Ambrose C, James M, Barnes G, Lin C, Bates G, Altherr M, Duyao M, Groot N, Church D, Wasmuth J J
Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown 02129.
Hum Mol Genet. 1992 Dec;1(9):697-703. doi: 10.1093/hmg/1.9.697.
Within the Huntington's disease (HD) candidate region of 4p16.3, the D4S127 locus displays strong linkage disequilibrium with the defect and anchors a conserved haplotype found on many HD chromosomes. To isolate genes from this region we have applied the exon amplification technique to overlapping cosmids spanning D4S127. Here, we report the discovery of a new gene encoding a novel member of a family of protein kinases that specifically phosphorylate the activated forms of G protein-coupled receptors. Such kinases are thought to participate in desensitization of specific receptors, thereby blocking further signal transduction. This gene must now be carefully scrutinized to determine whether it might be involved in HD.
在4号染色体短臂16.3区的亨廷顿舞蹈病(HD)候选区域内,D4S127基因座与该缺陷表现出强烈的连锁不平衡,并确定了在许多HD染色体上发现的一个保守单倍型。为了从该区域分离基因,我们将外显子扩增技术应用于跨越D4S127的重叠黏粒。在此,我们报告发现了一个新基因,它编码蛋白激酶家族的一个新成员,该蛋白激酶能特异性磷酸化G蛋白偶联受体的激活形式。这类激酶被认为参与特定受体的脱敏过程,从而阻断进一步的信号转导。现在必须仔细审查该基因,以确定它是否可能与HD有关。