Seven cases of intellectual disability analysed by genomewide SNP analysis. Rodney J. Scott
|
|
- Myles Warner
- 6 years ago
- Views:
Transcription
1 Seven cases of intellectual disability analysed by genomewide SNP analysis Rodney J. Scott
2 Ability to interrogate Genomic Material ~1930 Crude analyses 2012 Highly precise analyses
3 A (very) brief history of Genetics.. After Mendel
4 Karyotyping ~ 1930s, lost and rediscovered 1950s Transposable elements (100 s s bp in length, spread far apart) Restriction Fragment Sites frequency ~ 1/1,000,000 bp - 1/2000 bp (allowed for the development of FISH) DNA Microsatellite Markers spaced ~ 50,000 bp across the entire genome Single Nucleotide Polymorphisms (SNPs) 1 every bp!!!
5 Karyotyping
6 Fluorescent in situ hybridization (FISH)
7 Chromosome Genomic Hybridization (CGH)
8 Array CGH using overlapping fragments of DNA
9
10 Costs $ SNP arrays have developed very rapidly: Size: 50K 100K 320K 550K 1000K 5000K Year: Time (years) Offer the advantage of very dense coverage with up to 5,000,000 data points across the genome (array CGH only 30,000) Fine assessment of small gains or losses Identification of uniparental disomy
11 CNV terminology Log R Ratio Based on normalised intensity data. A value of 0 means there are 2 alleles present (balanced). Sig <0 means there is a deletion. Sig >0 means there is a duplication. B-allele Frequency Has a value of 0, 0.5, or 1. 0 = AA genotype 0.5 = AB genotype 1 = BB genotype Normal Log R ratio and B-allele frequency BB AB AA
12 CNV terminology Log R Ratio Based on normalised intensity data. A value of 0 means there are 2 alleles present (balanced). Sig <0 means there is a deletion. Sig >0 means there is a duplication. B-allele Frequency Has a value of 0, 0.5, or 1. 0 = AA genotype 0.5 = AB genotype 1 = BB genotype 1 copy gain BBB ABB AAB AAA
13 CNV terminology Log R Ratio Based on normalised intensity data. A value of 0 means there are 2 alleles present (balanced). Sig <0 means there is a deletion. Sig >0 means there is a duplication. B-allele Frequency Has a value of 0, 0.5, or 1. 0 = AA genotype 0.5 = AB genotype 1 = BB genotype 1 copy loss B A
14 Software Packages partek Partek Incorporated KaryoStudio/GenomeStudio Illumina SNP and Variation Suite 7 Golden Helix Nexus BioDiscovery
15 Capability Overview partek KaryoStudio SVS 7 Nexus User Friendly No Yes Yes Yes Visualisation OK Poor OK Tops Tests for Association Quality of output? N/A OK OK OK Poor OK Good Support Very Poor OK Tops OK Analysis types CNV (inc LOH) and SNP CNV CNV (inc LOH) and SNP CNV (inc LOH), and integration of expression and mirna data
16 Genome-wide SNP analysis as a new tool for cytogenetic analysis.
17 Case 1 Male Normal height and weight at birth. Growth retardation at 13 years (133 cmm <1 st percentile, head circumference 53 cm). Severe generalized psychomotor delay Dysmorphic facial features (open mouthed expression, thin upper lip, prominent cupids bow, smooth phitrum, up-tilted nose, low set ears, down slanting palpebral fissures with mild hypertelorism and high arched palate) Ventricular septal defect (poor peripheral circulation, tapering fingers, hyperventilation) Poor sleep and hand wringing.
18 Case 2 Male Severe intellectual disability Dysmorphic features (deep set eyes, right ptosis, hypoplastic alanase, very curly hair) Atrial septal defect (ASD) Ventricular septal defect (VSD), hypoplastic aortic arch and left ventricle, Multiple arteriovenous malformation (AVMs), mild coarctation. Hypoplasia of cerebellar vermis. Postnatal short stature Microcephaly Gastric oesophageal reflux Poor feeding Pulmonary HT.
19 Case 3 Female Previously identified apparently balanced translocation, t(x,6)(q13;q22.2) Complex cardiac defect, (aortic arch abnormality with narrowed right-sided carotid artery and large VSD).
20 Case 4 7 month old female conceived by intracytoplasmic sperm injection Born by caesarean section at 35 weeks due to decreased foetal movement. Severe hydrops fetalis (birth weight of 4000 grams due to oedema) and congenital chylothorax. Chromosome studies and karyotyping identified a complex, but apparently balanced, translocation involving chromosomes 1q25, 1q32, 2q23, 7q22 and 16q24. Both parents have normal chromosomes. At 7 months of age development was appropriate for corrected age (weight 90th centile, length and head circumference 75th centile). Gastro-oesophageal reflux and occasional oedema of legs, feet and sides of face. Facial appearance: flat nasal bridge, small nose with anteverted nares, wide mouth, and prominent epicanthic folds with stellate irides, suggestive of Williams Syndrome but MLPA analysis for William syndrome negative.
21 Cases 5 & 6 Female Dysmorphic features (hypotelorism and asymmetric nose), Single central incisor and short toes. Postnatal short stature Growth hormone deficiency. Male Mild developmental delay, Cataracts Optic atrophy Transposition of the great vessels Sensoneuronal (SN) deafness.
22 Case 7 Male with mild intellectual disability, Dysmorphic features (dysplastic ears, accessory nipple x 2 and camptodactyly of index finger), VSD Undescended testes Sensorineural hearing loss Postnatal short stature, treated with growth hormone & hypogonadotrophic hypogonadism.
23 Case 1 Two deletions were identified using SNP arrays: A 2.2 Mb deletion located on chromosome 1q44 (position: 240,761, ,994,271) A 1.2 Mb deletion on chromosome 13q31.1 (position: 82,281,240-83,456,591). The SNP array result of the 1q44 deletion was confirmed using FISH with BAC probe RP11-424N15 deleted. The deleted region 1q44 contains 4 genes with unknown function (MGC33370, PNAS-4, FAM36A and MGC12458), and ADSS (catalyses first step in conversion of IMP to AMP), HNRPU (RNA binding protein) and SMYD3 (histone methyl transferase). Region 13q31.1 contains no genes.
24
25 Case 2 LOH of entire chromosome 2 was identified in this patient using SNP arrays. Parental haplotype analysis was carried out using eleven microsatellite markers along the full length of chromosome 2. Six microsatellite markers (D2S319, D2S131, D2S390, D2S367, D2S380 and D2S326) were fully informative in this family and revealed a paternal isodysomy of chromosome 2 in the patient.
26
27 Maternal Proband Paternal Maternal Proband Paternal Chromosome 2 Microsatellite marker analysis D2S367 D2S380 Paternal isodisomy detected
28 Case 3 A duplication of approximately 4.5 Mb located on chromosome Xq (position: 83,722,520-88,224,080) was identified using SNP arrays. Region Xq contains four genes with unknown function and ZNF6 (a zinc finger protein of unknown function, located within a region which has been associated with mental retardation), CHM (membrane trafficking) and KLHL4 (unknown function, contains an actin binding domain).
29
30 Case 4 A deletion of approximately 1.7 Mb was identified on chromosome 7q (position: 103,396, ,403,796) using SNP arrays. FISH confirmed the deletion and its location at the breakpoint of the translocation between chromosome 2 and 7. The deletion of BAC clones RP11-612L03 and RP11-96B13 at 7q22. The deleted region at 7q contains eight genes with unknown function.
31
32 Cen Tel der 2 der 7 der 7 der 7 N 7 N 7 N 7
33 Case 5 An increase in copy number score (from 2 to 3,4,5 and 6) at numerous X chromosome loci were observed in this patient.
34
35 Cases 6 & 7 Case 6 and 7 No apparent chromosomal aberrations were detected in these two patients.
36 Conclusions Case 1: Deletion of 1q44 reported previously Case 2: Isodysomy of Ch2, 4 cases identified world wide. Paternal imprinting remains a possibility Cases 3 & 4: Previously identified translocations. Both were accompanied by genomic copy number changes at the break points. Previous technologies unable to reveal such changes. Case 5: 25 copy number changes identified on Ch X. 11/25 are likely to be polymorphisms
37 Conclusions ctd. Detection rate using the SNP array approach appears to be high (~71%) Could be due to ascertainment bias (all other assays were less sensitive). Parental testing required to confirm findins SNP array technology is superior to any other that is currently available Higher resolution arrays will yield more information (1M arrays are available)
38 Conclusions ctd. Microarray technology is cost effective (increased rate of anomaly detection) Cytogenetics merging with the power of Molecular Genetics When will karyotyping be replaced as the frontline cytogenetic request.
CHROMOSOMAL MICROARRAY (CGH+SNP)
Chromosome imbalances are a significant cause of developmental delay, mental retardation, autism spectrum disorders, dysmorphic features and/or birth defects. The imbalance of genetic material may be due
More informationMultiple Copy Number Variations in a Patient with Developmental Delay ASCLS- March 31, 2016
Multiple Copy Number Variations in a Patient with Developmental Delay ASCLS- March 31, 2016 Marwan Tayeh, PhD, FACMG Director, MMGL Molecular Genetics Assistant Professor of Pediatrics Department of Pediatrics
More informationFaravareh Khordadpoor (PhD in molecular genetics) 1- Tehran Medical Genetics Laboratory 2- Science and research branch, Islamic Azad University
Faravareh Khordadpoor (PhD in molecular genetics) 1- Tehran Medical Genetics Laboratory 2- Science and research branch, Islamic Azad University 1395 21 مشاوره ژنتیک و نقش آن در پیش گیری از معلولیت ها 20
More informationApplications of Chromosomal Microarray Analysis (CMA) in pre- and postnatal Diagnostic: advantages, limitations and concerns
Applications of Chromosomal Microarray Analysis (CMA) in pre- and postnatal Diagnostic: advantages, limitations and concerns جواد کریمزاد حق PhD of Medical Genetics آزمايشگاه پاتوبيولوژي و ژنتيك پارسه
More informationCase Report Persistent Mosaicism for 12p Duplication/Triplication Chromosome Structural Abnormality in Peripheral Blood
Case Reports in Genetics Volume 2013, Article ID 857926, 4 pages http://dx.doi.org/10.1155/2013/857926 Case Report Persistent Mosaicism for 12p Duplication/Triplication Chromosome Structural Abnormality
More informationChallenges of CGH array testing in children with developmental delay. Dr Sally Davies 17 th September 2014
Challenges of CGH array testing in children with developmental delay Dr Sally Davies 17 th September 2014 CGH array What is CGH array? Understanding the test Benefits Results to expect Consent issues Ethical
More information22q11.2 DELETION SYNDROME. Anna Mª Cueto González Clinical Geneticist Programa de Medicina Molecular y Genética Hospital Vall d Hebrón (Barcelona)
22q11.2 DELETION SYNDROME Anna Mª Cueto González Clinical Geneticist Programa de Medicina Molecular y Genética Hospital Vall d Hebrón (Barcelona) Genomic disorders GENOMICS DISORDERS refers to those diseases
More informationApproach to Mental Retardation and Developmental Delay. SR Ghaffari MSc MD PhD
Approach to Mental Retardation and Developmental Delay SR Ghaffari MSc MD PhD Introduction Objectives Definition of MR and DD Classification Epidemiology (prevalence, recurrence risk, ) Etiology Importance
More informationDysmorphology. Sue White. Diagnostic Dysmorphology, Aase. Victorian Clinical Genetics Services
Dysmorphology Sue White www.rch.unimelb.edu.au/nets/handbook Diagnostic Dysmorphology, Aase Dysmorphology Assessment Algorithm no Are the features familial? yes Recognised syndrome yes no AD/XL syndrome
More informationCase 1B. 46,XY,-14,+t(14;21)
Case 1B 46,XY,-14,+t(14;21) G-banded Chromosome telomere centromere G-dark bands AT-rich few genes G-pale bands GC-rich many genes telomere ideograms ideograms Conventional (light microscopy) p = short
More informationGenetic Testing 101: Interpreting the Chromosomes
Genetic Testing 101: Interpreting the Chromosomes Kristin Lindstrom, MD Division of Genetics and Metabolism Phoenix Children s Hospital AzAAP Pediatrics in the Red Rocks I have no disclosures for this
More informationInvestigation of chromosomal abnormalities and microdeletions in 50 patients with multiple congenital anomalies
Investigation of chromosomal abnormalities and microdeletions in 50 patients with multiple congenital anomalies Akbar Mohammadzadeh MD, PhD candidate in Medical Genetics Genetics Research Center University
More informationSharan Goobie, MD, MSc, FRCPC
Sharan Goobie, MD, MSc, FRCPC Chromosome testing in 2014 Presenter Disclosure: Sharan Goobie has no potential for conflict of interest with this presentation Objectives Review of standard genetic investigations
More informationCURRENT GENETIC TESTING TOOLS IN NEONATAL MEDICINE. Dr. Bahar Naghavi
2 CURRENT GENETIC TESTING TOOLS IN NEONATAL MEDICINE Dr. Bahar Naghavi Assistant professor of Basic Science Department, Shahid Beheshti University of Medical Sciences, Tehran,Iran 3 Introduction Over 4000
More information(i) Family 1. The male proband (1.III-1) from European descent was referred at
1 Supplementary Note Clinical descriptions of families (i) Family 1. The male proband (1.III-1) from European descent was referred at age 14 because of scoliosis. He had normal development. Physical evaluation
More informationChromosome Microarray Analysis (CMA)
Chromosome Microarray Analysis (CMA) Ina E. Amarillo, PhD FACMG Cytogenomics Lab (Associate Medical Director) Pathology (Assistant Professor) OUTLINE Clinical Indications for Cytogenomics Testing Cytogenomics
More informationClinical Genomics. Ina E. Amarillo, PhD FACMGG
Clinical Genomics Ina E. Amarillo, PhD FACMGG Associate Medical Director, Cytogenetics Lab (CaTG), Lab and Genomic Medicine Assistant Professor, Pathology and Immunology Outline Clinical Genomics Testing
More informationPrenatal Diagnosis: Are There Microarrays in Your Future?
Financial Disclosure UCSF Antepartum Intrapartum Management Course June 8 I have no financial relationship with any aspect of private industry Prenatal Diagnosis: Are There Microarrays in Your Future?
More informationCGH microarray studies in idiopathic developmental/ cognitive impairment: association of historical and clinical features and the De Vries Score
Clinical science Acta Medica Academica 2011;40(1):17-26 DOI 10.5644/ama2006-124.4 CGH microarray studies in idiopathic developmental/ cognitive impairment: association of historical and clinical features
More informationStructural Variation and Medical Genomics
Structural Variation and Medical Genomics Andrew King Department of Biomedical Informatics July 8, 2014 You already know about small scale genetic mutations Single nucleotide polymorphism (SNPs) Deletions,
More informationWhen to suspect Prader Willi Syndrome and how to diagnose it?
When to suspect Prader Willi Syndrome and how to diagnose it? Dr Chirita-Emandi Adela Dr Dobrescu Andreea Victor Babes University of Medicine and Pahrmacy Timisoara Emergency Hospital for Children Louis
More informationSupplementary note: Comparison of deletion variants identified in this study and four earlier studies
Supplementary note: Comparison of deletion variants identified in this study and four earlier studies Here we compare the results of this study to potentially overlapping results from four earlier studies
More informationGenomic structural variation
Genomic structural variation Mario Cáceres The new genomic variation DNA sequence differs across individuals much more than researchers had suspected through structural changes A huge amount of structural
More informationUNIT IX: GENETIC DISORDERS
UNIT IX: GENETIC DISORDERS Younas Masih Lecturer New Life College Of Nursing Karachi 3/4/2016 1 Objectives By the end of this session the Learners will be able to, 1. Know the basic terms related genetics
More informationSNP Array NOTE: THIS IS A SAMPLE REPORT AND MAY NOT REFLECT ACTUAL PATIENT DATA. FORMAT AND/OR CONTENT MAY BE UPDATED PERIODICALLY.
SAMPLE REPORT SNP Array NOTE: THIS IS A SAMPLE REPORT AND MAY NOT REFLECT ACTUAL PATIENT DATA. FORMAT AND/OR CONTENT MAY BE UPDATED PERIODICALLY. RESULTS SNP Array Copy Number Variations Result: LOSS,
More informationSNP Array NOTE: THIS IS A SAMPLE REPORT AND MAY NOT REFLECT ACTUAL PATIENT DATA. FORMAT AND/OR CONTENT MAY BE UPDATED PERIODICALLY.
SAMPLE REPORT SNP Array NOTE: THIS IS A SAMPLE REPORT AND MAY NOT REFLECT ACTUAL PATIENT DATA. FORMAT AND/OR CONTENT MAY BE UPDATED PERIODICALLY. RESULTS SNP Array Copy Number Variations Result: GAIN,
More informationSupplemental Information
ARTICLE Supplemental Information SUPPLEMENTAL TABLE 6 Mosaic and Partial Trisomies Thirty-eight VLBW infants were identified with T13, of whom 2 had mosaic T13. T18 was reported for 128 infants, of whom
More informationCase Report Child with Deletion 9p Syndrome Presenting with Craniofacial Dysmorphism, Developmental Delay, and Multiple Congenital Malformations
Case Reports in Genetics Volume 2013, Article ID 785830, 4 pages http://dx.doi.org/10.1155/2013/785830 Case Report Child with Deletion 9p Syndrome Presenting with Craniofacial Dysmorphism, Developmental
More informationStatistical Analysis of Single Nucleotide Polymorphism Microarrays in Cancer Studies
Statistical Analysis of Single Nucleotide Polymorphism Microarrays in Cancer Studies Stanford Biostatistics Workshop Pierre Neuvial with Henrik Bengtsson and Terry Speed Department of Statistics, UC Berkeley
More informationGenerating Spontaneous Copy Number Variants (CNVs) Jennifer Freeman Assistant Professor of Toxicology School of Health Sciences Purdue University
Role of Chemical lexposure in Generating Spontaneous Copy Number Variants (CNVs) Jennifer Freeman Assistant Professor of Toxicology School of Health Sciences Purdue University CNV Discovery Reference Genetic
More informationEvolution of Genetic Testing. Joan Pellegrino MD Associate Professor of Pediatrics SUNY Upstate Medical University
Evolution of Genetic Testing Joan Pellegrino MD Associate Professor of Pediatrics SUNY Upstate Medical University Genetic Testing Chromosomal analysis Flourescent in situ hybridization (FISH) Chromosome
More informationLab #10: Karyotyping Lab
Lab #10: Karyotyping Lab INTRODUCTION A karyotype is a visual display of the number and appearance of all chromosomes from a single somatic cell. A normal human karyotype would reveal 46 chromosomes (22
More informationIntroduction to Fetal Medicine: Genetics and Embryology
Introduction to Fetal Medicine: Genetics and Embryology Question: What do cancer biology, molecular biology, neurobiology, cell biology developmental biology and reproductive biology, all have in common?
More informationGenetic Testing for Single-Gene and Multifactorial Conditions
Clinical Appropriateness Guidelines Genetic Testing for Single-Gene and Multifactorial Conditions EFFECTIVE DECEMBER 1, 2017 Appropriate.Safe.Affordable 2017 AIM Specialty Health 2069-1217 Table of Contents
More informationTagawa, Masato; Harada, Naoki; Mori. is available at
NAOSITE: Nagasaki University's Ac Title Author(s) Citation Mirror duplication of chromosome 21 syndrome. Egashira, Masanori; Kondoh, Tatsuro Tagawa, Masato; Harada, Naoki; Mori Pediatrics international,
More informationCase Report Severe Psychomotor Delay in a Severe Presentation of Cat-Eye Syndrome
Case Reports in Genetics Volume 2015, Article ID 943905, 4 pages http://dx.doi.org/10.1155/2015/943905 Case Report Severe Psychomotor Delay in a Severe Presentation of Cat-Eye Syndrome Guillaume Jedraszak,
More informationCytogenetics 101: Clinical Research and Molecular Genetic Technologies
Cytogenetics 101: Clinical Research and Molecular Genetic Technologies Topics for Today s Presentation 1 Classical vs Molecular Cytogenetics 2 What acgh? 3 What is FISH? 4 What is NGS? 5 How can these
More informationCase Report Genotype-Phenotype Characterization of Wolf-Hirschhorn Syndrome Confirmed by FISH: Case Reports
Case Reports in Genetics Volume 2012, Article ID 878796, 5 pages doi:10.1155/2012/878796 Case Report Genotype-Phenotype Characterization of Wolf-Hirschhorn Syndrome Confirmed by FISH: Case Reports F. Sheth,
More informationCHROMOSOMAL NUMERICAL ABERRATIONS INSTITUTE OF BIOLOGY AND MEDICAL GENETICS OF THE 1 ST FACULTY OF MEDICINE
CHROMOSOMAL NUMERICAL ABERRATIONS INSTITUTE OF BIOLOGY AND MEDICAL GENETICS OF THE 1 ST FACULTY OF MEDICINE CHROMOSOMAL ABERRATIONS NUMERICAL STRUCTURAL ANEUPLOIDY POLYPLOIDY MONOSOMY TRISOMY TRIPLOIDY
More informationSyndromic X Linked Mental Retardation
Syndromic X Linked Mental Retardation Introduction : Dr. Yousef.A. Assaleh Dept. of Pediatric - faculty of medicine Zawia University Mental retardation is defined as incomplete or insufficient general
More informationAssociation for Molecular Pathology Promoting Clinical Practice, Basic Research, and Education in Molecular Pathology
Association for Molecular Pathology Promoting Clinical Practice, Basic Research, and Education in Molecular Pathology 9650 Rockville Pike, Bethesda, Maryland 20814 Tel: 301-634-7939 Fax: 301-634-7990 Email:
More informationCNV Detection and Interpretation in Genomic Data
CNV Detection and Interpretation in Genomic Data Benjamin W. Darbro, M.D., Ph.D. Assistant Professor of Pediatrics Director of the Shivanand R. Patil Cytogenetics and Molecular Laboratory Overview What
More informationIntroduction to Fetal Medicine: Genetics and Embryology
Introduction to Fetal Medicine: Genetics and Embryology Question: What do cancer biology, molecular biology, neurobiology, cell biology developmental biology and reproductive biology, all have in common?
More informationPROVIDER POLICIES & PROCEDURES
PROVIDER POLICIES & PROCEDURES COMPARATIVE GENOMIC HYBRIDIZATION (CGH) MICROARRAY TESTING FOR DEVELOPMENTAL DELAY, AUTISM SPECTRUM DISORDER AND INTELLECTUAL DISABILITY The purpose of this policy is to
More informationPractical challenges that copy number variation and whole genome sequencing create for genetic diagnostic labs
Practical challenges that copy number variation and whole genome sequencing create for genetic diagnostic labs Joris Vermeesch, Center for Human Genetics K.U.Leuven, Belgium ESHG June 11, 2010 When and
More informationSection C: Assessing Sentinel Facial Features
Section C: Assessing Sentinel Facial Features Fetal exposure to alcohol during the first trimester affects development of facial features. The areas most affected are the orbital region (eyes) and mid-face.
More informationWhat s the Human Genome Project Got to Do with Developmental Disabilities?
What s the Human Genome Project Got to Do with Developmental Disabilities? Disclosures Neither speaker has anything to disclose. Phase Two: Interpretation Officially started in October 1990 Goals of the
More informationAuthor's response to reviews
Author's response to reviews Title: Dystonia, facial dysmorphism, intellectual disability and breast cancer associated with a chromosome 13q34 duplication and overexpression of TFDP1: Case report Authors:
More informationApplication of Whole Genome Microarrays in Cancer: You should be doing this test!!
Application of Whole Genome Microarrays in Cancer: You should be doing this test!! Daynna Wolff, Ph.D. Director, Cytogenetics and Genomics Disclosures Clinical Laboratory Director and Employee, Medical
More informationand duodenal atresia. Two other families reported may have had the same syndrome. Case reports CASE 1 (III.8, FAMILY 1)
JMedGenet 1991; 28: 389-394 Autosomal dominant inheritance of abnormalities of the hands and feet with short palpebral fissures, variable microcephaly with learning disability, and oesophageal/duodenal
More informationUltrasound Anomaly Details
Appendix 2. Association of Copy Number Variants With Specific Ultrasonographically Detected Fetal Anomalies Ultrasound Anomaly Details Abdominal wall Bladder exstrophy Body-stalk anomaly Cloacal exstrophy
More informationGenetics and Developmental Disabilities. Stuart K. Shapira, MD, PhD. Pediatric Genetics Team
Genetics and Developmental Disabilities Stuart K. Shapira, MD, PhD Pediatric Genetics Team National Center on Birth Defects and Developmental Disabilities Centers for Disease Control and Prevention The
More informationPRADER-WILLI SYNDROME HOWARD WONG 3UU PER. 6 GENETICS SBS11QHG2 #24
PRADER-WILLI SYNDROME HOWARD WONG 3UU PER. 6 GENETICS SBS11QHG2 #24 PHYSIOLOGY Fig. 1 Fig. 2 Prader-Willi Syndrome affects both the physical and mental state of a person, starting from birth until the
More informationGenome-wide copy-number calling (CNAs not CNVs!) Dr Geoff Macintyre
Genome-wide copy-number calling (CNAs not CNVs!) Dr Geoff Macintyre Structural variation (SVs) Copy-number variations C Deletion A B C Balanced rearrangements A B A B C B A C Duplication Inversion Causes
More informationRandom Pearls in Dysmorphology and Genetics
Random Pearls in Dysmorphology and Genetics Marilyn C. Jones Professor of Clinical Pediatrics, UCSD Wellesley College, BA Columbia University P&S, MD Pediatric Residency and Fellowship in Dysmorphology,
More informationSupplementary Clinical Information
Supplementary Clinical Information Patient 1 This female was born as the second child of a twin after a pregnancy duration of 32 weeks. The birth was otherwise uncomplicated and her twin brother was healthy.
More informationWhat dysmorphologists should keep in mind during evaluation of patients with blepharophimosis and mental disability?
What dysmorphologists should keep in mind during evaluation of patients with blepharophimosis and mental disability? Aleksandra Jezela-Stanek, M.D., Ph. D. The Children s Memorial Health Institute, Warsaw
More informationChromosome 13. Introduction
Chromosome 13 Chromosome Disorder Outreach Inc. (CDO) Technical genetic content provided by Dr. Iosif Lurie, M.D. Ph.D Medical Geneticist and CDO Medical Consultant/Advisor. Ideogram courtesy of the University
More informationDNA-seq Bioinformatics Analysis: Copy Number Variation
DNA-seq Bioinformatics Analysis: Copy Number Variation Elodie Girard elodie.girard@curie.fr U900 institut Curie, INSERM, Mines ParisTech, PSL Research University Paris, France NGS Applications 5C HiC DNA-seq
More informationAn International System for Human Cytogenetic Nomenclature (2013)
ISCN 2013 An International System for Human Cytogenetic Nomenclature (2013) Editors Lisa G. Shaffer Jean McGowan-Jordan Michael Schmid Recommendations of the International Standing Committee on Human Cytogenetic
More informationNational Medical Policy
National Medical Policy Subject: Policy Number: Single Nucleotide Polymorphism (SNP) Chromosomal Microarray Analysis for Prenatal Testing and Intellectual Disability, Developmental Delay, and Multiple
More informationExploding Genetic Knowledge in Developmental Disabilities. Disclosures. The Genetic Principle
Exploding Genetic Knowledge in Developmental Disabilities How to acquire the data and how to make use of it Elliott H. Sherr MD PhD Professor of Neurology & Pediatrics UCSF Disclosures InVitae: clinical
More informationIntroduction to LOH and Allele Specific Copy Number User Forum
Introduction to LOH and Allele Specific Copy Number User Forum Jonathan Gerstenhaber Introduction to LOH and ASCN User Forum Contents 1. Loss of heterozygosity Analysis procedure Types of baselines 2.
More informationClinical Interpretation of Cancer Genomes
IGENZ Ltd, Auckland, New Zealand Clinical Interpretation of Cancer Genomes Dr Amanda Dixon-McIver www.igenz.co.nz 1992 Slovenia and Croatia gain independence USA and Russia declare the Cold War over Steffi
More informationMMB (MGPG) Non traditional Inheritance Epigenetics. A.Turco
MMB (MGPG) 2017 Non traditional Inheritance Epigenetics A.Turco NON TRADITIONAL INHERITANCE EXCEPTIONS TO MENDELISM - Genetic linkage (2 loci close to each other) - Complex or Multifactorial Disease (MFD)
More informationHeart and Lungs. LUNG Coronal section demonstrates relationship of pulmonary parenchyma to heart and chest wall.
Heart and Lungs Normal Sonographic Anatomy THORAX Axial and coronal sections demonstrate integrity of thorax, fetal breathing movements, and overall size and shape. LUNG Coronal section demonstrates relationship
More informationDe novo Ring Chromosome 6 in a Child with Multiple Congenital Anomalies
Kobe J. Med. Sci., Vol. 56, No. 2, pp. E79-E84, 2010 De novo Ring Chromosome 6 in a Child with Multiple Congenital Anomalies HADI AHMAD AHZAD 1, SITI FATIMAH RAMLI 1, TAN MAY LOONG 2, IMAN SALAHSHOURIFAR
More informationNovember 9, Johns Hopkins School of Medicine, Baltimore, MD,
Fast detection of de-novo copy number variants from case-parent SNP arrays identifies a deletion on chromosome 7p14.1 associated with non-syndromic isolated cleft lip/palate Samuel G. Younkin 1, Robert
More informationUnderstanding The Genetics of Diamond Blackfan Anemia
Understanding The Genetics of Diamond Blackfan Anemia Jason Farrar, MD jefarrar@ About Me Assistant Professor of Pediatrics at University of Arkansas for Medical Sciences & Arkansas Children s Hospital
More informationSection F: Discussing the diagnosis and developing a management plan
Section E: Formulating a diagnosis Information collected during the diagnostic assessment should be reviewed, ideally in a multi-disciplinary team context, to evaluate the strength of evidence to: Support
More informationEpigenetics and Chromatin Remodeling
Epigenetics and Chromatin Remodeling Bradford Coffee, PhD, FACMG Emory University Atlanta, GA Speaker Disclosure Information Grant/Research Support: none Salary/Consultant Fees: none Board/Committee/Advisory
More informationBirth mother Foster carer Other
PATIENT DETAILS NAME Sex Female Male Other Date of birth (DD/MM/YYYY) / / Age at assessment: Racial/ ethnic background Preferred language Hospital number (if applicable) Referral source, date, provider
More informationTo Be Your Local Expert A General Pediatrician s Story
To Be Your Local Expert A General Pediatrician s Story DDC Clinic mission: To enhance the quality of life for people with special needs caused by rare genetic disorders What Does It Take to Be Your Local
More informationApplication of Array-based Comparative Genome Hybridization in Children with Developmental Delay or Mental Retardation
Pediatr Neonatol 2008;49(6):213 217 REVIEW ARTICLE Application of Array-based Comparative Genome Hybridization in Children with Developmental Delay or Mental Retardation Jao-Shwann Liang 1,2 *, Keiko Shimojima
More informationHirschsprung's disease
Journal of Medical Genetics 1989, 26, 100-104 Interstitial deletion of distal 13q associated with Hirschsprung's disease M A LAMONT*, M FITCHETTt, AND N R DENNIS* From *the Department of Child Health,
More informationApproach to the Genetic Diagnosis of Neurological Disorders
Approach to the Genetic Diagnosis of Neurological Disorders Dr Wendy Jones MBBS MRCP Great Ormond Street Hospital for Children National Hospital for Neurology and Neurosurgery What is a genetic diagnosis?
More informationKlinefelter syndrome ( 47, XXY )
Sex Chromosome Abnormalities, Sex Chromosome Aneuploidy It has been estimated that, overall, approximately one in 400 infants have some form of sex chromosome aneuploidy. A thorough discussion of sex chromosomes
More informationGENOME-WIDE ANALYSIS BY SNP ARRAY
GENOME-WIDE ANALYSIS BY SNP ARRAY SNP ARRAY IN THE DIAGNOSIS OF INTELLECTUAL DISABILITY AND C O N G E N I T A L ABNORMALITIES Contents Introduction... 3 Conventional and molecular cytogenetics (FISH)...
More informationThe Chromosomal Basis of Inheritance
The Chromosomal Basis of Inheritance Factors and Genes Mendel s model of inheritance was based on the idea of factors that were independently assorted and segregated into gametes We now know that these
More informationMLL2 mosaic mutations and intragenic deletion duplications in patients with Kabuki syndrome
Clin Genet 2013: 83: 467 471 Printed in Singapore. All rights reserved Short Report 2012 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd CLINICAL GENETICS doi: 10.1111/j.1399-0004.2012.01955.x
More informationCYTOGENETICS Dr. Mary Ann Perle
CYTOGENETICS Dr. Mary Ann Perle I) Mitosis and metaphase chromosomes A) Chromosomes are most fully condensed and clearly distinguishable during mitosis. B) Mitosis (M phase) takes 1 to 2 hrs and is divided
More informationGenetic Disorders. n A genetic disorder is an abnormality
+ GENETIC DISORDERS + Genetic Disorders n A genetic disorder is an abnormality in an individual's DNA. Abnormalities can range from a small mutation in a single gene to the addition or subtraction of an
More informationNeonatal Hypotonia Guideline Prepared by Dan Birnbaum MD August 27, 2012
Neonatal Hypotonia Guideline Prepared by Dan Birnbaum MD August 27, 2012 Hypotonia: reduced tension or resistance to range of motion Localization can be central (brain), peripheral (spinal cord, nerve,
More informationOculodentodigital dysplasia and type III syndactyly: separate genetic entities or disease spectrum?
JMed Genet 1990; 27: 169-175 Oculodentodigital dysplasia and type III syndactyly: separate genetic entities or disease spectrum? L A Brueton, S M Huson, B Farren, R M Winter Abstract A family is described
More informationFeeding Disorders and Growth in Williams Syndrome
Feeding Disorders and Growth in Williams Syndrome Sharon M. Greis M.A., CCC/SLP BRS-S and Paige Kaplan M.B.B.Ch. Williams Syndrome Clinic The Children s Hospital of Philadelphia Pediatric Feeding & Swallowing
More informationImplementation of the DDD/ClinGen OGT (CytoSure v3) Microarray
Implementation of the DDD/ClinGen OGT (CytoSure v3) Microarray OGT UGM Birmingham 08/09/2016 Dom McMullan Birmingham Women's NHS Trust WM chromosomal microarray (CMA) testing Population of ~6 million (10%)
More informationProposal form for the evaluation of a genetic test for NHS Service Gene Dossier/Additional Provider
Proposal form for the evaluation of a genetic test for NHS Service Gene Dossier/Additional Provider TEST DISEASE/CONDITION POPULATION TRIAD Submitting laboratory: Manchester RGC Approved: September 2013
More informationThe Fetal Cardiology Program
The Fetal Cardiology Program at Texas Children s Fetal Center About the program Since the 1980s, Texas Children s Fetal Cardiology Program has provided comprehensive fetal cardiac care to expecting families
More informationSUPPLEMENTARY INFORMATION
doi: 1.138/nature8645 Physical coverage (x haploid genomes) 11 6.4 4.9 6.9 6.7 4.4 5.9 9.1 7.6 125 Neither end mapped One end mapped Chimaeras Correct Reads (million ns) 1 75 5 25 HCC1187 HCC1395 HCC1599
More informationCopy Number Variants of Uncertain Significance in Prenatal diagnosis Are the Goalposts Moving? Lisa Burvill-Holmes Bristol Genetics Laboratory
Copy Number Variants of Uncertain Significance in Prenatal diagnosis Are the Goalposts Moving? Lisa Burvill-Holmes Bristol Genetics Laboratory http://www.nbt.nhs.uk/genetics Microarray CGH in Prenatal
More informationCommon Genetic syndromes. Dr. E.M. Honey Department Genetics Division Human Genetics University of Pretoria
Common Genetic syndromes Dr. E.M. Honey Department Genetics Division Human Genetics University of Pretoria Definitions Deformation Malformation Disruption Dysplasia Syndrome Associations Complex Sequences
More informationChapter 15 Notes 15.1: Mendelian inheritance chromosome theory of inheritance wild type 15.2: Sex-linked genes
Chapter 15 Notes The Chromosomal Basis of Inheritance Mendel s hereditary factors were genes, though this wasn t known at the time Now we know that genes are located on The location of a particular gene
More informationNew and Developing Technologies for Genetic Diagnostics National Genetics Reference Laboratory (Wessex) Salisbury, UK - July 2010 BACs on Beads
New and Developing Technologies for Genetic Diagnostics National Genetics Reference Laboratory (Wessex) Salisbury, UK - July 2010 BACs on Beads Susan Gross, MD Division of Reproductive Genetics Professor
More informationsyndromes associated with brain malformation - dysmorphology Renske Oegema, MD, PhD clinical geneticist UMC Utrecht, NL Milano, 2018
syndromes associated with brain malformation - dysmorphology Renske Oegema, MD, PhD clinical geneticist UMC Utrecht, NL Milano, 2018 Miller Dieker syndrome, del 17p13.3 incl LIS1 en YWHAE Postnatal mild
More informationBasic Training. ISUOG Basic Training Examining the Upper Lip, Face & Profile
ISUOG Examining the Upper Lip, Face & Profile Learning objectives At the end of the lecture you will be able to: Describe how to obtain the 3 planes required to assess the anatomy of the fetal face Recognise
More informationAssessment of clinical scoring systems for the diagnosis of Williams-Beuren syndrome
Short Communication Assessment of clinical scoring systems for the diagnosis of Williams-Beuren syndrome D.E.S. Leme 1, D.H. Souza 1, G. Mercado 2, E. Pastene 2, A. Dias 3 and D. Moretti-Ferreira 1 1 Serviço
More informationUniversity of Groningen. Congenital heart defects and pulmonary arterial hypertension Frederikse, Wilhelmina
University of Groningen Congenital heart defects and pulmonary arterial hypertension Frederikse, Wilhelmina IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish
More informationSupplementary Note. Phenotype details in ten patients with deletions of 15q13
Supplementary Note. Phenotype details in ten patients with deletions of 15q13 IMR338, IMR338M, and IMR338Cc familial 3.95 Mb deletion BP3-BP5 The proband, IMR338, was initially reported by Sharp et al.
More informationTerminal Deletion of Chromosome 6q
Pediatr Neonatol 2008;49(3):88 93 CASE REPORT Terminal Deletion of Chromosome 6q Pen-Hua Su 1,2, Jia-Yuh Chen 1,2 *, Suh-Jen Chen 1,2, Kai-Chi Yang 2 1 Department of Pediatrics, Division of Neonatology,
More informationGenetics and Genomics: Applications to Developmental Disability
Tuesday, 12:30 2:00, B1 Objective: Genetics and Genomics: Applications to Developmental Disability Helga Toriello 616-234-2712 toriello@msu.edu Identify advances in clinical assessment and management of
More information