Genetics Chapter: Autosomal Inheritance

A pattern of inheritance where only one copy of a mutated gene from either parent is sufficient to cause a disorder.

A pattern of inheritance where two copies of a mutated gene are needed to cause a disorder.

A group of genes in bacteria that are involved in the metabolism of lactose.

A group of genes in bacteria that are involved in the production of tryptophan.

The process of controlling the amount of protein produced from mRNA.

The phenotype is affected by both genetics and environment.

The repressor protein is always bound to the operator, preventing gene expression.

3D shapes of mRNA that affect gene expression.

Lac operon activity will be greatly diminished, due to glucose's preference.

Phenotype may not manifest, or may be mild, if the environment triggers are not present.

The operon is inactive; gene expression is suppressed.

The operon is active; gene expression is enabled.

cAMP binding to the operon promotes gene expression. High glucose levels = low cAMP and operon OFF.

Premature termination of mRNA synthesis, potentially due to improper folding.

Proteins need proper folding to interact and properly function. Missing interaction = missing function.

Misfolded protein that can induce other normal proteins to misfold, making them infectious.

Changes in phosphorylation can affect protein function. The active site can be turned on or off.

Altering amino acids can change protein function. Entirely impossible to phosphorylate=loss of function.

A mutation in the RYR1 gene, associated with congenital myopathies, typically autosomal recessive.

A mutation that creates a premature stop codon in a gene, preventing proper protein synthesis.

A metabolic disorder caused by a deficiency in the enzyme aldolase B, leading to the accumulation of fructose-1-phosphate in the liver, causing damage.

A metabolic disorder due to a deficiency in enzymes involved in galactose metabolism, resulting in galactose accumulation. GALT deficiency is the most severe, leading to galacitol toxicity.

Phenylketonuria: A metabolic disorder caused by a deficiency in phenylalanine hydroxylase, leading to phenylalanine accumulation. The severity can vary.

Maple Syrup Urine Disease: A metabolic disorder caused by a deficiency in branched-chain α-keto acid dehydrogenase, leading to the accumulation of branched-chain amino acids.

The clinical presentation of a metabolic disorder depends on the expression of the affected pathway in different tissues. Tissues that utilize the pathway are more likely to be affected.

A disorder affecting the breakdown of amino acids is likely to cause a buildup of toxic amino acids or disrupt downstream pathways.

A less severe form of PKU, often referred to as 'hyperphenylalaninemia,' where phenylalanine levels are elevated but below the level causing significant symptoms.

Abnormalities in facial features that can be indicative of certain genetic disorders, including metabolic disorders.

Difficulty breathing or respiratory distress that can occur as a symptom of various metabolic disorders.

Enlargement of both the liver and spleen, a common clinical finding associated with certain metabolic disorders.

A condition where phenylalanine levels are elevated, but not due to mutations in the PAH gene, unlike PKU.

Low levels of lactose lead to low lac operon activity, and high trp levels induce formation of the aporepressor, inhibiting transcription.

Lac operon activity is suppressed despite high lactose levels. Glucose is preferred, and high trp creates the aporepressor.

Alzheimer's has varying inheritance patterns. APP, PSEN1, PSEN2 genes are linked to autosomal dominance. APOE-ε4 increases risk and severity.

Huntington's has a repeat expansion in the HTT gene. 27-35 repeats pose risk for offspring, while >35 leads to higher risk and severity.

Neural tube defects like Spina bifida and Myelomeningocele are linked to MTHFR and other genes. Folic acid metabolism plays a crucial role.

Syndactyly, where fingers or toes are fused, is caused by mutations in the HOXD13 gene, likely affecting apoptosis and proper finger development.

A protein that can't achieve its proper 3D shape (fold) will likely be unable to form both tertiary and quaternary structures. Tertiary structure refers to how a single polypeptide chain folds, while quaternary structure describes how multiple polypeptide chains interact. This inability to fold correctly can disrupt its function and prevent it from interacting with other molecules.

A prion or prion-like protein is one that has misfolded and, importantly, can also induce other normal proteins to misfold. This misfolding can spread, ultimately leading to a cascade of misfolded proteins and potential disease.

Phosphorylation is the process of adding a phosphate group to a protein. This can alter the protein's shape and activity, potentially turning it 'on' or 'off'. This is a common way to regulate protein function.

If a protein's amino acid sequence is altered, preventing phosphorylation, it can lose its function. This is because phosphorylation is often essential for the protein to activate and perform its task.

Serine and threonine are often used in phosphorylation because they are recognized by kinases. While this change might be inconsequential, the protein may still retain function if the kinases can phosphorylate threonine as well. However, if this change prevents phosphorylation entirely, the protein may be dysfunctional.

If a variant in the RYR1 gene is present on both copies of the chromosome (biallelic) and is a nonsense mutation (premature stop codon), it likely follows an autosomal recessive inheritance pattern. This means that both parents must carry the variant in order for the child to inherit the disorder.

High levels of tryptophan cause the formation of an aporepressor, which binds to the operator and prevents transcription of the trp operon genes. This reduces the production of tryptophan.

Even though free tryptophan levels are low, the abundance of tryptophan-tRNA molecules leads to ribosome stalling during translation, which activates attenuation and blocks translation of the trp operon genes.

Low lactose levels decrease lac operon activity. Additionally, high tryptophan levels form an aporepressor, which leads to the suppression of transcription.

Even with high lactose levels, the lac operon is suppressed in this scenario. Glucose is preferred as an energy source, and high tryptophan levels lead to the formation of an aporepressor, further inhibiting transcription.

Several genes are linked to Alzheimer's disease, with varying inheritance patterns. APP, PSEN1, and PSEN2 are involved in autosomal dominant inheritance. APOE-ε4 increases risk and severity, particularly when combined with mutations in other genes.