Lesson Explainer: Sex and Autosomal Linkage Biology

In this explainer, we will learn how to identify sex-linked traits and explain how autosomal linkage impacts inheritance of genes.

Have you ever wondered why certain traits, such as being bald or having freckles, only seem to show up in certain members of a family? These characteristics are genetically determined and can be passed down to us from our biological parents.

The genetic code for human characteristics is carried by the 46 chromosomes passed down to us from our biological parents. Chromosomes are passed down from parents to their offspring through their gametes (sex cells), as shown in Figure 1. Each biological parent passes down 22 autosomes and 1 sex chromosome. During the fusion of gametes or fertilization, the genes within the ovum and sperm from our biological parents combine to determine the characteristics we see in ourselves. This pattern of transmission of characteristics from the biological parents to the offspring is called inheritance. The order, location, and space between genes on each chromosome passed down to us by our biological parents can determine how genes are inherited.

Autosomes are chromosomes that do not help determine the biological sex. Chromosome pairs 1–22, or the first 44 chromosomes, in humans are autosomes. All autosomes form homologous chromosome pairs. A homologous chromosome pair is a pair of chromosomes that have similar lengths, the same centromere positioning, and the same genes at each location. Since chromosomes come in pairs, the genes on the chromosomes also come in pairs. The pairing of genes between the chromosomes is an important part of inheritance genetics because it helps determine the appearance of the characteristic. In homologous chromosome pairs, each chromosome carries the same genes in the same order and location.

While the order and location of the genes found on the autosomes are the same, the version of the gene may be different. Alternate versions of a gene are called alleles. Each chromosome can carry a different allele for the same gene. In a homologous pair, paired chromosomes carry the same genes at the same location but may have different alleles of those genes at that location. The version of each gene carried on the chromosome codes for a specific trait, like a blue eye color.

So, for example, on the homologous chromosome pair in Figure 2, we see a dominant allele (B for brown eye color) and a recessive allele (b for blue eye color) at the same location on each chromosome. We know that the combination of alleles is called the genotype. The genotype tells you the alleles for the characteristics that were inherited from the biological parents. We also know that the genotype helps determine the observable outcome, or the phenotype of the characteristic. So, in Figure 2, the genotype for eye color is Bb and the phenotype is brown eye color, as the allele for brown eye color is dominant.

Since all of the genes from our biological parents come in pairs on our chromosomes, the location of the genes can also affect their pattern of inheritance. Genes that are located on different chromosomes independently separate into different gametes during meiosis. So, for example, if the gene for hair color is located on chromosome 1 and the gene for eye color is located on chromosome 2, how the alleles for hair color are sorted does not affect how the alleles for eye color are sorted in gamete formation.

This independent sorting of alleles for a gene into different gametes is called the law of independent assortment. This law is one of the three laws developed by the 19th-century geneticist Gregor Mendel. It states that where the allele for one gene is sorted is not affected by another gene or alleles of another gene. Since alleles of genes independently and randomly separate, there is an equal chance for them to occur in an offspring. To help visualize this law, see Figure 3.

The law of independent assortment also applies to alleles for genes located on the same chromosome, if located far enough apart (see Figure 4). The alleles for a gene that are located far apart on the chromosome also independently separate into the gametes as a result of crossover in meiosis.

Crossover is the exchange of pieces of DNA between homologous chromosomes. This typically occurs during the first phase of meiosis. This process does not create new genes, but rather it just rearranges the allele combinations. The farther apart genes are on the same chromosome, the more likely a crossover may happen.

Chromosomes have a limited size, so not all genes can be located far apart or on different chromosomes to undergo independent assortment. Some genes on the same chromosome are located very near to one another. Genes that are located close to each other on the same chromosome are said to be linked. This means that they do not independently assort during gamete formation. Instead, genes located very near to one another on autosomes segregate together during gamete formation, making it possible for them to be inherited together. Genes located on a chromosome that are inherited together are called linked genes. If these linked genes are located on an autosome, they are called autosomal linked genes.

Linkage between genes also happens with the sex chromosome and impacts the patterns of inheritance of certain genes. There are two types of sex chromosomes that help determine a human’s biological sex: X and Y. The characteristics located on the X and Y chromosomes have specific inheritance patterns because of how genes are linked to the sex chromosomes that pass from the biological parents to the offspring.

The X and Y chromosomes are dramatically different in size and carry different numbers of genes (see Figure 5). The X chromosome is approximately three times as large as the Y chromosome. Such dramatically different sizes between the chromosomes are related to the different number of genes carried on each chromosome. The X chromosome carries about 900 genes, whereas the Y chromosome only carries about 55 genes. While some of the genes located on the X and Y chromosomes are homologous, the majority of the genes on these chromosomes are different.

With two types of sex chromosomes, either a homologous pair (XX) or a nonhomologous pair (XY) can be made. The homologous pair of YY chromosomes is only observed within male cells that contain an extra Y chromosome and is often indicative of a chromosomal abnormality in the offspring. As you can see, sex chromosomes do not always make a homologous pair. The genes that are only carried on the X and Y sex chromosomes can have a unique pattern of inheritance.

For example, only the Y chromosome has the “male-determining gene,” called the SRY gene, which causes the development of a male reproductive anatomy. Since the SRY gene is only carried by the Y chromosome, only the cells that have an XY genotype have the SRY gene and develop a male reproductive anatomy. This male reproductive anatomy is an example of a sex-linked trait. Traits of genes that are carried only on the sex chromosomes are called sex-linked traits. By observing the eye color of fruit flies, Dr. Thomas Morgan is the scientist who first recognized that the sex chromosomes carry genes found only on sex chromosomes.

Typically, the majority of fruit flies have red eyes. So, upon noticing a male fruit fly with white-colored eyes, Dr. Morgan started a series of experiments to determine the inheritance pattern of this trait. First, he crossed a male fruit fly with white eyes with a female fruit fly with red eyes. This produced a generation of offspring all with red eyes, proving to Dr. Morgan that the red eye color trait was dominant. Then, Dr. Morgan crossed the first-generation male offspring with the first-generation female offspring. As expected, in the second-generation offspring, of the fruit flies were red-eyed fruit flies and of them were white-eyed fruit flies. However, contrary to his expectations, all white-eyed fruit flies in the second generation were males.

Dr. Morgan predicted the probabilities of phenotype of fruit fly crosses with Punnett squares, which have been recreated in Figure 6. A Punnett square is a diagram that is used to predict and visualize the probability of genotypes for certain traits in the offspring. This technique helped Dr. Morgan explain why the white eye color only appeared in male fruit flies. This unexpected result is how Dr. Morgan determined that the white eye color in male fruit flies is a sex-linked trait. He realized that because male fruit flies only have one X chromosome, so whatever the eye color allele on the X chromosome would determine the phenotypic outcome.

Dr. Morgan was able to determine that the white eye color phenotype is a sex-linked trait carried by a gene on the X chromosome. Most sex-linked traits are carried on the X chromosome. This is because the X chromosome is large and carries many more genes than those carried by the Y chromosome. Sex-linked traits controlled by genes carried on the X chromosome are called X-linked traits and are more common in males than in females. This may at first seem surprising: if they are on the X chromosome, why are more males affected?

When a trait is carried by one gene, the allele that is recessive will only be observed if the dominant allele is absent. In female cells, there are two X chromosomes, which means that the recessive allele can be masked by the dominant allele. However, in male cells, there is only one X chromosome, so if the X chromosome is carrying the recessive allele, it will become the phenotype. This means females are unaffected carriers of recessive traits, whereas males are significantly impacted. This pattern of inheritance makes assigning genotypes to X-linked traits very easy because the recessive trait will be seen more often in males with XY chromosomes.

Two well-known examples of X-linked recessive traits that almost exclusively affect males are color blindness and hemophilia. Both color blindness and hemophilia are related to a recessive X-linked trait. In color blindness, the individual cannot distinguish between certain colors, like red and green. The genes that code for seeing red and green coloring are located on the X chromosome. Hemophilia is an inherited blood disorder in which the blood is unable to clot properly. Since color blindness and hemophilia are both X-linked recessive traits, XY male genotypes will carry this recessive allele. Females can also be carriers of recessive alleles, although they are not as affected as XY genotypes. The Punnett squares shown in Figure 7 demonstrate how the phenotype of a sex-linked trait can be predicted.

Example 2: Determining the Probability of Disease in X-Linked Traits

Duchenne muscular dystrophy (DMD) is an X-linked recessive condition in humans that causes muscle weakness and wasting.

The allele that correctly produces the dystrophin protein (D) is dominant to the allele that causes DMD (d).

A female with the genotype X^DX^d reproduces with a male with the genotype X^DY.

What is the probability, in percent, that the offspring will be a male with the disease?

Answer

To predict the phenotypic probabilities of sex-linked traits using a Punnett square, the sex chromosomes of each parent are placed on the top and left side of the square. Then, the alleles of the genes carried by the sex chromosomes of each parent are written next to the sex chromosome.

The female genotype is placed across the top of the square. Next, along the left side of the square, the male genotype is listed. The inside of each small square is completed by combining the sex chromosome on the side and top of the square quadrant. The genotype inside each of the smaller squares helps predict the potential phenotypes of the offspring. Since the dystrophin protein is an X-linked recessive trait, the probability of each offspring having a phenotype with Duchenne muscular dystrophy is 1 out of 4 (), and the probability of having a phenotype unaffected by DMD is 3 out of 4 (or ).

Therefore, if a female with the genotype X^DX^d reproduces with a male with the genotype X^DY, there is a probability that the offspring will be a male with Duchenne muscular dystrophy.

Not all sex traits are related to genes located on the sex chromosomes. In fact, some traits affected by the biological sex of the organism are located on autosomes but are influenced by the distinct sex hormones found in biological males (like testosterone) or biological females (like estrogen). Sex-influenced traits are genetic traits carried on autosomes instead of sex chromosomes.

For example, genetic hair loss is more observed in XY males than in XX females, but the gene for genetic hair loss (baldness) is not located on a sex chromosome. Instead, genetic hair loss is a trait located on an autosome. However, the dominance of the allele for genetic hair loss is influenced by the sex hormone testosterone. In men, the levels of testosterone are higher, and so the phenotype of genetic hair loss is expressed even if one allele is present. In females, genetic hair loss will only be observable if the genotype has two alleles of the gene for genetic hair loss.

Some genes carried on autosomes are only expressed in one biological sex. Sex-limited traits are autosomal traits that are only expressed by the presence or absence of sex hormones. Sex-limited traits are usually additional sex-specific features observed in only one biological sex. For example, both male and female humans carry the gene for milk production on an autosome. However, the phenotype of milk production (e.g., actual milk production or lactation) is only observed in females. So, while both males and females have autosomes carrying the gene for milk production, it is only ever observed in females.

Inheritance of a trait depends on the type of chromosome that is carrying the gene and the dominance of the trait. Hence, a tool that can handle more than one generation of trait information is needed. The difference between a pedigree chart and a Punnett square is that the pedigree chart can be used to easily determine the pattern of inheritance of a certain trait over several family generations. A pedigree chart can also help determine whether a trait is sex linked, sex influenced, or sex limited and helps with this deciphering. The structure of a pedigree chart is similar to that of a family tree. It shows how family members are related to each other and highlights the presence or absence of a trait as it relates to the relationship among parents, offspring, and siblings. A simple pedigree chart is shown in Figure 8.

How To: Drawing a Pedigree Chart

When drawing a pedigree chart, you first need to determine the familial relationships that will be depicted, starting with the relationship between the affected individual and their immediate family members (i.e., parents, offspring, and siblings). Once you have determined all the relationships you want to use in the diagram and gathered all the information you need, you are now ready to draw a pedigree chart. You will most likely be using the standardized symbols shown in the figure below.

1. Begin by drawing the affected individual, symbolized as a filled-in circle.
2. Next, include the symbols for the immediate family relationships, starting with the siblings. Draw the siblings of the affected individual, in chronological order, on either side of the filled-in circle. The oldest sibling should be positioned to the farthest left.
3. The sibling symbols should be connected to the affected individual through a single “sibling” line, as indicated in the figure.
4. If any of the siblings are married, make sure to leave space next to the sibling symbols to indicate any marriages using a “marriage line.”
5. Next, above the affected individual, draw the symbols representing the parents of the affected individual. Use a horizontal “marriage” line to connect the parents to the offspring.
6. Then, connect the affected individual’s generation and the parents’ generation of the affected individual through a “line of descent,” which is shown as a vertical line in the figure.
7. Below the affected individual, draw the symbols that represent any offspring of the affected individual. Connect them using another vertical line representing “the line of descent.”

You can continue to include as many generations as you want in the pedigree chart.

Pedigree charts show that if a trait is sex linked, then it will be phenotypically observed in males more often than in females. When this pattern is not observed, and instead males and females are equally affected, it is easy to say the trait is likely carried on an autosome. Similarly, with a pedigree chart, the dominance of a trait can be studied. A person with an autosomal dominant trait will also always have one parent with that trait. However, the parents of an individual with an autosomal recessive trait may not display a recessive trait within a pedigree chart.

Linkage of traits influences their inheritance across family generations. This is why we see certain traits, like color blindness and hemophilia, affecting certain members of a family but not others. Although the law of independent assortment states that genes randomly assort into gametes, this is not true for all characteristics. Genes for characteristics that are located near one another on an autosome are often inherited together, a process called autosomal linkage. For traits affected by the biological sex of the organism, there are three patterns of inheritance: sex-limited traits, sex-linked traits, and sex-influenced traits. A pedigree chart can help show the inheritance of a trait through several family generations and determine the inheritance pattern and dominance of the trait.

Let’s summarize what we have learned in this explainer.