UNIT 4: Sex Determination and Sex Linkage

Environmental Factors in Sex Determination

In some organisms, sex is not determined by chromosomes but by external environmental conditions.

• Temperature-Dependent Sex Determination (TSD): Found in many reptiles (e.g., crocodiles, alligators, many turtles). The temperature during a critical period of egg incubation determines the sex of the offspring.
• Social Sex Determination: In some fish (e.g., the Bluehead Wrasse), the social structure (e.g., the size or presence of a dominant male) can cause a female to change her sex.

Dosage Compensation and Barr Bodies

In mammals, females have two X chromosomes (XX) while males have one (XY). This difference in X-linked gene dosage is balanced through a process called **Dosage Compensation**.

• Dosage Compensation: The process by which the expression of X-linked genes is equalized between the sexes. In placental mammals, this is achieved by **inactivating one of the two X chromosomes in females**.
• Barr Bodies (Sex Chromatin): The inactivated X chromosome condenses into a compact, transcriptionally inactive structure called a Barr Body (or sex chromatin), which is visible near the nuclear envelope of female somatic cells.
• Lyon Hypothesis: Postulates that the inactivation of one X chromosome in female cells is random and occurs early in embryonic development, leading to a mosaic pattern of gene expression (e.g., the coat color pattern in Calico cats).

Genetic Balance Theory

Proposed by C.B. Bridges for sex determination in **Drosophila** (fruit flies).

• Sex is determined by the **ratio of X chromosomes to the sets of autosomes (A)**, not simply by the presence of the Y chromosome.
• Sex determination formula: Sex = Ratio of X / A sets.

  Ratio (X/A)	Genotype	Sex (Drosophila)
  1.0 (XX/AA)	XXAA	Female
  0.5 (XY/AA)	XYAA	Male
  1.5 (XXX/AA)	XXXAA	Metafemale (or Superfemale)
  0.33 (X0/AAA)	X0AAA	Metamale (or Supermale)

  The Y chromosome is primarily responsible for male fertility in Drosophila.

2. Sex-linked Inheritance

Sex-linked Inheritance

The pattern of inheritance resulting from genes located on the sex chromosomes (most commonly the **X chromosome**).

• Criss-cross Inheritance: A male (XY) transmits his X-linked trait to his daughter, who then transmits it to her son (i.e., from grandfather to grandson through an unaffected carrier daughter). This is characteristic of X-linked recessive traits.
• Males are Hemizygous: Since males (XY) only have one X chromosome, they express any trait coded on the X chromosome, even if it is recessive.

Fragile-X-Syndrome

A genetic condition causing a range of developmental problems, including learning disabilities and cognitive impairment.

• Cause: It is an X-linked dominant disorder (though with incomplete penetrance) caused by a mutation in the **FMR1 gene** on the X chromosome.
• Features: Characterized by an unusually long, thin, or "fragile" appearance of the X chromosome near the tip of the long arm in laboratory culture. It is the most common inherited cause of intellectual disability.

Sex-linked Inheritance: Haemophilia

An X-linked recessive bleeding disorder caused by a deficiency in one of the blood clotting factors (usually Factor VIII or Factor IX).

• Inheritance: Recessive allele 'h' is on the X chromosome.
  • X^H Y → Normal Male
  • X^h Y → Haemophiliac Male (Affected)
  • X^H X^H → Normal Female
  • X^H X^h → Carrier Female (Unaffected)
  • X^h X^h → Haemophiliac Female (Rare, requires affected father and carrier/affected mother)

Sex-linked Inheritance: Colour Blindness

The inability to distinguish between certain shades of color (most commonly red-green) due to a recessive gene on the X chromosome.

• Inheritance: Follows the same pattern as Haemophilia. The recessive allele 'c' for color blindness is on the X chromosome. It is much more common in males due to their hemizygous state.
• Genotype of an affected male: X^c Y.
• Genotype of a carrier female: X^C X^c.