Wang C Y, Hawkins-Lee B, Ochoa B, Walker R D, She J X
Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville 32610-0275, USA.
Am J Hum Genet. 1997 Jun;60(6):1461-7. doi: 10.1086/515469.
The urofacial (Ochoa) syndrome (UFS) is a rare autosomal recessive disease characterized by congenital obstructive uropathy and abnormal facial expression. The patients present with enuresis, urinary-tract infection, hydronephrosis, and voiding dysfunctions as a result of neurogenic bladders. To map the UFS gene, a genome screen using a combination of homozygosity-mapping and DNA-pooling strategies was performed in 20 selected patients, one patient pool, and three control pools (unaffected relatives). After analyses of 36 randomly chosen markers, D10S677 was identified as being linked to and associated with UFS, as suggested by a significant excess of homozygosity in patients compared with that in unaffected relatives (P < 10(-6)), as well as by the allelic-frequency differences between the patient pool and control pools. Ten additional markers flanking D10S677 and covering a 22-cM region then were analyzed to fine-map the UFS gene by use of haplotype (linkage disequilibrium) analysis. All 31 patients were found to be homozygous for two closely linked markers (D10S1726 and D10S198) located approximately 5 cM telomeric to D10S677, whereas only 12% of the unaffected relatives were homozygous for both markers (P < 10(-19)). Several patients are heterozygous at two markers immediately flanking D10S1726/D10S198, one on the centromeric side (D10S1433) and the other on the telomeric side (D10S603). These recombinational events place the UFS gene near D10S1726/D10S198 and within a 1-cM interval defined by D10S1433 and D10S603 on chromosome 10q23-q24.
泌尿生殖面（奥乔亚）综合征（UFS）是一种罕见的常染色体隐性疾病，其特征为先天性梗阻性肾病和异常面部表情。患者因神经源性膀胱而出现遗尿、尿路感染、肾积水和排尿功能障碍。为了定位UFS基因，对20名选定患者、一个患者样本库和三个对照样本库（未受影响的亲属）进行了基因组筛查，采用了纯合性定位和DNA池策略相结合的方法。在分析了36个随机选择的标记后，发现D10S677与UFS连锁并相关，这是由患者与未受影响亲属相比纯合性显著增加（P < 10(-6)）以及患者样本库和对照样本库之间的等位基因频率差异所表明的。然后分析了位于D10S677两侧并覆盖22厘摩区域的另外10个标记，以通过单倍型（连锁不平衡）分析来精细定位UFS基因。发现所有31名患者在位于D10S677端粒侧约5厘摩处的两个紧密连锁标记（D10S1726和D10S198）上均为纯合子，而只有12%的未受影响亲属在这两个标记上为纯合子（P < 10(-19)）。有几名患者在紧邻D10S1726/D10S198的两个标记上为杂合子，一个在着丝粒侧（D10S1433），另一个在端粒侧（D10S603）。这些重组事件将UFS基因定位在D10S1726/D10S198附近，并在10号染色体q23-q24上由D10S1433和D10S603定义的1厘摩区间内。
