Lecture 4.1: Chromosomal Abnormalities Flashcards
(46 cards)
What is a karyotype?
It is the actual picture of an individual’s collection of chromosomes
Is a preparation of the complete set of metaphase chromosomes in the cells of a species or in an individual organism, sorted by length, centromere location and other features
22 pairs of autosome chromosomes and 1 pair of sex chromosomes
Karyotypes
Describe the number of chromosomes and what they look like (size bands and centromere placement)
Karyograms
Are the study of the whole set of chromosomes arranged in pairs by size, and position of the centromere
Chromosome Ideogram
Is a graphical or schematic representation of chromosomes
Each arm of the chromosome is divided into regions, and the numbers assigned to each region get larger as the distance from the centromere to the telomere increases
Regions are identified by the specific morphological features that are consistently found in a chromosome, such as the presence of prominent Giemsa-staining bands
What is Karyotyping?
It is the process of pairing and ordering all the chromosomes of an individual
Why do we do Karyotyping?
To detect changes in chromosome number and also more subtle structural changes, such as chromosomal deletions, duplications, translocations, or inversions
How do we do Karyotyping?
Prepared from mitotic cells that have been arrested in metaphase or prometaphase, when chromosomes are most condensed
What tissues are used for Karyotyping?
A variety of tissue types can be used as a source of these cells: peripheral blood, skin biopsy, tumour biopsies or bone marrow samples
In embryos: amniotic fluid or chorionic villus specimens are used
Normal Chromosome Report: What to expect?
46, XX- normal female karyotype
46, XY- normal male karyotype
Indications for carrying out Karyotyping (5)
1) Prenatal screening
2) Birth defects
3) Abnormal sexual development
4) Infertility; Recurrent foetal loss
5) Leukaemia and related disorders
Chromosomal Abnormalities
1) Polyploidy
2) Aneuploidy
3) Chromosomal mutations: Deletion, Inversion, Translocation, Insertion,
Duplication
What is Polyploidy?
It is the heritable condition of possessing more than two complete sets of chromosomes
Polyploidy can occur in some tissues of animals that are otherwise diploid – endoploidy (human muscle tissues)
Polyploidy in Humans
It is lethal
Polyploidy occurs in humans in the form of triploidy, with 69 chromosomes (sometimes called 69,XXX)
Tetraploidy with 92 chromosomes (sometimes called 92,XXXX)
Triploidy is often caused by polyspermy
What is Aneuploidy?
Is the presence of an abnormal number of chromosomes in a cell
Aneuploidy is the most common and clinically significant type of human chromosome abnormality
Trisomies
In humans, the most common aneuploidies are trisomies, which represent about 0.3% of all live births
Trisomies represent about 35% of spontaneous abortions
What causes Aneuploidy?
The most common cause of aneuploidy is the nondisjunction of chromosomes during meiosis
The vast majority of trisomies arise from errors during maternal meiosis I (human oocytes can be arrested in prophase I for several decades)
Autosome Aneuploidies Conditions
Trisomy 21: Down’s Syndrome (viable)
Trisomy 18: Edwards’s Syndrome
Trisomy 13: Patau Syndrome
Why is Trisomy 21 viable?
Likely because the number of protein-coding sequences for chromosome 21 is the smallest of any human chromosome (except Y)
Thus, an additional copy of chromosome 21 would be predicted to perturb the normal equilibrium in cells less than an extra copy of any other autosome
Down syndrome: Three variations
47,XY(or XX),+21
Trisomy 21
Mosaic Down Syndrome: person has only some cells with an extra copy of
chromosome 21
Translocation Down Syndrome: a portion of chromosome 21 becomes attached (translocated) onto another chromosome, before or at conception
Down syndrome: Distinct Features
- Flattened face
- Small head
- Short neck
- Protruding tongue
- Upward slanting eye lids (palpebral fissures)
- Unusually shaped or small ears
- Poor muscle tone
- Broad, short hands with a single crease in the palm
- Relatively short fingers and small hands and feet
- Excessive flexibility
- Tiny white spots on the coloured part (iris) of the eye called Brushfield’s spots
- Short height
Down syndrome: Symptoms
- Mild to moderate intellectual disability (IQ 35–70)
- Congenital heart disease
- Haematological malignancies are more common in children with DS (acute
lymphoblastic leukaemia (ALL) 10x higher) - Hypothyroidism
- Gastrointestinal: lack of nerves in colon (constipation)
- Reduced fertility
- Eye disorders: strabismus, refractive errors, cataracts
- Hearing disorders: seen in 38–78% of DS children mostly due to infections
and malformations (can be treated)
Down syndrome: Diagnostic Methods
1) G-banded karyotype
2) Fluorescent in situ hybridization (FISH)
3) Quantitative fluorescence PCR (QF-PCR)
Edwards Syndrome
47,XX(or XY),+18
Occurs in around 1 in 6000 live births ( ~80% of affected individuals are female)
Modal lifespan is 5–15 days
5-10% of infants survive longer than 1 year
Edwards Syndrome: Symptoms
- Slow growth before birth (intrauterine growth retardation) and a low birth
weight - May have heart defects and abnormalities of other organs that develop
before birth - Issues with cognitive development (intellectual disabilities), which are
typically severe. - Weak cry and minimal response to sound
