Sarge 4-9 Anemias Thalessemias Flashcards
why are there high frequencies of certain anemia in parts of the world
malaria infection advantage for sickle cell, isolated populations
thalassemia
globin proteins quantities are low but the structure is normal, usually have nonsense or splice site mutations
sickle cell anemia
Glu6Val (E6V) mutation on beta chain, hemoglobin forms chains, stick in capillaries
heterozygote advantage
selective sickling of infected cells (AS red cells), phagocytosis of sickle cells
thalassemia phenotype
anemia, misshapen blood cells, spleonmegaly, large bones (facial)
cryptic splice site
new splice sites created by mutation in intron, may lead to stop codon inclusion. May be prevented from being used with an antisense oligonucleotide
when do sickle cell trait people show symptoms
heterozygotes can suffer sickle cell trait at low oxygen, high altitude
structure of hemoglobin
HbA: 2 beta units 2 alpha, heme groups in each subunit, many alpha helices
describe genomic features of hemoglobin
2alpha and 1beta subunits are on different chr, in cluster of related genes in order of expression. Under control of locus control regulator (LCR-beta), and HS-40 (alpha)
order of expression of Hb during development
zeta/eta until 6 weeks pregnant, then alpha/gamma until 6 months after birth (changes to regular alpha/beta)
alpha thalassemia defect
loss of alpha-globin alleles (usually not just point mutations)
beta0 thalassemia defect
no synthesis from an allele of beta-globin
beta+ thalassemia defect
intermedia= B+/B+, B0/B+, minor= B+/B reduced synthesis from an allele of beta-globin