HBG 23 ( Mutation)

• DNA mutations are inherited changes in the DNA sequence
• Mutations are permanent alterations of the gene sequence
• Mutations can happen at the nucleotide level or chromosome level
• Mutations are passed on to daughter cells or offspring
• Mutations are found in less than 1% of the population
• Mutations are usually associated with negative effects and outcomes
• Sometimes mutations may have positive effects such as adaptation and evolution
• Sometimes mutations may have no effect
• Mutation analysis often helps understand the function of a gene and diseases
• Germline mutations first occur in gametes and are heritable, while somatic mutations first occur in non-gamete cells and are non-heritable
• Germline mutations are found in all adult cells
• Somatic mutations are only found in the daughter cells of the mutated parental cells
• DNA mutations occur at the nucleotide level and can affect protein function
• Changes in nucleotide lead to changes in codon, amino acid, and protein function
• Classification of Gene Mutation:
• Point mutation/Base substitution
• Insertion & Deletion mutation
• Chromosome mutation
• Others (Numerical, Structural)
• Missense mutation involves the replacement of a nucleotide with another, leading to a different amino acid and protein sequence
• Nonsense mutation results in the incorporation of a STOP codon, leading to premature translation termination and a truncated protein
• Insertion or Deletion mutation involves adding or deleting a nucleotide, changing the entire amino acid sequence of the protein
• Silent mutation does not change the amino acid sequence
• Numerical Chromosome Mutation can lead to conditions like Down syndrome, Klinefelter syndrome, and Turner syndrome
• Chromosome mutations affect entire sections of genes, not just individual base pairs or codons
• Chromosome mutations can be structural (changes in chromosome structure) or numerical (changes in the number of chromosomes)
• Chromosome structural mutations include duplication, deletion, inversion, and translocation
• Mutation vs Polymorphism vs Variant:
• Mutation is rare, with less than 1% prevalence as a threshold
• Polymorphism is common
• Mutation results in loss or gain of function, which is rare
• Polymorphism refers to variations among individuals in a population, which is common
• Mutation is a process, while Polymorphism is a condition
• Mutation can lead to Polymorphism, which then leads to Variant
• Variant can be pathogenic, likely pathogenic, uncertain significance, likely benign, or benign
• Mutation involves changes different from the germ cell/line DNA
• Polymorphism involves differences between two or more germ cell/line DNAs
• Regulation of gene expression - Histone modifications:
• Histone modifications have global effects on gene expression
• Mechanisms of epigenetic memory: