Evaluation of Variability in Human Kidney Organoids
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PLATFORM ABSTRACTS Abstract Abstract Numbers Numbers Tuesday, November 6 41
American Society of Human Genetics 62nd Annual Meeting November 6–10, 2012 San Francisco, California PLATFORM ABSTRACTS Abstract Abstract Numbers Numbers Tuesday, November 6 41. Genes Underlying Neurological Disease Room 134 #196–#204 2. 4:30–6:30pm: Plenary Abstract 42. Cancer Genetics III: Common Presentations Hall D #1–#6 Variants Ballroom 104 #205–#213 43. Genetics of Craniofacial and Wednesday, November 7 Musculoskeletal Disorders Room 124 #214–#222 10:30am–12:45 pm: Concurrent Platform Session A (11–19): 44. Tools for Phenotype Analysis Room 132 #223–#231 11. Genetics of Autism Spectrum 45. Therapy of Genetic Disorders Room 130 #232–#240 Disorders Hall D #7–#15 46. Pharmacogenetics: From Discovery 12. New Methods for Big Data Ballroom 103 #16–#24 to Implementation Room 123 #241–#249 13. Cancer Genetics I: Rare Variants Room 135 #25–#33 14. Quantitation and Measurement of Friday, November 9 Regulatory Oversight by the Cell Room 134 #34–#42 8:00am–10:15am: Concurrent Platform Session D (47–55): 15. New Loci for Obesity, Diabetes, and 47. Structural and Regulatory Genomic Related Traits Ballroom 104 #43–#51 Variation Hall D #250–#258 16. Neuromuscular Disease and 48. Neuropsychiatric Disorders Ballroom 103 #259–#267 Deafness Room 124 #52–#60 49. Common Variants, Rare Variants, 17. Chromosomes and Disease Room 132 #61–#69 and Everything in-Between Room 135 #268–#276 18. Prenatal and Perinatal Genetics Room 130 #70–#78 50. Population Genetics Genome-Wide Room 134 #277–#285 19. Vascular and Congenital Heart 51. Endless Forms Most Beautiful: Disease Room 123 #79–#87 Variant Discovery in Genomic Data Ballroom 104 #286–#294 52. -
Synergistic Genetic Interactions Between Pkhd1 and Pkd1 Result in an ARPKD-Like Phenotype in Murine Models
BASIC RESEARCH www.jasn.org Synergistic Genetic Interactions between Pkhd1 and Pkd1 Result in an ARPKD-Like Phenotype in Murine Models Rory J. Olson,1 Katharina Hopp ,2 Harrison Wells,3 Jessica M. Smith,3 Jessica Furtado,1,4 Megan M. Constans,3 Diana L. Escobar,3 Aron M. Geurts,5 Vicente E. Torres,3 and Peter C. Harris 1,3 Due to the number of contributing authors, the affiliations are listed at the end of this article. ABSTRACT Background Autosomal recessive polycystic kidney disease (ARPKD) and autosomal dominant polycystic kidney disease (ADPKD) are genetically distinct, with ADPKD usually caused by the genes PKD1 or PKD2 (encoding polycystin-1 and polycystin-2, respectively) and ARPKD caused by PKHD1 (encoding fibrocys- tin/polyductin [FPC]). Primary cilia have been considered central to PKD pathogenesis due to protein localization and common cystic phenotypes in syndromic ciliopathies, but their relevance is questioned in the simple PKDs. ARPKD’s mild phenotype in murine models versus in humans has hampered investi- gating its pathogenesis. Methods To study the interaction between Pkhd1 and Pkd1, including dosage effects on the phenotype, we generated digenic mouse and rat models and characterized and compared digenic, monogenic, and wild-type phenotypes. Results The genetic interaction was synergistic in both species, with digenic animals exhibiting pheno- types of rapidly progressive PKD and early lethality resembling classic ARPKD. Genetic interaction be- tween Pkhd1 and Pkd1 depended on dosage in the digenic murine models, with no significant enhancement of the monogenic phenotype until a threshold of reduced expression at the second locus was breached. -
Genotyping of Breech Flystrike Resource – Update
Project No: ON-00515 Contract No: PO4500010753 AWI Project Manager: Bridget Peachey Contractor Name: CSIRO Agriculture and Food Prepared by: Dr Sonja Dominik Publication Date: July 2019 Genotyping of breech flystrike resource – update Published by Australian Wool Innovation Limited, Level 6, 68 Harrington Street, THE ROCKS, NSW, 2000 This publication should only be used as a general aid and is not a substitute for specific advice. To the extent permitted by law, we exclude all liability for loss or damage arising from the use of the information in this publication. AWI invests in research, development, innovation and marketing activities along the global supply chain for Australian wool. AWI is grateful for its funding, which is primarily provided by Australian woolgrowers through a wool levy and by the Australian Government which provides a matching contribution for eligible R&D activities © 2019 Australian Wool Innovation Ltd. All rights reserved. Contents Executive Summary .................................................................................................................... 3 1 Introduction/Hypothesis .................................................................................................... 5 2 Literature Review ............................................................................................................... 6 3 Project Objectives .............................................................................................................. 8 4 Success in Achieving Objectives ........................................................................................ -
Cellular Ciliary Phenotyping Indicates Pathogenicity of Novel Variants in IFT140 and Confrms a Mainzer–Saldino Syndrome Diagnosis Machteld M
Oud et al. Cilia (2018) 7:1 https://doi.org/10.1186/s13630-018-0055-2 Cilia SHORT REPORT Open Access Cellular ciliary phenotyping indicates pathogenicity of novel variants in IFT140 and confrms a Mainzer–Saldino syndrome diagnosis Machteld M. Oud1,2* , Brooke L. Latour1,2‡, Zeineb Bakey1,2‡, Stef J. Letteboer1,2, Dorien Lugtenberg1, Ka Man Wu1,2, Elisabeth A. M. Cornelissen3, Helger G. Yntema1,4, Miriam Schmidts1,2,5, Ronald Roepman1,2† and Ernie M. H. F. Bongers1† Abstract Background: Mainzer–Saldino syndrome (MZSDS) is a skeletal ciliopathy and part of the short-rib thoracic dysplasia (SRTD) group of ciliary disorders. The main characteristics of MZSDS are short limbs, mild narrow thorax, blindness, and renal failure. Thus far, variants in two genes are associated with MZSDS: IFT140, and IFT172. In this study, we describe a 1-year-old girl presenting with mild skeletal abnormalities, Leber congenital amaurosis, and bilateral hear- ing difculties. For establishing an accurate diagnosis, we combined clinical, molecular, and functional analyses. Methods: We performed diagnostic whole-exome sequencing (WES) analysis to determine the genetic cause of the disease and analyzed two gene panels, containing all currently known genes in vision disorders, and in hearing impairment. Upon detection of the likely causative variants, ciliary phenotyping was performed in patient urine- derived renal epithelial cells (URECs) and rescue experiments were performed in CRISPR/Cas9-derived Ift140 knock out cells to determine the pathogenicity of the detected variants in vitro. Cilium morphology, cilium length, and intrafa- gellar transport (IFT) were evaluated by immunocytochemistry. Results: Diagnostic WES revealed two novel compound heterozygous variants in IFT140, encoding IFT140. -
Nephrin Mutations Can Cause Childhood-Onset Steroid-Resistant Nephrotic Syndrome
BRIEF COMMUNICATION www.jasn.org Nephrin Mutations Can Cause Childhood-Onset Steroid-Resistant Nephrotic Syndrome Aure´lie Philippe,*† Fabien Nevo,*† Ernie L. Esquivel,*† Dalia Reklaityte,*† ʈ Olivier Gribouval,*† Marie-Jose`phe Teˆte,*‡ Chantal Loirat,§ Jacques Dantal, Michel Fischbach,¶ Claire Pouteil-Noble,** Ste´phane Decramer,†† Martin Hoehne,‡‡ Thomas Benzing,‡‡ Marina Charbit,‡ Patrick Niaudet,*†‡ and Corinne Antignac*†§§ † *Inserm U574, Hoˆpital Necker-Enfants Malades, Universite´ Paris Descartes, Faculte´deMe´ decine Rene´ Descartes, BRIEF COMMUNICATION ‡Pediatric Nephrology and §§Department of Genetics, Hoˆpital Necker-Enfants Malades, Assistance Publique-Hoˆpitaux de Paris, and §Pediatric Nephrology Department, Universite´ Paris VII, Assistance Publique-Hoˆpitaux de Paris, Hoˆpital ʈ Robert Debre´, Paris, ITERT, Department of Nephrology and Clinical Immunology, CHU Nantes, Nantes, ¶Nephrology Dialysis Transplantation Children’s Unit, Hoˆpital de Hautepierre, Strasbourg, **Transplantation and Nephrology Unit, Centre Hospitalier Lyon-Sud, Pierre-Be´nite, and ††Department of Pediatric Nephrology, Hoˆpital des Enfants, and Inserm, U858/I2MR, Department of Renal and Cardiac Remodeling, Toulouse, France; and ‡‡Department of Medicine IV, University of Cologne, Cologne, Germany ABSTRACT Classically, infants with mutations in NPHS1, which encodes nephrin, present with but has since been described in other nephrotic syndrome within the first 3 mo of life (congenital nephrotic syndrome of populations.3–5 Nephrin is a single-pass the Finnish-type), and children with mutations in NPHS2, which encodes podocin, transmembrane protein consisting of present later with steroid-resistant nephrotic syndrome. Recently, however, eight extracellular Ig-like modules, a fi- NPHS2 mutations have been identified in children with congenital nephrotic syn- bronectin type III–like motif, and a cy- drome. Whether NPHS1 mutations similarly account for some cases of childhood tosolic C-terminal tail. -
NPHS2 Antibody (Podocin) (R30382)
NPHS2 Antibody (Podocin) (R30382) Catalog No. Formulation Size R30382 0.5mg/ml if reconstituted with 0.2ml sterile DI water 100 ug Bulk quote request Availability 1-3 business days Species Reactivity Human, Mouse, Rat Format Antigen affinity purified Clonality Polyclonal (rabbit origin) Isotype Rabbit IgG Purity Antigen affinity Buffer Lyophilized from 1X PBS with 2.5% BSA and 0.025% sodium azide/thimerosal UniProt Q9NP85 Applications Western blot : 0.5-1ug/ml Limitations This NPHS2 antibody is available for research use only. Western blot testing of NPHS2 antibody and rat kidney tissue lysate. Predicted molecular weight ~42kDa. Description NPHS2, also called Podocin (PDCN), is a protein which lines the podocytes and assists in maintaining the barrier at the glomerular basement membrane. NPHS2 is a causative gene for Familial idiopathic nephrotic syndromes, which represents a heterogeneous group of kidney disorders, and include autosomal recessive steroid-resistant nephrotic syndrome, which is characterized by early childhood onset of proteinuria, rapid progression to end-stage renal disease and focal segmental glomerulosclerosis. By positional cloning, it was mapped to 1q25-31. It is almost exclusively expressed in the podocytes of fetal and mature kidney glomeruli, and encodes a new integral membrane protein, podocin, belonging to the stomatin protein family. Boute et al.(2000) found ten different NPHS2 mutations, comprising nonsense, frameshift and missense mutations, to segregate with the disease, demonstrating a crucial role for podocin in the function of the glomerular filtration barrier. Application Notes The stated application concentrations are suggested starting amounts. Titration of the NPHS2 antibody may be required due to differences in protocols and secondary/substrate sensitivity. -
NPHS2 Gene Mutation, Atopy, and Gender As Risk Factors for Steroid-Resistant Nephrotic Syndrome in Indonesians
Paediatrica Indonesiana VOLUME 51 September NUMBER 5 Original Article NPHS2 gene mutation, atopy, and gender as risk factors for steroid-resistant nephrotic syndrome in Indonesians Dedi Rachmadi, Dany Hilmanto, Ponpon Idjradinata, Abdurahman Sukadi Abstract QUHFHQW\HDUVPROHFXODUJHQHWLFVWXGLHVKDYH Background 6WHURLGUHVLVWDQWQHSKURWLFV\QGURPH 6516 RIWHQ EHHQZHOOGHYHORSHGLQFOXGLQJVWXGLHVIRU GHYHORSVLQWRHQGVWDJHUHQDOGLVHDVH3UHYLRXVVWXGLHVKDYH JHQHVLQYROYHGLQWKHSDWKRJHQHVLVRIQHSKURWLF reported that NPHS2JHQHPXWDWLRQJHQGHUDQGDWRSLFKLVWRU\ V\QGURPH2ISDUWLFXODULQWHUHVWLVWKHJHQH DUHULVNIDFWRUVDVVRFLDWHGZLWK6516,QWHUHWKQLFVRFLRFXOWXUDO I DQGHQYLURQPHQWDOGLIIHUHQFHVKDYHDOVREHHQVXJJHVWHGWRDIIHFW encoding a protein that maintains the diaphragm slit WKHVHPXWDWLRQV RISRGRF\WHV*HQHPXWDWLRQDQDO\VLVLVLPSRUWDQW Objective7RDQDO\]HSRVVLEOHULVNIDFWRUVIRU6516LQFOXGLQJ with regards to phenotype and predicting the severity NPHS2JHQHPXWDWLRQV &o7DQGGHO* JHQGHUDQG RIFOLQLFDOPDQLIHVWDWLRQV The NPHS2 gene encodes DWRSLFKLVWRU\LQ,QGRQHVLDQVXEMHFWVZLWK6516 the podocin protein and is located on chromosome Methods$FDVHFRQWUROVWXG\ZLWKVXEMHFWVFRQVLVWLQJRI 6516SDWLHQWVDQGFRQWUROVXEMHFWVZDVXQGHUWDNHQLQ T0XWDWLRQRIWKLVJHQHKDVEHHQDVVRFLDWHG ,QGRQHVLDQWHDFKLQJFHQWUHKRVSLWDOVIURP6HSWHPEHUWR ZLWKSRRUVWHURLGUHVSRQVHLQWUHDWPHQWRIQHSKURWLF 'HFHPEHU$QDO\VLVRIWKHNPHS2JHQHPXWDWLRQLQ V\QGURPH 16 3UHYLRXVVWXGLHVKDYHVKRZQWKDW &o7ZDVSHUIRUPHGE\DPSOLILFDWLRQUHIUDFWRU\PXWDWLRQV\VWHP SRNS patients with an NPHS2JHQHPXWDWLRQKDG SRO\PHUDVHFKDLQUHDFWLRQ $5063&5 ZKLOHWKDWIRUWKH NPHS2JHQHPXWDWLRQLQGHO*ZDVSHUIRUPHGE\UHVWULFWLRQ -
Blueprint Genetics Short Rib Dysplasia / Asphyxiating Thoracic Dysplasia Panel
Short Rib Dysplasia / Asphyxiating Thoracic Dysplasia Panel Test code: MA1101 Is a 18 gene panel that includes assessment of non-coding variants. Is ideal for patients with a clinical suspicion of asphyxiating thoracic dystrophy or short-rib dysplasia with or without polydactyly. The genes on this panel are included in the Comprehensive Growth Disorders / Skeletal Dysplasias and Disorders Panel. About Short Rib Dysplasia / Asphyxiating Thoracic Dysplasia Short-rib dysplasia (SRD) with or without polydactyly refers to a group of autosomal recessive skeletal ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a trident aspect of the acetabular roof. SRD encompasses Ellis-van Creveld syndrome (EVC), Jeune syndrome or asphyxiating thoracic dystrophy (ATD), short rib- polydactyly syndromes (SRPS, Beemer-Langer type, Majewski type, Saldino-Noonan type, Verma-Naumoff type), and Mainzer-Saldino syndrome (MZSDS). Polydactyly is variably present, and there is phenotypic overlap in the various forms of SRDs, which differ by visceral malformation and metaphyseal appearance. Nonskeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Availability 4 weeks Gene Set Description Genes in the Short Rib Dysplasia / Asphyxiating Thoracic Dysplasia Panel and their clinical significance Gene Associated phenotypes Inheritance ClinVar HGMD CSPP1 Jeune asphyxiating thoracic dystrophy, Joubert -
CG/CA Genotypes Represent Novel Markers in the NPHS2 Gene Region Associated with Nephrotic Syndrome
Journal of Genetics (2020)99:33 Ó Indian Academy of Sciences https://doi.org/10.1007/s12041-020-1188-9 (0123456789().,-volV)(0123456789().,-volV) RESEARCH ARTICLE CG/CA genotypes represent novel markers in the NPHS2 gene region associated with nephrotic syndrome LEILA ESMAELI CHAMGORDANI, NASIM EBRAHIMI, FARZANE AMIRMAHANI and SADEQ VALLIAN* Genetics Division, Faculty of Biological Sciences and Technologies, Department of Cellular and Molecular Biology and Microbiology, University of Isfahan, Isfahan, Iran *For correspondence. E-mail: [email protected]. Received 15 November 2019; revised 10 January 2020; accepted 14 January 2020 Abstract. Nephrotic syndrome (NS) is considered as a primary disease of the kidney that represents a heterogeneous group of glomerular disorders occurring mainly in children. It is generally divided into steroid-sensitive and steroid-resistant forms, depending upon the patient’s response to steroid therapy. Among the genes involved, the NPHS2 gene has been reported as the causative gene in steroid resistant form of nephrotic syndrome. In the present study, heterozygosity rate, allelic frequency and linkage of rs2274625 and rs3829795 markers were investigated in the NPHS2 gene region. To determine the SNP alleles, tetra-primer ARMS PCR was used. After genotyping rs2274625 and rs3829795 polymorphic markers in 120 unrelated individuals and nine trios families, the data were analysed using various computer programs such as UCSC Genome Browser, dbSNP and SNPper. Based on the statistical analysis of the results, for rs2274625 marker, allele frequency for C and T alleles was 97% and 3%, respectively. For rs3829795 marker allele frequency for G and A alleles was 55% and 45%, respectively. -
Gene Ontology Functional Annotations and Pleiotropy
Network based analysis of genetic disease associations Sarah Gilman Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy under the Executive Committee of the Graduate School of Arts and Sciences COLUMBIA UNIVERSITY 2014 © 2013 Sarah Gilman All Rights Reserved ABSTRACT Network based analysis of genetic disease associations Sarah Gilman Despite extensive efforts and many promising early findings, genome-wide association studies have explained only a small fraction of the genetic factors contributing to common human diseases. There are many theories about where this “missing heritability” might lie, but increasingly the prevailing view is that common variants, the target of GWAS, are not solely responsible for susceptibility to common diseases and a substantial portion of human disease risk will be found among rare variants. Relatively new, such variants have not been subject to purifying selection, and therefore may be particularly pertinent for neuropsychiatric disorders and other diseases with greatly reduced fecundity. Recently, several researchers have made great progress towards uncovering the genetics behind autism and schizophrenia. By sequencing families, they have found hundreds of de novo variants occurring only in affected individuals, both large structural copy number variants and single nucleotide variants. Despite studying large cohorts there has been little recurrence among the genes implicated suggesting that many hundreds of genes may underlie these complex phenotypes. The question -
Partial Uniparental Isodisomy of Chromosome 16 Unmasks a Deleterious Biallelic Mutation in IFT140 That Causes Mainzer-Saldino Syndrome Benjamin M
Helm et al. Human Genomics (2017) 11:16 DOI 10.1186/s40246-017-0111-9 PRIMARY RESEARCH Open Access Partial uniparental isodisomy of chromosome 16 unmasks a deleterious biallelic mutation in IFT140 that causes Mainzer-Saldino syndrome Benjamin M. Helm1,2, Jason R. Willer3, Azita Sadeghpour3, Christelle Golzio3,4, Eric Crouch5, Samantha Schrier Vergano1,6, Nicholas Katsanis3* and Erica E. Davis3* Abstract Background: The ciliopathies represent an umbrella group of >50 clinical entities that share both clinical features and molecular etiology underscored by structural and functional defects of the primary cilium. Despite the advances in gene discovery, this group of entities continues to pose a diagnostic challenge, in part due to significant genetic and phenotypic heterogeneity and variability. We consulted a pediatric case from asymptomatic, non-consanguineous parents who presented as a suspected ciliopathy due to a constellation of retinal, renal, and skeletal findings. Results: Although clinical panel sequencing of genes implicated in nephrotic syndromes yielded no likely causal mutation, an oligo-SNP microarray identified a ~20-Mb region of homozygosity, with no altered gene dosage, on chromosome 16p13. Intersection of the proband’s phenotypes with known disease genes within the homozygous region yielded a single candidate, IFT140, encoding a retrograde intraflagellar transport protein implicated previously in several ciliopathies, including the phenotypically overlapping Mainzer-Saldino syndrome (MZSDS). Sanger sequencing yielded a maternally inherited homozygous c.634G>A; p.Gly212Arg mutation altering the exon 6 splice donor site. Functional studies in cells from the proband showed that the locus produced two transcripts: a majority message containing a mis-splicing event that caused a premature termination codon and a minority message homozygous for the p.Gly212Arg allele. -
NPHS2 (Podocin) Mutations in Nephrotic Syndrome
0031-3998/05/5705-0054R PEDIATRIC RESEARCH Vol. 57, No. 5, Pt 2, 2005 Copyright © 2005 International Pediatric Research Foundation, Inc. Printed in U.S.A. NPHS2 (Podocin) Mutations in Nephrotic Syndrome. Clinical Spectrum and Fine Mechanisms GIANLUCA CARIDI, FRANCESCO PERFUMO, AND GIAN MARCO GHIGGERI Laboratory on Pathophysiology of Uremia [G.C., G.M.C.], and Renal Unit [F.P., G.M.C.], Istituto Giannina Gaslini, 16148 Genova, Italy. ABSTRACT Nephrotic syndrome (NS) is the most frequent cause of iments with the common R229Q polymorphism demonstrated an proteinuria in children and is emerging as a leading cause of altered interaction with nephrin that affects the stability of the uremia. Molecular studies in families with recessive NS have led functional unit. Overall, data are here presented that underscore to the discovery of specialized molecules endowed in podocytes a major role of inherited defects of NPHS2 in NS in children that play a role in proteinuria. This review focalizes the key (including a relevant impact in sporadic cases) and give the position of podocin (NPHS2 gene) in this rapidly evolving field functional rationale for the association. A practical compendium and furnishes a compendium to those involved in clinics and is also given to clinicians involved in the management of NS that genetics of NS. Screening for NPHS2 mutations have been done should modify the classic therapeutic approach. (Pediatr Res 57: in sporadic NS and familial cases with recessive inheritance, 54R–61R, 2005) documenting a mutation detection rate of 45–55% in families and 8–20% in sporadic NS according to the different groups and considering all the clinical phenotypes.