Genetic mutations in humans
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Genetic Mutations in Humans
Human Gene Mutation Database (HGMD): A Comprehensive Repository
The Human Gene Mutation Database (HGMD) is a critical resource for understanding genetic mutations in humans. It contains a vast collection of published germline mutations in nuclear genes associated with human inherited diseases. As of June 2020, HGMD includes over 289,000 different gene lesions identified in more than 11,100 genes, curated from nearly 73,000 articles . This database is indispensable for researchers, clinicians, and genetic counselors, providing essential data for genetic diagnosis and next-generation sequencing studies .
Types of Genetic Mutations
Genetic mutations in humans can be categorized into several types. These include single nucleotide variants, short insertions or deletions, and large structural variants (SVs). Pathogenic mutations can also involve micro-deletions, micro-insertions, duplications, repeat expansions, inversions, gross deletions, and complex rearrangements. Each type of mutation can have different implications for genetic diseases and their inheritance patterns.
De Novo Mutations and Their Impact
De novo mutations, which are new mutations that occur in an individual and are not inherited from either parent, play a significant role in genetic diseases. These mutations are particularly prominent in neurodevelopmental disorders such as intellectual disability, autism, and schizophrenia. Studies have shown that de novo mutations are more numerous in the offspring of older fathers and tend to occur more frequently in early-replicating, genic regions. These mutations contribute to genetic diversity and can provide insights into the mechanisms of human mutagenesis .
Mutation Hotspots and Mechanisms
Certain regions of the human genome are more prone to mutations, known as mutation hotspots. These hotspots can result from normal biological processes like meiotic recombination or DNA replication errors, as well as from aberrant repair mechanisms. Understanding these hotspots and the mechanisms behind them is crucial for identifying regions of the genome that are susceptible to mutations and their potential role in diseases.
Mutation Rates and Fitness Consequences
The human mutation rate per nucleotide site per generation is estimated to be about 1.1 × 10⁻⁸, resulting in approximately 70 new mutations per diploid genome per generation. Most of these mutations are paternal in origin. The fitness consequences of these mutations vary, with many being mildly deleterious. It is estimated that around 20% of new missense mutations result in a loss of function, while 53% have mildly deleterious effects. These mutations contribute to the genetic basis of complex diseases and influence the genetic diversity within populations .
Conclusion
Genetic mutations in humans are a complex and multifaceted area of study, with significant implications for medical research, genetic diagnosis, and understanding human evolution. Resources like the Human Gene Mutation Database (HGMD) provide invaluable data for researchers and clinicians, helping to elucidate the mechanisms and consequences of genetic mutations. Understanding the types, rates, and impacts of these mutations is essential for advancing our knowledge of human genetics and improving health outcomes.
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