l13;pedigrees

Mendelian Context: Gregor Mendel discovered simple inheritance patterns using pea plants ( $Pisum\,sativum$ ). These plants are ideal for study because they possess several single-gene traits, are easy to observe, and allow for breeding to be conducted in a controlled environment.
Challenges in Human Genetics: Studying inheritance in humans is significantly more complex for several reasons:
- Complexity: Human genetics is enormously complex compared to simple Mendelian traits.
- Reproductive Rate: Humans reproduce much more slowly than plants or insects.
- Ethical Constraints: Controlled breeding of humans in laboratory settings is impossible as it would breach fundamental bioethical concepts (such as autonomy, beneficence, and non-maleficence).
The Solution - Pedigrees: To overcome these challenges, scientists observe genetic patterns in human families by constructing family trees called pedigrees. These diagrams show how specific traits are passed down from one generation to the next.

To standardize the mapping of family traits, specific symbols are utilized in pedigree construction:

Male: Represented by a square symbol.
Female: Represented by a circle symbol.
Trait Expression: When an individual expresses the trait or phenotype being studied, their symbol is filled in (shaded).
Mating/Parents: A horizontal line drawn between two symbols indicates they have produced children together.
Offspring: Children are drawn in a separate row underneath their parents, connected to them by vertical lines.
Labeling System:
- Generations: Identified by Roman numerals ( $I, II, III, etc.$ ).
- Individuals: Within each generation, individuals are numbered from left to right using Arabic numerals ( $1, 2, 3, etc.$ ).
- Example: Individual $II-4$ refers to the fourth person in the second generation.

Allele: Alternative forms of a gene. Most traits discussed involve two alleles.
Genotype: The genetic makeup of an individual (e.g., $AA, Aa, aa$ ).
Phenotype: The observable physical or biochemical characteristics of an individual (e.g., deaf vs. hearing).
Wild Type: Refers to the most common or dominant phenotype found in nature.
Heterozygote/Carrier: An individual possessing two different alleles for a trait ( $Aa$ ). In the context of recessive disorders, a carrier does not show the phenotype but can pass the recessive allele to offspring.

Pedigrees are used to identify various types of inheritance:

Autosomal Recessive: The trait is found on non-sex chromosomes. It typically requires two copies of the recessive allele for expression ( $aa$ ). Characteristics often include the trait "skipping" generations or two unaffected parents having an affected child.
Autosomal Dominant: The trait is expressed if at least one dominant allele is present ( $AA$ or $Aa$ ). Every affected individual usually has at least one affected parent.
X-Linked Recessive: The gene for the trait is located on the X chromosome. These traits often appear more frequently in males ( $X^h Y$ ) because they only have one X chromosome. A female must be homozygous recessive ( $X^h X^h$ ) to express the trait.

Natural Prevalence: Albinism occurs in various species, including peacocks and red-necked wallabies.
Definition: Albinos are individuals (human or animal) with little or no colored pigment in their skin, eyes, hair, or feathers.
Genetics: Albinism is an autosomal recessive trait controlled by a single gene.
Analysis of Albinism Pedigree:
- If individuals $I-1$ and $I-2$ (unaffected) have an affected child ( $II-3, aa$ ), it proves both parents are carriers ( $Aa$ ).
- Probability Calculation: Individual $II-6$ expresses albinism ( $aa$ ). Individual $II-7$ is unaffected but has an affected child ( $III-4, aa$ ), meaning $II-7$ must be a heterozygote ( $Aa$ ). The cross is $aa \times Aa$ . The probability that their fifth child (represented by "?") will have albinism is $50\%$ .

Condition: Cystic fibrosis is an autosomal recessive respiratory disease affecting the lining of the lungs.
Alleles: Use $G$ (dominant) and $g$ (recessive).
Genotype Identification:
- An affected individual (shaded) has the genotype $gg$ .
- If two unaffected parents ( $I-1$ and $I-2$ ) have an affected child ( $II-2$ ), the parents must be heterozygous ( $Gg$ ).
- Unshaded offspring ( $II-1$ ) could be homozygous dominant ( $GG$ ) or heterozygous ( $Gg$ ).

Condition: Haemophilia is an X-linked recessive blood-clotting disorder.
Alleles: $X^H$ (normal), $X^h$ (haemophilia), and $Y$ (Y-chromosome).
Case Analysis:
- Genotypes: An affected male ( $I-1$ ) is $X^h Y$ . An unaffected female who has an affected son must be a carrier ( $X^H X^h$ ).
- Probability Example: For a couple consisting of a carrier female ( $III-1 : X^H X^h$ ) and an unaffected male ( $III-2 : X^H Y$ ), we use a Punnett square to determine the health of their sons.
- Punnett Square for Sons:
  - The father contributes the $Y$ chromosome to all sons.
  - The mother contributes either $X^H$ or $X^h$ .
  - Potential male genotypes: $X^H Y$ and $X^h Y$ .
  - Probability: There is a $50\%$ probability that a son born to this couple will have haemophilia.

The Hapsburg Jaw: How is the Hapsburg jaw related to genetics and inheritance?
- Note: This historical example illustrates the result of selective/in-breeding where specific recessive or dominant physical traits become prominent within a lineage.
Pedigree Interpretation: Identifying patterns.
- Question: How do we know a trait is X-linked recessive?
- Answer: Often by observing that only males are affected, or that affected fathers do not pass the trait to their sons, but all their daughters become carriers.
True/False Concepts:
- Statement: Individuals $II-1$ and $II-2$ have had one daughter and two sons.
- Status: True (based on square/circle symbols connected to them).
- Statement: All children of $I-1$ and $I-2$ are heterozygotes.
- Status: This depends on the specific outcome; if parents are $Aa \times Aa$ , offspring could be $AA, Aa,$ or $aa$ .