Structural alterations involve changes such as deletion, inversion, duplication, or translocation of chromosome segments during cell division.
A frameshift mutation is the result of insertions or deletions that alter the reading frame of the triplet codons, thereby altering translation and the structure and function of the protein product.
The final configuration of a frameshift mutation results in an abnormal amino acid chain due to the altered reading frame, which can lead to a dysfunctional protein.
The mechanisms include base excision repair, nucleotide excision repair, and DNA mismatch repair.
In lysosomal storage diseases, a deficiency or dysfunction of lysosomal enzymes leads to the accumulation of insoluble intermediates in lysosomes, causing cellular dysfunction.
Telomeres protect the ends of chromosomes from deterioration and fusion with adjacent chromosomes.
Mitochondrial DNA is inherited exclusively from the mother, as only ova contribute mtDNA to offspring.
Environmental factors such as excessive exposure to ultraviolet light, radiation, or certain chemicals can cause mutations in DNA.
Mutations may result in the synthesis of a defective enzyme with reduced activity or in a reduced amount of a normal enzyme, leading to intracellular accumulation of substrates or products of alternative pathways, which can be cytotoxic.
Both alleles at a given gene locus must be mutated.
Posttranslational modifications include chemical changes of amino acid side chains, the addition of carbohydrate moieties, or proteolytic cleavage of polypeptides.
1. Single-gene disorders, 2. Chromosomal disorders, 3. Complex multigenic disorders.
Nondisjunction is the failure of chromosome pairs to separate during cell division, leading to an abnormal number of chromosomes in cells.
Mutations in somatic cells are not heritable and are important in tumor genesis, while mutations in germ cells can be transmitted to progeny and lead to inherited diseases.
They can escape the bridge-fusion-breakage cycle, but this enhances tumorigenesis due to chromosomal instability.
Individual proteins in a proteome do not function in isolation; they form networks that respond to various signals, contributing to diverse cellular functions.
mRNA (messenger RNA) carries the genetic information from DNA to the ribosome, where tRNA (transfer RNA) brings the corresponding amino acids to form a protein.
Examples include Duchenne’s muscular dystrophy and agammaglobulinemia.
Complex multigenic disorders arise from interactions between gene variants and environmental factors, with no single gene being solely responsible for the disease.
It is caused by defects in the dystrophin gene, which codes for a membrane-associated cytoskeletal protein in skeletal and cardiac muscle.
Single-gene disorders are caused by mutations in DNA of a single gene, such as point, frameshift, and trinucleotide-repeat mutations.
Aneuploidy refers to an abnormal karyotype resulting from errors in meiosis or mitosis, leading to either extra or fewer chromosomes.
Autosomal recessive disorders have a 25% chance of being inherited by offspring from heterozygous parents, with homozygous animals usually exhibiting clinical disease early in life.
Mosaicism is the presence of two or more populations of cells with different karyotypes in the same organism, often resulting from mitotic errors.
Male animals have only one X chromosome, making them more susceptible to X-linked recessive disorders, while females typically require mutations from both parents to be affected.
Enzyme deficiencies include glycogen synthase, muscle glycogen phosphorylase, liver glycogen phosphorylase, and glucose-6-phosphatase.
A missense mutation is a base-pair substitution that changes the mRNA codons, resulting in a different amino acid being incorporated into the protein, altering its synthesis.
Frameshift mutations alter the reading frame of codons, which changes the sequence of amino acids in the resulting protein, potentially leading to an abnormal protein structure and function.
Mitosis is somatic cell division for growth and tissue regeneration, while meiosis occurs in germline cells to produce ova or spermatozoa.
Their telomeres are significantly shortened, leading to cell senescence or death.
DNA-repair pathways are inappropriately activated, resulting in the formation of dicentric chromosomes.
Somatic cells are mitotic and disorders involving them are not heritable, while germline cells are meiotic and disorders can be inherited.
A silent mutation is a base-pair substitution that changes the mRNA codons but does not affect the amino acid sequence of the resulting protein.
It is estimated that 20,000 genes can encode as many as a million different proteins.
A deficiency of lysosomal acid hydrolases leading to incomplete breakdown of substrates and accumulation of partially degraded insoluble metabolites within lysosomes.
Only one allele of a mutated gene is necessary for disease, meaning if one parent carries a mutated allele, each offspring has a 50% chance of inheriting the mutation.
A nonsense mutation is a base-pair substitution that changes the mRNA codons to a 'stop' code, prematurely halting the synthesis of the polypeptide chain.
It leads to substantial chromosomal instability and numerous mutations.
Single-gene disorders of mitochondria may exhibit non-Mendelian inheritance patterns influenced by factors like trinucleotide-repeat mutations and genomic imprinting.
1. Formation of an abnormal protein 2. Reduction in the amount of protein synthesized 3. Formation of abnormal proteins without impairing any step in protein synthesis 4. Modification in the rate of synthesis, posttranslational mechanisms, or transporting of proteins out of the cell.
Glycogenosis type III (Cori’s disease), caused by a deficiency of an enzyme involved in glycogen degradation, resulting in the accumulation of structurally abnormal glycogen within hepatocytes.
