Sex Determination and Sex-Linked Inheritance

In humans, sex is determined by the sex chromosomes (XX in females, XY in males), and sex-linked inheritance describes traits controlled by genes on the X (or Y) chromosome, which show different patterns in males and females. In brief: the father’s sperm decides the sex of the child, because every egg carries an X, while a sperm carries either X (girl) or Y (boy). Males have only one X chromosome, so a single recessive allele on the X, such as red-green color blindness or hemophilia A, shows up in the male phenotype. Females need two copies to be affected.

Sex-linked traits explain why some conditions are far more common in males. This guide explains sex determination in humans and other organisms, shows how to set up crosses for X-linked traits, covers carriers and the pattern of inheritance, works through color blindness and hemophilia examples and corrects common mistakes.

How is sex determined in humans?

Humans have 23 pairs of chromosomes. Twenty-two pairs are autosomes, which are the same in both sexes, and one pair is the sex chromosomes. Females have two X chromosomes (XX), and males have one X and one smaller Y chromosome (XY).

The X chromosome is large and carries about 800 to 900 protein-coding genes, many of them having nothing to do with sex. The Y chromosome is small with about 50 to 70 protein-coding genes. The key gene for male development is SRY (sex-determining region Y), located on the Y chromosome. In an embryo with SRY, the gonads develop into testes, which produce testosterone and cause male development. Without SRY, the gonads develop into ovaries.

Meiosis in a woman gives eggs that all carry one X. Meiosis in a man gives sperm: half carry an X and half carry a Y. If a sperm with X fertilizes the egg, the child is XX (girl). If a sperm with Y fertilizes it, the child is XY (boy). The chance is about 50 percent each, and the actual proportion at birth is slightly higher for boys, around 105 boys per 100 girls.

How is sex determined in other organisms?

• Birds, butterflies and some reptiles: the female is the heterogametic sex (ZW) and the male is ZZ.
• Grasshoppers: males are XO (one X) and females are XX.
• Bees and ants: females develop from fertilized eggs (diploid) and males from unfertilized eggs (haploid).
• Crocodiles, many turtles and some lizards: the temperature at which the eggs are incubated determines the sex.
• Some fish can change sex during their lifetime, such as clownfish and wrasses.

What is sex-linked inheritance?

A sex-linked gene is located on a sex chromosome. The term usually refers to genes on the X chromosome (X-linked), because the Y has few genes. Males are hemizygous for X-linked genes, which means they have only one allele, and it is always expressed, whether dominant or recessive. Females have two alleles and can be homozygous or heterozygous.

X-linked recessive disorders include red-green color blindness (affecting about 8 percent of males of Northern European ancestry, and about 0.5 percent of females), hemophilia A and B, and Duchenne muscular dystrophy. They have these characteristic patterns:

• They affect many more males than females.
• An affected father cannot pass the trait to his sons, as sons get his Y, but all his daughters become carriers.
• A carrier mother has a 50 percent chance of passing the allele to each child. Half of her sons are affected, and half of her daughters are carriers.
• The trait often skips generations through carrier females.

How do you set up an X-linked cross?

Write the alleles as superscripts on the X chromosome, such as X^H for the normal allele and X^h for the recessive hemophilia allele. The Y chromosome carries no allele for this gene and is written as Y. Then follow the usual Punnett square steps.

1. Write the genotypes: for example, X^HX^h (carrier woman) × X^HY (unaffected man).
2. List the gametes: the mother gives X^H or X^h; the father gives X^H or Y.
3. Fill in the square and note the sex and phenotype of each child.

X-linked recessive crosses compared

Worked example: color blindness and hemophilia

Example 1: color blindness

A man with red-green color blindness (X^cY) and a woman with normal vision whose father was color blind have children. What are the probabilities?

1. The woman’s father was X^cY, and he gave her his X^c. She has normal vision, so her other X carries the normal allele: she is X^CX^c, a carrier.
2. Cross X^CX^c × X^cY: the possible children are X^CX^c (carrier girl), X^cX^c (color-blind girl), X^CY (normal boy) and X^cY (color-blind boy), each with 25 percent.
3. The probability that a child is color blind is 25 + 25 = 50 percent. For a son, it is 50 percent. For a daughter, it is 50 percent.

Example 2: hemophilia in a royal family

Queen Victoria was a carrier of hemophilia B, probably through a new mutation, and she passed the allele to several of her descendants, who were members of European royal families. Her son Leopold had hemophilia, and two of her daughters, Alice and Beatrice, were carriers. They passed it on to royal families in Russia, Spain and Germany. Tsar Nicholas II’s son Alexei had hemophilia, inherited from his mother Alexandra, who was a granddaughter of Victoria. This history is a classic example of a family tree showing X-linked inheritance.

What is X-inactivation?

Since females have two X chromosomes and males have one, the female cells would have double the dose of X genes. To balance this, one of the two X chromosomes in each female cell is randomly switched off early in development. The inactive X condenses into a dense structure called a Barr body. As a result, a female carrier is a mosaic of cells with the active X from the mother in some places and the active X from the father in others. A famous example is the tortoiseshell cat, whose patches of orange and black fur result from X-inactivation, so tortoiseshell cats are almost always female.

How was sex linkage discovered?

In 1910 Thomas Hunt Morgan found a white-eyed male fruit fly among red-eyed flies. His crosses showed that the white-eye trait was inherited in a pattern related to sex, and he concluded that the gene is on the X chromosome. This was the first evidence that a particular gene is located on a particular chromosome. Nettie Stevens and Edmund Wilson had shown in 1905 that sex is determined by chromosomes. The SRY gene was identified in 1990.

Which mistakes are common?

Mistake 1: Saying that the mother decides the sex of the baby

The father’s sperm, with X or Y, decides the sex.

Mistake 2: Writing alleles on the Y for X-linked traits

The Y has no allele for these genes. Write X^hY, with the allele only on the X.

Mistake 3: Saying that fathers can pass X-linked traits to sons

A father gives his Y to his sons. His X-linked alleles go only to his daughters.

Mistake 4: Thinking that carriers are always male

Carriers of X-linked recessive traits are female. A male with the allele is affected.