X-Linked Inheritance

Chromosome*s that both males and females possess in matched sets are called autosome*s. The X and Y-chromosomes that determine the sex of an individual in mammals follow a different pattern and are called allosome*s. The genes present on the X and Y-chromosomes are called sex-linked genes. Sex-linked genes on the X-chromosome are X-linked genes. Genes on the Y-chromosome are Y-linked.

Females have two X-chromosomes. Males have one X and one Y-chromosome.

Females have two X-chromosomes. Males have one X and one Y-chromosome.
Females have two X-chromosomes. Males have one X and one Y-chromosome.

With both an X and a Y-chromosome, males inherit both X and Y-linked traits, while females only inherit X-linked traits. Since males have only one copy of each sex chromosome, they are hemizygous for all sex-linked genes, and they always express the phenotype* of the allele* they get. In other words, their phenotypes always match their genotype*s.

Females get two copies of X-linked genes, demonstrating the more typical dominant-recessive expression patterns of non-sex linked traits.

These patterns cause expression patterns of sex-linked traits to differ between male and female offspring.

The X-chromosome is larger and contains more genes than the Y-chromosome, so most sex-linked traits are X-linked traits.

Wild-type fruit flies have dark red eyes, but there are recessive alleles of this eye color gene (called the white gene) that cause individuals to have white eyes. As a recessive trait, the white eye phenotype is masked by the presence of a wild-type (red encoding) allele. If the white gene were on an autosome, it would exhibit classical Mendelian inheritance patterns . However, the gene is on the X-chromosome, making it an excellent illustration of sex-linked inheritance patterns.

Select one male and one female individual for the P1 generation and click 'begin' to explore eye color inheritance patterns in fruit flies:

Since this particular gene that controls eye color is on the X-chromosome, females (XX) carry two copies, and males (XY) only carry one. In females, the presence of one dominant red encoding allele (XW) will produce red eyes even if the individual is heterozygous for the white allele. Females can be:

  • Homozygous dominant for the red encoding allele - genotype: XWXW; phenotype: red eyes.
  • Heterozygous - genotype XWXw; phenotype: red eyes.
  • Homozygous recessive with two white encoding alleles - genotype XwXw; phenotype white eyes.
Three allele combinations possible in females.
Three allele combinations possible in females.

With only one copy of the X-chromosome, all males are hemizygous for this gene. They have only two options:

  • Hemizygous dominant - genotype: XWY; phenotype: red eyes
  • Hemizygous recessive - genotype: XwY; phenotype: white eyes.
  • Two allele combinations possible in males.
    Two allele combinations possible in males.

    Observing the ratio of male and female red and white-eyed individuals produced with reciprocal cross*es shows the difference between sex-linked and classic Mendelian inheritance patterns. Reciprocal crosses involve crossing true breeding red and white-eyed individuals.

    Two reciprocal crosses are possible
    Two reciprocal crosses are possible A) a true-breeding red-eyed female with a white-eyed male and B) a true-breeding white-eyed female with a red-eyed male.

    Performing the first reciprocal cross: a true-breeding red-eyed female (homozygous dominant) with a true-breeding white-eyed male (hemizygous recessive) results in an F1 generation comprised entirely of red-eyed individuals. 100% of the F1 generation having red-eyes is consistent with what would be predicted based on Mendelian inheritance of a recessive allele. However, with an X-linked gene, the reason for red eyes differs between males and females.

    All the female offspring are heterozygous, receiving an X-chromosome with a red allele from their mother and an X-chromosome with the white allele from their father. The presence of the red allele from the mother masks the white allele. Male offspring only have one X-chromosome, which they received from their female parent. Since the female parent is homozygous, whichever allele the males get, they will receive a red-eye allele.

    Females are red-eyed because the presence of the recessive copy is masked. Males are red-eyed because they only have one copy of the gene, and that copy is for the red allele.

    The females’ phenotype and genotype are consistent with the patterns discovered by Mendel, but the males, as hemizygotes, are not.

    The differences between the sexes become more apparent in a cross using the red-eyed F1 male and red-eyed F1 females. This cross produces a 3:1 ratio of red-eyed to white-eyed individuals, but all white-eyed individuals are male. No females have white eyes because they received one of their X-chromosomes from their hemizygous dominant, red-eyed father. The male offspring all received their single X-chromosome from the heterozygous female parent, so half received a red allele, and half received a white allele.

    First three generations of the first reciprocal cross
    First three generations of the first reciprocal cross.

    Inheritance patterns with the other reciprocal cross (homozygous recessive female with hemizygous dominant male) diverge from the Mendelian pattern more quickly. The F1 generation contains an equal proportion of white and red-eyed individuals, but all males have white eyes, and all females have red eyes.

    First three generations of the second reciprocal cross
    First three generations of the second reciprocal cross.

    Crossing these F1’s again results in a 1:1 ratio of red and white-eyed individuals, but in the F2, half the female offspring and half the male offspring have red eyes.

    In both reciprocal crosses, patterns of inheritance beyond the F2 generation vary depending on which F2 individuals are chosen for the cross.

    X-linked recessive phenotypes are more commonly observed in males because males are hemizygous for sex-linked traits. Females can be heterozygous for a trait and therefore carry the recessive allele without expressing it. These carrier females have a 50% chance of passing the recessive alleles to their male offspring. These male offspring can not be carriers. If they receive the recessive allele, they will express the recessive trait.

    Females expressing detrimental recessive traits like Hemophilia are particularly rare because the only way for a female to be more than a carrier is for a female carrier to produce a daughter with an affected male. The extreme case of an affected female mating with an affected male produces 100% affected offspring.

    Test your understanding of the patterns discussed above with the x-linked gene fill in the blank and multiple choice questions

    Video Overview Related Content

    Subject tag: