Maple Syrup Urine Disease: Identification and Carrier-Frequency Determination of a Novel Founder Mutation in the Ashkenazi Jewish Population Lisa Edelmann,

Slides:

Advertisements

Similar presentations

Gene Preference in Maple Syrup Urine Disease Mary M. Nellis, Dean J. Danner The American Journal of Human Genetics Volume 68, Issue 1, Pages (January.

Advertisements

Maple Syrup Urine Disease: Identification and Carrier-Frequency Determination of a Novel Founder Mutation in the Ashkenazi Jewish Population Lisa Edelmann,

Lisa Edelmann, Raj K. Pandita, Bernice E. Morrow

Molecular Diagnostics in Preimplantation Genetic Diagnosis

Alternative Splicing of a Novel Glycophorin Allele GPHe(GL) Generates Two Protein Isoforms in the Human Erythrocyte Membrane by Cheng-Han Huang, Olga O.

Mutation Spectrum of the Survival of Motor Neuron 1 and Functional Analysis of Variants in Chinese Spinal Muscular Atrophy Yu-jin Qu, Jin-li Bai, Yan-yan.

Betaine, Dimethyl Sulfoxide, and 7-Deaza-dGTP, a Powerful Mixture for Amplification of GC-Rich DNA Sequences Marco Musso, Renata Bocciardi, Sara Parodi,

Yanggu Shi, Sharon F. Terry, Patrick F. Terry, Lionel G

A Missense Mutation (R565W) in Cirhin (FLJ14728) in North American Indian Childhood Cirrhosis Pierre Chagnon, Jacques Michaud, Grant Mitchell, Jocelyne.

A Clinical Grade Sequencing-Based Assay for CEBPA Mutation Testing

Mutations in the Liver Glycogen Phosphorylase Gene (PYGL) Underlying Glycogenosis Type VI (Hers Disease) Barbara Burwinkel, Henk D. Bakker, Eliezer Herschkovitz,

Genetic testing for high-risk colon cancer patients1

Evidence Consistent with Human L1 Retrotransposition in Maternal Meiosis I Brook Brouha, Christof Meischl, Eric Ostertag, Martin de Boer, Yue Zhang, Herman.

DNA Diagnostics by Surface-Bound Melt-Curve Reactions

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

Toward a Survey of Somatic Mutation of the NF1 Gene in Benign Neurofibromas of Patients with Neurofibromatosis Type 1 Ingrid Eisenbarth, Kim Beyer, Winfrid.

Sequence Analysis and Homology Modeling Suggest That Primary Congenital Glaucoma on 2p21 Results from Mutations Disrupting Either the Hinge Region or.

Gail Billingsley, Sathiyavedu T. Santhiya, Andrew D

Volume 54, Issue 3, Pages (September 1998)

Investigation of the human stem cell factor KIT ligand gene, KITLG, in women with 46,XX spontaneous premature ovarian failure Emily S. Hui, B.A., Ekemini.

Catherine E. Keegan, Anthony A. Killeen

A Novel Syndrome Combining Thyroid and Neurological Abnormalities Is Associated with Mutations in a Monocarboxylate Transporter Gene Alexandra M. Dumitrescu,

Mutations in a Novel Gene with Transmembrane Domains Underlie Usher Syndrome Type 3 Tarja Joensuu, Riikka Hämäläinen, Bo Yuan, Cheryl Johnson, Saara.

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

Volume 58, Issue 4, Pages (October 2000)

Size Polymorphisms in the Human Ultrahigh Sulfur Hair Keratin-Associated Protein 4, KAP4, Gene Family Naoyuki Kariya, Yutaka Shimomura, Masaaki Ito

Peter Ianakiev, Michael W

Structure of the GM2A Gene: Identification of an Exon 2 Nonsense Mutation and a Naturally Occurring Transcript with an In-Frame Deletion of Exon 2 Biao.

Molecular Diagnostics in Preimplantation Genetic Diagnosis

Pseudoexon Activation as a Novel Mechanism for Disease Resulting in Atypical Growth- Hormone Insensitivity Louise A. Metherell, Scott A. Akker, Patricia.

A Multi-Exonic BRCA1 Deletion Identified in Multiple Families through Single Nucleotide Polymorphism Haplotype Pair Analysis and Gene Amplification with.

A Nonsense Mutation in CRYBB1 Associated with Autosomal Dominant Cataract Linked to Human Chromosome 22q Donna S. Mackay, Olivera B. Boskovska, Harry.

Kimberly C. Sippel, Rebecca E. Fraioli, Gary D. Smith, Mary E

A Presenilin-1 Truncating Mutation Is Present in Two Cases with Autopsy-Confirmed Early-Onset Alzheimer Disease Carolyn Tysoe, Joanne Whittaker, John.

Genetic Background of Congenital Chloride Diarrhea in High-Incidence Populations: Finland, Poland, and Saudi Arabia and Kuwait Pia Höglund, Mari Auranen,

Mutations of MYO6 Are Associated with Recessive Deafness, DFNB37

Volume 119, Issue 4, Pages (October 2000)

Long-Range Polymerase Chain Reaction for Specific Full-Length Amplification of the Human Keratin 14 Gene and Novel Keratin 14 Mutations in Epidermolysis.

The γ-Crystallins and Human Cataracts: A Puzzle Made Clearer

The Origins of Hypertrophic Cardiomyopathy–Causing Mutations in Two South African Subpopulations: A Unique Profile of Both Independent and Founder Events

Andrew H. Huber, W.James Nelson, William I. Weis Cell

Volume 86, Issue 1, Pages (July 1996)

Gail Billingsley, Sathiyavedu T. Santhiya, Andrew D

A Novel Point Mutation Affecting the Tyrosine Kinase Domain of the TRKA Gene in a Family with Congenital Insensitivity to Pain with Anhidrosis Shinichi.

Lisa Edelmann, Jianli Dong, Robert J. Desnick, Ruth Kornreich

Sadaf Naz, Chantal M. Giguere, David C. Kohrman, Kristina L

Amplification Refractory Mutation System, a Highly Sensitive and Simple Polymerase Chain Reaction Assay, for the Detection of JAK2 V617F Mutation in Chronic.

A Mutation in the Variable Repeat Region of the Aggrecan Gene (AGC1) Causes a Form of Spondyloepiphyseal Dysplasia Associated with Severe, Premature.

Feras M. Hantash, Arlene Rebuyon, Mei Peng, Joy B

Characterization of a Germline Mosaicism in Families with Lowe Syndrome, and Identification of Seven Novel Mutations in the OCRL1 Gene Véronique Satre,

Maspardin Is Mutated in Mast Syndrome, a Complicated Form of Hereditary Spastic Paraplegia Associated with Dementia Michael A. Simpson, Harold Cross,

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

Maternal Transmission of the 3 bp Deletion within Exon 7 of the STS Gene in Steroid Sulfatase Deficiency Margarita Valdes-Flores Journal of Investigative.

Identification of FOXP2 Truncation as a Novel Cause of Developmental Speech and Language Deficits Kay D. MacDermot, Elena Bonora, Nuala Sykes, Anne-Marie.

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,

Infantile Alexander Disease: Spectrum of GFAP Mutations and Genotype-Phenotype Correlation Diana Rodriguez, Fernande Gauthier, Enrico Bertini, Marianna.

The Gene Mutated in Variant Late-Infantile Neuronal Ceroid Lipofuscinosis (CLN6) and in nclf Mutant Mice Encodes a Novel Predicted Transmembrane Protein

Identification of a Lethal Form of Epidermolysis Bullosa Simplex Associated with a Homozygous Genetic Mutation in Plectin Maryse Bonduelle, Linda De.

Volume 57, Issue 6, Pages (June 2000)

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

Arun Kumar, Satish C. Girimaji, Mahesh R. Duvvari, Susan H. Blanton

Two Exon-Skipping Mutations as the Molecular Basis of Succinic Semialdehyde Dehydrogenase Deficiency (4-Hydroxybutyric Aciduria) Ken L. Chambliss, Debra.

Is Screening of the Candidate Gene Necessary in Unrelated Partners of Members of Families with Herlitz Junctional Epidermolysis Bullosa? Alfred Klausegger,

Mutation of the Ca2+ Channel β Subunit Gene Cchb4 Is Associated with Ataxia and Seizures in the Lethargic (lh) Mouse Daniel L Burgess, Julie M Jones,

Kit-Sing Au, Adelaide A. Hebert, E. Steve Roach, Hope Northrup

Exon Skipping in IVD RNA Processing in Isovaleric Acidemia Caused by Point Mutations in the Coding Region of the IVD Gene Jerry Vockley, Peter K. Rogan,

Identification of a New Splice Form of the EDA1 Gene Permits Detection of Nearly All X- Linked Hypohidrotic Ectodermal Dysplasia Mutations Alex W. Monreal,

Warfarin Pharmacogenetics: CYP2C9 and VKORC1 Genotypes Predict Different Sensitivity and Resistance Frequencies in the Ashkenazi and Sephardi Jewish.

Identification of Novel pro-α2(IX) Collagen Gene Mutations in Two Families with Distinctive Oligo-Epiphyseal Forms of Multiple Epiphyseal Dysplasia Paul.

K. Miura, M. Obama, K. Yun, H. Masuzaki, Y. Ikeda, S. Yoshimura, T

Presentation transcript:

Maple Syrup Urine Disease: Identification and Carrier-Frequency Determination of a Novel Founder Mutation in the Ashkenazi Jewish Population Lisa Edelmann, Melissa P. Wasserstein, Ruth Kornreich, Claude Sansaricq, Selma E. Snyderman, George A. Diaz The American Journal of Human Genetics Volume 69, Issue 4, Pages 863-868 (October 2001) DOI: 10.1086/323677 Copyright © 2001 The American Society of Human Genetics Terms and Conditions

Figure 1 Genomic organization of polymorphic markers tightly linked to the genes encoding E1α, E1β, and E2 and genotype data for markers flanking E1β. A, Organization of STR markers used in analysis of the BCKDHB locus, and their relative spacing, in both physical and genetic distance. BCKDHB spans ∼240 kb, and the 3′ end lies ∼1 Mb upstream of D6S251. B, Results of genotyping analysis of patients with intermediate (boxed) or classic (underlined) MSUD. The parents of individual 5 are denoted by circles. Individual 9 is a patient with a known mutation (i.e., E2ΔAT). The American Journal of Human Genetics 2001 69, 863-868DOI: (10.1086/323677) Copyright © 2001 The American Society of Human Genetics Terms and Conditions

Figure 2 Results of mutation analysis of AJ patients with MSUD. A, C, and D, Changes (arrows) from expected wild-type sequence, which is shown below the traces. The affected codon is boxed, and the predicted amino acid change is indicated below the codon. The different sequence traces correspond to exon 5 in individual 4 (A), to exon 10 in individual 2 (C), and to exon 7 in individual 1 (D). B, Representative digestion of exon 5 amplimers with NlaIV (New England Biolabs). The sizes of 100-bp-ladder marker fragments (lane M) are indicated to the left of the gel. The samples shown were amplified from the genomic DNA of individuals 1 (lane 1), 5 (lane 2), 6 (lane 3), 7 (lane 4), and 9 (lane 5). Undigested amplimers are 237 bp in length, whereas digested products are predicted to be 99 bp and 128 bp in length. The American Journal of Human Genetics 2001 69, 863-868DOI: (10.1086/323677) Copyright © 2001 The American Society of Human Genetics Terms and Conditions

Figure 3 Ribbon representations of portions of E1β crystal structure, showing positions of mutated residues. The E1 crystal-structure data were obtained from the NCBI Structure (Molecular Modeling Database). Swissprot-Pdb Viewer was used to generate models and image files. A, Ribbon diagram of β-sheets d, e, and g, with the side chains of E146, R183, and E239, respectively, which are shown in white. The mutated residue, R183, is indicated by the arrow, side-chain hydrogen-bond interactions are indicated by dashed lines, and the coordinated K+ ion is labeled directly. For clarity of presentation, main-chain hydrogen interactions have been omitted. B, Overview of entire molecule, except for structures overlying the sheet containing R183. The residues altered by missense mutations, R183 and G228, are indicated by bent and dashed arrows, respectively, and their side chains are shown in white. The α-carbon backbone of residues truncated by the nonsense mutation E372X are shown in white. The American Journal of Human Genetics 2001 69, 863-868DOI: (10.1086/323677) Copyright © 2001 The American Society of Human Genetics Terms and Conditions