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10.1016/j.ajhg.2017.09.018 http://scihub22266oqcxt.onion/10.1016/j.ajhg.2017.09.018 C5673636!5673636!29100090     free     free     free Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Am+J+Hum+Genet 2017 ; 101 (5): 789-802 Nephropedia Template TP {{tp|p=29100090|t=2017. Exome-wide Association Study Identifies GREB1L Mutations in Congenital Kidney Malformations |pdf=|usr=}}{{29100090}} gab.com Text Exome-wide Association Study Identifies GREB1L Mutations in Congenital Kidney Malformations JO: Am J Hum Genet http://www.kidney.de/pget.php?&tw=1&pmid=29100090 #FOAvip Renal agenesis and hypodysplasia (RHD) are major causes of pediatric chronic kidney disease and are highly genetically heterogeneous. We conducted whole-exome sequencing in 202 case subjects with RHD and identified diagnostic mutations in genes known to be associated with RHD in 7/202 case subjects. In an additional affected individual with RHD and a congenital heart defect, we found a homozygous loss-of-function (LOF) variant in SLIT3, recapitulating phenotypes reported with Slit3 inactivation in the mouse. To identify genes associated with RHD, we performed an exome-wide association study with 195 unresolved case subjects and 6,905 control subjects. The top signal resided in GREB1L, a gene implicated previously in Hoxb1 and Shha signaling in zebrafish. The significance of the association, which was p = 2.0 × 10?5 for novel LOF, increased to p = 4.1 × 10?6 for LOF and deleterious missense variants combined, and augmented further after accounting for segregation and de novo inheritance of rare variants (joint p = 2.3 × 10?7). Finally, CRISPR/Cas9 disruption or knockdown of greb1l in zebrafish caused specific pronephric defects, which were rescued by wild-type human GREB1L mRNA, but not mRNA containing alleles identified in case subjects. Together, our study provides insight into the genetic landscape of kidney malformations in humans, presents multiple candidates, and identifies SLIT3 and GREB1L as genes implicated in the pathogenesis of RHD. Twit Text FOAVip Exome-wide Association Study Identifies GREB1L Mutations in Congenital Kidney Malformations ????Am J Hum Genet http://www.kidney.de/pget.php?&tw=1&pmid=29100090 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=29100090 #FOAvip English Wikipedia <ref>{{Cite pmid|29100090}}</ref> Exome-wide Association Study Identifies GREB1L Mutations in Congenital Kidney Malformations #MMPMID29100090 Sanna-Cherchi S; Khan K; Westland R; Krithivasan P; Fievet L; Rasouly HM; Ionita-Laza I; Capone VP; Fasel DA; Kiryluk K; Kamalakaran S; Bodria M; Otto EA; Sampson MG; Gillies CE; Vega-Warner V; Vukojevic K; Pediaditakis I; Makar GS; Mitrotti A; Verbitsky M; Martino J; Liu Q; Na YJ; Goj V; Ardissino G; Gigante M; Gesualdo L; Janezcko M; Zaniew M; Mendelsohn CL; Shril S; Hildebrandt F; van Wijk JA; Arapovic A; Saraga M; Allegri L; Izzi C; Scolari F; Tasic V; Ghiggeri GM; Latos-Bielenska A; Kiryluk AM; Mane S; Goldstein DB; Lifton RP; Katsanis N; Davis EE; Gharavi AG Am J Hum Genet 2017[Nov]; 101 (5): 789-802 PMID29100090show ga Renal agenesis and hypodysplasia (RHD) are major causes of pediatric chronic kidney disease and are highly genetically heterogeneous. We conducted whole-exome sequencing in 202 case subjects with RHD and identified diagnostic mutations in genes known to be associated with RHD in 7/202 case subjects. In an additional affected individual with RHD and a congenital heart defect, we found a homozygous loss-of-function (LOF) variant in SLIT3, recapitulating phenotypes reported with Slit3 inactivation in the mouse. To identify genes associated with RHD, we performed an exome-wide association study with 195 unresolved case subjects and 6,905 control subjects. The top signal resided in GREB1L, a gene implicated previously in Hoxb1 and Shha signaling in zebrafish. The significance of the association, which was p = 2.0 × 10?5 for novel LOF, increased to p = 4.1 × 10?6 for LOF and deleterious missense variants combined, and augmented further after accounting for segregation and de novo inheritance of rare variants (joint p = 2.3 × 10?7). Finally, CRISPR/Cas9 disruption or knockdown of greb1l in zebrafish caused specific pronephric defects, which were rescued by wild-type human GREB1L mRNA, but not mRNA containing alleles identified in case subjects. Together, our study provides insight into the genetic landscape of kidney malformations in humans, presents multiple candidates, and identifies SLIT3 and GREB1L as genes implicated in the pathogenesis of RHD. äExome-wide Association Study Identifies GREB1L Mutations in Congenital(epmc).pdf DeepDyve Pubget Overpricing