Eubanks J H, Altherr M, Wagner-McPherson C, McPherson J D, Wasmuth J J, Evans G A
Molecular Genetics Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037.
Genomics. 1992 Mar;12(3):510-6. doi: 10.1016/0888-7543(92)90442-u.
Genes encoding G-protein-coupled receptors, including dopamine, serotonin, muscarinic cholinergic, and adrenergic receptors, play an important role in neurotransmission and may be involved in the pathophysiology of diseases such as Alzheimer's disease, Parkinson's disease, or Huntington's disease (HD). We mapped the gene encoding the D5 dopamine receptor (DRD5) to human chromosome 4p, an area implicated in HD and the Wolf-Hirschhorn syndrome, using gene-specific amplification with the polymerase chain reaction on a panel of somatic cell hybrids carrying different human chromosomes. Further localization of the DRD5 gene was carried out through the isolation and analysis of yeast artificial chromosomes, fluorescence in situ suppression hybridization to human metaphase chromosomes, and analysis of a panel of somatic cell hybrids subdividing human chromosome 4 into nine regions. The human DRD5 gene is located at 4p15.1-p15.33, centromeric to the location of the Huntington's disease locus although not in the obligate area containing the HD gene. The localization of the DRD5 gene to 4p15.1-p15.33 suggests the possibility that cis-position effects could be responsible for the altered D1-type dopamine receptor number observed in HD tissues or that the DRD5 gene could be a candidate for some of the abnormalities associated with the Wolf-Hirschhorn syndrome.
编码G蛋白偶联受体的基因，包括多巴胺、5-羟色胺、毒蕈碱型胆碱能和肾上腺素能受体，在神经传递中发挥重要作用，可能参与诸如阿尔茨海默病、帕金森病或亨廷顿舞蹈病（HD）等疾病的病理生理过程。我们利用聚合酶链反应进行基因特异性扩增，在一组携带不同人类染色体的体细胞杂种上，将编码D5多巴胺受体（DRD5）的基因定位到人类4号染色体短臂，该区域与HD及沃尔夫-赫希霍恩综合征有关。通过酵母人工染色体的分离和分析、对人类中期染色体的荧光原位抑制杂交以及对一组将人类4号染色体细分为9个区域的体细胞杂种的分析，对DRD5基因进行了进一步定位。人类DRD5基因位于4p15.1 - p15.33，在亨廷顿舞蹈病基因座的着丝粒侧，尽管不在包含HD基因的必然区域内。DRD5基因定位到4p15.1 - p15.33提示，顺式位置效应可能是HD组织中观察到的D1型多巴胺受体数量改变的原因，或者DRD5基因可能是与沃尔夫-赫希霍恩综合征相关的一些异常情况的候选基因。
