2.(c) Draw pedigrees for autosomal recessive and sex-linked inheritance using examples from human.

Understanding Pedigrees and Standard Symbols

A pedigree is a chart that illustrates the lineage of a family and indicates the presence or absence of a particular genetic trait or disorder in each member across generations. Standardized symbols are used to make pedigrees universally understandable:

• Squares: Represent males.
• Circles: Represent females.
• Diamonds: Represent individuals of unknown sex.
• Shaded symbols: Indicate individuals who express the trait or are affected by the disorder.
• Unshaded symbols: Indicate unaffected individuals.
• Half-shaded symbols (or a dot inside): Indicate carriers (heterozygous for a recessive trait but not expressing it).
• Horizontal line between two individuals: Represents a mating or marriage.
• Vertical line extending down from a mating line: Leads to offspring.
• Siblings: Are connected to a horizontal line above them, listed in birth order from left to right.
• Generations: Are denoted by Roman numerals (I, II, III, etc.) on the left side.
• Individuals within a generation: Are numbered consecutively with Arabic numerals (1, 2, 3, etc.).

Autosomal Recessive Inheritance

Autosomal recessive conditions arise from mutations in genes located on one of the 22 pairs of autosomal (non-sex) chromosomes. For an individual to express an autosomal recessive trait, they must inherit two copies of the mutated recessive allele, one from each parent. Individuals with only one copy of the recessive allele are carriers; they do not typically show symptoms but can pass the allele to their offspring.

Characteristics of Autosomal Recessive Inheritance in Pedigrees:

• Males and females are affected in roughly equal proportions.
• The trait often appears to "skip generations" because carriers (heterozygotes) are unaffected.
• Affected individuals usually have unaffected parents (who are carriers).
• If both parents are carriers, there is a 25% chance for each child to be affected, a 50% chance to be a carrier, and a 25% chance to be homozygous dominant (unaffected and non-carrier).
• Consanguinity (marriage between relatives) increases the likelihood of observing autosomal recessive conditions, as relatives are more likely to share the same recessive alleles.

Pedigree Example for Autosomal Recessive Inheritance (e.g., Cystic Fibrosis)

Let 'A' be the dominant allele (normal) and 'a' be the recessive allele (affected).

       I
       O ---- O
       |      |
       A/a    A/a
      /|\
     / | \
    /  |  \
   /   |   \
  O    O    []
 II    A/A  A/a  a/a
       1    2    3

Explanation:

• Generation I: Both parents are unaffected circles (O), but they are carriers (A/a) as they produce an affected child.
• Generation II:
  • II-1 (O) is an unaffected female (A/A or A/a).
  • II-2 (O) is an unaffected female (A/A or A/a).
  • II-3 ([]) is an affected male (a/a), indicated by a shaded square. This demonstrates that unaffected parents can have affected offspring, characteristic of recessive inheritance.
• Human Examples: Cystic Fibrosis, Sickle Cell Anemia, Tay-Sachs Disease, Phenylketonuria (PKU).

Sex-Linked Inheritance (X-linked Recessive)

Sex-linked inheritance refers to the transmission of genes located on the sex chromosomes (X or Y). In humans, most clinically significant sex-linked traits are X-linked, as the X chromosome carries many genes, while the Y chromosome carries very few. We will focus on X-linked recessive inheritance, which is a common pattern.

Characteristics of X-linked Recessive Inheritance in Pedigrees:

• Males are affected much more frequently than females because males have only one X chromosome (XY), so a single recessive allele on the X chromosome will result in the trait. Females (XX) would need two copies of the recessive allele to be affected.
• Affected males pass the recessive allele to all their daughters, making them carriers, but never to their sons (as sons inherit the Y chromosome from their father).
• Sons of carrier mothers have a 50% chance of being affected. Daughters of carrier mothers have a 50% chance of being carriers.
• There is no father-to-son transmission.
• The trait can appear to skip generations, typically passing from an affected grandfather through a carrier daughter to an affected grandson.

Pedigree Example for Sex-Linked (X-linked Recessive) Inheritance (e.g., Hemophilia A)

Let X^A be the dominant allele (normal) and X^a be the recessive allele (affected). Y is the Y chromosome.

      I
      O ---- []
      |      |
      XAXa   XAY
      |
      |\
      | \
     O  []
II   XAXa XaY
     1   2

Explanation:

• Generation I:
  • I-1 (O) is an unaffected female carrier (X^AX^a).
  • I-2 ([]) is an unaffected male (X^AY). This represents a scenario where a carrier mother passes the trait.
• Generation II:
  • II-1 (O) is an unaffected female, who is a carrier (X^AX^a).
  • II-2 ([]) is an affected male (X^aY), inheriting the recessive X^a allele from his mother.
• Another scenario (Father affected, Mother unaffected):

       I
       O ---- []
       |      |
       XAXA   XaY
      /|\
     / | \
    /  |  \
   /   |   \
  O    O    O
 II   XAXa XAXa XAY
      1    2    3

Explanation:

• Generation I:
  • I-1 (O) is an unaffected female (X^AX^A).
  • I-2 ([]) is an affected male (X^aY).
• Generation II:
  • II-1 (O) and II-2 (O) are unaffected female carriers (X^AX^a), inheriting the X^a from their father.
  • II-3 (O) is an unaffected male (X^AY), inheriting his X from his mother. There is no father-to-son transmission of the X-linked trait.
• Human Examples: Hemophilia A and B, Red-Green Color Blindness, Duchenne Muscular Dystrophy.

Comparative Table: Autosomal Recessive vs. X-linked Recessive Inheritance

Feature	Autosomal Recessive	X-linked Recessive
Chromosome Affected	Autosomal chromosomes (1-22)	X chromosome (sex chromosome)
Sex Predominance	Affects males and females equally	Males affected significantly more than females
Parents of Affected	Usually unaffected carriers	Affected male's mother is usually a carrier
Generation Skipping	Common; trait skips generations	Common; trait skips generations, often from grandfather (affected) through mother (carrier) to grandson (affected)
Father-to-Son Transmission	Possible	Never occurs
Affected Daughters	Requires two recessive alleles (aa)	Rare; requires affected father (XaY) and at least carrier mother (XAXa) or affected mother (XaXa)
Carrier Status	Both males and females can be carriers (Aa)	Only females can be carriers (XAXa); males are either affected or unaffected