• Polymerization with deoxyhemoglobin
• Stiffen RBCs
• Occlusion of vessels
• Insufficient oxygen delivery
• Tissue damage

• mutation which causes dec to no synthesis of the a-globin chain and causes an anemic phenotype
• Hemoglobin inable to carry oxygen without the a-globin chain

• encodes a transcription factor which induces high levels of adult β-globin
• as levels of KLF1 inc, it inc the conc of BCL11A and adult β-globin while represses levels of γ-globin
• KLF1 concentration are low in embryonic and fetal stages

• directly inhibit production of γ-globin in response to inc KLF1

Human Hemoglobins

in adult blood

• A --> α₂β₂ --> 94%
• A₂ --> α₂δ₂ --> <3.5%
• F --> α₂γ₂ --> <2.5%
• H --> β₄ --> 0%
• Bart's --> γ₄ --> 0%

• GAG --> AAG at codon 6
• milder version of sickle cell
• prevalent in W Africa
• must be observed comparatively to other similar diseases

α-Thalassemia

Clinical Phenotypes

• Silent Carrier --> normal in all appearances
• Thalassemia Trait --> mild anemic characteristics
• HbH Disease --> severe anemic characteristics
• Hb Bart hydrops fetalis --> sever anemia, usually causes death in utero

• good area for recombination and unequal crossovers which almost always lead to deletions
• look for larger deletions
• deletions may include other nearby genes
• chromosome rearrangement

α-Thalassemia

Mental Retardation Phenotypes

• ATR-16 and ATR-X --> global significant mental and physical delay
• Helicase-TF mutant produced on affected chromosome and universally used

• Before switch to adult β-globin, β-globin production turned down/off which leads to production of only the α-globin
• mutations --> defective transcription, mRNA processing, abnormal translation
• Phenotype characterized by imbalance of α-globin and non-α-globins
• co-inheritance with α-thal produces milder phenotype