Numerical Chromosomal Aberrations PDF

31 Numerical Chromosomal Aberrations by Dr.Ezat Mersal At the end of this lecture, you will be able to:- Define cytogenetics. Differentiate between karyotype & ideogram Interpret normal human karyotype Enlist steps of karyotyping...

31 Numerical Chromosomal Aberrations by Dr.Ezat Mersal At the end of this lecture, you will be able to:- Define cytogenetics. Differentiate between karyotype & ideogram Interpret normal human karyotype Enlist steps of karyotyping Understand the clinical importance of karyotyping Classify human chromosomes Outline chromosomal abnormalities (aberrations) Enlist different forms of numerical chromosomal aberrations Understand the underlying mechanisms of numerical aberrations Mention some clinical syndromes related to numerical aberrations Interpret some abnormal forms of human karyotypes  Isthe study of the structure and properties of chromosomes, chromosomal behaviour during mitosis and meiosis, chromosomal influence on the phenotype and the factors that cause chromosomal changes (Hare and Singh, 1979). © 2015 John Wiley & Sons, Inc. All rights reserved.  Cytogenetic methods to detect chromosomal abnormalities underlying human birth defects usually involve analysis of mitotic chromosomes. © 2015 John Wiley & Sons, Inc. All rights reserved.   We have to analyze Chromosomes and Genes to detect the genetic abnormalities.  Genetic abnormalities Emin can range from relatively six harmless to severe: from vitamin deficiencies and food allergies to cancer, birth defects and infant mortality.  Genetic errors may arise from deletions or insertions of genetic material, abnormal numbers of whole chromosomes or genes, and even from misplacement of a single base in the DNA sequence. © 2015 John Wiley & Sons, Inc. All rights reserved. V  Study of human chromosomes is done through the Cmj) & visualization and analysis of chromosomes which occurs by two methods: 1. Conventional methods (Banding techniques, karyotyping) G banding: Geimsa staining technique Q banding: Quinacrine fluorescent staining technique R banding: reverse technique C banding: centromere staining technique (selective staining for centromere) > - ii. 2. Advanced methods (Molecular techniques) Fluorescence in situ hybridization (FISH) © 2015 John Wiley & Sons, Inc. All rights reserved.  94945 Es  Karyotype: particular &characteristics that identifies and describes a certain set of chromosome.  Theses characteristics which are described by karyotype are: 1. The chromosome number 2. Relative size of different chromosomes 3. Position of centromere and length of chromosomal arm 4. Presence of secondary constrictions and & satellites 5. Banding pattern of chromosomes 6. Features of sex chromosomes des me  Karyotyping : laboratory process of preparation of the karyotype. It is the routine conventional method for chromosomal analysis.  · Ideogram : diagrammatic representation of the karyotype with all of the pairs of chromosomes arranged in order of size. © 2015 John Wiley & Sons, Inc. All rights reserved.  0:% is ↓ gi :30 > - & 10 - - - &jeii Desig 2 sse des Bi e46751) / 4: stop > - © 2015 John Wiley & Sons, Inc. All rights reserved. © 2015 John Wiley & Sons, Inc. All rights reserved.  * senario - vie's a barbody 1. Diagnosis of sex  During fetal life  Doubtful cases of hermaphrodism  Sex chromosome abnormalities e.g Turner syndrome  Olympic games (gender verification only for women athletes) 2. Diagnosis of infertility, miscarriage and cases of repeated abortion 3. Diagnosis of some cases of cancers & blood disorders. 4. Diagnosis of chromosomal aberrations (numerical & structural abnormalities) © 2015 John Wiley & Sons, Inc. All rights reserved.  normal male normal female © 2015 John Wiley & Sons, Inc. All rights reserved. Definition:  It means any deviation from the normal number (numerical) or structure (structural).  It may occur in autosomes or in allosomes (sex chromosome).  Clinically, most of these aberrations result in mental /or developmental retardation &s 59. Causes:  Radiation  Viral infections (Rubella) D  Old aged pregnancy  Cytotoxic drugs & autoimmune diseases © 2015 John Wiley & Sons, Inc. All rights reserved.  el gis No o Jes ↑ 42 -N - 4.995 05 1 © 2015 John ·ex: Wiley & Sons, Inc. All rights reserved.  ~ 150 a) Euploidy: Extra chromosomal b) Aneuploidy: one chromosome is missed or added. set is present. The karyotype does not show multiple of the basic haploid number, but only shows addition The karyotype shows exact or loss of one chromosome. multiple of the basic haploid Examples: number and exceeding the ▪ Trisomy: an extra chromosome is present. Karyotype (2n + 1). 3 copies of one diploid number. chromosomes are present instead of 2. Examples: Monosomy: one chromosome is lost. ▪ Triploid (3N) ▪ ▪ Tetraploid (4N) Karyotype (2n – 1). One copy of certain ▪ Polyploid (5N, 6N,…) chromosome is present instead of 2. © 2015 John Wiley & Sons, Inc. All rights reserved. © 2015 John Wiley & Sons, Inc. All rights reserved.  & - Euploidy Aneuploidy Number of Extra chromosomal set (3n, 4n, Only one chromosome is added or lost chromosomes 5n) (2n+1) / (2n – 1) &=00 - 2 - 1 Marked variation(triploid, Minimal variation (nullisomy, monosomy, Genotype tetraploid, polyploid) trisomy & tetrasomy) 242405 + 1 + 2 o je % Marked, may lead to the T Phenotype Minimal, imbalanced mutation formation of new species- - - o& His Frequently inG plants, rarely in Location Both animals & plants animals bril's Fig Meiotic nondisjunction,W E mitotic Cause Complete nondisjunction - nondisjunction & chromosomal loss © 2015 John Wiley & Sons, Inc. All rights reserved.  Magno :09ei5 No © 2015 John Wiley & Sons, Inc. All rights reserved.  Nondisjunction means failure of the chromosomes to separate properly during meiosis (I &II), causing the resulting cells to have incorrect number of chromosomes. It occurs when pairs of homologous chromosomes (meiosis I) or sister chromatids (II) fail to separate during meiosis. 46 : 00  yes Causes: Old maternal age increases the risk of:- 1. Misalignment gene 2. Incomplete synapsis = - Z j 3. Dysfunction of the mitotic spindles that facilitates chromosome migration. is Sets: > - © 2015 John Wiley & Sons, Inc. All rights reserved.  47 : 35  Genetic consequence © 2015 John Wiley & Sons, Inc. All rights reserved.  W W 150 1 58 % 25 / 25 · % ·... 150 % © 2015 John Wiley & Sons, Inc. All rights reserved.  Autosomes Sex chromosomes 1. Trisomy 21 Trisomy 2. Trisomy 18 1. Triple XXX syndrome Trisomy 3. Trisomy 13 2. XXY syndrome Are usually lethal in humans Monosomy & animals so, not frequently Monosomy 1. XO syndrome seen E ·I S © 2015 John Wiley & Sons, Inc. All rights reserved. © 2015 John Wiley & Sons, Inc. All rights reserved. Trisomy of chromosome 21 (2n+1) Clinical features: Mongoloid facies: lateral upward slanting of the eye, epicanthic eye fold depressed carryotape nasal bridge, small external ear MR, small genitalia, cardiac anomalies, hypotonia, characteristic simian palmar crease © 2015 John Wiley & Sons, Inc. All rights reserved. Trisomy of chromosome 13 (2n+1) Clinical features: Microphthalmos Microcephaly, Mental retardation (MR) Micrognathia Hypotonia Clenched hands Cleft lip/palate © 2015 John Wiley & Sons, Inc. All rights reserved. Trisomy of chromosome 18 (2n+1) Clinical features: Majority die before birth If born, 95% die within 1st month Small head, clenched hand, heart & kidney abnormalities © 2015 John Wiley & Sons, Inc. All rights reserved.  sex cromative = barrbody Monosomy of sex chromosome (45-XO) Clinical features: Short statured female Low set ears Short webbed neck Coarctation of the aorta Streak ovary…..amenorrhea & infertility © 2015 John Wiley & Sons, Inc. All rights reserved. Trisomy of sex chromosome (47+XXY) Clinical features: Tall statured male Abnormal hair distribution Gynecomastia Testicular atrophy…..infertility © 2015 John Wiley & Sons, Inc. All rights reserved. Trisomy of sex chromosome (47+XXX) Clinical features: Phenotype: female Delayed motor milestones Mental defect Attention deficit hyperactivity disorder (ADHD) & learning disabilities. © 2015 John Wiley & Sons, Inc. All rights reserved. © 2015 John Wiley & Sons, Inc. All rights reserved.  Basic genetics : a human approach / BSCS. Dubuque, IA, Kendall/Hunt Pub. Co., c1999. 147 p. QH431.B305 1999  Genes, ethnicity, and ageing. Edited by Lincoln H. Schmitt, Leonard Freedman, Rayma Pervan. Nedlands, Australia, Centre for Human Biology, University of Western Australia ; Singapore, River Edge, NJ, World Scientific, c1995. 100 p.QH455.G45 1995  Genetic polymorphisms and susceptibility to disease. Edited by M. S. Miller and M. T. Cronin. New York, Taylor & Francis, 2000. 266 p.  GENETIC ANALYSIS AN INTEGRATED APPROACH Mark F. Sanders , John L. Bowman Second edition 2015 ISBN 978 0-321-94890-8 (student edition) www.pearsonhighered.com  Boundless Biology: Modern Understandings of Inheritance https://courses.lumenlearning.com/boundless- biology/  Anthony JF Griffiths, William M Gelbart, Jeffrey H Miller, and Richard C Lewontin (1999): modern genetic analysis