Lecture 2: Mendelian and Non-Mendelian Genetics I Flashcards
Unit Inheritance
Parental phenotypes do not “blend” in offspring.
Segregation
Genes exist in pairs; only one member of each pair is transmitted to offspring.
One of Mendel’s basic principles of heredity.
Independent Assortment
Genes at different loci are transmitted independently. This is due to random recombination of maternal and paternal chromosomes.
One of Mendel’s basic principles of heredity.
Mendelian Inheritance
Refers to the single gene transmission of inherited traits from generation to generation; not all inheritance follows these rules.
Autosomal Dominant Inheritance
Only one copy of a mutant allele is necessary for the expression of an autosomal dominant trait.
Clinical characteristics:
- Variable Expressivity
- Incomplete Penetrance
- De novo mutations
Variable Expressivity
The same genetic condition can present with different clinical symptoms at different ages and with varying degrees of severity–even within the same family.
E.g. hair color.
Penetrance
The proportion of individuals heterozygous for a given autosomal dominant gene mutation who have any of the known phenotypic effects of the gene.
Complete Penetrance
All heterozygotes known to have the gene for the condition have the phenotype.
Reduced (Incomplete) Penetrance
Not all heterozygotes known to have the gene have clinical (phenotypic) features of the disorder.
New (De Novo) Mutations
New gene mutations that can occur. Often found at “hot spots” in the genome.
Autosomal Recessive Inheritance
Two copies of a mutant allele are necessary for expression of an autosomal recessive trait.
E.g. Cystic Fibrosis
Characteristics:
- Less expressive variability
- Penetrance is usually complete
- Ethnic predispositions, i.e. sickle cell
X-Linked Recessive Inheritance
The mutated allele is on the X chromosome.
-E.g. Hemophilia
Characteristics:
- Male to male transmission not observed.
- All daughters of affected male are carriers
- Males much more likely to be affected
Obligate Carrier
An individual who may be clinically unaffected but who must carry a gene mutation based on analysis of the family history; usually applies to disorders inherited in an autosomal recessive and X-linked recessive manner.
Lyonization
Only one X chromosome is active in each somatic cell of a female mammal. Inactivation usually occurs randomly in early embryonic life.
Any cells derived from affected cells with have the same inactivated X.
Skewed (non-random) X-Inactivation
When the inactivation of one X chromosome is favored over the other in all cells of the body.
High ratios become medically significant, which can result in symptomatic carriers.
Symptomatic females tend to be less severely affected than males.
E.g. Duchenne MD
X-Linked Dominant Inheritance
Only one copy of a mutant allele on the X-Chromosome is necessary for expression of an X-linked dominant trait, whether in a male or female.
Characteristics:
- Females are more likely to be affected.
- Much less common than X-linked recessive disorders.
- No male-male transmission
E.g. Incontinentia Pigmenti
mtDNA
Mitochondrial DNA; encodes some of the subunits needed for the oxidative phosphorylation chain.
Most of the subunits are encoded by nuclear DNA, however.
Heteroplasmy
Mixture of normal and abnormal DNA; usually refers to mtDNA.
Homoplasmy
All DNA is the same (i.e. all normal or all abnormal); usually refers to mtDNA.
mtDNA Segregation
Occurs randomly as the cell divides; mixtures of normal and abnormal separate in varying proportions.
mtDNA composition changes over time by what mechanisms?
- Chance variation (genetic drift).
2. Selective (replicative) advantage.
Threshold Effect
A certain percentage of abnormal mtDNA molecules may be tolerated without symptoms. Once the threshold is reached, symptoms appear.
Threshold varies from tissue to tissue (think ATP needs) and person to person.
What organ systems are likely to be affected by human mitochondrial disorders?
Those with large ATP requirements.
E.g. CNS, skeletal muscle, eye muscle, heart muscle.
Less commonly, GI tract, pancreas, bone marrow, ANS.
Why are mitochondrial disorders difficult to identify and diagnose?
Heteroplasmy; random mixtures of normal and abnormal mtDNA in each mitochondria obscure identification.
Though it is theoretically possible, it is very difficult.
How many copies of mtDNA do mitochondria have?
Hundreds, as opposed to two in the nucleus.
Achondroplasia
A condition that is a good example of dominant inheritance. It is also known as dwarfism.
- 80% of all cases are de novo.
- 90% due to one of two mutations.
Principles of Autosomal Dominant Inheritance
- Only one gene copy is necessary for expression.
- Multiple generations are affected, but can also be de novo.
- Male to male transmission observed.
(these are a few)
Marfan Syndrome
A syndrome that has many varying symptoms with varying severity.
Cardinal manifestations are bone overgrowth, joint laxity, and cardiovascular pathologies.
A good example of “Variable Expressivity.”
Non-Mendelian Inheritance
Any pattern of inheritance in which traits do not segregate in accordance with Mendel’s laws.
Examples:
- Mitochondrial
- Trinucleotide Repeats
- Mosaicism
How does age affect mitochondrial function and why?
Function decreases.
Hypotheses:
-Damage to mtDNA from free radicals.
-Increased mutation rate due to a lack of repair enzymes
Three Parent I.V.F.
Taking the nucleus of a mother out of an affected cell with mutant mtDNA and placing it into a de-nucleated cell with normal mtDNA.
