Chromosomal Abnormalities Flashcards
(58 cards)
Chromosomes are made up of?
DNA & Proteins (histones) = chromatin, and their condensation forms chromosomes this process occurs as the cell divide
What is meant by karyotyping?
- To identify the chromosome
Done by:
- Harvesting living tissue (WBC)
- You arrest the cell in metaphase (it provides a clear & condensed view of the chromosome)
- Next, you harvest the cell
- Then, incubate the cell in a hypotonic solution
- Stain it with Giemsa dye
- View the chromosomes under the microscope, arranging them from long to short
How are chromosomes distinguished from one another?
1) Length
2) Banding (G-banding “dark & light banding”)
3) Location of the centromere
How does G-banding (Giemsa staining) work?
- It stains dark in the AT-rich sites of the chromosome (They are gene-poor)
& - Light stain in GC-rich part of the chromosome (they are active in transcription which makes them incorporate less of the Giemsa stain)
What is a centromere?
It is a constriction/narrowing of the sister chromatids dividing the chromosome into a short arm (P-petite) & a long arm (q) each arm is divided into regions and regions are divided into sub-regions (which describes the different areas of chromosomes)
What is the classification of chromosomes? and it is based on what?
- Based on the position of the centromere
1) Metacentric chromosomes: central centromeres and the arms are approximately equal in length
2) Submetacentric chromosomes: The centromere is not in the center and the arms are clearly not the same length
3) Acrocentric chromosomes: centromeres are near to one of the ends
Which chromosomes are acrocentric?
chromosome 13, 14, 15, 21 & 22
They do not have short arms only long arms which makes them attach to each other easily (21 + 14)
What are the types of chromosomal abnormalities?
1) Numerical:
1a) Polyploidy (an extra set of the entire genome 3n (triploidy “due to dispermy, where the egg is fertilized by two sperms”)/4n (tetraploidy “occurs due to failure in cytokinesis”) “ya3ni extra 23”)
1b) Aneuploidy (change in the number of an individual chromosome “extra 1 or missing 1”), like:
- Monosomy: One chromosome is missing (2n-1 “45”)
- Monosomy X (Turner syndrome)
- Trisomy: one chromosome consists of three copies (2n+1 “47”)
- Trisomy 13 (patau syndrome)
- Trisomy 18 (Edwards syndrome)
- Trisomy 21 (Down syndrome)
2) Structural:
2a) Deletion (loss in a chromosomal segment)
2b) Duplication (extra copy of a chromosomal segment) like tandem duplication (duplication of one of the segments and adding it)
2c) Inversion (reversed order of a segment)
2d) Translocation (the transfer of a chromosomal segment to another one “there is no problem with the person who have balanced translocation”)
What causes polyploidy?
1) It could be due to an egg being fertilized by two sperms (dispermy)
2) It could also be due to the failure of cytokinesis or all of the chromosomes ended up in the same cell leaving the other with none
What are the causes of aneuploidy?
1) Non-disjunction in meiosis 1: During meiosis 1 as the cell divides the chromosomes do not get equally distributed and one of the ova gets an extra chromosome which in turn results in the monosome (one less chromosome) of the other egg as they get fertilized by a sperm one of the zygotes will contain 47 and the other 45 (here two ova are tri and two are mono)
2) Non-disjunction in meiosis 2: occurs in meiosis 2, As a result, we will have 2-normal ova, 1-tri, and 1-mono
What is Down syndrome (Trisomy 21)?
-1 in every 600 births: 1:600
- An extra copy of chromosome 21, when meiosis is occurs the cell gets an extra copy of chromosome 21
What are the presenting characteristics of Down syndrome?
- Craniofacial features: brachycephaly (back of the head is flat) with flat occiput, upward slanting palpebral fissure, open mouth with protruding tongue, short nose with depressed nasal bridge, epicanthus (folds under the eye), small and low-set ear, short and webbed neck
- Neurocognitive: Intellectual disability & hypotonia
- Growth: Microcephaly, short stature, and increased weight in adolescent
- Hands & feet:
- Brachydactyly (short fingers)
- Clinodactyly (deviation of the 5th finger)
- Single palmar crease
- Sandal gap (wide space between the first and second toe)
- Eyes: brush field spots (speckling of the iris), lens opacities, strabismus
- Ears: hearing loss
- Cardiac: endocardial cushion defect, VSR, ASD, Patent ductus arteriosus
- GI anomalies
- Endocrine: gonadal deficiency, infertility, hypothyroidism
- Leukemia
How do we diagnose Down syndrome (Trisomy 21)?
By Karyotyping which confirms the diagnosis and determines the reassurance risk.
Down syndrome could be due to:
- Nondisjunction trisomy 21 (94%)
- Robertsonian translocation (3%)
- Mosaic (2%)
With advanced maternal age does the significance of down syndrome increase of decrease?
Increase
In the case of nondisjunction of chromosome 21 (trisomy 21), what is the chance of it being from the mother and father?
Maternal meiosis 1 90% of cases
Paternal meiosis 2 10% of cases
What is the percentage of the recurrent risk?
2% for mothers younger than 30
What is Robertsnian translocation?
In 3% of the cases down syndrome patients might have it due to the translocation between 21q and the long arm of another acrocentric chromosome usually 14 or 22, it can be inherited from a parent with the same translocation but balanced or it can occur from the beginning they will show 46 but an extra chromosome will be attached to 21q that will be appear as 1 copy
Is there a relationship between maternal age and Robertsnian translocation?
No, but has a high recurrence rate especially when the mother is the carrier 10-15% compared to 5% if the father is the carrier
What is meant by balanced robertsnian translocation?
when the attachment of one chromosome to another doesn’t affect the total number of chromosomes and does not show any symptoms, for example, if chromosome 14 is attached to 21 but the total number of chromosomes of that cell stays at 46
CAN IVF reduce the risk of Robertsnian translocation?
Yes you can choose a non-affected embryo
What is mosaic Down syndrome?
- About 2% of individuals with Down syndrome are mosaic
- Occurs in the earliest cell divisions (post-zygotic)
- The phenotype may be milder than that of typical trisomy 21
If there’s a Down syndrome person, let’s say we tested 50 of his WBCS in karyotyping, u can find that 30 of them have 46c and 20 of them have 47c so a rare mixture of normal and abnormal cells which we call mosaic down syndrome
How does it happen?
-it starts with a normal egg and normal sperm
-now after fertilization and AFTER normal meiosis 1 & 2, when the NORMAL zygote starts dividing, a non-disjunction can occur (so during postzygotic division) and that’s what leads to mosaic Down syndrome
-so for ppl with mosaic, their features and IQ have variations, ppl with a higher amount of abnormal 47c cells obviously have more Down syndrome appearance and symptoms, while those with fewer abnormal cells have less of those features or milder than others, so’s why mosaic patients differ from one to another.
Which syndrome is related to Trisomy 18?
Edwards syndrome
What are the characteristics of Edward syndrome?
- Occurs in 1 every 6000 births
- Craniofacial: prominent occiput, short palpebral fissures, hypertelorism (widely spaced), microphthalmia, low-set ears, micrognathia (small chin/jaw), short neck
- Growth: microcephaly, growth deficiency
- Neurocognitive: severe developmental delay, brain malformation
Hands & Feet:
- Clenched hands with overlapping fingers
- Short hallux, dorsiflexed
- Hypoplastic or absent thumb
- Single palmar crease
- Rocker bottom feet
- Skeletal, genitourinary, GI, & cardiovascular malformation
- 5-10% survive the first year
What is the characteristic of Patau syndrome?
- Occurs in 1 every 10,000 births
- Craniofacial: sloping forehead, microphthalmia, hypotelorism, upslanting palpebral fissures, low-set malformed ears, cleft lip and palate
- Neurocognitive: severe developmental delay, brain malformation (holoprosencephaly)
- Growth: microcephaly, growth deficiency
- Skin: scalp defects (cutis aplasia)
- Cardiac, skeletal, and genitourinary malformation
- 90% die within the first year
