Sharp J D, Wheeler R B, Schultz R A, Joslin J M, Mole S E, Williams R E, Gardiner R M
Department of Paediatrics and Child Health, Royal Free and University College Medical School, Rayne Institute, University Street, London WC1E 6JJ, UK.
Eur J Paediatr Neurol. 2001;5 Suppl A:29-31. doi: 10.1053/ejpn.2000.0430.
CLN6, the gene for variant late infantile neuronal ceroid lipofuscinosis, was mapped to a 4 cM region on chromosome 15q22-23. Subsequently the critical region was narrowed to less than 1 cM between microsatellite markers D15S988 and D15S1000 by additional marker typing in an expanded family resource. A physical map was constructed across this region using YAC and PAC clones and sequence was generated from two PAC clones. This sequence was analysed together with overlapping sequence generated by the Human Genome Project to identify genes within the region using an in silico cloning approach. In all, 29 genes have been identified and 18 have been analysed for mutations by direct sequencing. This powerful new approach will lead to the identification of CLN6.
CLN6基因，即变异型晚发性婴儿神经元蜡样脂褐质沉积症的相关基因，被定位到15号染色体q22 - 23区域的一个4厘摩的区间。随后，通过在一个扩大的家系资源中进行额外的标记分型，关键区域被缩小到微卫星标记D15S988和D15S1000之间小于1厘摩的范围。利用酵母人工染色体（YAC）和细菌人工染色体（PAC）克隆构建了该区域的物理图谱，并从两个PAC克隆中生成了序列。将该序列与人类基因组计划产生的重叠序列一起进行分析，采用电子克隆方法在该区域内鉴定基因。总共鉴定出29个基因，其中18个通过直接测序分析了突变情况。这种强大的新方法将有助于鉴定CLN6基因。
