Lichter-Konecki U, Broman K W, Blau E B, Konecki D S
Center for Medical Genetics, Marshfield Medical Research Foundation, Marshfield, WI, USA.
Am J Hum Genet. 2001 Jan;68(1):264-8. doi: 10.1086/316923. Epub 2000 Nov 22.
Autosomal dominant renal Fanconi syndrome is a genetic model for the study of proximal renal tubular transport pathology. We were able to map the locus for this disease to human chromosome 15q15.3 by genotyping a central Wisconsin pedigree with 10 affected individuals. After a whole-genome scan with highly polymorphic simple sequence repeat markers, a maximum LOD score of 3.01 was calculated for marker D15S659 on chromosome 15q15.3. Linkage and haplotype analysis for an additional 24 markers flanking D15S659 narrowed the interval to approximately 3 cM, with the two highest single-point LOD scores observed being 4.44 and 4.68 (for D15S182 and D15S537, respectively). Subsequently, a complete bacterial artificial chromosome contig was constructed, from the High Throughput Genomic Sequence Database, for the region bounded by D15S182 and D15S143. The identification of the gene and gene product altered in autosomal dominant renal Fanconi syndrome will allow the study of the physiology of proximal renal tubular transport.
常染色体显性遗传性肾范科尼综合征是研究近端肾小管转运病理的一种遗传模型。我们通过对威斯康星州中部一个有10名患者的家系进行基因分型，将该疾病的基因座定位到人类染色体15q15.3。在用高度多态性的简单序列重复标记进行全基因组扫描后，计算出位于染色体15q15.3上的标记D15S659的最大对数优势（LOD）分数为3.01。对D15S659两侧的另外24个标记进行连锁和单倍型分析，将间隔缩小到约3厘摩，观察到的两个最高单点LOD分数分别为4.44和4.68（分别对应于D15S182和D15S537）。随后，从高通量基因组序列数据库构建了一个完整的细菌人工染色体重叠群，用于覆盖由D15S182和D15S143界定的区域。确定常染色体显性遗传性肾范科尼综合征中发生改变的基因和基因产物，将有助于研究近端肾小管转运的生理学。
