Causes of genetic disorders in humans
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Genetic Mutations and Human Genetic Disorders
Genetic disorders in humans are primarily caused by changes or mutations in the DNA sequence. These mutations can be as small as a single nucleotide change or as large as missing or extra chromosomes, large chromosomal rearrangements, deletions, insertions, or substitutions of nucleotides. Some mutations are inherited from parents, while others occur spontaneously (de novo) during a person’s lifetime. These genetic changes can disrupt normal biological processes, leading to a wide range of diseases, from severe disorders to mild predispositions that may only manifest under certain environmental conditions 1249.
Chromosomal Abnormalities and Copy-Number Variations
Some genetic disorders are caused by chromosomal abnormalities, such as having extra or missing chromosomes, or by large-scale rearrangements of chromosome structure. Another important cause is copy-number variation (CNV), where sections of the genome are duplicated or deleted, affecting the dosage of genes critical for normal development. These genomic rearrangements can lead to a variety of disorders, especially those affecting the nervous system, and contribute to differences in cognitive, behavioral, and psychological traits 110.
Single-Gene Disorders and Inheritance Patterns
Single-gene disorders result from mutations in one specific gene. These can be inherited in different ways:
- Recessive disorders require mutations in both copies of a gene (from each parent).
- Dominant disorders occur when a mutation in just one copy of a gene is enough to cause disease. Some disorders are also linked to mutations in mitochondrial DNA, which is inherited only from the mother 16.
Expandable DNA Repeats
Certain genetic disorders are caused by the expansion of simple DNA repeats within the genome. These repeat expansions can disrupt gene expression and are responsible for nearly 30 hereditary diseases, many of which affect the nervous system. The unusual structure of these repeats makes them prone to expansion during DNA replication and repair, leading to disease .
Epigenetic Changes and Disease
Epigenetic modifications, such as DNA methylation and changes in chromatin structure, can also cause genetic disorders. These changes do not alter the DNA sequence itself but affect how genes are turned on or off. Epigenetic changes can be inherited or triggered by environmental factors, and they play a significant role in the development and expression of many diseases, including cancer and neurological disorders 2345.
Complex Disorders: Interaction of Genes and Environment
Many common diseases, such as cardiovascular disease, diabetes, and some psychiatric conditions, are caused by a combination of genetic and environmental factors. In these cases, multiple genetic variants each contribute a small effect, and environmental influences such as lifestyle, infections, or toxins can trigger or worsen the disease. The interplay between genetic susceptibility and environmental exposures makes these disorders complex and variable in their presentation 2458.
Conclusion
In summary, genetic disorders in humans arise from a variety of causes, including mutations in single genes, chromosomal abnormalities, copy-number variations, repeat expansions, and epigenetic changes. These genetic alterations can be inherited or occur spontaneously, and their effects can range from severe disease to mild predispositions influenced by environmental factors. Understanding these causes is crucial for accurate diagnosis, management, and the development of targeted therapies for genetic diseases.
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