O'Malley K L, Rotwein P
Department of Anatomy and Neurobiology, Washington University School of Medicine, St Louis, MO 63110.
Nucleic Acids Res. 1988 May 25;16(10):4437-46.
The gene for the catecholamine biosynthetic enzyme, tyrosine hydroxylase (TH), has been previously mapped to human chromosome 11 p15.5 in the vicinity of the loci for insulin (INS) and for the oncogene Harvey Ras 1 (HRAS). Here we show that gene probes derived from recombinant clones containing either human TH or INS cross-hybridize with each other. Direct DNA sequencing demonstrates that these genes are physically linked on chromosome 11. The TH gene is 5' to INS and is separated by only 2.7 kb of flanking DNA. Both genes have the same transcriptional polarity and form a head-to-tail linkage group with insulin-like growth factor 2 (IGF-2) in the order: 5' - TH - INS - IGF-2 - 3'. Because of the close physical proximity of these genes, previously described polymorphisms for INS are identical to those observed with TH. The localization of TH to the highly polymorphic INS locus provides four new restriction fragment length polymorphisms which should help determine rapidly whether defects in TH are responsible for bipolar affective disorder in the Old Order Amish and other populations.
儿茶酚胺生物合成酶酪氨酸羟化酶（TH）的基因先前已被定位到人类染色体11 p15.5，位于胰岛素（INS）基因座和癌基因哈维鼠肉瘤病毒癌基因同源物1（HRAS）基因座附近。在此我们表明，源自含有人类TH或INS的重组克隆的基因探针彼此交叉杂交。直接DNA测序表明这些基因在染色体11上物理相连。TH基因位于INS基因的5'端，仅被2.7 kb的侧翼DNA隔开。这两个基因具有相同的转录极性，并与胰岛素样生长因子2（IGF-2）形成头对头的连锁群，顺序为：5'-TH-INS-IGF-2-3'。由于这些基因在物理上非常接近，先前描述的INS多态性与TH观察到的多态性相同。TH定位于高度多态的INS基因座提供了四种新的限制性片段长度多态性，这应该有助于快速确定TH缺陷是否是导致老派阿米什人和其他人群双相情感障碍的原因。
