Linked Genes

Have you ever wondered why people with blonde hair also have blue eyes? Or why red-green color blindness is more common in males than females? These questions can be answered by understanding linked genes. While a great deal of focus has been put on Mendelian genetics, there are many exceptions in which genes do not follow the laws proposed by Mendel. In the following, we will explore the linked genes and sex-linked genes that defy Mendel's laws.

Linked Genes Defined

Linked genes, or linkage, refer to a set of genes that tend to be inherited together because the genes are positioned close to each other on the same chromosome. This positioning leads to these genes being inherited together at much greater frequencies than Mendel's law of independent assortment would predict. Recall that a key assumption for the law of independent assortment is that genes are located on different chromosomes or very distant from each other on the same chromosome. Therefore, linked genes positioned close to each other on the same chromosome are an exception to the law of independent assortment.

Linked vs Unlinked Genes

To compare ratios between linked and unlinked genes, we should first look at the chromosome segregation that occurs during meiosis.

For unlinked genes, two heterozygous parents, AaBb, where A and B are genes located on different chromosomes, will produce four types of gametes found in equal proportions: the four combinations of gametes are AB, Ab, aB, ab, each having a frequency of 25% (Fig. 1) Importantly, note how each chromatid stays intact and is not separated during the entire process of meiosis.

In contrast, linked genes are found in close proximity to each other on the same chromatid. Therefore, since chromatids tend to remain largely intact throughout meiosis, these genes are more likely to be inherited together into a gamete (Fig. 2). In other words, certain alleles are always packaged together.

There is an exception to this rule called crossing over or homologous recombination. Recombination occurs during prophase I of meiosis to increase genetic diversity. During recombination, homologous chromosomes are separated and exchange fragments of their DNA with each other (Fig. 3). This leads to new alleles on the same chromosome.

In the above example, alleles AB are linked on the blue chromosome, and alleles ab are linked on the red chromosome. Following recombination, the new possible gamete genotypes will be AB, Ab, aB, and ab, just like unlinked genes.

However, the location of a recombination event on a chromosome is completely random; therefore, it is much more unlikely that Ab and aB alleles will be inherited together. Imagine that, instead of between genes A and B, a recombination event took place at the top of the chromosome. In this case, alleles AB and ab will still be inherited together.

For this reason, the original allele pairs, AB and ab, are called parental chromatids. While the less likely, Ab and aB alleles are called recombinant chromatids. The closer the two genes are, the less likely a recombination event will occur between them. In very tight linkage, the parental chromatids will almost always be seen, with few cases of recombinant chromatids.

Table 1. Differences between unlinked and linked genes.

Examples of Linked Genes

One example of linked genes includes hair color and eye color genes. While there is not just one gene that contributes to hair color and another gene that contributes to eye color, there is some evidence that two of the genes involved in hair color and eye color are linked. This is why we might see individuals with blue eyes also have blonde hair or why a person with red hair might also have light skin.

Linkage can also be useful for determining the position of genes on a chromosome. If we follow the law of independent assortment, we see that the parental chromatids will be found in the offspring 50% of the time. For example, if we have chromosome 1 with alleles AB and chromosome 2 with alleles ab, we expect to see 50% of the offspring have recombinant alleles, Ab and aB, and 50% have parental alleles, AB and ab. In the case of linkage, we should expect to see parental alleles much more commonly than recombinant alleles. Therefore, if we see this occur, we can assume that the two genes are linked and close together on the same chromosome. If this process is repeated for multiple different genes, a genetic map or linkage map can be generated.

Sex-linked Genes

Thomas Hunt Morgan originally found Sex-linked genes during his research of fruit fly genetics. He noticed that eye color in fruit flies did not follow typical Mendelian genetics. Instead, he noticed that when he crossed a red-eyed female with a red-eyed male, the offspring produced a 2:1:1 ratio of red-eyed females: red-eyed males: white-eyed males. Therefore, just like linked genes, sex-linked genes are another example that does not follow Mendelian genetics.

Genes are found on chromosomes; the X and Y sex chromosomes are no exception. Sex-linked genes are genes found on the X and Y chromosomes and therefore are biased, to be found in one sex over the other. Males have one X chromosome inherited from the mother and one Y chromosome inherited from the father. In contrast, females have two X chromosomes that are inherited from each parent. This difference makes the inheritance of traits different between males and females. Females can be homozygous or heterozygous for a specific X-linked gene; however, males will only have one copy of the X-linked gene. Therefore, if a male inherits a recessive allele from their mother, they will express that recessive trait.

Sex-linked genes are denoted by X^B for dominant or X^b for recessive, where B is the gene of interest. The X represents that the gene is located on the X chromosome, while the superscript denotes the allele.

Practice Problems for Sex-linked Genes

Punnett Squares are very useful for tackling practice problems; remember to include X and Y to represent the X and Y chromosomes, respectively.

Overall, the child has a 25% chance of being colorblind. If the child is a biological female, they have a 0% chance of being color blind as both X^BX^B and X^BX^b have a normal-colored vision. However, if the child is a male, they have a 50% chance (X^BY or X^bY).