Week 2 - P2 - L3 - Genetics: Duplicate Genes, Environmental Influences, and Sex-Influenced Traits

Duplicate Genes

Definition: Duplicate genes occur when two genes within the genome share the same function due to a duplication event.
Genetic Characteristics:
- Duplicate genes are distinguished by a specific phenotypic ratio in the $F_{2}$ generation of a dihybrid cross: a $15:1$ ratio.
- The phenotype is produced as long as at least one dominant allele is present from either of the two genes.
- For example, if the two genes are labeled $A$ and $B$ , an individual only needs one dominant allele ( $A$ or $B$ ) to express the dominant phenotype.
Example: Fruit Shape in Shepherd’s Purse (a weed):
- The two genes involved are identified as $T$ and $V$ .
- Phenotypes:
  - Triangular Fruit Shape: Produced if the individual has at least one dominant allele for either gene (Genotypes: $T-V-$ , $T-vv$ , or $ttV-$ ).
  - Ovate Fruit Shape: Produced only if the individual is homozygous recessive for both genes (Genotype: $ttvv$ ).
- Crossing Experiment:
  - Parental ( $P$ ) Generation: A cross between a homozygous dominant individual ( $TTVV$ ; triangular) and a homozygous recessive individual ( $ttvv$ ; ovate).
  - $F_{1}$ Generation: All offspring are heterozygotes ( $TtVv$ ) and exhibit the triangular fruit shape.
  - $F_{2}$ Generation: When the $F_{1}$ generation is self-crossed, the resulting ratio is $15$ triangular offspring for every $1$ ovate offspring.
  - Explanation: $15$ out of $16$ possible combinations contain at least one dominant $T$ or $V$ allele, resulting in the triangular shape. Only the single $ttvv$ combination results in the ovate shape.
Human Application: Research published previously suggested that the shape of the human brain might be influenced by duplicate genes; however, this is difficult to investigate in humans, making plants like Shepherd’s Purse a clearer model for study.

Environmental Impact on Phenotype

General Principle: The environment can significantly affect the phenotypic expression of a genotype.
Distinction from Complex Diseases:
- Complex Diseases: These involve many genes working in combination with environmental factors (e.g., skin color or hair color).
- Environmental Effect on Single Genes: This focus looks specifically at how external factors impact the expression of a singular gene.
Example: Temperature Sensitivities:
- Arctic Fox:
  - Winter: The fox produces white fur as a protective mechanism to blend into the snow.
  - Summer: As the temperature changes, the fox grows brown fur.
- Siamese Cats:
  - These cats possess a temperature-sensitive variant in the enzyme tyrosinase, which is responsible for melanin (pigment) production.
  - This variant works best at room temperature rather than core body temperature.
  - Extremities: Areas such as the tips of the ears, tips of the tail, and paws (which are closer to room temperature and cooler than the rest of the body) develop darker pigment.
  - Body Regions: Warmer regions of the body do not reach the threshold for the enzyme to function optimally, resulting in lighter hair.
  - Variation exists even among Siamese cats; phenotypic expression can look slightly different between individuals.
Example: Chemical/Dietary Impacts:
- Phenylketonuria (PKU):
  - Inheritance: Autosomal recessive condition caused by variants in the PAH gene.
  - Prevalence: Affects approximately $1 \text{ in } 15,000$ individuals in Australia, which equates to roughly $20$ to $25$ babies per year.
  - Detection: All babies in Australia are tested at birth via a heel prick test to allow for early detection and immediate dietary intervention.
  - Normal Mechanism: In individuals without PKU, dietary protein is digested into nutrients. The amino acid phenylalanine is converted into tyrosine by the enzyme phenylalanine hydroxylase (the product of the PAH gene).
  - Lack of Enzyme: In individuals with PKU, the enzyme does not function properly. This leads to a toxic accumulation of phenylalanine and a deficiency of tyrosine.
  - Consequences: The accumulation is neurotoxic and can lead to severe intellectual disability.
  - Treatment: Management involves a very strict diet low in phenylalanine from birth, which can effectively "rescue" the phenotype and prevent health complications.

Congenital Lactase Deficiency

Alternative Name: Congenital alactasia.
Inheritance: Autosomal recessive condition associated with variants in the LCT gene.
Mechanism:
- The LCT gene provides instructions for producing the lactase enzyme.
- Variants interfere with the enzyme's function, causing an inability to digest lactose (the sugar found in breast milk and formula).
- Normal Function: Usually, lactase breaks down lactose into galactose and glucose for absorption.
- Deficiency Function: Infants cannot break down the sugar, leading to severe digestive issues.
Treatment: Management requires a lifelong lactose-free diet, beginning with lactose-free formula in infancy.

Sex-Influenced and Sex-Limited Traits

Overview: Sex can influence gene expression in ways that are not necessarily linked to genes located on the sex chromosomes (X or Y).
Sex-Influenced Characteristics:
- These are inherited traits where the same gene is expressed differently in males and females, often due to the influence of hormones.
- These are typically autosomal genes.
- Example: Pattern Baldness:
  - The condition is caused by an allele (referred to as allele $B$ ).
  - In XY Individuals (Males): The trait behaves as an autosomal dominant condition.
    - Genotypes $BB$ and $Bb$ result in baldness.
    - Genotype $bb$ results in no baldness.
  - In XX Individuals (Females): The trait behaves as an autosomal recessive condition.
    - Genotype $BB$ results in hair loss/baldness (though often less pronounced than in males).
    - Genotypes $Bb$ and $bb$ result in no baldness.
  - Case Study: The Adams family line (including US Presidents John Adams and John Quincy Adams) shows this inheritance pattern.
  - Proof of Autosomal Inheritance: Pedigrees show males passing the trait to both males and females, which would be impossible if the gene were strictly X-linked or Y-linked.
Sex-Limited Characteristics:
- These are traits that appear or develop in only one of the sexes, even though both sexes may carry the genes (on either autosomal or sex chromosomes).
- Examples:
  - Ovary Development: Limited to XX individuals.
  - Milk Production: Limited to XX individuals.
  - Sperm Development: Limited to XY individuals.