A Member of a Gene Family on Xp22

Slides:

Advertisements

Similar presentations

Schematic drawing of the human X chromosome and physical map the Xp interval carrying the ND gene. A 640-kb yeast artificial chromosome (YAC) clone was.

Advertisements

Human Meiotic Recombination Products Revealed by Sequencing a Hotspot for Homologous Strand Exchange in Multiple HNPP Deletion Patients Lawrence T. Reiter,

Imprinting-Mutation Mechanisms in Prader-Willi Syndrome

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

Volume 6, Issue 4, Pages (October 2000)

Microarray-Based Comparative Genomic Hybridization Using Sex-Matched Reference DNA Provides Greater Sensitivity for Detection of Sex Chromosome Imbalances.

Volume 74, Issue 11, Pages (December 2008)

Der(22) Syndrome and Velo-Cardio-Facial Syndrome/DiGeorge Syndrome Share a 1.5- Mb Region of Overlap on Chromosome 22q11 B. Funke, L. Edelmann, N. McCain,

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

Michael Cullen, Stephen P

Reciprocal Crossovers and a Positional Preference for Strand Exchange in Recombination Events Resulting in Deletion or Duplication of Chromosome 17p11.2

Undifferentiated Small Round Cell Sarcomas with Rare EWS Gene Fusions

High-Resolution Mapping of Genotype-Phenotype Relationships in Cri du Chat Syndrome Using Array Comparative Genomic Hybridization Xiaoxiao Zhang, Antoine.

Clustered 11q23 and 22q11 Breakpoints and 3:1 Meiotic Malsegregation in Multiple Unrelated t(11;22) Families Tamim H. Shaikh, Marcia L. Budarf, Livija.

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

Recombination between Palindromes P5 and P1 on the Human Y Chromosome Causes Massive Deletions and Spermatogenic Failure Sjoerd Repping, Helen Skaletsky,

High Frequency of Mosaicism among Patients with Neurofibromatosis Type 1 (NF1) with Microdeletions Caused by Somatic Recombination of the JJAZ1 Gene

The SPCH1 Region on Human 7q31: Genomic Characterization of the Critical Interval and Localization of Translocations Associated with Speech and Language.

Genomic Rearrangements Resulting in PLP1 Deletion Occur by Nonhomologous End Joining and Cause Different Dysmyelinating Phenotypes in Males and Females

Michael Field, Patrick S

X-Linked Late-Onset Sensorineural Deafness Caused by a Deletion Involving OA1 and a Novel Gene Containing WD-40 Repeats Maria T. Bassi, Rajkumar S. Ramesar,

Molecular Characterization and Gene Content of Breakpoint Boundaries in Patients with Neurofibromatosis Type 1 with 17q11.2 Microdeletions Dieter E.

T. Ohta, K. Buiting, H. Kokkonen, S. McCandless, S. Heeger, H

Molecular Cytogenetic Evidence for a Common Breakpoint in the Largest Inverted Duplications of Chromosome 15 A.E. Wandstrat, J. Leana-Cox, L. Jenkins,

A Multicolor FISH Assay Does Not Detect DUP25 in Control Individuals or in Reported Positive Control Cells Yanina Weiland, Jürgen Kraus, Michael R. Speicher

Human Epidermal Differentiation Complex in a Single 2

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,

Characterization of Human KAP24

Barbara R. Migeon, Catherine H. Lee, Ashis K

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

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.

A Human Homologue of the Drosophila melanogaster diaphanous Gene Is Disrupted in a Patient with Premature Ovarian Failure: Evidence for Conserved Function.

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.

Mutations in the ZNF41 Gene Are Associated with Cognitive Deficits: Identification of a New Candidate for X-Linked Mental Retardation Sarah A. Shoichet,

Imprinting at the SMPD1 Locus: Implications for Acid Sphingomyelinase–Deficient Niemann-Pick Disease Calogera M. Simonaro, Jae-Ho Park, Efrat Eliyahu,

Renata C. Gallagher, Birgit Pils, Mohammed Albalwi, Uta Francke

John D. Rioux, Valerie A. Stone, Mark J

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

Copy-Number Variations Measured by Single-Nucleotide–Polymorphism Oligonucleotide Arrays in Patients with Mental Retardation Janine Wagenstaller, Stephanie.

Disruption of Contactin 4 (CNTN4) Results in Developmental Delay and Other Features of 3p Deletion Syndrome Thomas Fernandez, Thomas Morgan, Nicole Davis,

High-Resolution Molecular Characterization of 15q11-q13 Rearrangements by Array Comparative Genomic Hybridization (Array CGH) with Detection of Gene Dosage

Small Evolutionarily Conserved RNA, Resembling C/D Box Small Nucleolar RNA, Is Transcribed from PWCR1, a Novel Imprinted Gene in the Prader-Willi Deletion.

Molecular and Fluorescence In Situ Hybridization Characterization of the Breakpoints in 46 Large Supernumerary Marker 15 Chromosomes Reveals an Unexpected.

Michael A. Rogers, Hermelita Winter, Christian Wolf, Jürgen Schweizer

A Novel 22q11.2 Microdeletion in DiGeorge Syndrome

Koji Suzuki, Tania Bustos, Richard A. Spritz

Localization of Multiple Melanoma Tumor–Suppressor Genes on Chromosome 11 by Use of Homozygosity Mapping-of-Deletions Analysis Eleonora K. Goldberg,

Reciprocal Crossovers and a Positional Preference for Strand Exchange in Recombination Events Resulting in Deletion or Duplication of Chromosome 17p11.2

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

Sex-Linked period Genes in the Silkmoth, Antheraea pernyi

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

Characterization of New Members of the Human Type II Keratin Gene Family and a General Evaluation of the Keratin Gene Domain on Chromosome 12q13.13 Michael.

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

Opitz G/BBB Syndrome in Xp22: Mutations in the MID1 Gene Cluster in the Carboxy- Terminal Domain Karin Gaudenz, Erich Roessler, Nandita Quaderi, Brunella.

Characterization and Mutation Analysis of Human LEFTY A and LEFTY B, Homologues of Murine Genes Implicated in Left-Right Axis Development K. Kosaki,

3q29 Microdeletion Syndrome: Clinical and Molecular Characterization of a New Syndrome Lionel Willatt, James Cox, John Barber, Elisabet Dachs Cabanas,

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,

Volume 57, Issue 3, Pages (March 2000)

Der(22) Syndrome and Velo-Cardio-Facial Syndrome/DiGeorge Syndrome Share a 1.5- Mb Region of Overlap on Chromosome 22q11 B. Funke, L. Edelmann, N. McCain,

Identification of TSIX, Encoding an RNA Antisense to Human XIST, Reveals Differences from its Murine Counterpart: Implications for X Inactivation Barbara.

Volume 21, Issue 23, Pages (December 2011)

A 22q11.2 Deletion That Excludes UFD1L and CDC45L in a Patient with Conotruncal and Craniofacial Defects Sulagna C. Saitta, James M. McGrath, Holly Mensch,

Christa Lese Martin, Andrew Wong, Alyssa Gross, June Chung, Judy A

Darryl Y. Nishimura, Ruth E. Swiderski, Charles C. Searby, Erik M

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

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

The Breakpoint Region of the Most Common Isochromosome, i(17q), in Human Neoplasia Is Characterized by a Complex Genomic Architecture with Large, Palindromic,

Sequence Homology between 4qter and 10qter Loci Facilitates the Instability of Subtelomeric KpnI Repeat Units Implicated in Facioscapulohumeral Muscular.

Presentation transcript:

A Member of a Gene Family on Xp22 A Member of a Gene Family on Xp22.3, VCX-A, Is Deleted in Patients with X-Linked Nonspecific Mental Retardation Maki Fukami, Stefan Kirsch, Simone Schiller, Alexandra Richter, Vladimir Benes, Brunella Franco, Koji Muroya, Ercole Rao, Sabine Merker, Beate Niesler, Andrea Ballabio, Wilhelm Ansorge, Tsutomu Ogata, Gudrun A. Rappold The American Journal of Human Genetics Volume 67, Issue 3, Pages 563-573 (September 2000) DOI: 10.1086/303047 Copyright © 2000 The American Society of Human Genetics Terms and Conditions

Figure 1 Deletion map and mental status of 15 patients. In the “MR” column, a plus sign (+) denotes mental retardation, and a minus sign (−) denotes normal intelligence. Sequence-tagged-site loci are shown in black, gene loci are shown in red. The RPS6KA3 gene is thought to reside proximal to DXS85 and is not depicted on this map. The blackened portions of the horizontal bars represent positive loci confirmed by molecular studies, and the unblackened portions represent absent loci. The physical locus order is based on published reports (Schaefer et al. 1993; van Slegtenhorst et al. 1994; Ferrero et al. 1995; Herrell et al. 1995), with one exception—the locus order of DXS6834 and DXS1139 is based on the physical map established in the present study. The underlined loci indicate the boundaries of the critical region of the gene for MRX. The American Journal of Human Genetics 2000 67, 563-573DOI: (10.1086/303047) Copyright © 2000 The American Society of Human Genetics Terms and Conditions

Figure 2 Physical map and detailed deletion map of patients 11 and 13. A, Physical maps outlining the relationship between chromosomal markers, the clone contig, and DNA deletions in patients 11 and 13. Solid lines represent YAC clones (Ferrero et al. 1995), double lines cosmid clones, and the dotted line a PAC clone. The names of PACs and cosmid clones are as follows: 118G17, RPCI1-118G17; 21L7, LLNc110-21L7; 21J18, LLNc110-21J18; H09154, ICRFc104-H09154; 45O15, LLNc110-45O15; A05122, ICRFc104-A05122; and E10129, ICRFc104-E10129. Black dots represent positive markers in the respective clones. Cosmids 45O15 and A05122 overlap. “11” and “13” denote cases 11 and 13, respectively. The blackened portions of the horizontal bars represent loci that are present, unblackened portions represent absent loci, and gray-shaded portions represent the breakpoint region. Underlined loci indicate the borders of the MRX critical region. B, Diagram presenting the MRX critical interval (as defined by individuals 11 and 13) flanked by markers 40BT and DXS1139 (shown in boldface), which reside on two overlapping cosmids. Deletion intervals in cases 11 and 13 are indicated. Black dots represent sequence-tagged sites established on the basis of the genomic sequence data, and gray rectangles represent trapped putative exons. Genomic sequencing was carried out between markers 40BT and K6 (28 kb in total). The position of the trapped putative exons was established on the basis of the genomic sequence. The American Journal of Human Genetics 2000 67, 563-573DOI: (10.1086/303047) Copyright © 2000 The American Society of Human Genetics Terms and Conditions

Figure 3 A, Refined deletion map indicating the region between markers DXS6837 and KAL. The position of VCX-A, -B1, -B, and -C is shown in red. For the VCX-C locus, marker DXS1134 was tested. Cases are as depicted in figure 1. Blackened portions of the horizontal bars represent loci present in the respective cases, and unblackened portions represent absent loci. B, Sequence organization of the CRI-S232 element, modified from that reported by Li et al. (1992). All instances of CRI-S232 share a very similar structure. The size of CRI-S232 is variable between individuals, covers ∼7 kb of DNA, and is not drawn to scale. CRI-S232 is divided into four regions by EcoRI, XmnI, Bgl II, and SstI. Regions b and c contain different repeat units. The VCX cDNA is 1,019 bp long, divided into two exons, and not drawn to scale. Repeat unit RU1 is contained within the translated portion of exon II. VCX is located in regions b–d. The arrowheads below the VCX exons indicate primers used to amplify the exons. The long arrows below the arrowheads represent the DNA interval that was sequenced in the present study, except for the unstable RU2 repeat unit of <2 kb. The GenBank accession number for the genomic sequence is AJ243947 (GenBank Overview). The American Journal of Human Genetics 2000 67, 563-573DOI: (10.1086/303047) Copyright © 2000 The American Society of Human Genetics Terms and Conditions

Figure 4 A, DNA sequence comparison of different members of the VCX and VCY family. Gray-shaded portions of the horizontal bars represent exons, and the colored portions within exon II represent the 30-bp repeat units. In VCX-A, the number of repeat units is 8–12, on the basis of data on 50 control males investigated in the present study. In three individuals, 10, 12, and 14 repeat units were detected in VCX-C. The percentages indicate the degree of similarity between VCX-A and other VCX-family members. B, Amino acid comparison of members of the VCX family. Red, pink, green, and light blue represent the specific 10-amino-acid (30-bp) repeats schematically outlined in figure 5A. Differing amino acids are shown in dark blue. The American Journal of Human Genetics 2000 67, 563-573DOI: (10.1086/303047) Copyright © 2000 The American Society of Human Genetics Terms and Conditions

Figure 5 Expression study by northern analysis. The 1.0-kb signal in testis was revealed after overnight exposure. The hybridization probe does not distinguish among the various members of the VCX/-Y family. The American Journal of Human Genetics 2000 67, 563-573DOI: (10.1086/303047) Copyright © 2000 The American Society of Human Genetics Terms and Conditions