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. CONCLUSION: 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.
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. CONCLUSION: 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.
Authors: S A Feather; S Malcolm; A S Woolf; V Wright; D Blaydon; C J Reid; F A Flinter; W Proesmans; K Devriendt; J Carter; P Warwicker; T H Goodship; J A Goodship Journal: Am J Hum Genet Date: 2000-03-17 Impact factor: 11.025
Authors: T Ogata; K Muroya; I Sasagawa; T Kosho; K Wakui; S Sakazume; K Ito; N Matsuo; H Ohashi; T Nagai Journal: Kidney Int Date: 2000-12 Impact factor: 10.612
Authors: K Nagata; T Yamamoto; H Chikumi; T Ikeda; H Yamamoto; K Hashimoto; K Yoneda; E Nanba; H Ninomiya; K Ishitobi Journal: J Hum Genet Date: 2000 Impact factor: 3.172
Authors: C Bingham; M P Bulman; S Ellard; L I Allen; G W Lipkin; W G Hoff; A S Woolf; G Rizzoni; G Novelli; A J Nicholls; A T Hattersley Journal: Am J Hum Genet Date: 2000-11-20 Impact factor: 11.025
Authors: Stefanie Weber; Jaclyn C Taylor; Paul Winyard; Kari F Baker; Jessica Sullivan-Brown; Raphael Schild; Tanja Knüppel; Aleksandra M Zurowska; Alberto Caldas-Alfonso; Mieczyslaw Litwin; Sevinc Emre; Gian Marco Ghiggeri; Aysin Bakkaloglu; Otto Mehls; Corinne Antignac; Escape Network; Franz Schaefer; Rebecca D Burdine Journal: J Am Soc Nephrol Date: 2008-02-27 Impact factor: 10.121
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