24th February 2024

Basics of inheritance and the pedigree

Inheritance

Our fundamental understanding of inheritance stems from experiments performed by Gregor Mendel on peas. Several essential concepts arose from these experiments:

• Dominant and recessive genes – Dominant gene variants (alleles) tend to impact the phenotype when present (Homozygous dominant or heterozygote); Recessive alleles affect the phenotype when the genotype is homozygous recessive.
• Segregation – Each gamete only obtains one allele of a gene during meiosis.
• Independent assortment – Genes from different loci are transmitted independently from each other.

These principles of inheritance can be visualised using a Punnett square. When drawing a Punnett square, capital letters are used to denote the dominant allele, while lowercase letters are used to represent the recessive allele.

Image Source: Wikimedia Commons (2013). Punnett hetero homoblue, Licensed under a creative commons licence. Available for free at: https://commons.wikimedia.org/wiki/File:Punnett_hetero_homoblue.svg (Accessed: 5 January 2024).

Pedigree

A thorough history, including family history, will provide vital information about the inheritance pattern and valuable clues to the underlying genetic condition. Geneticists will use a pedigree to visualise the information gathered from the family history. The pedigree will highlight the relationship between the index patient and all other family members. While candidates will not be expected to draw a pedigree during the MRCP exam, it is a helpful tool to visualise the family history as it can reveal valuable clues to the pattern of inheritance of the conditions.

Image Source: Wikimedia Commons (2006). Pedigree chart B, Licensed under a creative commons licence. Available for free at: https://commons.wikimedia.org/wiki/File:PedigreechartB.png (Accessed: 5 January 2024).

References

• Read, A., & Donnai, D. (2021). Chapter 1: What can we learn from family history? In New Clinical Genetics: A guide to genomic medicine (4th ed.). United Kingdom: Scoin Publishing Limited.
• Turnpenny, P. D., & Ellard, S. (2017). Patterns of inheritance. In Emery’s Elements of Medical Genetics. China: Elsevier.