Modes of Inheritance Flashcards
What are the qualities of an autosomally dominant allele?
Requires single copy to manifest in phenotype, ½ chance of being affected, Commonly ‘gain of function’, Vertical pedigree pattern
What are the qualities of an autosomally recessive allele?
Requires 2 copies of gene to be present to show in phenotype, ¼ chance of being affected, Commonly ‘loss of function’, Horizontal pedigree pattern
When is a characteristic considered autosomal dominant?
Characteristic is dominant if it manifests in a heterozygote. At least 1 parent affected. Transmitted by M and F and affected equally.
Provide two examples of conditions caused by autosomally dominant alleles
HUNTINGTON’S DISEASE – affects 1/20,000
Causes motor, cognitive + psychiatric dysfunction ‘hyperkinesia’. Symptoms: diff. concentrating, depression, stumbling, involuntary jerking, problems swallowing. Caused by unstable CAG triplet repeats on chromosome 4 causing Huntington protein aggregate which is toxic leading to cell death. Treatment is to ease symptoms but no cure.
OSTEOGENESIS IMPERFECTA – 1/15,000 Type 1 (insufficient collagen) vs Type 2/3/4 (abnormal protein) cause interruption w/normal protein function which weakens connective tissue particularly bone. These brittle bones that break easily. Other symptoms are hearing loss, breathing, short height, blue tinge to whites of eye. Ranges from mild to severe.
What are the possible outcomes of a mutated gene?
GAIN OF FUNCTION: Mutated gene forms protein w/new function e.g. longer lifespan -> increased effect
DOMINANT NEGATIVE EFFECT: Mutated gene produces protein that binds together, reducing activity e.g. dimers or multimers -> don’t function properly
INSUFFICIENT: Mutated gene means less protein produced (not enough for normal function)
What are the qualities of an autosomal recessive characteristic?
No affected parent. Transmitted by M or F and equally affected. Usually no family history. Can be carriers vs homozygous recessive. Horizontal pedigree pattern – ¼ chance of being affected if 2 heterozygous parents, ½ chance of carrier. Skips generations
What is an example of an autosomal recessive condition?
CYSTIC FIBROSIS – affects 1/3000
Mutation in CFTR gene on chromosome 7 (encodes Cl- channel) leads to disruption of salt/water regulation, forming thick mucus + symptoms. Symptoms are failure to thrive, impaired airway defense causing respiratory infections, digestive issues. The defective Cl- channel are an example of loss of function.
What is a loss of function?
Where a protein works less well, is degraded faster and present in inadequate amounts.
What are qualities of X-linked recessive disorders?
Any damage to X chromosome will have worse impact on a boy as they only have one copy of the X chromosome. Thus males have 1 in 2 risk of having disorder. Females have 1 in 2 chance of being carrier. Mostly unaffected parents. Transmitted by carrier F. Mainly M affected (may have affected uncles), females can be carriers
What are 2 examples of X-linked recessive disorders?
HAEMOPHILIA
Blood clotting disorder which causes easy bruising, heavy/more frequent bleeding. Due to factors VIII or IX being missing.
FABRY’S DISEASE
Female carriers show subtle signs of disease. Build-up of fat causes acroparaesthesias (episodes of pain in hand + feet), angiokeratomas (small dark red spots on skin), hypohidrosis (decreased sweat), tinnitus (ringing in ears), GIT issues, corneal opacity (cloudiness in front part of eyes).
What are qualities of X-linked dominant disorders?
Similar to autosomal dominant pattern. Seen in both sexes. ALL daughters and NO sons of affected father are affected. Condition milder and more variable in females and males.
What is an example of an X-linked dominant disorder?
X-LINKED HYPOPHOSPHATEMIA
Kidneys can’t retain phosphate leading to vitamin D resistance rickets. XLH gene mutation resulting in inactivity of PHEX protein (enzyme this is active primarily in bones and teeth). Results in rickets, growth problems, serum phosphorus, osteomalacia, fractures and pseudofractures.
What are qualities of Y-linked disorders and what is an example of a Y-linked disorder?
Affects only M. ALL sons of an affected father are affected. Vertical pattern.
·RETINITIS PIGMENTOSA
Mutation in RPY gene retinal cells produces defective protein. Symptoms include trouble seeing at night and decreased peripheral vision.
What are qualities of mitochondrial disorders?
Maternally inherited. Affected father NEVER affects children but affected mother may affect kids. Vertical pattern. Can get unrelated multi-system symptoms especially motor and nerve function.
Why is variability seen in expression of mitochondrial disorders?
There are multiple mitochondria in each cell and all mitochondria inherited from mother via random segregation. Severity of symptoms varies with:
- Amount of WT (wild type) to mutated mtDNA
- Severity of mutation
