The Post-Mendelian Era or Neo-Mendelian Genetics refers to the transformative period in genetics that followed the rediscovery of Gregor Mendel’s foundational work in the early 20th century. While Mendel’s laws of inheritance laid the groundwork for classical genetics, scientists soon recognized that inheritance patterns in many organisms could not be fully explained by Mendel’s simple models alone. This new era marked a paradigm shift, moving beyond the basic principles of dominant and recessive traits to incorporate a broader, more complex understanding of heredity. It gave rise to numerous groundbreaking discoveries that redefined genetic science and deepened our comprehension of biological inheritance.  

There were many discoveries, such as the Chromosome Theory of Inheritance, Linkage and Recombination, Multiple Alleles, Polygenic Inheritance, Epistasis, Pleiotropy, Sex-Linked Inheritance, Environmental Influence, Molecular Genetics, Genomics, and Genetic Mapping. 

In the previous lectures on Mendelian's Inheritance, we usually learn about traits that have just two choices, like tall vs. short plants or round vs. wrinkled seeds. These are called contrasting characters, and they are controlled by two forms of a gene, called alleles (for example, T or t for height, and R or r for seed shape). Pretty simple, right? 

But here’s where it gets exciting! Not all traits are remains with just two choices. Sometimes, a single trait can appear in many different forms. This happens when a gene is controlled not just by two alleles, but by more than two alleles. This is what we call multiple alleles. 

Multiple alleles is defined as the situation where a gene has more than two allelic forms within a population. This contrasts with the simple Mendelian inheritance, where a gene typically has only two alleles: one dominant and one recessive. Multiple alleles increase genetic diversity and allow for a broader range of phenotypic expressions.

Have you ever wondered what happens when two purebred plants don’t just follow the usual rules of inheritance i.e., Law of Dominance? 

Well, that’s where incomplete dominance comes into play!

In incomplete dominance, neither allele is completely dominant over the other. Instead of one trait winning out, you get a blend of both kind of like mixing two colors to create something totally new!

Incomplete dominance is a type of genetic inheritance where the phenotype of a heterozygote is intermediate between the phenotypes of the homozygous parents. Unlike complete dominance, where one allele completely masks the effect of another, incomplete dominance results in a blending of traits. 

Codominance is a form of genetic inheritance where both alleles in a heterozygous individual are fully expressed, resulting in a phenotype that simultaneously shows both traits without blending. Unlike incomplete dominance, where the traits blend to form an intermediate phenotype, codominance allows for the simultaneous expression of both alleles. 

Penetrance is a term which is used to describe the "proportion of individuals with a particular genotype who actually express the expected phenotype". It provides a measure of the likelihood that a gene will manifest as a trait or disease in an individual who carries a genetic mutation associated with that condition.

In the present example, the penetrance of breast cancer in women with the BRCA1 mutation is 70% (70/100*100) (see formula in figure). This means that there is a 70% likelihood that a woman carrying this mutation will develop breast cancer by age 70.

Type of Penetrance

Factors Influencing Penetrance

1. Modifier Genes: Other genes that can influence the expression of the trait. They might enhance or suppress the effect of the primary gene.

2. Environmental Factors: External factors such as diet, lifestyle, and exposure to toxins can affect the likelihood that a genetic trait is expressed.

3. Age: Some genetic traits or diseases manifest only after a certain age, such as many types of cancer or neurodegenerative disorders.

4. Epigenetic Factors: Changes in gene expression that do not involve alterations to the DNA sequence itself, such as DNA methylation and histone modification, can affect penetrance.

5. Sex: The expression of some traits may be influenced by the sex of the individual, possibly due to hormonal differences or sex-linked genetic interactions.

Mendelian genetics, which predicts uniform traits, expressivity explains variations in trait manifestation. But, Expressivity refers to the variability in the degree or intensity of a phenotype expressed by individuals with the same genotype. It shows how the same genetic makeup can result in different phenotypic severities. 

Expressivity is another key concept in genetics that describes the degree to which a genotype is expressed in an individual. Unlike penetrance, which deals with whether a trait is expressed at all, expressivity focuses on the variation in the manifestation of the trait among individuals who exhibit it. 

Example: Polydactyly

• Gene Involved: Polydactyly can be caused by mutations in various genes, one common one being GLI3.

• Inheritance Pattern: Typically autosomal dominant, meaning only one copy of the mutated gene is needed for the trait to potentially be expressed.

Imagine a family where a parent and their three children all carry the same mutation associated with polydactyly:

Even though the parent and all three children have the same genetic mutation, the way polydactyly is expressed varies widely:

• Parent: Mild expression (small, non-functional extra digit).

• Child 1: Mild to moderate expression (small, partially formed extra finger).

• Child 2: Moderate expression (well-formed, extra finger).

• Child 3: Severe expression (two well-formed, functional extra fingers).

Types of Expressivity

1. Variable Expressivity: The same genotype can result in a range of phenotypes of varying severity and characteristics. This means that even if all individuals have the same mutation, they might not show the trait to the same extent.

2. Constant Expressivity: In rare cases, a trait is expressed to the same degree in all individuals who exhibit it. This is less common in complex traits and diseases.

Factors Influencing Expressivity

1. Modifier Genes: Other genes can modify the expression of the primary gene, leading to differences in the phenotype.

2. Environmental Factors: External conditions, such as nutrition, climate, and exposure to toxins, can influence the severity of the trait.

3. Epigenetic Changes: Chemical modifications to DNA and histones that regulate gene expression can lead to variations in how a trait is expressed.

4. Age: The age at which the phenotype appears can vary, and the severity may change over time.

5. Sex: Some traits may express differently in males and females due to hormonal and physiological differences.

Sometimes, a person can show a trait or condition that looks just like it came from a genetic mutation, but surprisingly, it’s not caused by their genes at all. Instead, it’s caused by environmental factors such as chemicals, infections, or nutrition. This is called a phenocopy "a phenocopy looks genetic, but it’s actually environmental".

A phenocopy is when an individual shows a phenotype that copies (mimics) a genetic disorder, even though their DNA does not carry the mutation that usually causes it.

Key Characteristics of Phenocopy

1. Induced by Environment: Phenocopies arise due to environmental factors, such as exposure to chemicals, nutritional deficiencies, infections, or other external conditions.

2. Non-Heritable: Unlike genetic mutations, phenocopies are not passed on to offspring because they are not caused by changes in the DNA sequence.

3. Mimics Genetic Phenotype: The resulting phenotype is similar to one that could be caused by a specific genetic mutation, making it challenging to distinguish from genetic conditions without further investigation.