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Health and Disease

Mendelian Laws: How Does a Better Understanding of These Principles Help With the Diagnosis and Treatment of Complex Diseases?

“Mendelian diseases” are single-gene diseases that are caused by mutant genes that interfere with the specific function and phenotype shown in a genome [3]. These single-gene conditions can be readily modelled using Mendelian laws of inheritance and our understanding of these conditions is generally more complete.

From an obscure 1866 paper titled “Experiments on Plant Hybridization” published in the “Proceedings of the Natural History Society of Brünn” an Augustinian friar named Gregor Mendel is synonymous today as being the Father of modern genetics. His genius was to combine his talents for the biological sciences as well as his love of mathematics during his study of biological inheritance with garden pea plants. He devised a methodical process of developing statistical expectations about inheritance data through monohybrid and dihybrid crosses that is still studied today [1]. By doing so he moved the study of inheritance from being an observational art form like Darwin’s pangenesis and the blended inheritance theorems into a modern scientific process that was not only quantifiable and reproducible, but which also be applied in the understanding of a wide number of genetic conditions such as thalassemia and Duchenne muscular dystrophy [2].

His three principles of inheritance have continued to be widely used in scientific research today to explain the basic characteristics of inheritance.

“Mendelian diseases” are single-gene diseases that are caused by mutant genes that interfere with the specific function and phenotype shown in a genome [3]. These single-gene conditions can be readily modelled using Mendelian laws of inheritance and our understanding of these conditions is generally more complete. However, these diseases are extremely infrequent, accounting for less than 1-7% of all registered single-gene and complex diseases worldwide [8].

A solid understanding of Mendel’s discoveries and principles potentially offers us the ability to track diseases through family pedigrees. Mendelian diseases also tend to be less influenced by external factors and observational studies as well as genome research has expanded our knowledge as to which alleles are the dominant and recessive forms. This knowledge allows us to fairly accurately predict the statistical probability of specific genetic conditions occurring in future generations. In families with these Mendelian conditions, this understanding can be put to good use in helping individuals or families from a clinical point of view [4][5][6].

An example of the use of this knowledge of Mendel’s laws within medicine is in those suffering from thalassemia. In a situation where both parents are carriers for the thalassemia gene, the offspring would have a 25% chance of having severe thalassemia/ thalassemia major [7]. These unfortunate babies would have blood cells that undergo constant rapid breakdown, requiring regular blood transfusions leading to suffering and a reduced lifespan. Amniocentesis to confirm the foetus’s thalassemia status could be performed to help the parents make an informed choice as to whether to continue with the pregnancy.

However, not all diseases are based on the simple Mendelian single-gene model of inheritance. Complex diseases are those conditions that are caused by a combination of genetic, environmental, and lifestyle factors, some, or most of which have not yet been identified. In real life, complex diseases are far more common than Mendelian disorders and include conditions such as Alzheimer’s disease, Type 2 diabetes, heart disease, and multiple sclerosis [9]. These diseases may involve a number of different genes which are influenced by a multitude of external factors leading to a complex of different disease phenotypes. In this situation, the individual is said to have a genetic predisposition to having that disease, where despite carrying the genes, they are not necessarily destined to have the condition.

These conditions do not conform to standard Mendelian Laws of inheritance and reaching a full understanding of the disease is complicated and requires detailed comprehension of the external factors at play, if indeed they can be full identified [10]. Furthermore, interactions of these external factors with the genes as well as between themselves make this challenge even more complex.

However, whilst they may not fully conform to standard Mendelian Laws, the fundamental principles of Dominance, Uniformity and Segregation can still be applied to some extent in helping to understand the dynamics at play within these diseases. Increasing research and understanding of the external factors may help us to create better mathematical models in which we can apply these Mendelian Laws. Conversely knowing the way in which these laws govern genetic inheritance, may in fact help us to identify external influences which were previously unidentified furthering our understanding of the disease as a whole [11].

Given his love for biology and mathematics, I am certain that Gregor Mendel would very much approve of such an approach as well as be amazed at how far his little garden experiment has taken us and the field of genetics over the past 150 years.

Natalie Ho, Youth Medical Journal 2022

References

1. Admin. (2021, March 5). Mendel’s laws of inheritance-mendel’s laws and experiments. BYJUS. Retrieved February 28, 2022, from https://byjus.com/biology/mendel-laws-of-inheritance/

2. Admin. (2021, February 9). Mendelian disorders -different types of mendelian disorders. BYJUS. Retrieved March 1, 2022, from https://byjus.com/biology/mendelian-disorders/

3. Nature Publishing Group. (n.d.). Nature news. Retrieved March 1, 2022, from https://www.nature.com/scitable/topicpage/mendelian-genetics-patterns-of-inheritance-and-single-966

4. Fullick, A. (2015). Edexcel A level biology B. Pearson.

5. U.S. National Library of Medicine. (n.d.). Sex-linked recessive: Medlineplus Medical Encyclopedia. MedlinePlus. Retrieved March 1, 2022, from https://medlineplus.gov/ency/article/002051.htm#:~:text=Sex%2Dlinked%20diseases%20are%20passed,the%20other%20parent%20is%20normal.

6. Alliance, G. (2009, July 8). Inheritance patterns. Understanding Genetics: A New York, Mid-Atlantic Guide forPatients and Health Professionals. Retrieved March 1, 2022, from https://www.ncbi.nlm.nih.gov/books/NBK115561/

7. NHS. (n.d.). NHS choices. Retrieved March 1, 2022, from https://www.nhs.uk/conditions/thalassaemia/causes/

8. Rahit, K. M. T. H., & Tarailo-Graovac, M. (2020, February 25). Genetic modifiers and rare mendelian disease. Genes. Retrieved March 1, 2022, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140819/

9. U.S. National Library of Medicine. (2021, May 14). What are complex or multifactorial disorders?: Medlineplus Genetics. MedlinePlus. Retrieved March 1, 2022, from https://medlineplus.gov/genetics/understanding/mutationsanddisorders/complexdisorders/

10. Nature Publishing Group. (n.d.). Nature news. Retrieved March 1, 2022, from https://www.nature.com/scitable/topicpage/complex-diseases-research-and-applications-748/

11. Alliance, G. (2010, February 17). Classic mendelian genetics (patterns of inheritance). Understanding Genetics: A District of Columbia Guide for Patients and Health Professionals. Retrieved March 1, 2022, from https://www.ncbi.nlm.nih.gov/books/NBK132145/

By Natalie Ho

Natalie Ho is a sixth-form student at the City of London Freemen's School in the UK. She hopes to study medicine at university in the future and is particularly interested in the fields of paediatrics and neurosurgery.

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