT1 with BWS. Human KVLQT1 is paternally imprinted in embryos. In this study we present a contig and transcript map of distal mouse 7 and we physically and genetically map mouse Kvlqt1 to the region. Mouse Kvlqt1 is strongly expressed in heart, lung, gut, kidney and uterus. While its early developmental expression is maternal in origin, the paternal allele becomes increasingly active during development. Late juvenile and adult animals show complete biallelism, suggesting an explanation for the lack of parent of origin bias in JLN and long QT.
小鼠7号远端染色体包含一个至少由五个印记基因组成的基因簇。人类的同区域位于11p15.5，与多种遗传疾病有关。与该区域基因的印记状态一致，贝克威思-维德曼综合征（BWS）和威尔姆斯瘤均与母源信息缺失有关。长QT综合征和耶尔韦尔和朗格-尼尔森（JLN）综合征也定位于11p15.5。与BWS和威尔姆斯瘤不同，这些综合征没有显示出任何亲代来源偏向。最近的定位克隆已确定KVLQT1是11p15.5上导致长QT综合征和JLN综合征易感性增加的基因。其他研究将KVLQT1与BWS联系起来。人类KVLQT1在胚胎中是父源印记的。在本研究中，我们展示了小鼠7号远端的重叠群和转录图谱，并将小鼠Kvlqt1进行了物理和遗传定位。小鼠Kvlqt1在心脏、肺、肠道、肾脏和子宫中强烈表达。虽然其早期发育表达起源于母源，但父源等位基因在发育过程中变得越来越活跃。幼年后期和成年动物表现出完全的双等位基因表达，这为JLN和长QT综合征中缺乏亲代来源偏向提供了解释。
