Mapping of a new locus for congenital anomalies of the kidney and urinary tract on chromosome 8q24.
BACKGROUND
Congenital anomalies of the kidney and urinary tract (CAKUT) account for the majority of end-stage renal disease in children (50%). Previous studies have mapped autosomal dominant loci for CAKUT. We here report a genome-wide search for linkage in a large pedigree of Somalian descent containing eight affected individuals with a non-syndromic form of CAKUT.


METHODS
Clinical data and blood samples were obtained from a Somalian family with eight individuals with CAKUT including high-grade vesicoureteral reflux and unilateral renal agenesis. Total genome search for linkage was performed using a 50K SNP Affymetric DNA microarray. As neither parent is affected, the results of the SNP array were analysed under recessive models of inheritance, with and without the assumption of consanguinity.


RESULTS
Using the non-consanguineous recessive model, a new gene locus (CAKUT1) for CAKUT was mapped to chromosome 8q24 with a significant maximum parametric Logarithm of the ODDs (LOD) score (LOD(max)) of 4.2. Recombinations were observed in two patients defining a critical genetic interval of 2.5 Mb physical distance flanked by markers SNP_A-1740062 and SNP_A-1653225.


CONCLUSIONS
We have thus identified a new non-syndromic recessive gene locus for CAKUT (CAKUT1) on chromosome 8q24. The identification of the disease-causing gene will provide further insights into the pathogenesis of urinary tract malformations and mechanisms of renal development.
Ashraf
Shazia
S
1Department of Pediatrics and of Human Genetics, University of Michigan, Ann Arbor, USA.
Hoskins
Bethan E
BE
Chaib
Hassan
H
Hoefele
Julia
J
Pasch
Andreas
A
Saisawat
Pawaree
P
Trefz
Friedrich
F
Hacker
Hans W
HW
Nuernberg
Gudrun
G
Nuernberg
Peter
P
Otto
Edgar A
EA
Hildebrandt
Friedhelm
F
D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D002898:Chromosomes, Human, Pair 8; D005260:Female; D006239:Haplotypes; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007668:Kidney / Q000002:abnormalities*; D008126:Lod Score; D008297:Male; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D014551:Urinary Tract / Q000002:abnormalities*