title: Mapping a new suggestive gene locus for autosomal dominant nephrolithiasis to chromosome 9q33.2-q34.2 by total genome search for linkage.
abstract: 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.
authors.affiliation: Department of Pediatrics and Communicable Diseases, University of Michigan, 8220C MSRB III, 1150 West Medical Center Drive, Ann Arbor, MI 48109-0646, USA.
authors.forename: Matthias T F
authors.initials: MT
authors.lastname: Wolf
authors.forename: Isabella
authors.initials: I
authors.lastname: Zalewski
authors.forename: Félix Claverie
authors.initials: FC
authors.lastname: Martin
authors.forename: Rainer
authors.initials: R
authors.lastname: Ruf
authors.forename: Dominik
authors.initials: D
authors.lastname: Müller
authors.forename: Hans C
authors.initials: HC
authors.lastname: Hennies
authors.forename: Stella
authors.initials: S
authors.lastname: Schwarz
authors.forename: Franziska
authors.initials: F
authors.lastname: Panther
authors.forename: Massimo
authors.initials: M
authors.lastname: Attanasio
authors.forename: Hilaria G
authors.initials: HG
authors.lastname: Acosta
authors.forename: Anita
authors.initials: A
authors.lastname: Imm
authors.forename: Barbara
authors.initials: B
authors.lastname: Lucke
authors.forename: Boris
authors.initials: B
authors.lastname: Utsch
authors.forename: Edgar
authors.initials: E
authors.lastname: Otto
authors.forename: Peter
authors.initials: P
authors.lastname: Nurnberg
authors.forename: Victor Garcia
authors.initials: VG
authors.lastname: Nieto
authors.forename: Friedhelm
authors.initials: F
authors.lastname: Hildebrandt
mesh_terms: 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