What is a base substitution?
It’s a single gene mutation in which one base pair is replaced by another. In molecular genetics it’s called point mutation
What is a silent substitution?
Does not change the amino acid sequence and have no consequences
What is a missense mutation?
Produce a change in single amino acid
What is a nonsense mutation?
Produce one of the three stop codon (UAA, UAG, UGA) causing premature termination of the polypeptide chain
What happens in a deletion and insertion mutations?
It can result in extra or missing amino acids in a protein, often detrimental
What is a frameshift mutation?
When the number of missing or extra base pairs is not a multiple of three. This changes the entire reading frame from that point on.
What is a duplication mutation?
duplication of the whole gene
What happens at splice-site mutations?
Happens at intron-exon boundaries, alter the spicing signal that is necessary for proper excision of an intron
What is a promoter mutation?
It decreases the affinity of RNA polymerase for a promoter site, often resulting in reduced production of mRNA and reduced production of a protein
What is an enhancer mutation?
Mutation in the enhancer region of the DNA which results in reduced protein production.
What are expanded repeat mutations?
affects tandem repeated DNA sequences that occur within or near certain disease-related gene
What are gain of function mutations?
They result in overexpression of the product or inappropriate expression. It produces dominate disorders
What genotype results in loss of function mutations?
recessive diseases
What genotype in loss of function mutations is sufficient for normal function?
hterozygous. 50% of the protein product is lost but the 50% that remains is sufficient for normal function
What are the normal subunit genes of adult Hb?
Normal individual has two normal βgenes and four normal α genes and is associated with a heme group
What populations are mostly affected by sickle cell disease?
Affects mostly African-American, Middle Eastern and Mediterranean population
***What is the cause of sickle cell disease?****
single missense mutation that affects a substitution of a valine for glutamic acid at position 6 of the β-globin polypeptide chain
What is generalized thalassemia?
α & β globin chain is structurally normal but reduced in quantity
What is α-Thalassemia?
α-chain is reduced and there are excess β-chains
What are the main causes of α-Thalassemia?
deletions of the α-globin genes
What is HbH disease?
The loss or abnormality of three of the α-genes
What are the clinical manifestations of HbH disease?
IT produces moderately severe anemia and splenomegaly
What is the cause of hydrops fetalis?
Loss of all four α-genes
What are the clinical manifestations of hydrops fetalis?
Condition in which there is a massive buildup of fluid.
What is β- Thalassemia?
β-chain is reduced & excess α-chains
What are the issues with excess α-chains?
Excess α-chain causes precipitation and damages the cell membranes of red blood cell precursors. This leads to premature erythrocyte destruction and anemia
What is β-Thalassemia minor?
Mutation in one copy of chromosome 11. It involves little or no anemia and does not ordinarily require clinical management.
What is it called when β-globin is completely absent?
β^0-Thalassemia
What is it called when β-globins are reduced to about 10-30% of the normal amount
β+ Thalassemia
What is HPFH?
(hereditary persistence of fetal hemoglobin): occurs when fetal hemoglobin, encoded by the α-globin genes and by two β-globin like genes called Aγ & Gγ continues to be produced after birth
