5.  &  GENE CLUSTERS

6. Hb

8. Double Helix DNA

9. ATGATG GTGT Exon1 TAA TAG TGA Exon 2 CCAATTATAA AGAG Initiation Codon Termination Codon 5’ 3’ Intron HUMAN GENE

10. Transcription Initiation Transcription Termination ‘CAT ‘TATA’ Box Box Exon 1Exon 2 Exon 3 5’3’ Intron 1 Intron 2 Promoter region Translation Initiation Codon (ATG) Polyadenylation Signal Translation Termination Codon (TAA)

12. Mild and Silent Beta-Thalassemia Mutations

13. IVS 1 - 5 (G->C) / IVS 1 - 5 (G->C) IVS 1 - 5 (G->C) / - 25 bp del IVS 1 - 1(G->A) / IVS 1 – 1(G -> A) IVS 1 - 1 (G-T) / IVS 1 - 1 (G -> T) -25 bp del / -25 bp del Cd 8 (-AA) / Cd 8 (-AA)

14. IVS 1 - 5 (G->C) / - 88 (C->A) IVS 1 - 5 (G->C) / Poly A IVS 1– 5 (G->C) / CD 26 (G->A) IVS 1 – 5 (G->C) / IVS II-837 (T-C) -25 bp del / CD 27 (G->T)

15. IVS II–1 (G->A) / IVS II – 1 (G->A) IVS 1-6 (T->C) / IVS 1-6 (T->C) CD 27 (G->T) / CD 39 (G->T) CD 26 (G->A) / 619 bp del CD 26 (G->A) / IVS 1 – 130 (G->C) CD 30 (G->A) / CD 30 (G->A) IVS 1-6 (T->C) / Undefined IVS 1-6(T->C) / IVS II-848(C->A)

16. 1. Homozygous or compound heterozygous state for  thalassemia a)Inheritance of mild  thalassemia alleles b)Co-inheritance of  thalassemia c)Increased Hb F response  Xmn1 –polymorphism   promoter mutations  Trans-acting HPFH genetic determinants

17. 2. Heterozygous state for  thalassemia a) Co-inheritance of extra  globin genes (  ) b) Dominantly inherited  thalassemia (Hyperunstable  chain  variants) 3. Compound heterozygous for  thalassemia and  chain variants e.g. Hb E 4. Compound heterozygotes for  thalassemia and HPFH.

18.  -Thalassemia genotypes of parents Hb. F values in parents Co-inheritance of  thalassemia Age at presentation Level of Hb. at presentation Level of Hb. A

19.  -Thalassemia

20. Hb F  2  2 (  4) Hb Barts Hb A2  2  2 Hb A  2  2 (  4 ) Hb H FAILURE OF a-GLOBIN LEADS TO:

21.  -Thalassemia - 1 in Trans Single gene deletion on both chromosomes Very common in our area Patients are Microcytic Hypochromic Normal Hemoglobin Electrophoresis No risk of hemoglobin Bart’s hydrops fetalis

22.  -Thalassemia - 1 in CIS  Deletion of both  genes on one chromosome.  Common in Southeast Asian, Filipino.  Fortunately is not recorded in our area.  Diagnosis: Microcytic hypochromic, normal Hb electrophoresis, DNA studies  Risk of transmission of Hb Bart’s hydrops fetalis

23. Deletional Hb H Disease  3  genes are detected (-  /--)  Parents has to be -  /  --   This type is common in South Asia and not common in our locality.  Fairly severe anemia with hemolysis