Biology: Genotype, Phenotype, and Inheritance

Mendelian Inheritance and Mitochondrial Genetics

• Mendelian inheritance is a set of primary rules relating to the transmission of hereditary characteristics from parent organisms to the offspring.

Recombination

• Recombination is the exchange of genetic material between homologous chromosome pairs, strands, or cross-over.
• Segments of DNA exchanged result in shuffling of genetic material.
• Resolvase enzyme function: cleaves homologous chromosomes at Holiday Junctions to separate DNA strands.

Calculating Recombination Frequency

• Recombination frequency is calculated as: number of recombinants / total number of meiosis.
• 1 cM (centiMorgan) is approximately equal to 1Mb (megabase).

Autosomal Dominant Inheritance

• Characteristics of Autosomal dominant inheritance (AD):
  • Each affected individual has at least one affected parent.
  • No skipping of generations.
  • Transmitted by either sex equally.
  • Examples: Huntington's disease, Marfan syndrome.
• Marfan Syndrome: a connective tissue disorder, caused by mutations in FBN1 gene, characterized by patients being very tall.

Autosomal Recessive Inheritance

• Characteristics of Autosomal recessive inheritance (AR):
  • Both males and females can be affected.
  • If both parents are affected, usually all children are affected as well.
  • Affected individuals with normal partners have normal children.
  • Both copies of the gene have to be mutated for expression of the abnormal phenotype.
• Two factors that increase the risk of recessive disease:
  • Both parents come from a high-risk population.
  • Consanguinity (partners share an ancestor).

X-Linked Recessive Inheritance

• Characteristics of X-Linked Recessive Inheritance:
  • Mainly males are affected since one mutant copy of the gene on the X-chromosome is sufficient to manifest the phenotype in males.
  • No male-to-male disease transmission.

X-Linked Dominant Inheritance

• Characteristics of X-Linked Dominant Inheritance:
  • Either sex can be affected.
  • Usually at least one parent is affected.
  • For an affected male, all of his daughters, but none of his sons are affected.

Y-Linked Inheritance

• Characteristics of Y-Linked Inheritance:
  • Only males are affected.
  • All sons of an affected father are affected.

Incomplete Dominance and Non-Penetrance

• Incomplete Dominance: dominant allele does not completely mask the effects of a recessive allele, causing a mix.
• Incomplete/Non-Penetrance: some mutation carriers may not show disorder features.
• Variable Expression: people with the same genotype can exhibit different symptom severities.
• Anticipation: symptoms of a genetic disorder appear at a younger age in each new generation, often with increased severity.

Mitochondrial Inheritance

• Mitochondrial inheritance is only inherited from the mother because only the head of the sperm is involved in the fusion with the oocyte.
• If a female has a mitochondrial trait, all her offspring inherit it.
• If a male has a mitochondrial trait, no offspring inherit it.
• Only 1 allele is present in each individual, so dominance is not an issue.

Heteroplasmy and Homoplasmy

• Heteroplasmy: a mixture of normal and abnormal mitochondria within each cell.
• Homoplasmy: mitochondria within a cell are the same, all normal or all mutant.

Mitochondrial DNA Replacement Therapy

• A method to prevent the passing of mitochondrial diseases from a mother to her child.
• It involves replacing faulty mitochondrial DNA in the mother's egg with healthy mitochondrial DNA from a donor.
• This way, the child inherits genetic material from three individuals, ensuring the child has functioning mitochondria.