Discrepant cytogenetic, MLPA and array CGH results on a der(X)(pter->q27.2::p22.31->pter): the advantages of an integrated approach. M N Collinson, S Huang,

Slides:

Advertisements

Similar presentations

Karyotype images This PowerPoint file contains a number of images of karyotypes that may be useful for teaching of genetics concepts. You may use these.

Advertisements

Karyotype images This PowerPoint file contains a number of images of karyotypes that may be useful for teaching of genetics concepts. You may use these.

Maternal Cell Contamination resulting in

Applications of Molecular Cytogenetics

Patterns of Chromosome Inheritance

KEY CONCEPT A combination of methods is used to study human genetics.

NYU SCHOOL OF MEDICINE CYTOGENETICS LECTURE 2

Chromosomal Structure and Chromosomal Mutations

Zoo-352 Principles of genetics Lecture 3 The cell cycle and its checkpoints.

Dr. Nasser A Elhawary Professor of Medical Genetics

Applications of Molecular Cytogenetics Dr Mohammed Alqahtani CSLT(CG), CLSp(CG), RT,MBA, Ph.D Genomic Medicine Unit Founder & Director Center of Excellence.

Human Chromosomes: Genotype/Phenotype Muhammad Faiyaz-Ul-Haque, PhD, FRCPath Human Chromosomes: Genotype/Phenotype Muhammad Faiyaz-Ul-Haque, PhD, FRCPath.

Public Meeting on the Guidance Document for IVDMIAs Arthur L. Beaudet, M.D. James R. Lupski, M.D. February 8,

KARYOTYPE TESTS. KARYOTYPE =  Image of all the chromosomes from the nucleus of a cell  Can be done to identify genetic disorders.

Molecular cytogenetic practical

Human Medical Genetics

Status report on gap closure of the human chromosome 5 BAC map Authentication of C5 BAC maps Map and sequence status Gap status and steps used to close.

KEY CONCEPT A combination of methods is used to study human genetics.

Cytogenetic Disorders  Numeric Abnormalities  Structural Abnormalities.

Genetics: Karyotypes and Sex-linked traits March , 2010.

Genetics: Getting Down to the Basics. Turner syndrome Ginette Talbot, MSc, GCG Genetic Counsellor May 23, 2015.

Karyotype Notes. A karyotype is a “ picture ” of a person ’ s chromosomes. Each person has 46 chromosomes, in 23 pairs. Pairs 1-22 are called Autosomes.

CHROMOSOMAL MECHANISMS OF TUMOUR PROGRESSION IN OSTEOSARCOMA

Javad Jamshidi Fasa University of Medical Sciences, October 2014 Session 3 Medical Genetics Chromosomes And Cell division.

 Autosome: the first 22 homologous pairs of chromosomes  Sex Chromosome: X and Y chromosome (the 23 rd set of chromosomes)  Female: XX  Male: XY.

HAPPY WEDNESDAY In 36 words, compare and contrast mitosis vs meiosis. Use the following words Anaphase Chromosome Cancer Cytokinesis Diploid Gamete.

L.S. Rector 1, N.A. Yamada 2, M.E. Aston 1, M.C. Sederberg 1 R.A. Ach 2, P. Tsang 2, E. Carr 2, A. Scheffer-Wong 2, N. Sampas 2, B. Peter 2, S. Laderman.

Javad Jamshidi Fasa University of Medical Sciences, October 2014 Session 3 Medical Genetics Chromosomes And Cell division.

KEY CONCEPT A combination of methods is used to study human genetics.

Dr. Derakhshandeh, PhD PND & PGD Prenatal Diagnosis Preimplantation Diagnosis.

Prenatal Approach (Chromosomal) Shahram Savad MD, Medical Genetics.

Department of Human Genetics

Cytogenetic and molecular cytogenetic analysis in clinical genetics

Fluorescence in situ hybridization (FISH). Figs

KEY CONCEPT A combination of methods is used to study human genetics.

The array comparative genomic hybridization (aCGH/CMA) technology

Chromosomal Mutations & Karyotypes

Genetics: Karyotypes and X-linked traits

KEY CONCEPT A combination of methods is used to study human genetics.

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

KEY CONCEPT A combination of methods is used to study human genetics.

What do your chromosomes look like?

Michael H. Land, MD, Maria I. Garcia-Lloret, MD, Michael S

How do scientists identify chromosomes?

KEY CONCEPT A combination of methods is used to study human genetics.

Genetics Chapters

X-linked genetics traits

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

K. Gersak, A. Veble Reproductive BioMedicine Online

Representative results of the FISH analyses. 1. 1, patient 1153; 1

Crypt Y chromosome fragment resulting from an X;Y translocation in a patient with premature ovarian failure De-Hua Cheng, M.Sc., Yue-Qiu Tan, Ph.D.,

Fishing for Chromosomes

Kathleen M. Murphy, Julie S. Cohen, Amy Goodrich, Patricia P

Human Genetics and Pedigrees

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

What are they?? How do we use them?

CHROMOSOMES As a eukaryotic cell prepares to divide the DNA

High-Throughput Analysis of Subtelomeric Chromosome Rearrangements by Use of Array-Based Comparative Genomic Hybridization Joris A. Veltman, Eric F.P.M.

Unusual pseudo dicentric, psu dic (1;19)(q10;q13

Fertilization The process of haploid gametes joining together to form a diploid cell with 2n chromosomes. n chromosomes come from the male parent and n.

KEY CONCEPT A combination of methods is used to study human genetics.

KEY CONCEPT A combination of methods is used to study human genetics.

What are they?? How do we use them?

KEY CONCEPT A combination of methods is used to study human genetics.

Genetics Chapters

CHROMOSOMES As a eukaryotic cell prepares to divide the DNA

KEY CONCEPT A combination of methods is used to study human genetics.

Sex-Linked Traits.

Presentation transcript:

Discrepant cytogenetic, MLPA and array CGH results on a der(X)(pter->q27.2::p22.31->pter): the advantages of an integrated approach. M N Collinson, S Huang, JN Macpherson, VK Maloney, AC Skinner, A Karcanias, NA Affara, NS Thomas

30 year old female with premature ovarian failure (POF) molecular genetic testing for a FRAXA premutation cytogenetic analysis only one allele found ?45,X or 46,XY 46,XX

MLPA with the Rett syndrome kit MRC-Holland kit PO15C

LIST OF PROBES USED FOR FISH TO CONFIRM DELETION Centromere RP1-142F18 Normal (Xq27.2) RP1-315J21 Deleted (Xq27.3) RP11-79A21 Deleted (Xq27.3) RP11-37P24 Deleted (fragile X locus) RP11-161L9 Deleted (fragile X locus) RP11-64L19 Deleted (Xq28) RP11-533H4 Deleted (Xq28) RP11-76K17 Deleted (Xq28) RP11-402H20 Deleted (Xq28) Telomere

FISH with a probe for the FRAXA gene RP11-161L9 X centromere (control)

Blind cytogenetic analysis – 3 control slides and 3 slides from POF patient scored by 3 independent analysts Analyst Slide 1 2 3 4 5 6 X 

Partial karyotype of the X chromosomes (abnormal X on the right)

MLPA with the subtelomere probe kit MRC-Holland kit PO36B

FISH with the Xp and Xq subtelomere probes CY29 (Xp subtelomere) c8.1/2 (Xq subtelomere)

Array-CGH Agilent 244K oligoarray

FISH with SHOX probe RP11-946P8 DXZ2 (X centromere control)

MLPA with SHOX kit PO18B Duplication of SHOX POF case

Array CGH with chip specifically designed for NORMAL CASE FEMALE CONTROL MALE CONTROL Array CGH with chip specifically designed for sex chromosome abnormalities

Array CGH with chip specifically designed for POF CASE FEMALE CONTROL MALE CONTROL Array CGH with chip specifically designed for sex chromosome abnormalities

L.M. Russell et al, Cytogenet Genome Res 116:181-185 (2007)

Original cytogenetic analysis – 1/30 metaphases 45,X Blind FISH study with X centromere probe (DXZ2) POF case Control Metaphases 1/30 45,X (3.3%) 1/30 45,X (3.3%) Interphase cells 8/100 45,X (8%) 6/100 45,X (6%)

Summary An integrated approach was required to establish the true nature of the X chromosome abnormality Highlights the fact that one should be cautious of any shifts from the baseline when analysing array CGH as it may mask significant changes in log ratios We still do not have a satisfactory explanation of our results other than mosaicism Deletions of this region of Xq have been reported in association with POF