Sex-Linked & Pedigrees

Humans have 22 pairs of autosomes (non-sex chromosomes) and one pair of sex chromosomes. Females are XX. Males are XY. This unequal setup creates unique inheritance patterns for genes on the X and Y chromosomes.

Sex Determination

The SRY gene on the Y chromosome is the master switch for male development. It triggers testis formation, which leads to testosterone production and male sex characteristics. Without SRY, the default developmental pathway is female.

X-Linked Recessive Inheritance

The X chromosome carries hundreds of genes. Males have only one X, so they express whatever allele is on it - they are hemizygous for X-linked genes. Females have two X chromosomes, so they can be carriers (heterozygous) without showing symptoms.

Key features of X-linked recessive traits:

• Affected individuals are almost always male (one bad copy is enough)
• Carrier females ($X^{A}$ $X^{a}$) are usually unaffected but can pass the allele to sons
• Affected fathers cannot pass the trait to sons (fathers give Y to sons, not X)
• All daughters of an affected father are at least carriers (they inherit his X)

Classic examples: hemophilia A, red-green color blindness, Duchenne muscular dystrophy.

X-Linked Dominant Inheritance

X-linked dominant traits are expressed in both males AND females who carry even one copy. However, because females have two X chromosomes and X-inactivation occurs randomly, affected females may show milder or more variable symptoms than affected males.

Key features:

• Affected fathers pass the trait to ALL daughters (they all get his X) but NO sons (they get Y)
• Affected mothers pass the trait to approximately half of all children regardless of sex
• Both males and females are affected, but females may show variable expressivity

Y-Linked Inheritance

The Y chromosome is small and carries very few genes (about 50-60 protein-coding genes). Y-linked traits pass exclusively from father to son.

The most important Y-linked gene is SRY (sex-determining region Y). Y-linked traits are rare and always appear in all male descendants of an affected father.

X-Inactivation and Barr Bodies

Females have twice as many X-linked genes as males. To balance gene dosage, each female cell randomly inactivates one X chromosome early in embryonic development. The inactivated X condenses into a Barr body - a dark, inactive clump visible at the edge of the nucleus.

This process is random: in some cells the maternal X is active, in others the paternal X is active. The result is a mosaic of two cell populations.

The classic example is the calico cat. Coat color is X-linked, with one allele for orange and one for black. A heterozygous female ($X^{O}$ $X^{B}$) randomly inactivates one X in each patch of skin, producing a patchwork of orange and black fur. Male cats (XY) can only be orange or black, never calico.

Pedigree Analysis

A pedigree is a family tree that tracks a trait across generations. The MCAT expects you to look at a pedigree and determine the most likely inheritance pattern.

Pedigree symbols:

• Circles = female, Squares = male
• Filled = affected, Open = unaffected
• Half-filled = carrier (for recessive traits)
• Horizontal line = mating pair
• Vertical line = parent-to-offspring connection

How to Read a Pedigree

Use this decision tree:

Step 1: Is it dominant or recessive?

• If two unaffected parents have an affected child, the trait is recessive (both parents must be carriers)
• If every affected individual has at least one affected parent, the trait is likely dominant

Step 2: Is it autosomal or X-linked?

• If affected fathers have affected sons, it is NOT X-linked (must be autosomal)
• If the trait appears much more frequently in males, consider X-linked recessive
• If an affected father passes the trait to ALL daughters, consider X-linked dominant

Quick Reference: Inheritance Pattern Clues