Mapping a new suggestive gene locus for autosomal dominant nephrolithiasis to chromosome 9q33.2-q34.2 by total genome search for linkage.
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 Z(max) = 1.99 (theta = 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 Z(max) = 2.7 (theta = 0) for markers D9S1881-D9S164, thereby identifying 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.


CONCLUSIONS
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.
Wolf
Matthias T F
MT
Department of Pediatrics and Communicable Diseases, University of Michigan, 8220C MSRB III, 1150 West Medical Center Drive, Ann Arbor, MI 48109-0646, USA.
Zalewski
Isabella
I
Martin
Félix Claverie
FC
Ruf
Rainer
R
Müller
Dominik
D
Hennies
Hans C
HC
Schwarz
Stella
S
Panther
Franziska
F
Attanasio
Massimo
M
Acosta
Hilaria G
HG
Imm
Anita
A
Lucke
Barbara
B
Utsch
Boris
B
Otto
Edgar
E
Nurnberg
Peter
P
Nieto
Victor Garcia
VG
Hildebrandt
Friedhelm
F
D000368:Aged; D002874:Chromosome Mapping; D002899:Chromosomes, Human, Pair 9; D005260:Female; D008040:Genetic Linkage; D016678:Genome; D006801:Humans; D007669:Kidney Calculi / Q000235:genetics*; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged