Genes and Alleles

Parents may have different shapes and alleles for the same gene, which contributes to genetic diversity.
Genes are subject to constant change due to various mechanisms, including:
- Mutations: Errors that occur during DNA replication can result in alterations in the DNA sequence.
- Environmental Factors: Such as exposure to chemicals, radiation (e.g., sunlight), and other natural elements (like radon).
- Chemical Exposure: While contemporary society has introduced more chemicals, the natural world has always been chemically rich.

A gene is defined as a specific sequence of nucleotides at a particular location in the genome.
The structure of a gene consists of various regions, including coding and non-coding sequences.
In the human population, many genes have a small number of variants that represent the majority.
- For example, most individuals carry the same variant of the beta globin gene, but some individuals exhibit variants leading to conditions such as sickle cell disease or thalassemia.
Variants of a gene found with a high prevalence in the population are termed alleles.
- Major alleles are frequently termed wild type, representing the common variant found in nature.
- Minor allele variants appear less frequently in the population.

Polymorphism refers to the presence of multiple variants of a specific gene within a population.
Some genes are described as highly polymorphic, indicating a wide variety of alleles, whereas others have very few variants.
Human beings have two copies of most genes, one inherited from each parent, leading to potential differences in allele forms between maternal and paternal contributions.

Alleles can be classified as dominant or recessive based on their functional impact rather than their population representation.
For instance, a mutation located on an autosomal chromosome (non-sex chromosome) can be categorized as:
- Autosomal Dominant: Where the presence of one dominant allele (denoted as A) is sufficient for the trait to manifest.
- Autosomal Recessive: Where two recessive alleles (denoted as a) are necessary for the trait to present.

In a situation where one parent carries a dominant mutation (A) and the other carries a normal allele (a):
- Genotypes:
- AA (individual with disorder),
- Aa (carrier with disorder),
- aa (normal individual).
Affected individuals can pass on their alleles, showcasing inheritance patterns among offspring.

A pedigree can help in elucidating inheritance patterns of traits such as autosomal dominant conditions, exemplified by a family exhibiting adult-onset progressive sensorineural deafness.
Affected individuals can be traced across generations, displaying that the trait manifests in each generation and is equally distributed among sexes.
When evaluating pedigrees:
- Each generation should have affected individuals for dominant traits.
- Equal male and female representation in affected individuals is expected.
- From an affected parent mated with an unaffected parent, the offspring should exhibit a 50% chance of being affected.

Incomplete penetrance occurs when not all individuals with a certain genotype express the expected phenotype (e.g., 95% of individuals with the retinoblastoma gene develop eye cancer).
Variable expressivity indicates the varying severity and presentation of a phenotype among individuals with the same genotype (e.g., neurofibromatosis type 1).
Both incomplete penetrance and variable expressivity can manifest simultaneously, leading to variations in the expression of genetic disorders.

For recessive genetic disorders, an individual with the homozygous recessive genotype (AA) presents the disorder, while heterozygous individuals (Aa) remain carriers without showing symptoms.
The likelihood of recessive disorders increases in small, isolated populations due to inbreeding, which amplifies the chance of carriers mating with one another.
Genetic counseling and pedigree analysis can assist in determining the probability of recurrences of recessive traits in families.