1 Basic Human Genetics: Reproductive Health and Chromosome Abnormalities Professor Hanan Hamamy Department of Genetic Medicine and Development Geneva University Switzerland Training Course in Sexual and Reproductive Health Research Geneva 2014
2 Categories of Genetic Diseases Single gene abnormalities _ Autosomal dominant Chromosomal abnormalities Numerical Multifactorial e.g.diabetes Acquired somatic abnormalities e.g. cancer Autosomal recessive Structural X-linked Microdeletions Mitochondrial Imprinting
3 Types of Chromosome Abnormalities Numerical: Trisomy Monosomy Mosaicism Triploidy Structural: Translocation Deletion Inversion Microdeletions and microinsertions
4 46 Chromosomes in a human cell as seen under the microscope
5 Frequencies of chromosome abnormalities A chromosome abnormality is present in 40-50% of all recognized first-trimester pregnancy loss. Approximately 1 in 6 of all pregnancies results in spontaneous miscarriage. Birth prevalence of chromosome abnormalities is 0.5-1%.
6 Chromosome abnormalities can cause: Infertility Repeated spontaneous abortions Stillbirths Infant mortality Birth defects Sexual ambiguity or abnormality in sexual development Unexplained short stature in female children Intellectual disability
7 Trisomy Presence of an extra chromosome, the total number of chromosomes is 47 in a somatic cell. Trisomy usually results from meiotic nondisjunction. There are 3 of number 21 chromosomes
8 Monosomy Absence of one chromosome, so the total number of chromosomes is 45 chromosomes in a somatic cell. Usually only seen as 45,X, (autosomal monosomy is usually lethal). Monosomy usually results from meiotic non-disjunction.
9 There are 2 types of cells in an individual, for example normal 46,XY cells and abnormal trisomic cell line 47,XY,+21. The two cell lines are derived from the same zygote due to mitotic nondisjunction. Mosaicism
10 Triploidy Presence of 3 haploid sets : 23 x 3= 69 chromosomes (haploid set =23, diploid set =46). Usually incompatible with life and seen only in abortions. May results from 2 sperms fertilising the ovum or retainment of the polar body with the ovum.
11 Normal meiosis, the 46 chromosomes become 23 in each gamete
12 Non-disjunction during meiosis means that one daughter cell gets 24 chromosomes and the other 22 chromosomes
13 Fertilisation of the gamete carrying 24 chromosomes (extra number 21 ) with a normal gamete having 23 chromosomes results in a zygote of 47 chromosomes (trisomy 21 zygote)
14 Reciprocal translocation = exchange of segments between 2 nonhomologous chromosomes Exchange of segments
15 Robertsonian translocation occurs between 2 acrocentric chromosomes with breaks near centromeres and union of the long arms
16 Carriers of balanced translocations are healthy but They are at risk of having offspring with unbalanced chromosome constitution This may present as: Repeated spontaneous abortions Stillbirths Birth defects Intellectual disability
17 Deletion: loss of part of a chromosome
18 Pericentric inversion: two breaks with inversion of the segment in between
19 Karyotype description 46,XX normal female karyotype 46,XY normal male karyotype 45,X monosomy X = Turner syndrome 47,XY,+21 trisomy 21 = Down syndrome 46,XY, 5p- deletion of part of short arm of chromosome 5 = Cri du Chat syndrome 46, XX, t(2;4)(q22;q23) translocation between long arms of chromosomes 2 and 4 with breakpoints at region 2 band 2 for chromosome 2 and region 2 band 3 for chromosome 4
20 Consequences of chromosome abnormalities Infertility: examples: Turner and Klinefelter syndromes. Repeated spontaneous abortions: healthy carriers of translocations and inversions. Stillbirths and infant deaths: where the chromosome abnormality is very severe for example trisomy 13 and trisomy 18. Congenital disorders : for example Down syndrome, microdeletion syndromes.
21 Syndromes with chromosome abnormalities
22 Chromosome abnormalities at birth Trisomy /1000 births Trisomy /1000 births Trisomy /1000 births 45,X 0.2/1000 female births 47XXX 1/1000 female births 47,XXY 1/1000 male births 47,XYY 1/1000 male births Other unbalanced rearrangements 1/1000 births Balanced rearrangements Total 3/1000 births
23 Down syndrome (DS) The overall prevalence at birth is approximately 1 in 650 to 1 in 700 births. May be higher in some countries where women continue to bear children at an advanced age.
24 Clinical features of DS The most common finding in the newborn period is severe hypotonia. Single palmar creases are found in 50% of Down syndrome children in contrast to 2-3% of the general population. Congenital cardiac abnormalities are present in 40-45% of babies with Down syndrome. Hypothyroidism.
25 Facial features of DS Upward sloping palpebral fissures Brushfield spots and bilateral epicanthic folds Small ears Protruding tongue
26 Natural history of DS Affected children show a broad range of intellectual disability with IQ scores ranging from 25 to 75. The average IQ of young adults with Down syndrome is around 40 to 45. Social skills are relatively well advanced and most children with Down syndrome are happy and very affectionate.
27 Natural history of DS Adult height is usually around 150cm. In the absence of a severe cardiac anomaly, which leads to early death in 15-20% of cases, average life expectancy is years. Most affected adults develop Alzheimer disease in later life due to dosage effect of the amyloid precursor protein gene.
28 Chromosome abnormalities in Down syndrome 95% of cases are trisomy 21, 47,XX,+21 (47,XY,+21), risk of having trisomy 21 increases with advanced maternal age. 4% are due to translocation between chromosome 21 and another acrocentric with a total number of chromosomes =46, but the genetic material of chromosome 21 is present in triplicate. The translocated chromosome is usually inherited from a normal carrier parent. Such a translocation carrier parent has a risk of having a Down syndrome with each pregnancy (about 20% if mother is carrier and 5% if father is carrier). 1% mosaic cases ( 46,XY/47,XY,+21).
29 Salihu, 2003, Obstet Gynecol
30 Meiosis in Robertsonian translocation carrier who has 45 chromosomes ( only one 21) but the other chromosome 21 is translocated to chromosome 22 = normal amount of genetic material
31 The gamete carrying 23 chromosomes but one is a translocation 21/22 is fertilised by a normal gamete resulting in a zygote with translocation Down syndrome
32 Turner syndrome: monosomy X The two main medical problems are short stature and ovarian failure. Ovarian failure leads to primary amenorrhea and infertility. Estrogen replacement therapy should be initiated at adolescence for the development of secondary sexual characteristics and long-term prevention of osteoporosis.
33 Normal female karyotype and Monosomy X
34 Turner syndrome features Lymphedema at birth Low posterior hair-line Increased carrying angles at the elbows Short fourth metacarpals Widely spaced nipples Coarctation of the aorta present in 15% of cases
35 Chromosome anomalies in Turner syndrome 45,X = 50% Mosaics: 46,XX/45,X = 35% Structural abnormalities (deletion, isochromosome, ring X)
36 Turner syndrome is being detected early in pregnancy as a result of routine detailed ultrasound scanning, which can reveal either generalized edema (hydrops) or swelling localized to the neck (nuchal cyst or thickened nuchal pad).
37 Klinefelter syndrome: 47,XXY Infertility. Hypogonadism. Diminished secondary sexual characters. Clumsiness or mild learning difficulties. The overall verbal IQ is reduced by points below that of unaffected siblings and controls. 30% of adult males will show gynecomastia (enlargement of the breasts).
40 XYY MALES Fertility is normal. Physical appearance is normal and stature is usually above average. Intelligence is mildly impaired, with an overall IQ score of points below a control sample. The additional Y chromosome must arise as a result of non-disjunction in paternal meiosis II or as a post-zygotic event.
41 XXX females These women usually have no physical abnormalities but can show a mild reduction of between 10 and 20 points in intellectual skills below their siblings. This is rarely of sufficient severity to require special education. Women with a 47,XXX karyotype usually show normal fertility and have children with normal karyotypes.
42 Chromosome microdeletion syndromes
43 Prader-Willi syndrome Hypotonia Poor sucking and feeding in neonates Fair skin and hair Downturned mouth corners Hyperthermia Gestational history of diminished fetal movements Hyperphagia and obesity Short stature Small hands and feet Mental subnormality Narrow bifrontal diameter Hypogonadotropic hypogonadism Caused by microdeletion of paternal 15q (75%)
44 Diagnosis of microdeletion syndromes FISH techniques using specific probes. Array comparative genomic hybridisation (array CGH). Microdeletions usually cannot be detected in the standard banded karyotype.
46 Indications for chromosome analysis in lymphocytes o Multiple congenital abnormalities o Unexplained mental retardation o Sexual ambiguity or abnormality in sexual development o Infertility o Recurrent miscarriage o Unexplained stillbirth o Unexplained short stature in female children o Malignancy and chromosome breakage syndromes
47 Conclusions Around 20,000 chromosome abnormalities have been registered in laboratory databases. Chromosome abnormalities contribute to about 8% of all birth defects. Chromosome abnormalities can be diagnosed in the fetus through chorion villus biopsy or amniocentesis (prenatal diagnosis), or by preimplantation genetic diagnosis following IVF.
CHROMOSOMAL DISORDERS LEARNING OBJECTIVES Describe the normal karyotype Define various types of structural abnormalities of chromosmes including: Deletion,Ring chromosome,inversion, isochromosome and translocations
CHROMOSOMES AND DISEASE Date: September 29, 2005 * Time: 8:00 am- 8:50 am * Room: G-202 Biomolecular Building Lecturer: Jim Evans 4200A Biomolecular Building email@example.com Office Hours: by appointment
Abnormalities of Chromosome Structure Structural rearrangements result from chromosome breakage, followed by reconstitution in an abnormal combination. Whereas rearrangements can take place in many ways,
ANEUPLOIDY Having too many or too few chromosomes compared to a normal genotype Aneuploid organisms have unbalanced sets of chromosomes due to an excess or deficiency of individual chromosomes This creates
Genetic Disorders Things Can Go Wrong With DNA and Chromosomes I. Overview of DNA Structure A. Review 1. A gene is a segment of DNA that codes for a particular protein 2. Proteins determine the physical
AP Psychology 2.2 Behavioral Genetics Article Chromosomal Abnormalities About 1 in 150 babies is born with a chromosomal abnormality (1, 2). These are caused by errors in the number or structure of chromosomes.
Chromosomes, Karyotyping, and Abnormalities (Learning Objectives) Learn the components and parts of a metaphase chromosome. Define the terms karyotype, autosomal and sex chromosomes. Explain how many of
CHROMOSOMAL ABNORMALITIES Chromosomal abnormalities represent changes in chromosomes number (46 in human somatic cells) or their structural modifications. Thus, there are genomic mutations (that explains
Congenital and Genetic Disorders BIO 375 Pathophysiology Review of Genetic Control Genetic information for each cell is stored on chromosomes: Each body cell contains 2 sets (diploid) of chromosomes; one
Turner Syndrome Introduction Turner syndrome is a genetic disorder that affects a girl's development. Girls who have it are short, and most are infertile. Girls and women with Turner syndrome are at risk
Cytogenetics Chromosomal Genetics Sophie Dahoun Service de Génétique Médicale, HUG Geneva, Switzerland firstname.lastname@example.org Training Course in Sexual and Reproductive Health Research Geneva 2010 Cytogenetics
Lecture 32: Numerical Chromosomal Abnormalities and Nondisjunction Meiosis I Meiosis II Centromere-linked markers Female Male 46,XX 46,XY Human chromosomal abnormalities may be numerical or structural.
Sex Chromosome Problems Discovered Through Prenatal Diagnosis Turner Syndrome 45,X Published by PacNoRGG The Pacific Northwest Regional Genetics Group Introduction The purpose of this booklet is to provide
CHROMOSOMES Dr. Fern Tsien, Dept. of Genetics, LSUHSC, NO, LA Cytogenetics is the study of chromosomes and their structure, inheritance, and abnormalities. Chromosome abnormalities occur in approximately:
Genetic Disorders During Meiosis Karyotypes Genetic Technologies Learning goals Understand the errors that can occur during meiosis and identify some disorders using karyotypes Understand Mendel s 2 laws
RECURRENT PREGNANCY LOSS DR.RAJALAKSHMI SRINIVASAN SPECIALIST GYNECOLOGIST ZULEKHA HOSPITAL DUBAI RECURRENT PREGNANCY LOSS -RM Clinically recognized consecutive or non consecutive pregnancy losses before
Chromosomal Abnormalities George E Tiller, MD, PhD Regional Chief, Dept. Genetics Southern California Permanente Medical Group Los Angeles, CA Objectives of Lecture list several indications for karyotyping
4.2: Sexual Reproduction pg. 169 Asexual Reproduction is reproduction that requires only one parent and produces genetically identical offspring. Sexual Reproduction is reproduction that requires two parents
Genetics Nsg 3027 Women s Health Introduction Genetic disorders occur approximately 1 in 20 or 30% of pediatric admissions National Health Care Goals: Increase prenatal screening to 90% of pregnancies.
Name Period Chapter 15: The Chromosomal Basis of Inheritance Concept 15.1 Mendelian inheritance has its physical basis in the behavior of chromosomes 1. What is the chromosome theory of inheritance? The
Appendix B Karyotyping and Genetic Disorder BIOLOGY 3201 CURRICULUM GUIDE 137 138 BIOLOGY 3201 CURRICULUM GUIDE Karyotyping Introduction You are a genetic counselor whose job is to discuss with expecting
1 CELL DIVISION Cell division is the process by which cells replicate in order to replace cell loss, repair tissue damage and reproduce the organism. Two types of cell division are encountered in the Eukaryotic
Important points In each human cell, except the egg and sperm cells, there are 46 paired chromosomes of varying size One chromosome of each pair is inherited from each parent The autosomes are chromosomes
Genetic Mutations Indicator 4.8: Compare the consequences of mutations in body cells with those in gametes. Agenda Warm UP: What is a mutation? Body cell? Gamete? Notes on Mutations Karyotype Web Activity
Genetics of Turner syndrome Rosemarie Kelly Principal genetic Counsellor National Centre for Medical Genetics National Centre for Medical Genetics Clinical Genetics Cytogenetics Molecular Genetics www.genetics.ie
PATIENT CONSENT FORM PrenatalSafe Non-Invasive Prenatal Test (NIPT) This blood test is designed to measure the combined maternal and fetal DNA present in maternal blood, and is considered a genetic test.
PATIENT CONSENT FORM PrenatalSafe Non-Invasive Prenatal Test (NIPT) This blood test is designed to measure the combined maternal and fetal DNA present in maternal blood, and is considered a genetic test.
Genetics II Answered Review Questions 1. Explain the incomplete dominance inheritance pattern. Alleles can show different degrees of dominance and recessiveness in relation to each other. We refer to this
A test your patients can trust. A simple, safe, and accurate non-invasive prenatal test for early risk assessment of Down syndrome and other conditions. informaseq Prenatal Test Simple, safe, and accurate
Heredity - Patterns of Inheritance Genes and Alleles A. Genes 1. A sequence of nucleotides that codes for a special functional product a. Transfer RNA b. Enzyme c. Structural protein d. Pigments 2. Genes
1. Why is the white-eye phenotype always observed in males carrying the white-eye allele? a. Because the trait is dominant b. Because the trait is recessive c. Because the allele is located on the X chromosome
Slide 1 Welcome to chapter 9. The following chapter is called "Preimplantation Genetic Diagnosis (PGD)". The author is Dr. Maria Lalioti. Slide 2 The learning objectives of this chapter are: To learn the
C1. Duplications and deficiencies involve a change in the total amount of genetic material. Duplication: a repeat of some genetic material Deficiency: a shortage of some genetic material Inversion: a segment
Lab 5: Human Genetic Disorders Adapted from Learn.Genetics http://learn.genetics.utah.edu/content/disorders/whataregd/ and Bio10 Laboratory Activities by V. Annen A genetic disorder is a disease that is
1 Chapter 11 - Chromosome Mutations Questions to be considered: 1) how are changes in chromosome number (different from haploid or diploid) defined? 2) how do changes in chromosome number occur? 3) what
Chapter 24 Genetics and Genomics Genetics study of inheritance of characteristics Genome complete set of genetic instructions Genomics field in which the body is studied in terms of multiple, interacting
Chapter 8: Variation in Chromosome Structure and Number Student Learning Objectives Upon completion of this chapter you should be able to: 1. Know the principles and terminology associated with variations
Harvard-MIT Division of Health Sciences and Technology HST.035: Principle and Practice of Human Pathology Dr. Badizadegan Genetic Disorders HST.023 Spring 2003 Genetic Disorders Cytogenetic Disorders Gross
4.2 Meiosis Assessment statements State that meiosis is a reduction division of a diploid nucleus to form haploid nuclei. Define homologous chromosomes. Outline the process of meiosis, including pairing
3 CHAPTER Heredity and Environment Chapter Preview Much is determined at the moment of conception, when a sperm and ovum unite to initiate the developmental processes that will culminate in the birth of
Cell division How does a single cell become a human being? Every time a cell divides, a copy is made of all the DNA in every chromosome Fertilized egg Blastula Many things happen Number of cells increase
State Standards Standard 2: CHAPTER 8 CELLULAR REPRODUCTION: CELLS FROM CELLS Standard 5a: Standard 5b: Standard 2a: Standard 2b: The life cycle of a multicellular organism includes This sea star embryo
A Chromosome Study In this activity, you will create a karyotype from a page of mixed chromosomes. Karyotypes are created by matching homologous pairs and numbering them from largest to smallest. Abnormalities,
NATIONAL DOWN SYNDROME SOCIETY down syndrome Down syndrome affects people of all ages, races and economic levels. It is one of the most frequently occurring chromosomal abnormalities, occurring once in
The Skinny: Genetic testing of miscarriage tissue is controversial and some people question if testing is helpful or not. This summary will: 1) outline the arguments for and against genetic testing; 2)
1. A karyotype shows the visual appearance of an individual s chromosomes. The karyotype below shows the chromosomes of a person with a genetic disorder. Scientists use observable evidence to direct their
information for patients Turner Syndrome CCLINICAL GENETICS LINICAL GENETICS PROOF Introduction Humans are usually born with 46 chromosomes, which are arranged in 23 pairs. One of each pair of chromosomes
What Is Genetic Counseling? Helping individuals and families understand how genetics affects their health and lives What does the career involve? Explore family histories to identify risks Reducing risks
E - Bio @ Horton AP Biology Unit Cell Reproduction Notes Meiosis Sexual Reproduction A. Halving the Chromosome Number 1. Meiosis is nuclear division reducing chromosome number from diploid (2n) to haploid
Chromosomes Chapter 13 What is a Chromosome? Chromosome is the highly condensed form of DNA Wrapped into nucleosomes Wrapped into chromatin fiber Condensed during metaphase into the familiar shape Humans
Chapter 8: The Cellular Basis of Reproduction and Inheritance Introduction Stages of an Organism s Life Cycle: Development: All changes that occur from a fertilized egg or an initial cell to an adult organism.
Chapter 8 Part II Meiosis Since this is a biology class, we get to talk about how babies are made! The first major step in making babies is having the right type of cells We already discussed how to make
Human Chromosomes lab 5 Objectives Upon completion of this activity, you should be able to: describe the structure of human chromosomes with reference to size, centromere position, and presence or absence
Practice problems (with answers) This is the degree of difficulty of the questions that will be on the test. This is not a practice test because I did not consider how long it would take to finish these
This fact sheet describes epigenetics which refers to factors that can influence the way our genes are expressed in the cells of our body. In summary Epigenetics is a phenomenon that affects the way cells
1. PRENATAL DIAGNOSIS OF CHROMOSOMAL DISORDERS - molecular aspects Ana Stavljenić-Rukavina Zagreb University School of Medicine, Croatia The standard measures for population health outcomes is based on
Noninvasive prenatal screen for pregnancy What is QNatal TM Advanced Noninvasive Prenatal Screening? The QNatal Advanced prenatal screen is a noninvasive test that provides a high degree of accuracy for
GENETICS LABORATORIES GENETICS LABORATORIES Prenatal Chromosomal Microarray Many couples face important decisions regarding the type of prenatal testing they wish to have for their current pregnancy. For
MCB41: Second Midterm Spring 2009 Before you start, print your name and student identification number (S.I.D) at the top of each page. There are 7 pages including this page. You will have 50 minutes for
Reciprocal Translocations Information for patients What are Chromosomes? We are all made up of tiny building blocks called cells. These cells are controlled by information stored in long thin strands of
Syndrome Review 1: Common Trisomies and Sex Chromosome Variations Cynthia M. Powell, M.D. Associate Professor of Pediatrics and Genetics The University of North Carolina at Chapel Hill National Birth Defects
Mitosis and Meiosis Mitosis Classwork 1. Identify two differences between meiosis and mitosis. 2. Provide an example of a type of cell in the human body that would undergo mitosis. 3. Does cell division
The Developing Person Through the Life Span 8e by Kathleen Stassen Berger Chapter 3 Heredity and Environment PowerPoint Slides developed by Martin Wolfger and Michael James Ivy Tech Community College-Bloomington
CH 13 Meiosis Inheritance of genes Genes are the units of heredity, and are made up of segments of DNA. Genes are passed to the next generation via reproductive cells called gametes (sperm and eggs). Each
your questions answered the reassurance of knowing A guide for parents-to-be on noninvasive prenatal testing. Accurate answers about your baby s health simply, safely, sooner. What is the verifi Prenatal
information for patients Chromosome Translocations CCLINICAL GENETICS LINICAL GENETICS Introduction You may have been told that you, or a member of your family, have what is known as a chromosome translocation.
Exam #2 BSC 2011 2004 Fall NAME Key answers in bold _ FORM B Before you begin, please write your name and social security number on the computerized score sheet. Mark in the corresponding bubbles under
Islamic University of Gaza Human Karyotype Training Course Manual Prepared by: Mazen Ali Abo Zayed 1 Table of contents Title Page No. 1. Objectives 3 2. Introduction to Karyotyping 3 3. Materials and Methods
Medical Policy Preimplantation Genetic Testing Table of Contents Policy: Commercial Coding Information Information Pertaining to All Policies Policy: Medicare Description References Authorization Information
August 2012 content 8 Preimplantation genetic diagnosis new method of screening of 24 chromosomes with the Array CGH method...2 Maintaining fertility new opportunities in GENNET...3 Hysteroscopy without
ANEUPLOIDY DIAGNOSTICS DIAGNOSTICS EXCELLENCE 6182 DIAGNOSTICS PERFORMED OVER 10 YEARS OF EXPERIENCE PGS-NGS 360 PGD DIAGNOSIS SINCE 2005 TRANSLOCATION DIAGNOSIS NEXT GENERATION SEQUENCING Innovators in
Prenatal Diagnosis Program Prenatal Screenings and Diagnosis What is prenatal diagnosis? Prenatal diagnosis refers to the use of one or more tests to determine if a developing baby has a problem before
Meiosis and Sexual Life Cycles Chapter 13 1 Ojectives Distinguish between the following terms: somatic cell and gamete; autosome and sex chromosomes; haploid and diploid. List the phases of meiosis I and
Genetics 1 DEP 4053 Christine L. Ruva, Ph.D. Heredity and Prenatal Development: Chapter 3 PRINCIPLES OF HEREDITARY TRANSMISSION Genotype Phenotype Chromosomes: in the nucleus of the cell store and transmit
Screening Programmes Fetal Anomaly When a scan shows a nuchal translucency (NT) measurement of 3.5 millimetres or more Information for parents Aim We have given you this leaflet because your baby s nuchal
Introduction Chapter 8 Cancer cells start as normal body cells, get genetic mutations, Divide uncontrollably, and run amok, causing disease. Introduction In a healthy body, cell division allows for growth,
Gestational Carrier Page 1 of 6 This information is intended for all couples considering a pregnancy using a gestational carrier. It is also intended for couples proceeding with a gestational carrier pregnancy
Human Karyotyping Lab # Background: Occasionally chromosomal material is lost or rearranged during the formation of gametes or during cell division of the early embryo. Such changes, primarily the result
7 Chapter 2 Scientific basis What genes are 2.1 The inheritance of all our characteristics, including susceptibility to genetic diseases, is dependent on genes and chromosomes. Genes are large molecules