NDT Advance Access originally published online on March 1, 2005
Nephrology Dialysis Transplantation 2005 20(5):909-914; doi:10.1093/ndt/gfh754
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Mapping a new suggestive gene locus for autosomal dominant nephrolithiasis to chromosome 9q33.2–q34.2 by total genome search for linkage
1 University Children's Hospital, Freiburg University, Freiburg, 2 Hospital Universitario N.S. de Candelaria, Unidad de Investigación, Santa Cruz de Tenerife, Spain 3 Max-Delbrueck Center for Molecular Medicine, Berlin-Buch, 4 University Children's Hospital, Pediatric Nephrology, Cologne University, Cologne, Germany and 5 Pediatric Nephrology, Charité, Humboldt University, Berlin
Correspondence and offprint requests to: Friedhelm Hildebrandt, MD, Department of Pediatrics and Communicable Diseases, University of Michigan, 8220C MSRB III, 1150 West Medical Center Drive, Ann Arbor, MI 48109-0646, USA. Email: fhilde{at}umich.edu
Background. Nephrolithiasis is a complex, multifactorial disease resulting from genetic and environmental interaction. The pathogenesis of nephrolithiasis is far from being understood. So far, no gene locus for autosomal dominant nephrolithiasis only has been described. We here identified a new suggestive gene locus for autosomal dominant nephrolithiasis by a genome-wide search for linkage in a Spanish kindred with nephrolithiasis.
Methods. Clinical data, blood and urine samples of 18 individuals from a Spanish kindred with nephrolithiasis were collected. We performed a genome-wide search for linkage using 380 polymorphic microsatellite markers.
Results. Nephrolithiasis segregated in this Spanish kindred in a pattern compatible with autosomal dominant inheritance. The total genome search yielded the highest two-point LOD score of Zmax = 1.99 (
= 0) for marker D9S159 on chromosome 9q33.2–q34.2. Multipoint analysis of 24 polymorphic markers used for further fine mapping resulted in a LOD score of Zmax = 2.7 ( = 0) for markers D9S1881–D9S164, thereby identifiying a new gene locus for autosomal dominant nephrolithiasis (NPL1). Two recombination events define D9S1850 as the centromeric flanking marker and D9S1818 as the telomeric flanking marker, restricting the NPL1 locus to a 14 Mb interval.
Conclusion. We here identified a new suggestive gene locus (NPL1) for autosomal dominant nephrolithiasis. It is localized on chromosome 9q33.2–q34.2. The identification of the responsible gene will provide new insights into the molecular basis of nephrolithiasis.
Keywords: haplotype analysis; nephrolithiasis; recombination