Genetics 1 Flashcards
What is a malformation?
A morphological defect of an organ or part of the body caused by an intrinsically abnormal development process.
What is a disruption?
An extrinsic breakdown or interference with an originally normal developmental process.
What is a deformation?
Caused by mechanical factors and can normally be fixed with surgery.
What is dysplasia?
Abnormal organisation of cells into tissues. Caused by a single gene defect and is prone to a high recurrence risk.
What is a sequence?
A pattern of multiple abnormalities derived from a single known anomaly or mechanical factor.
What is a syndrome?
Multiple abnormalities that are thought to be pathologically related and not representing a sequence.
What is an association?
Non-random occurrence in two or more individuals. Cause is typically unknown.
What are the three types of chromosomal abnormalities? Give examples.
Structural - deletions, translocations or insertions
Numerical - aneuploidy
Mosaicism - caused by mitotic non-disjunction
What is robertsonian translocation?
Chromosome breaks at centromeres and the two long arms fuse together to form one long chromosome with a single centromere.
What is aneuploidy?
Loss or gain of one or more chromosomes.
What is monosomy?
The loss of one chromosome. Almost always lethal.
Example of monosomy?
Turners syndrome (X)
Symptoms of Turners syndrome?
- Webbed neck
- Aortic defects
- Urinary defects
- Short stature
How is Turners syndrome treated?
Growth hormone and oestrogen replacement.
What is trisomy?
Gain of one chromosome. Can be tolerated on certain chromosomes.
Give three examples of trisomy.
- Trisomy 13: Patay syndrome
- Trisomy 18: Edwards syndrome
- Trisomy 21: Down syndrome
Symptoms of Patay syndrome?
- Heart defects
- Mental retardation
- Cleft palate
Symptoms of Edwards syndrome?
- Heart defects
- Kidney malformation
- Digestive tract defects
- Mental retardation
Symptoms of Down syndrome?
- Craniofacial defects (small ears and epicanthic folds)
- Short stature
- Cardiac defects
- Mental retardation
- Limb defects (sandal toe gap)
What is tetrasomy?
Gain of two chromosomes. Can be tolerated on some chromosomes.
What is an example of tetrasomy?
Klinefelter’s syndrome (XXY)
Symptoms of Klinefelter’s syndrome?
- Taller than average
- Infertility
- Phenotypically male
- Learning disabilities (IQ of 80-90)
What are the rare variants of Klinefelter’s syndrome?
XXXY and XXXXY
What is dosage compensation?
Mechanism that ensures equivalent gene expression between males and females.
What three mechanisms are used in dosage compensation?
1) Inactivation of the X chromosome in females
2) Increased gene expression of the X chromosome in males
3) Decreased expression of both X chromosomes in hermaphrodites
What is Di George syndrome and its symptoms?
- Caused by a micro deletion
- Cardiac defects
- Thymic hypoplasia
- Cleft palate
- Hypokalaemia
What is Marie-Charcot-Tooth disease and its symptoms?
- Caused by a micro duplication
- Muscular weakness and foot drop
- Demyelination of peripheral nerves in adolescence, leading to absent reflexes, slow conduction and lack of sensation in lower limbs
How is MCTDT1A treated?
Physiotherapy and corrective surgery
What are chromosomes stained with to see the banding?
Giemsa
Which arm of the chromosome is smaller.
P arm
What is the advantages of next generation sequencing?
- Increased sequencing volume (can sequence millions of DNA fragments simultaneously)
- Greater sensitivity to rare variants
How does Sanger/NGS sequencing work?
Fluorescent DNA polymerase adds nucleotides onto a growing template DNA strand.
What is copy number variation?
When the number of copies of a particular gene varies between individuals.
What are the implications of copy number variations?
Some cancers (breast cancer) are associated with increased copy numbers of particular genes whilst other disorders are associated with deletions (Prader-Willi and Angelman syndrome).
Give example of a mutation in the same gene causing different disorder.
Cystic fibrosis and CAVD (congenital absence of the Vas Deferens)
Give an example of the same disease caused by a different gene.
Haemophillia (F8 and F9 gene on X chromosome)
Give an example of a disorder with two different patterns of inheritance.
Epidermolysis bullosa (autosomal recessive or dominant)
