Genetics Flashcards
What type of genetic disorder if Neurofibromatosis
Autosomal Dominant with 100% penetrance (NFM1 gene)
- Cafe au lait macules
- Neurofibromas
- Benign CNS tumors/occular
- Macules in the iris (leash nodules)
What type of genetic disorder if Marfan’s Syndrome
Autosomal Dominant with incomplete penetrance with variable expressivity (FBN 1 gene)
- Posterior dislocate of the lens
- Pectus excavatum
Duchenne Muscular Dystrophy
X-Linked Recessive
Haemophilia A
X-Linked Recessive
Fabry Disease
X-Linked Recessive
Haemachromatosis
Autosomal Recessive
Turner Syndrome
45X (Monosomy)
- Short stature
- Ovarian dysgenesis
- Lack of secondary sex characteristics
- Infetility
- Congential problems with heart and kidney’s
Klinefelter Syndrome
47XXY (Trisomy)
- Secondary sex characteristics
- Testicular atrophy
- Infertility
Prader-Willi syndrome
Deletion of paternal Chromosome 15 or paternal disomy.
Loss of expression of SNERPIN region of chromosome 15 Materanlly imprinted (therefore rely on paternal copy)
Angelman syndrome
Deletion of maternal Chromosome 15 or paternal disomy.
Intellectual impairment
Wide mouth with thin upper lip
Ataxia with wide based gait
Characteristics of trinucleotide repeats
1) Intergenerational instability
2) Anticipation (phenotype can get worse over generations)
3) Premutation
4) Sometime genotype-phenotype correlation
Myotonic dystrophy
Due to trinucleotide repeat pattern Thresholds: >50 = disease <37 = no disease - Muscle weakness - Myotonia - Infertility - Male pattern baldness
Fragile X Syndrome
Males > Females
Trinucleotide repeat (CGG repeat)
50-200 = permutation, >200 = disease
- Intellectual disability
Huntington disease
Trinucleotide repeat (CAG repeat)
Anticipation
Threshold
< 29 = Normal, children unlikely to be affected
>29 = unstable, children may develop
>36 = Some will develop disease, children (especially of men )
> 40 = All will develop HD
- Chorea
- Cognitive impairment
- Psychiatric symptoms
Neurofibramatosis chromosomal locations
NF 1 = 17
NF 2 = 22
Tuberous Sclerosis
TS 1 = 9
Ts 2 = 16
Gold standard diagnosis of Muscular Dystrophy
Genetic testing for an expanded CTG repeat in the DMPK gene
On which chromosome is the CFTR gene present?
Chromosome 7
A man presents with Burkitt lymphoma and is found to have the 8;14 translocation in the tumor. This translocation activates an oncogene with which of the following functions?
MYC oncogene which functions as a pleiotropic transcriptional regulator of cell proliferation, differentiation, and apoptosis
On which chromosome is the HFE gene present?
Chromosome 6
On which chromosome is the Von Williebrands factor gene present?
Chromosome 12
Inheritance of homocystinuria
Rare autosomal recessive disorder.
Characterized by severe elevations in plasma and urine homocysteine concentrations
Genotype of homocystinuria
Loss of function mutation in the CBS gene resulting in a deficiency of cystathionine B synthesise. This affects the metabolism of the amino acid methionine leading to an elevation of homocystinuria.
Inheritance of Fragile X
X-linked disorder and the most common inherited cause of intellectual disability
Genetics of Fragile X
Loss-of-function mutation in the fragile X mental retardation 1 (FMR1) gene –> to an expansion of the CGG triplet repeat –> leading to reduced levels of fragile X mental retardation protein (FMRP).
What is the typical inheritance pattern of Alport syndrome?
X-linked
Which of the following is the most common single gene found in maturity onset diabetes of the young (MODY)?
Hepatic nuclear factor 1 alpha (50%)
Glucokinase (20%)
Mutated GCK = MODY 2 = high fasting glucose but do no go on to develop diabetes
Mutated HNF1alpha/HFN4alpha respond particularly well to oral sulphonureas
Mutated HFN1Beta also causes renal cysts and renal failure
Formula for incidence in rare AR using the carrier frequency
Carrier Frequency = 2 x square root of incidence
What is Karyotype useful in identifying
Trisomy, Aneuploidy
