Sex-Linked Traits

Definition of Sex-Linked Traits

Sex-linked traits are determined by genes found on the X and Y chromosomes. Unlike typical Mendelian genetics, where both sexes have two copies of each chromosome, sex-linked traits are determined by the inheritance of sex chromosomes which differ between the sexes. Females inherit two copies of the X chromosome, one from each parent. In contrast, males inherit one copy of the X chromosome from the mother and one copy of the Y chromosome from the father.

Therefore, females can be either homozygous or heterozygous for X-linked traits based on their two alleles for a given gene, while males will only have one allele for a given gene. In contrast, females do not have a Y chromosome for Y-linked traits, so they cannot express any Y-linked traits.

Sex-Linked Genes

By convention, sex-linked genes are denoted by the chromosome, either X or Y, followed by a superscript to denote the allele of interest. For example, for gene A which is X-linked, a female might be X^AX^a, where X represents the 'X' chromosome, 'A' represents the dominant allele of the gene, and 'a' represents the recessive allele of the gene. Therefore, in this example, the female will have one copy of the dominant allele and one copy of the recessive allele.

Sex-linked genes determine sex-linked traits. Sex-linked genes can follow three inheritance patterns:

• X-linked dominant
• X-linked recessive
• Y-linked

We will look at both male and female inheritance for each inheritance pattern separately.

X-linked Dominant Genes

Just like dominant traits in autosomal genes, which only need one copy of the allele to express the trait of interest, X-linked dominant genes work similarly. If a single copy of the X-linked dominant allele is present, the individual will express the trait of interest.

X-linked Dominant Genes in Females

Since females have two copies of the X chromosome, a single X-linked dominant allele is sufficient for the female to express the trait. For example, a female who is X^AX^A or X^AX^a will express the dominant trait as they have at least one copy of the X^A allele. In contrast, a female who is X^aX^a will not express the dominant trait.

X-linked Dominant Genes in Males

A male has only one X chromosome; therefore, if a male is X^AY, they will express the dominant trait. If the male is X^aY, they will not express the dominant trait (Table 1).

Table 1: Comparing Comparing genotypes for an X-linked recessive gene for both sexes

X-linked Recessive Genes

In contrast to X-linked dominant genes, X-linked recessive alleles are masked by a dominant allele. Therefore, a dominant allele must be absent for the X-linked recessive trait to be expressed.

X-linked Recessive Genes in Females

Females have two X-chromosomes; therefore, both X chromosomes must have the X-linked recessive allele for the trait to be expressed.

X-linked Recessive Genes in Males

Since males only have one X-chromosome, having a single copy of the X-linked recessive allele is sufficient to express the X-linked recessive trait (Table 2).

Table 2: Comparing genotypes for an X-linked recessive gene for both sexes

Y-linked Genes

In Y-linked genes, the genes are found on the Y chromosome. Since only males have a Y-chromosome, only males will express the trait of interest. Furthermore, it will be passed from father to son only (Table 3).

Table 3: Comparing genotypes for an X-linked recessive gene for both sexes

Common Sex-Linked Traits

The most common example of a sex-linked trait is eye color in the fruit fly.

Thomas Hunt Morgan was the first to discover sex-linked genes in fruit flies (Fig. 2). He first noticed a recessive mutation in fruit flies that turned their eyes white. Using Mendel's theory of segregation, he expected that crossing a red-eyed female with a white-eyed male would produce progeny all with red eyes. Sure enough, following Mendel's law of segregation, all offspring in the F1 generation had red eyes.

When Morgan crossed the F1 offspring, a red-eyed female with a red-eyed male, he expected to see a 3:1 ratio of red eyes to white eyes because that is what Mendel's law of segregation suggests. While this 3:1 ratio was observed, he noticed that all the female fruit flies had red eyes while half of the male fruit flies had white eyes. Therefore, it was clear that the inheritance of eye color was different for female and male fruit flies.

He proposed that eye color in fruit flies must be on the X chromosome because patterns of eye color differed between males and females. If we revisit Morgan's experiments using Punnett squares, we can see that eye color was X-linked (Fig. 2).

Sex-Linked Traits in Humans

Humans have 46 chromosomes or 23 pairs of chromosomes; 44 of those chromosomes are autosomes, and two chromosomes are sex chromosomes. In humans, the sex chromosome combination determines the biological sex during birth. Biological females have two X chromosomes (XX), while biological males have one X and one Y chromosome (XY). This chromosome combination makes males hemizygous for the X chromosome, which means they only have one copy.

Just like autosomes, genes can be found on the X and Y chromosomes. In humans, the X and Y chromosomes are differently sized, with the X chromosome being much larger than the Y chromosome. This size difference means there are more genes on the X chromosome; therefore, many traits will be X-linked, rather than Y-linked, in humans.

Males will be more likely to inherit X-linked recessive traits than females since inheritance of a single recessive allele from an affected, or carrier mother will be sufficient to express the trait. In contrast, heterozygous females will be able to mask the recessive allele in the presence of the dominant allele.

Examples of Sex-Linked Traits

Examples of X-linked dominant traits include Fragile X syndrome and Vitamin D resistant rickets. In both of these disorders, having one copy of the dominant allele is sufficient to display symptoms in both males and females (Fig. 3).

Examples of X-linked recessive traits include red-green color blindness and hemophilia. In these cases, females need to have two recessive alleles, but males will express traits with only one copy of the recessive allele (Fig. 4).

X-linked recessive inheritance. Carrier mothers will pass on the mutation to the son or carrier daughters (left) while affected fathers will pass only have carrier daughters (right)

Since there are very few genes on the Y chromosome, examples of Y-linked traits are limited. However, mutations in certain genes, such as the sex-determining region (SRY) gene and the testis-specific protein (TSPY) gene, can be passed from father to son through Y chromosome inheritance (Fig. 5).

Y-linked inheritance. Affected fathers pass on the mutations to only their sons