Mendelian Inheritance: Genes and Types

Genes can be said to be the bedrock of Genetics. They are the basic unit of heredity that can be passed from parents to offspring. Coined from the name of the biologist that proposed the rules of inheritance, Gregor Mendel; Mendelian inheritance is used to describe the biological inheritance principles of how certain traits are inherited by offspring from their parents. There are different types of Mendelian inheritance like autosomal dominant, autosomal recessive, X-linked dominant, X-linked recessive and mitochrondial. These modes of inheritance are expressed in single-gene diseases. Let us discuss them:

In autosomal dominant, the offspring requires only a single copy of a gene variant to develop a disease or condition. In this inheritance mode, one of the parents of the child needs to possess the gene. It is important to note that this inheritance pattern occurs in every generation. Examples of diseases that can be expressed through autosomal dominant inheritance are neurofibromatosis, Huntington's disease and familial hypercholesterolemia among others.

 

On the other hand, in autosomal recessive, each parent contributes a gene variant each for the offspring to have two copies of the gene variant to develop a disease or condition. Here, the pattern may not be seen in every generation. Examples of diseases that are expressed through this inheritance pattern are sickle-cell anemia, Tay-sachs disease, phenylketonuria and so on.

The X-linked dominant is a sex-linked mode of inheritance. Here, it is common to see that both males and females carry the trait in each generation. The only thing is that fathers cannot pass their X chromosomes to their sons, instead they pass it to their daughters and pass their Y chromosomes to their sons. Consequently, females are mostly affected here. Examples of diseases that are expressed in this inheritance patterns are ornithine transcarbamylase deficiency and hypophatemic rickets.

X-linked recessive like their dominant counterpart are sex linked. However, here males that have an affected allele on their X chromosomes are unable to pass the traits to their sons because they are hemizygous. Their daughters nonetheless, will carry those traits. Mothers that are heterozygous and healthy can pass the affected traits to their sons. So here, males are mostly affected and these affected males are seen in every generation. Hemophilia A and Duchenne muscular dystrophy are some diseases expressed by the X-linked recesssive.

In mitochondrial, female parents are the only ones that can pass the affected traits even though both males and females can be affected. It is possible for this inheritance pattern to appear in each generation and Kearns-Sayre syndrome is a disease that can be expressed by this patterns.

References

National Human Genome Research Institute "Gene" October 16 2023

https://www.genome.gov/genetics-glossary/Gene#:~:text=Genes%20are%20passed%20from%20parents,approximately%2020%2C000%20protein%2Dcoding%20genes.

 National Library of Medicine "Classic Mendelian Genetics (Patterns of Inheritance)"

https://www.ncbi.nlm.nih.gov/books/NBK132145/#:~:text=There%20are%20five%20basic%20modes,and%20complex%20multi%2Dfactorial%20diseases.

Genetic Foundation of Migraines

On May 3rd, a study in the journal Neuron was published on research of why some families are more susceptible to getting migraines and how genetics could influence which type of migraine someone would get. There is two possible ways that migraines were thought to be inherited which is through linkage or polygenic inheritance. Linkage, or the passing down of chromosomes from parent to child, have three genes associated, CACNA1A, ATP1A2, and SCN1A.

The scientists believed that these types of genes control the severe migraines that show stroke like symptoms and fall under the Mendelian model for inheritance. For polygenic inheritance, it carries the idea that a group of genes collectively contribute that characteristic even if each gene only contributes a tiny amount. 

For the research, the scientists created a polygenic risk score which estimated the genetic burden of common variants. They gathered data from a previous genome association wide study. Hundreds and thousands of loci that were linked to migraines were incorporated. Researchers then tested the influence of the risk score and the three mendelian linked genes with a large family of migraine sufferers in Finland. They used genetic data of 1589 families compared them to a control family.  The researchers found out that time and time again results proved that the polygenic common variants were driving migraine risk way more than the mendelian traits. The end result was that it was more likely the person with the migraine has a greater genetic burden of common polygenic variants to blame. 

I believe this research is a good start with good findings to a problem that 15-20% of adults go through. If we can continue to build on research and find out what biological pathways the genes affect than we can find a better solution to a problem that almost a quarter of adults face on a daily basis.