4.8 Unit Summary and Review

Gene variants are slight differences in DNA sequences that occur at specific locations in the genome, contributing to individual uniqueness. While many variants do not impact health, some may increase or reduce disease risk. Variants can be inherited (germline) or occur during a person’s lifetime (somatic). Variants can be classified by their effects, such as morphological, lethal, or conditional, depending on their influence on traits, development, or survival. Some variants are “silent,” meaning they do not alter protein function or phenotype.

Genetic disorders are categorized into four main types: single gene disorders, chromosomal conditions, multifactorial conditions, and mitochondrial disorders. Naming genetic conditions varies based on factors such as the genetic mutation involved or affected body parts, while a formal committee standardizes gene nomenclature. Genetic predisposition is an increased likelihood of developing certain diseases based on inherited genetic variations, although lifestyle and environmental factors can also play a significant role.

Mutations in a single gene cause single-gene disorders and can follow dominant, recessive, or X-linked inheritance patterns. Despite their rarity, these diseases affect millions globally, including conditions like cystic fibrosis (CF), sickle cell anemia, and Tay-Sachs disease. Advances in genetic testing have improved diagnostics, but treatments for many single-gene disorders remain limited.

The concepts of penetrance and expressivity explain the extent to which a genotype results in the expected phenotype and the variability of phenotypes among individuals with the same genotype. Pleiotropy, where one gene affects multiple traits, and polygenic inheritance, where multiple genes influence a single trait, further illustrate the complexity of genotype-phenotype relationships. Complex traits and diseases often result from multifactorial influences, combining genetic, environmental, and epigenetic components, leading to continuous phenotypic variation.

Inherited disorders can result from abnormal chromosomal behaviour during meiosis, leading to numerical or structural chromosome abnormalities. Chromosomal disorders, such as Down syndrome (trisomy 21) and Turner syndrome (monosomy X), can be identified using karyograms, revealing chromosome number or structure abnormalities. Nondisjunction, a failure in chromosome separation during meiosis, can cause aneuploidy, leading to trisomy or monosomy. Structural rearrangements, including inversions and translocations, may cause genetic disorders or contribute to cancer. X inactivation helps mitigate the effects of extra X chromosomes, as seen in conditions like Klinefelter syndrome. Chromosomal mosaicism occurs when some cells have differing chromosomal compositions, as observed in conditions like mosaic Turner syndrome.

Mitochondrial disorders result from mutations in mitochondrial DNA, which impair energy production in cells and can affect multiple organ systems, particularly those with high energy demands, such as the heart, brain, and muscles. Symptoms range from muscle weakness, exercise intolerance, and vision problems to neurological issues like seizures, hearing loss, and ataxia. In children, developmental delays may occur. Diagnosis typically involves medical history, physical exams, genetic testing, and muscle biopsies. While no cure exists, treatment focuses on managing symptoms through therapies, medications, and supportive care.