Haplotype-Sharing Analysis Implicates Chromosome 7q36 Harboring DPP6 in Familial Idiopathic Ventricular Fibrillation Marielle Alders, Tamara T. Koopmann,

Slides:

Advertisements

Similar presentations

Date of download: 9/19/2016 Copyright © The American College of Cardiology. All rights reserved. From: Novel Insight Into the Natural History of Short.

Advertisements

A Haplotype at STAT2 Introgressed from Neanderthals and Serves as a Candidate of Positive Selection in Papua New Guinea Fernando L. Mendez, Joseph C.

Copyright © 2001 American Medical Association. All rights reserved.

A Cardiac Sodium Channel Mutation Cosegregates With a Rare Connexin40 Genotype in Familial Atrial Standstill by W. Antoinette Groenewegen, Mehran Firouzi,

Ece D. Gamsiz, Emma W. Viscidi, Abbie M

Volume 9, Issue 1, Pages (January 2012)

Volume 64, Issue 3, Pages (September 2003)

Strong Evidence That KIAA0319 on Chromosome 6p Is a Susceptibility Gene for Developmental Dyslexia Natalie Cope, Denise Harold, Gary Hill, Valentina.

Michael H. Duyzend, Xander Nuttle, Bradley P

Soraya Beiraghi, Swapan K. Nath, Matthew Gaines, Desh D

Genomewide Linkage Scan Identifies a Novel Susceptibility Locus for Restless Legs Syndrome on Chromosome 9p Shenghan Chen, William G. Ondo, Shaoqi Rao,

Homozygous Deletion of the Very Low Density Lipoprotein Receptor Gene Causes Autosomal Recessive Cerebellar Hypoplasia with Cerebral Gyral Simplification

A Novel Alu-Like Element Rearranged in the Dystrophin Gene Causes a Splicing Mutation in a Family with X-Linked Dilated Cardiomyopathy Alessandra Ferlini,

I. Silveira, I. Alonso, L. Guimarães, P. Mendonça, C. Santos, P

Andrea Gaedigk, Amanda K. Riffel, J. Steven Leeder

A Defect in the TUSC3 Gene Is Associated with Autosomal Recessive Mental Retardation Masoud Garshasbi, Valeh Hadavi, Haleh Habibi, Kimia Kahrizi, Roxana.

Tamara Rogers, David Chandler, Dora Angelicheva, P. K

Mapping of Primary Congenital Lymphedema to the 5q35.3 Region

A Gene Mutated in Nephronophthisis and Retinitis Pigmentosa Encodes a Novel Protein, Nephroretinin, Conserved in Evolution Edgar Otto, Julia Hoefele,

Autosomal-Recessive Early-Onset Retinitis Pigmentosa Caused by a Mutation in PDE6G, the Gene Encoding the Gamma Subunit of Rod cGMP Phosphodiesterase

Evidence for a Nonallelic Heterogeneity of Epidermodysplasia Verruciformis with Two Susceptibility Loci Mapped to Chromosome Regions 2p21–p24 and 17q25

Volume 65, Issue 6, Pages (June 2004)

Towfique Raj, Manik Kuchroo, Joseph M

Sequence and Haplotype Analysis Supports HLA-C as the Psoriasis Susceptibility 1 Gene Rajan P. Nair, Philip E. Stuart, Ioana Nistor, Ravi Hiremagalore,

Duplication of the MECP2 Region Is a Frequent Cause of Severe Mental Retardation and Progressive Neurological Symptoms in Males Hilde Van Esch, Marijke.

Survival of Male Patients with Incontinentia Pigmenti Carrying a Lethal Mutation Can Be Explained by Somatic Mosaicism or Klinefelter Syndrome The.

Identification of a Genetic Locus for Ichthyosis Vulgaris on Chromosome 10q22.3– q24.2 Ping Liu, Qingyu Yang, Xu Wang, Aiping Feng, Tao Yang, Rong Yang,

Howard B. Yeon, Noralane M. Lindor, J.G. Seidman, Christine E. Seidman

The Gene for Human Fibronectin Glomerulopathy Maps to 1q32, in the Region of the Regulation of Complement Activation Gene Cluster Martin Vollmer, Martin.

International Journal of Cardiology

Airong Li, Sonia Davila, Laszlo Furu, Qi Qian, Xin Tian, Patrick S

Mutation of Solute Carrier SLC16A12 Associates with a Syndrome Combining Juvenile Cataract with Microcornea and Renal Glucosuria Barbara Kloeckener-Gruissem,

Germline Epigenetic Silencing of the Tumor Suppressor Gene PTPRJ in Early-Onset Familial Colorectal Cancer Ramprasath Venkatachalam Gastroenterology

Hal M. Hoffman, Fred A. Wright, David H. Broide, Alan A

A Locus for Brachydactyly Type A-1 Maps to Chromosome 2q35-q36

Mapping of Charcot-Marie-Tooth Disease Type 1C to Chromosome 16p Identifies a Novel Locus for Demyelinating Neuropathies Valerie A. Street, Jeff D. Goldy,

Identification of a Kir3.4 Mutation in Congenital Long QT Syndrome

A Recurrent Expansion of a Maternal Allele with 36 CAG Repeats Causes Huntington Disease in Two Sisters Franco Laccone, Wilhelm Christian The American.

Koji Suzuki, Tania Bustos, Richard A. Spritz

Shuhua Xu, Wei Huang, Ji Qian, Li Jin

Linkage Analysis Identifies a Novel Locus for Restless Legs Syndrome on Chromosome 2q in a South Tyrolean Population Isolate Irene Pichler, Fabio Marroni,

Linkage Analysis of X-linked Cone-Rod Dystrophy: Localization to Xp11

Next-Generation Sequencing Identifies Mutations of SMPX, which Encodes the Small Muscle Protein, X-Linked, as a Cause of Progressive Hearing Impairment

Early repolarization syndrome caused by de novo duplication of KCND3 detected by next-generation sequencing Samuel Chauveau, MD, Alexandre Janin, PharmD,

Retinitis Pigmentosa and Progressive Sensorineural Hearing Loss Caused by a C12258A Mutation in the Mitochondrial MTTS2 Gene Fiona C. Mansergh, Sophia.

Meiotic Microdeletion Breakpoints in the BRCA1 Gene Are Significantly Associated with Symmetric DNA-Sequence Elements Beatrice Schmucker, Michael Krawczak

IRX3 variant as a modifier of Brugada syndrome with frequent ventricular fibrillation Yoshitaka Kimura, MD, Takeshi Aiba, MD, PhD, Tetsuo Sasano, MD,

A Defect in the TUSC3 Gene Is Associated with Autosomal Recessive Mental Retardation Masoud Garshasbi, Valeh Hadavi, Haleh Habibi, Kimia Kahrizi, Roxana.

Autosomal-Dominant Striatal Degeneration Is Caused by a Mutation in the Phosphodiesterase 8B Gene Silke Appenzeller, Anja Schirmacher, Hartmut Halfter,

Dosage-Dependent Severity of the Phenotype in Patients with Mental Retardation Due to a Recurrent Copy-Number Gain at Xq28 Mediated by an Unusual Recombination

A Unique Point Mutation in the PMP22 Gene Is Associated with Charcot-Marie-Tooth Disease and Deafness Margaret J. Kovach, Jing-Ping Lin, Simeon Boyadjiev,

Hereditary Isolated Renal Magnesium Loss Maps to Chromosome 11q23

Familial Nontoxic Multinodular Thyroid Goiter Locus Maps to Chromosome 14q but Does Not Account for Familial Nonmedullary Thyroid Cancer Graham R. Bignell,

Oligodontia Is Caused by Mutation in LTBP3, the Gene Encoding Latent TGF-β Binding Protein 3 Abdul Noor, Christian Windpassinger, Irina Vitcu, Marija.

S. Fernandes, S. Paracchini, L. H. Meyer, G. Floridia, C

Anthony M. Raizis, Martin M. Ferguson, David T. Nicholls, Derek W

Volume 71, Issue 6, Pages (March 2007)

Early Onset of Severe Familial Amyotrophic Lateral Sclerosis with a SOD-1 Mutation: Potential Impact of CNTF as a Candidate Modifier Gene Ralf Giess,

Relative expression levels of three PTPN22 transcripts.

Mutations in CHEK2 Associated with Prostate Cancer Risk

A Gene for an Autosomal Dominant Scleroatrophic Syndrome Predisposing to Skin Cancer (Huriez Syndrome) Maps to Chromosome 4q23 Young-Ae Lee, Howard P.

A Definitive Haplotype Map as Determined by Genotyping Duplicated Haploid Genomes Finds a Predominant Haplotype Preference at Copy-Number Variation Events

Identification of a New Gene Locus for Adolescent Nephronophthisis, on Chromosome 3q22 in a Large Venezuelan Pedigree Heymut Omran, Carmen Fernandez,

Simone Sanna-Cherchi, Gianluca Caridi, Patricia L

A New Familial Amyotrophic Lateral Sclerosis Locus on Chromosome 16q12

Epigenetic Allele Silencing Unveils Recessive RYR1 Mutations in Core Myopathies Haiyan Zhou, Martin Brockington, Heinz Jungbluth, David Monk, Philip Stanier,

A Haplotype at STAT2 Introgressed from Neanderthals and Serves as a Candidate of Positive Selection in Papua New Guinea Fernando L. Mendez, Joseph C.

A Locus for Autosomal Dominant Hereditary Spastic Ataxia, SAX1,Maps to Chromosome 12p13 I.A. Meijer, C.K. Hand, K.K. Grewal, M.G. Stefanelli, E.J. Ives,

Duplication of the MECP2 Region Is a Frequent Cause of Severe Mental Retardation and Progressive Neurological Symptoms in Males Hilde Van Esch, Marijke.

Mapping of a New SGBS Locus to Chromosome Xp22 in a Family with a Severe Form of Simpson-Golabi-Behmel Syndrome L.M. Brzustowicz, S. Farrell, M.B. Khan,

Presentation transcript:

Haplotype-Sharing Analysis Implicates Chromosome 7q36 Harboring DPP6 in Familial Idiopathic Ventricular Fibrillation Marielle Alders, Tamara T. Koopmann, Imke Christiaans, Pieter G. Postema, Leander Beekman, Michael W.T. Tanck, Katja Zeppenfeld, Peter Loh, Karel T. Koch, Sophie Demolombe, Marcel M.A.M. Mannens, Connie R. Bezzina, Arthur A.M. Wilde The American Journal of Human Genetics Volume 84, Issue 4, Pages 468-476 (April 2009) DOI: 10.1016/j.ajhg.2009.02.009 Copyright © 2009 The American Society of Human Genetics Terms and Conditions

Figure 1 Pedigrees of the Three IVF Families Used for the Haplotype-Sharing Analysis Affected subjects (SCD or resuscitated after IVF) are shown as filled circles (females) or squares (males). A slash indicates that the subject is deceased, and a dot indicates obligate carrier. The numbers after SCD or IVF indicate the age of the subject at the time of the event. Individuals included in the analysis are indicated with an arrow. Numbers inside symbols indicate the number of individuals present of that sex and status; for example, individual B-1 has four unaffected sisters. The American Journal of Human Genetics 2009 84, 468-476DOI: (10.1016/j.ajhg.2009.02.009) Copyright © 2009 The American Society of Human Genetics Terms and Conditions

Figure 2 Mapping of the IVF Locus (A) Result of the haplotype-sharing analysis. The length of the shared segment in number of SNPs is plotted, and the largest shared haplotype, of 301 contiguous SNPs on chromosome 7q36, is indicated by an arrow. (B) Shared 7q36 chromosomal region, discovered after initial haplotype-sharing analysis and after extended haplotyping in additional families. The position of the markers and genes (in Mb) is shown, according to the human genome build 36.3. Isoforms 1, 2, and 3 of DPP6 are also known as isoforms L, S, and K, respectively. Only validated genes are indicated. The American Journal of Human Genetics 2009 84, 468-476DOI: (10.1016/j.ajhg.2009.02.009) Copyright © 2009 The American Society of Human Genetics Terms and Conditions

Figure 3 Haplotypes in the Ten IVF Families Haplotype analysis in the ten families (A to J) with the risk haplotype. Probands are labeled −1. Affected subjects (SCD or resuscitated after IVF) are shown as filled circles (females) or squares (males). A slash indicates that the subject is deceased, and a dot indicates an obligate carrier. Individuals included in the haplotype-sharing analysis are indicated (B-1, A-1, A-2, C-1), as well as individuals from whom a cardiac biopsy was used for expression studies (A-2, B-1, H-2, I-1, and J-1). The risk haplotype is colored black. Families E, G, H, and I carry recombinants, which are indicated with an arrow. The smallest shared segment, based on these recombinations, is indicated with a black bar next to the haplotype. From individuals labeled with an asterisk, DNA was extracted from paraffin-embedded tissues, and the haplotypes of individuals labeled with a “+” were inferred from their children. The American Journal of Human Genetics 2009 84, 468-476DOI: (10.1016/j.ajhg.2009.02.009) Copyright © 2009 The American Society of Human Genetics Terms and Conditions

Figure 4 Expression Analysis of the DPP6 Gene (A) Reverse Transcriptase PCR on biopsies of three patients heterozygous for SNP rs3807218. The contribution of the A allele, which is on the risk haplotype, is increased relative to that of the G allele. (B) DPP6 mRNA expression in cardiac biopsies from affected individuals, relative to HPRT expression. The quantification of all DPP6 isoforms with primers in exon 6 and 8 was performed on five patient samples, and isoform-specific analysis was performed on two patient samples. Bars represent standard errors. The American Journal of Human Genetics 2009 84, 468-476DOI: (10.1016/j.ajhg.2009.02.009) Copyright © 2009 The American Society of Human Genetics Terms and Conditions

Figure 5 A 12-Lead ECG Recording of a Resuscitated Male No specific conduction or repolarization abnormalities are observed. Regular sinus rhythm is disturbed by spontaneous monomorphic extrasystoles (indicated with an asterisk) with a short coupling interval, a left bundle branch block morphology, and a superior axis. The fourth extrasystole initiates ventricular fibrillation, for which defibrillation was required (not shown). The American Journal of Human Genetics 2009 84, 468-476DOI: (10.1016/j.ajhg.2009.02.009) Copyright © 2009 The American Society of Human Genetics Terms and Conditions

Figure 6 Survival The survival curve of risk-haplotype carriers (black) and noncarriers (gray), demonstrating a median survival of 58 years for individuals carrying the high-risk haplotype. The American Journal of Human Genetics 2009 84, 468-476DOI: (10.1016/j.ajhg.2009.02.009) Copyright © 2009 The American Society of Human Genetics Terms and Conditions