Discuss monogenic and polygenic inheritance in man, citing suitable examples.

Monogenic Inheritance

Monogenic inheritance, also known as Mendelian inheritance, refers to inheritance patterns determined by a single gene. These genes typically have a clear dominant or recessive allele, leading to predictable phenotypic ratios in offspring. Several distinct patterns fall under monogenic inheritance, including autosomal dominant, autosomal recessive, X-linked dominant, and X-linked recessive inheritance.

Autosomal Dominant Inheritance

In autosomal dominant inheritance, a single copy of the dominant allele is sufficient to express the phenotype. Affected individuals typically have at least one affected parent. A classic example is Huntington’s disease.

Example: Huntington's Disease

Huntington's disease is a neurodegenerative disorder caused by a mutation in the *HTT* gene. The mutated gene contains an expanded CAG repeat. Individuals with 40 or more repeats will develop the disease, usually in mid-life. The disease is autosomal dominant, meaning each child of an affected parent has a 50% chance of inheriting the disease.

Autosomal Recessive Inheritance

Autosomal recessive inheritance requires two copies of the recessive allele for the phenotype to be expressed. Affected individuals often have unaffected parents who are carriers of the recessive allele. Cystic fibrosis is a prime example.

Example: Cystic Fibrosis

Cystic fibrosis is a genetic disorder affecting the lungs and digestive system. It is caused by mutations in the *CFTR* gene. Individuals must inherit two copies of the mutated gene (one from each parent) to exhibit the disease. Carrier frequency for cystic fibrosis is relatively high in populations of European descent.

X-linked Inheritance

X-linked inheritance refers to genes located on the X chromosome. Males (XY) are more likely to express X-linked recessive traits because they only have one X chromosome. Females (XX) have two X chromosomes, so a recessive allele on one X chromosome can be masked by the dominant allele on the other.

Example: Hemophilia

Hemophilia is a bleeding disorder caused by mutations in genes on the X chromosome. It is more common in males because they only have one X chromosome. Females can be carriers, and affected males inherit the gene from their mothers.

Polygenic Inheritance

Polygenic inheritance, in contrast to monogenic inheritance, involves the combined action of multiple genes, each contributing a small effect to the phenotype. These genes often interact in complex ways, making the inheritance patterns more difficult to predict. Polygenic traits typically show a continuous variation in the population, rather than distinct categories.

Characteristics of Polygenic Inheritance

• Continuous Variation: Phenotypes exhibit a wide range of values, forming a bell-shaped distribution.
• Additive Effects: Each gene contributes a small, additive effect to the overall phenotype.
• Environmental Influence: Environmental factors often play a significant role in shaping the phenotype.

Examples of Polygenic Inheritance

Example: Human Height

Human height is a classic example of a polygenic trait. Hundreds of genes contribute to height, each with a small effect. Environmental factors, such as nutrition and healthcare, also play a crucial role. The distribution of human heights in a population closely resembles a normal distribution.

Example: Skin Color

Skin color is another example of a polygenic trait. Multiple genes influence melanin production, leading to a continuous spectrum of skin tones. Environmental factors, such as sun exposure, also affect skin pigmentation.

Feature	Monogenic Inheritance	Polygenic Inheritance
Gene Involvement	Single gene	Multiple genes
Phenotypic Variation	Discrete categories	Continuous variation
Predictability	Highly predictable	Less predictable
Environmental Influence	Generally less significant	Often significant

Complex Inheritance: Combining Monogenic and Polygenic Effects

Many human traits do not fit neatly into either monogenic or polygenic categories. These traits often involve complex interactions between multiple genes and environmental factors, demonstrating a combination of both inheritance patterns.

Case Study: Type 2 Diabetes

Case Study Title: Type 2 Diabetes – A Complex Inheritance

Type 2 diabetes involves a predisposition based on multiple genetic loci affecting insulin sensitivity and secretion. While some monogenic forms of diabetes exist (MODY), most cases are polygenic, with numerous genes contributing to risk. Environmental factors like diet and exercise significantly influence disease onset and progression. Genome-wide association studies (GWAS) have identified hundreds of genetic variants associated with increased risk, highlighting the complex interplay between genes and environment. This is an example of a complex trait influenced by both monogenic and polygenic factors.