Introduction:
Skin is the human body's largest organ, a first-line barrier to preventing diseases. But sometimes, skin conditions can negatively impact health. Besides diet, physical activity, hygiene, and environmental factors, genes also significantly determine the skin's overall health. The skin consists of various cell types that express specific molecules and possess different properties facilitating complex interactions and intercellular communication, which is important for maintaining the skin's structural integrity. Over the past several years, the genetic basis of many skin conditions has been explained using classical genetic techniques.
How Is Genetic Testing Done?
Genetic testing involves the analysis of a person's blood, skin, hair, or other body tissue to look at DNA (deoxyribonucleic acid), chromosomes, or proteins for changes or mutations associated with a genetic condition. Mutations can affect all or part of a gene, leading to abnormal function leading to disease. There are mainly three types of genetic tests available in laboratories:
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Cytogenetic (to look at whole chromosomes).
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Biochemical (to measure proteins produced by genes).
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Molecular (to look for small DNA variations).
What Is a Skin DNA Test?
The skin DNA Test refers to a specialized DNA test for skin health. It helps analyzes genetic mutations causing alterations in normal skin health. Genetic testing for skin diseases helps determine genetic risks related to skin health, including skin tone, texture, allergic reactions, inflammation, photosensitivity, skin aging, oxidative stress, environmental pollutants' effect, and nutritional requirements for healthy skin.
What Are the Benefits of Genetic Testing for Skin Conditions?
Human genomics can reveal essential information about an individual's health and possible risks to skin health. Genetic testing is an efficient and accurate skin care DNA testing that predicts genetic threats associated with skin health. It requires an individual’s saliva sample. The skin DNA test helps evaluate the risks associated with skin health and appearance.
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Skin Texture - The skin DNA test provides information on genetic risks related to skin texture parameters, such as firmness, smoothness, elasticity, and healing.
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Oxidative Stress - The test reveals an increased oxidant level risk that causes stress on the body's antioxidant defense system.
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Biological Aging - The genetic predisposition to early natural skin aging can also be predicted.
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Skin Photoaging - The test reveals the risk of sun sensitivity and the development of freckles and wrinkles.
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Inflammation Response - It predicts the genetic risks for skin inflammation due to chemical exposure and other environmental factors, including allergies, dryness, rashes, etc.
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Cellulite Formation - The test can determine cellulite formation and deposition, a genetic risk in many people.
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Stretch Marks - The test can also predict the risks of stretch marks.
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Acne Formation - The test helps identify the susceptibility of a person to develop acne.
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Pollution Effect - The risk of developing skin disorders due to the harmful effects of pollution.
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Sugar or Glycation Effect - The test can predict the risk of the formation of glycation products in skin aging. In addition, the self-repair of skin is also determined.
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Micronutrient Requirements - Genetic testing can provide information on the risks of micronutrient imbalance to improve the diet for healthy skin.
What Is the Classical Genetic Approach to Identify Pathogenic Mutations in Skin Diseases?
Functional and positional cloning are two major methods used in the isolation of the gene responsible for a given phenotype:
Functional Cloning of Genes In Several Inherited Skin Diseases:
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Over the past several decades, ultrastructural, histological, and immunological analyses have provided an idea of the defects underlying the pathologies of various inherited skin disorders. This molecular information has greatly helped researchers in gene isolation by knowing its function.
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Functional cloning has been the most suitable approach for skin diseases, providing information on the defective gene product and its general biological function.
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A classic example of functional cloning and reverse genetic approach are autosomal dominant blistering skin diseases - epidermolysis bullosa simplex (EBS) and epidermolytic hyperkeratosis (EH).
Epidermolysis Bullosa Simplex (EBS): It is a skin condition characterized by keratinocyte fragility within the basal layer, leading to skin blistering. Ultrastructural analyses of an individual with EBS had previously shown abnormal subcellular localization and aggregation of keratin intermediate filaments, indicating a role for keratins in the pathology of the condition.
Epidermolytic Hyperkeratosis (EH): It is presented by cytolysis in the epidermis's suprabasal layers and the basal keratinocytes' hyperproliferation. It was previously known that undifferentiated keratinocytes expressing KRT5 (gene) and KRT14 turn off these genes, which leads to the expression of KRT1 and KRT10. KRT1 and KRT10 are the markers of terminal differentiation. However, it was later investigated if EH's was the genetic basis for a defect involving terminal differentiation of keratinocytes. This investigation involved developing transgenic mice with dominant-negative Keratin10.
LAMA5 in Junctional Epidermolysis Bullosa (JEB): It is another good example of functional cloning to identify and isolate skin disorders genes, including the LAMA 5 genes found in the junctional form of epidermolysis bullosa.
- Positional Cloning of Genes In Several Inherited Skin Diseases: For skin conditions where the molecular defect was unknown, but a clear inheritance pattern was noticed among related people, positional cloning, or forward genetics, was done. Examples of position cloning approach include:
Localized Autosomal Recessive Hypotrichosis (LAH) and DSG4: One of the best examples of positional cloning is the discovery of a novel desmoglein, DSG4, as the main underlying cause of localized autosomal recessive hypotrichosis (LAH) in humans. Mutations identified in people with LAH and comparative genomics studies defined the critical role of DSG4.
Calcium pumps in Hailey-Haley and Darier's disease: Position cloning also aided in elucidating the cause of another skin condition, Hailey–Hailey disease. In this disease, cellular adhesion is lost between epidermal cells (acantholysis), resulting in crusted plaques, erosions, and blisters. Although ultrastructural analysis of the areas of the lesions revealed subcellular abnormalities in the localization of keratin intermediate filaments, the gene that encodes a protein involved in keratinocyte adhesion had not been identified. Later the gene was eventually found to be ATP2C1, a calcium pump that encodes the calcium or magnesium ATPase of the Golgi apparatus required for the integrity of the epidermal calcium gradient.
Like Hailey - Hailey disease is another autosomal dominant disease, Darier's disease is characterized by cell separation of suprabasal epidermal cells resulting in warty papules, plaques, and nail abnormalities. Although electron microscopy revealed structural defects, such as abnormal subcellular desmosomal protein distribution, the pathophysiology remained unclear.
Conclusion:
Recently, a lot of progress has been made in explaining genetics as the basis of skin diseases using classical genetic techniques. In addition, the genetic basis of many skin conditions has been explained using classical genetic testing methods. Functional and positional cloning are two genetic approaches has been the most fruitful in driving various discoveries.
