Chromosomal abnormalities Flashcards
How do you analyse chromosomes?
Using a metaphase spread= fix chromosomes on slide & stain them
Karyotype picture produced and can identify chromosome banding
What should each chromosome contain?
P arm, Q arm and centromere
How do scientists identify chromosomes?
1- Size
2- Banding pattern
3- Centromere position
What are acrocentric chromosomes?
Centromere is located very near the top of the chromosome so only the q arm (very little/ no p arm)
What is a normal female karyotype?
22 pairs XX
What is a normal male karyotype?
22 pairs XY
What abnormalities can be picked up on a karyotype?
- Abnormal chromosome number
- Abnormal chromosome material location
- Abnormal amounts of chromosome material (bits missing or extra)
What are the 3 main types of chromosomal abnormalities?
Aneuploidies
Microdeletions
Translocations
What is aneuploidy?
Abnormal number of copies of an individual chromosome
What is Monosomy?
1 chromosome missing, Total= 45
What is Trisomy?
1 chromosome extra, Total= 47
What is polyploidy?
Abnormal number of sets of chromosomes
What is Monoploid?
One set, Total= 23 pairs
What is Diploid?
Two sets, Total= 46 pairs
What is Triploid?
Three sets, Total= 69 pairs
What are deletions?
Loss of a segment of genetic material from a chromosome
What are duplications?
Gain of a segment of genetic material from a chromosome
What are microdeletions/ microduplications?
too small to be seen on a karyotype
What is the consequence of deletions & duplications?
depends on which genes are in the deleted/ duplicated region
What is a translocation?
Relocation of chromosome material to the wrong place
What is a reciprocal translocation?
2 different chromosomes have exchanged segments with each other
What is a Robertsonian translocation?
An entire acrocentric chromosome attaches to another at the centromere
What is a balanced translocation?
All chromosome material present (just in the wrong place)
What is an unbalanced translocation?
Relocation has resulted in loss and/ or gain of chromosome material
What is down syndrome?
Trisomy 21 (3 copies of chromosome 21)
What are the 6 clinical features of Down’s syndrome?
- Characteristic facial features
- Mild= moderate intellectual disability
- Short stature
- Congenital heart disease
- Endocrine problems
- Increased risk of leukaemia and Alzheimer’s
What are 10 phenotypic changes associated with Down’s syndrome?
- Up-slanting palpebral fissues
- Prominent epicanthic folds
- Flat nasal bridge/ flat facial profile
- Low set small ears
- Furrowed tongue
- Single transverse palmer crease
- Clinodactyly
- Brushfield spots
- Sandal- toe deformity
- Excess nuchal skin
What is Edward’s Syndrome?
trisomy 18
What are the 6 clinical features of Edward’s syndrome?
- Intra-uterine growth restriction
- Most die during pregnancy/ neonatal period
- Overlapping fingers
- Rocker-bottom feet
- Congenital heart/kidney disease
- Small head size (microcephaly)
What is Patau’s syndrome?
Trisomy 13
What are 6 clinical features of Patau’s syndrome?
- Intra-uterine growth restriction
- Most die during pregnancy/ neonatal period
- Cleft lip/ palate
- Extra fingers/ toes
- Brain abnormalities
- Congenital heart disease
What is Antenatal combined screening?
Combined scan for down’s syndrome, edwards syndrome and pataus syndrome, done via blood test & ultrasound scan
What is Klinefelter syndrome?
47 XXY
What are 4 clinical features of Klinefelters syndrome?
- Tall stature
- Normal intellect
- Infertile- often diagnosed in a fertility clinic
- Little facial/ body hair
What is Turner syndrome?
Monosomy X (45, XO)
What are the 7 clinical features of Turner syndrome?
- Infertility
- Short stature
- Lymphoedema (puffy hands and feet)
- Webbed neck
- Endocrine abnormalities
- Congenital heart disease
- Normal intellect
What is Di George syndrome?
22q11.2 microdeletion
What are 6 clinical features of Di George syndrome?
- Congenital heart and Kidney disease
- Nasal speech
- Characteristic facial features
- Hypocalcaemia
- Intellectual disability (mild- severe)
- Increased risk of psychiatric disorders
What is Prader Willi syndrome?
15q11.2-q13 microdeletion most common mechanism
What are 6 clinical features of Prader Willi syndrome?
- Low tone at birth
- Short stature
- Characteristic facial features
- Challenging behaviours + hyperphagia
- Intellectual disability
- Absent/ incomplete pubertal development
How is Chronic myeloid leukaemia caused?
- Reciprical translocation between chromosomes 9 and 22 resulting in the Philadelphia chromosome
-BCR gene from chromosome 22 fuses with ABL gene from chr9 creating a fusion oncogene called BCR::ABL
What does BCR::ABL do?
- Directs production of mutant protein which drives conversion of normal bone marrow stem cells into leukaemic cells
What are balanced reciprocal translocations associated with?
Recurrent miscarriage and multiple congenital anomalies
What do robertsonian translocations involving chromosome 21 cause?
Recurrent miscarriage and recurrent down syndrome
