Chapter 11: Principles of Molecular Disease: Lessons from the Hemoglobinopathies Flashcards
type of mutation due to nucleotide substitutions, deletions, insertions, or rearrangements
loss of function mutations
due to deletions a-globin genes
alpha-thalassemias
due to a reduction in the abundance of b-globin
beta-thalassemias
missense mutation which locks hemoglobin in its high oxygen affinity state (gain of function mutation)
Hemoglobin Kempsey
novel property mutation due to amino acid substitution
sickle cell
the yellow breakdown product of normal heme
bilirubin
a blood disorder caused by a genetically determined change in the molecular structure of hemoglobin
hemoglobinopathy
What do mutations in the coding region result in?
structurally abnormal proteins that have a loss or gain of function or a novel property that causes disease
What do mutations on noncoding regions result in (2)?
mutations that alter the stability or splicing of the mRNA or mutations that disrupt regulatory elements or change gene dosage
What do mutations in regulatory elements result in?
they alter the abundance of mRNA or the time or cell type which the gene is expressed
What do mutations in the coding region or regulatory domains result in?
a decrease in the amount of the protein produced
α and α-like chains-genes are clustered on what chromosome?
16
β and β-like chains-genes are on what chromosome?
11
How many β-globin genes are in the diploid genome?
2
How many α-globin genes are in the diploid genome?
4
Which type of globin gene has prenatal consequences, α or β?
α - it is seen in fetal and postnatal life; β has no prenatal consequnces
What are the two most conserved amino acids?
His92 and Phe42
What is the percentage of HbF in adults?
1%
What is the percentage of HbA2 in adults?
2%
What is required for expression of all genes in the β-globin cluster?
LCR
Which is an embryonic α-like globin?
zeta-globin
When is onset of β-thalassemia apparent?
2-6 months after birth
