L5 - Gene interaction 1: departure from Mendelian ratios Flashcards
Amorphic (null) -
produces no protein at all, or protein product completely lack of function (usually recessive) - eg. CFTR 508 allele
Hypomorphic (leaky)
Protein function is reduced either due to less protein made, or product itself displays less activity (usually recessive) - e.g. alleles of the gene encoding Tyrosinase - in the pathway that produces melanin from tyrosine
Types of loss of function
Amorphic and hypomorphic
Types of gain of function
Hypermorphic, antimorphic, dominant lethal and neomorphic
Hypermorphic
Increase in activity, either more protein is made or the protein itself has greater activity (usually dominant) - e.g. Heredity pancreatitis (HP)
Antimorphic (dominant negative)
Disturbance in function that interferes with protein encoded by a normal allele (usually applies to situations when a protein operates as a hetero- or homo-multimer) - e.g. Mutations in FBN1 ( lead to truncation of FBN1 protein and causes Marfan syndrome)
Dominant lethal
Only see this class of mutant later on inline, since onset of a disease is caused by accumulation of the mutant product - e.g. Huntington’s disease (progressive condition)
Huntington’s disease is caused by…
a triplet expansion in the HD locus (>36 CAG), giving a polyglutamine tract in the protein. Leads to aggregation of protein into neurotoxic fibrils
* Heterozygous individual develops HD, because mutant polypeptide will aggregate regardless of presence of wild-type protein
Neomorphic
Alters the function of the protein (‘new form’) so usually dominant - e.g. antennapedia in Drosophila - gene mutated so that protein now causes development of legs where eyes should be
Incomplete (partial) dominance
results in a ‘blend’ of characteristics
Codominance
where the presence of both allele id detected equally - e.g. blood type AB
Genetic load
The collection of lethal alleles in the population
Inheritance of genes on the X chromosome (X-linkage)
- Will occur most frequently in males (bus they only have one copy of X)
- Cannot be passed from father to son
- All daughters of affected fathers are carriers
In X-linkage, if the mom is a carrier and the father is normal,
half of the sons of a carrier will be affected and half of the daughters will be carriers
Maternal Inheritance
Mitochondria and chloroplasts contain their own circular genome. These organelles are inherited from teh maternal side of a cross
Mitochondrial cytopathy
- number of human diseases are caused by the mutations in mtDNA
- can only be passed on by the mother
- An affected mother will transmit the disorder to all offspring!!
- so affects both sexes!
- but offspring of affected fathers are normal
What is matrilineal?
it does not follow any of the autosomal or sex-linked inheritance patterns as it is only passed down the maternal line
Mendelian ratios appear when..
mutations are fully penetrant and show consistent expressivity
Discrepancy between phenotype and genotype (give rise to non-mendelian ratio) can arise due to:
1) Incomplete penetrance
2) variable expressivity
What is incomplete penetrance?
When the phenotype associated with a genotype FAILS to appear in some cases - e.g. polydactyly: a dominant phenotype, yet only 25-30% of individual who carry the mutant allele develop extra digits
What is variable expressivity?
When phenotype varies in the degrees of magnitude - e.g. Individuals with Wardenburg syndrome (autosomal dominant)
- Such an allele is also pleiotropic - i.e. affects more than one character
Penetrance and expressivity are controlled by…
1) genotype at other loci
2) environmental factors
What can be inherited in matrilineal fashion only?
Mitochondrial and plastid DNA
What does epistasis mean?
Most phenotypes are controlled by various genes interacting with each other. Epistasis modifies Mendelian ratios!
