gene and chromosomal mutation Flashcards
(40 cards)
what is the definition of a germline mutation?
germline mutations are mutations whichoccur in germ cells and gametes, and may be transmitted to the offspring and in successive generations. If the mutation has an adverse effect on the phenotype of an organism, the mutant condition is known as a hereditary disease or a genetic disorder
what is the definition of a somatic mutation?
a somatic mutation occurs in somatic cells, and are not inherited by the progeny and not passed on to the next generation
what is the definition of a point mutation?
a point mutation involves chemical changes that affect the DNA sequence of just one gene, and involve changes at specific gene locuses, resulting in a change of one or a few bases in the DNA sequence. two types of point mutations are nucleotide substitutions and nucleotide insertions or deletions
what happens in a missense mutation (nucleotide substitution)
a nucleotide substitution in a DNA sequence occurs, resulting in the translation of a different amino acid being coded into the polypeptide sequence. the specific 3D conformation of the protein is changed, and the function of the protein is altered
what happens in a nonsense mutation (nucleotide substitution)
a nucleotide substitution in a DNA sequence occurs, resulting in a codon for an amino acid being changed into stop codon, leading to the premature termination of translation, and a truncated polypeptide. the specific 3D conformation of the protein is changed, and the function of the protein is altered, resulting in non-functional proteins
what happens in a silent mutation (nucleotide substitution)
a nucleotide substitution in a DNA sequence occurs, changing the mRNA codon of the triplet codon. however, the same amino acid is inserted into the protein because of the degeneracy of the genetic code. the amino acid sequence of the polypeptide is unchanged, resulting in no change in the specific 3D conformation of the protein, and the function of the protein is not altered
what happens in a neutral mutation (nucleotide substitution)
a nucleotide substitution in a DNA sequence occurs, changing the mRNA codon and amino acid translated. however, the resulting amino acid substitution produces no detectable change in the function of the protein translated. this could arise from the substitution of the original amino aicd with an amino acid of similar physical and chemical properties, or the substitution of an amino acid that is non-essential to that protein’s structure and function
what happens in a missense mutation (nucleotide insertion or deletion of dNTPs in multiples of 3)
an mRNA codon is added or deleted and the resulting polypeptide has an amino acid added or deleted respectively. the specific 3D conformation of the protein may be changed, leading to a change in the function of the protein
what happens in a nonsense mutation (nucleotide insertion or deletion of dNTPs in multiples of 3)
a stop codon is added, leading to premature termination of translation, and a truncated polypeptide. the specific 3D conformation of the protein is changed, and the function of the protein is altered, resulting in non-functional proteins.
what happens in an extensive missense mutation (nucleotide insertion or deletion of dNTPs not in multiples of 3)
since the resulting mRNA is read as a series of non-overlapping codons, a frameshift mutation occurs, where mRNA codons subsequent to the insertion or deletion site are changed, leading to the subsequent change of the polypeptide sequence. this leads to the incorrect specific 3D conformation of the protein and a change in the function of the protein
what happens in a nonsense mutation (nucleotide insertion or deletion of dNTPs not in multiples of 3)
the mRNA codons subsequent to the insertion or deletion site are changed, and a codon for an amino acid is changed to a stop codon, resulting in a truncated protein. the specific 3D conformation of the protein is changed, and the function of the protein is altered, resulting in non-functional proteins.
what is the genetic and molecular basis of sickle-cell anemia？
sickle-cell anemia involved a mutation in the beta-globin gene, which encodes one of the polypeptide subunits that make up haemoglobin. a thymine is subsituted for an adenine at one position along the haemoglobin gene, resulting in a missense mutation. the sixth amino acid in the polypeptide is changed from a glutamate which is hydrophilic, to a valine which is hydrophobic. the specific 3D conformation and function of the protien is altered, as it creates a hydrophobic spot on the outside of the haemoglobin that sticks to the hydrophobic region on a adjacent protein’s beta chain. the mutant haemoglobin subunits tend to stick to one another when the oxygen concnetration is low, and the agrregated proteins form fibre-like structures within red blood cells.
what are the physiological effects of sickle-cell anemia?
the fibre-like structures cause the red blood cells to lose their normal morphology and become sickle-shaped. sickled cells are less able to move through capillaries and can block blood flow, resulting in severe pain and cell death of the surrounding tissue due to shortage in oxygen. the sickled red blood cells are also fragile and easily destroyed, further decreasing the oxygen carrying capacity of blood
what are some spontaneous mutations that may occur during DNA replication and repair?
DNA polymerase sometimes inserts the wrong nucleotide/too many/too few nucleotides into the DNA sequence. DNA polymerase makes mistakes at a rate of about 1 in every 100,000 nucleotides.
what are some attempts are correct for spontaneous mutations that occur during DNA replication and repair?
- during proofreading, DNA polymerase enzymes recognise mistakes and replace the incorrectly inserted nucleotide so that replication can continue.
- mismatch repair reduces the final error rate even further, as enzymes recognise and fix these deformities by removing the incorretly paired nucleotide and replacing it with the correct nucleotide
what are some spontaneous mutations that may occur during DNA slippage?
daughter or parental DNA strand slips during DNA replication followed by folding back of the strand. hence, there is a mispairing between the daughter DNA strand and the parental template strand. this causes parts of the DNA which are folded back to be copied more than once. if this duplicated DNA segment corresponds to a gene, it will result in gene duplication
what are some physical mutagens?
- X-rays results in the production of free radicals of water which are chemically very reactive and interact with DNA to produce double-stranded breaks leading to chromosomal rearrangements and deletions
- UV are absorbed by bases of DNA, and result in the production of a covalent attachment between adjacent pyrimidines in one strand, or base pair substitutions, insertions or deletions. DNA replication and transcription may also be blocked by UV rays
what are some chemical mutagens?
- base analogues are molecular structures that are similar to the bases normally found in DNA, and may be incorporated into DNA in place of the normal bases during DNA replication, producing base substitutions
- base-modifying agents modify the chemical structure and properties of bases, which leads to mispairing during DNA replication and base substitution
- intercalating agents are flat molecules with multiple ring structures, which insert themselves between adjaent bases in one or both strands of the DNA helix, leading to insertions or deletions during DNA synthesis and hence frameshift mutations.
what happens in a deletion chromosomal aberration?
- when a chromosome breaks in one or more places, and a portion of it is lost, the missing piece is referred to as a deletion, which can occur as a terminal or intercalary deletion.
- if a deletion affects the same gene loci on both homologous chromosomes, the effect is usually lethal,
- if only one of a homologous pair of chromosomes is affected, the effect on the phenotype is that alleles on the non-deficient homologue will be expressed, even if recessive
what happens in a duplication chromosomal aberration
- duplications arise as a result of unequal crossing over between synapsed chromosomes during meiosis or through a replication error prior to meiosis.
- effects of duplications include gene redundancy and phenotypic variations. duplications have also been deemed as an important source of genetic variation during evolution
what happens in an inversion chromosomal aberration?
- an inversion does not involve a loss of genetic information, but simply rearranges the linear sequence
- an inversion requires two breaks along the length of the chromosome and subsequent reinsertion of the inverted segment, forming a chromosomal loop prior to breakage. the newly created sticky ends are brought close together and rejoined
- organisms heterozygous for inversions may produce aberrant gametes that have a major impact on their offspring.
- inversions may also result in position effects which lead to altered gene expression, due to new positioning of a gene within the genome
what happens in a translocation chromosal aberration
- translocation is the movement of a chromosomal segment to a new location in the genome
- reciprocal translocation involves the exhange of segments between two non-homologous chromosomes
- genetic information is not lost or gained, but there is only a rearrangement of genetic material, so the presence of a translocation does not directly alter the viability of individuals
- a translocation may produce a position effect as it may realign certain genes in relation to other genes
what happens during monosomy?
- monosomy only occurs for the X chromosome, as evident in the 45, X turner syndrome, where affected individuals have only 45 chromosomes
- invidiuals generally have female external genitalia and internal ducts, but the ovaries are rudimentary. they also generally have a short stature, skin flaps on the back of the neck, and underdeveloped breasts.
what happens during the 47 klinefelter syndrome?
- trisomy occurs when an individual has more than 1 X chromosome, as evident in the 47, klinefelter syndrome.
- these individuals have genitalia and internal ducts that are usually male, but their testes are rudimentary. they are generally tall and have long arms and legs, and large hands and feet. feminine sexual development is not entriely suppressed
- this ambiguous sexual development is referred to as interseuxality
