Genetic diseases Flashcards
What are some examples of autosomal dominant diseases?
- Huntington disease
- Myotonic dystrophy
- Polycystic kidney disease
- Ehlers Danlos syndrome
What is Ehlers Danlos syndrome and what is its cause?
- Connective tissue disorder.
- Symptoms include:
1. Bruising easily
2. Thin skin
3. Fragile blood vessels
4. Easily damageable hollow organ - Caused by mutations in collagen gene (esp. COL3A1)
What are some examples of autosomal recessive diseases?
- Cystic fibrosis
- Spinal muscular atrophy
- Congenital adrenal hyperplasia
What are some examples of numerical abnormalities?
- Turner syndrome: XO
- Down syndrome: Trisomy 21
- Edward’s syndrome: Trisomy 18
What is the cause of Down syndrome?
- Trisomy 21
- Result of chromosome non-disjunction
- Most commonly occurs during meiosis, especially during egg formation
- > 90% of cases inherited maternally
- Risk of non-disjunction and thus acquiring the disease increases as maternal age increases
What is an example of disease causing insertion/deletion?
- 22q.11.2 deletion syndrome.
- Causes schizophrenia and other associated neurological disorders.
- Causes DeGeorge’s syndrome.
What is an example of disease causing reciprocal translocation?
- Philadelphia chromosome.
- Balanced translocation between chromosomes 9 and 22.
- Found in ~95% of patients with chronic myeloid leukaemia.
What are the common genetic disorders caused by sex chromosome non-disjunction?
- Turner’s syndrome (45 XO)
- Klinefelter’s syndrome (47 XXY)
- XYY male
What are the symptoms of Turner’s syndrome?
- Webbed neck
- Short
- Infertility
What are the symptoms of Klinefelter’s syndrome?
- Tall and thin
- Gynecomastia
- Learning impairment (mild)
- Infertility
What are examples of X-linked recessive disorders?
- Duchenne muscular dystrophy
- Haemophilia
- Red-green colour blindness
What are the causes and symptoms of DMD?
- Mutation in Dystrophin gene on X-chromosome
- Progressive muscle weakness and degeneration
What are the causes and symptoms haemophilia?
- Haemophilia A: Factor VIII affected
- Haemophilia B: Factor IX affected
- Ineffective blood clot formation results in excessive bleeding.
What is an example of an X-linked dominant disorder?
- Rett syndrome.
- Caused by a mutation in MeCP2 gene, which makes protein involved in methylation.
- Associated with neurological disorders such as seizures, inability to talk and hand movements.
What is Campomelic Dysplasia?
- Mutation of SOX9 gene on chromosome 17.
- Causes sex reversal and skeletal dysplasia in males.
What are the diseases associated with maternal uniparental disomy?
- 7: Silver-Russell syndrome
- 11: Silver-Russell syndrome
- 14: Maternal UPD14 syndrome (Temple syndrome)
- 15: Prader-Willi syndrome
What are the diseases associated with paternal uniparental disomy?
- 6: Transient neonatal diabetes
- 11: Beckwith-Weidemann syndrome
- 14: Paternal UPD14 syndrome (Kagami-Wang syndrome)
- 15: Angelman syndrome
What is Beckwith-Weidemann syndrome?
- Paternal uniparental disomy of chromosome 11.
- Foetal overgrowth with increased risk of childhood tumours.
- Overexpression of IGF2 in placental cells (paternal).
- No expression of CDKN1C (maternal).
What is Angelman syndrome?
- Paternal uniparental disomy 15.
- Severe developmental delays.
- Ataxic movement.
- Short attention spans.
- No expression of UBE3A.
What is Silver-Russell syndrome?
- Maternal uniparental disomy 7/11.
- Slow pre-/postnatal growth.
What is Prader-Willi syndrome?
- Maternal uniparental disomy 15.
- Neurological problems such as hypotonia, respiratory difficulties, sleeping disorders…
- Excess weight gain
- Delayed weight gain
What are examples of mitochondrial diseases?
- DIDMOAD
- Kearns-Sayre syndrome
- LHON
What are examples of trinucleotide expansion diseases?
- Fragile-X syndrome: Caused by CGG repeat
- Myotonic dystrophy: Caused by CTG repeat
- Huntington disease: Casued by CAG repeat
- Friedreich ataxia: Caused by GAA repeat
What causes fragile-X syndrome?
- CGG repeat on exon 1 of FMR1 gene on X-chromosome.
- TNEs prevent the FMR1 gene from being transcribed, preventing the production of FMRP, which is essential in cognitive development.
What are the symptoms of fragile-X syndrome?
- Learning disabilities
- Long face/large ears
- Increased risk of seizures
- Autism
What causes Friedreich’s ataxia?
- GAA repeats on intron 1 of Frataxin gene on chromosome 9.
- Trinucleotide repeats cause increased epigenetic modifications (including histone modifications) to the Frataxin gene, suppressing its transcription and expression.
What are the symptoms of Freidreich’s ataxia?
- Speech and movement abnormalities
- Heart disease
- Diabetes
What causes myotonic dystrophy?
- CTG repeats on 3’ end of DMPK gene in chromosome 19.
- Accumulation of abnormal pre-mRNA sequesters RNA-binding proteins and prevents them from carrying out their normal functions (alternative splicing).
What are the symptoms of myotonic dystrophy?
- Progressive muscular dystrophy
2. Myotonia (difficulty relaxing muscles post-contraction)
What causes Huntington’s disease?
- CAG repeats in Huntingtin gene in chromosome 4.
- CAG repeats sequence causes polyQ (Gln) strand in Huntingtin protein.
- PolyQ sequences in Huntingtin gene cause formation of polyQ-huntingtin aggregates when the protein is cleaved.
- Aggregates damage mitochondria, leading to the stimulation of apoptosis.
What are the symptoms of Huntington’s disease?
- Intellectual decline
- Myoclonus
- Dystonia
- Dementia
