Normal human hbs Six including hba Each has a tetrameric structure Two a or a-like genes Clustered on chromosome 16 Two non-a genes Clustered on chromosome 11
Normal Human Hbs • Six including HbA • Each has a tetrameric structure – Two α or α-like genes • Clustered on chromosome 16 – Two non-α genes • Clustered on chromosome 11
Globin Tertiary structure Heme Eight helices: A-H 3 Phe 42D Two globins highly conserved H G E Phe 42 wedges heme porphyrin ring into B heme pocket ·Mut:Hb Hammersmith Helix A His 92: covalently w.B. Saunders Company items and derived items copyright o 2002 by W.B. Saunders Company links heme iron Mut: Hb Hyde park
Globin Tertiary Structure • Eight helices: A-H • Two globins highly conserved – Phe 42: wedges heme porphyrin ring into heme pocket • Mut: Hb Hammersmith – His 92: covalently links heme iron • Mut: Hb Hyde Park
1 BLCR E I Gene cluster: A Lm m-HIHHHrl group of adjacent Chromosome 11: B-globin genes genes that are Hd- 40 v52 vs1 vo2 val a2 a1 81 identical or HIHI Pseudogenes related 40 60 kb Chromosome 16: a-globin genes 2. Codons Pseudogene. 13031104 105146 B-globin gene 850-900bp DNA Sequence Exon 1 Exon 2 Intron 2 Exon 3 homologous with 1313299100141cdns a known gene but a-glo gel is non-functional Exon 1 Exon 2 Exon 3 020040608010001001600bp
Gene cluster: A group of adjacent genes that are identical or related. Pseudogene: DNA sequence homologous with a known gene but is non-functional
Ancestry of The Hemoglobin Genes Ancestral Globin Gene Duplication Mutation t Transposition g Duplications and mutations 「②言 Fetus d Adt etus Adult Embryo Pseudogenes Embryo Pseudogenes oglobin gene family B-globin gene family chromosome 16 chromosome 11
Developmental Expression of Globin Genes and Globin Switching
Developmental Expression of Globin Genes and Globin Switching