| Normal Chromosome 16 Chromosome 16 contains the genetic codes for the zeta and alpha hemoglobin chains.Each chromosome has two loci alpha chains 1 and 2. This equals a total of four loci of material coding for the alpha hemoglobin chain. See the image for a visual representation of these loci.In the genotypic notation of alpha thalassemia an "" represents the presence of an alpha locus. A "-" represents a deletion of a locus.The notation for the normal number of alpha loci is /. The amount of Hb A produced by this normal gene is 97-98 %.(drawing modified from Harmening, 1999) | View Page |
| Chromosome 16 Alpha Thalassemia Silent Carrier In the Silent Carrier (-/), only one loci is deleted or inactive. Hemoglobin A is still able to be made to its fullest amount, 97-98%.(drawing modified from Harmening, 1999) | View Page |
| Chromosome 16 Alpha Thalassemia Intermedia When three loci of alpha chains are deleted (--/-) or inactive, only 70-90% of Hemoglobin A is made. The excess beta chains that remain unpaired form the tetramers of Hemoglobin H.(drawing modified from Harmening, 1999) | View Page |
| Chromosome 16 Alpha Thalassemia Major The complete deletion of alpha chain loci (--/--) in alpha thalassemia major is incompatible with life. None of the vital alpha chains needed for every normal adult hemoglobin can be produced. (drawing modified from Harmening, 1999) | View Page |
| Alpha Thalassemia Minor - Homozygous In the homozygous state (-/-), both parents contribute one missing locus.(drawing modified from Harmening, 1999) | View Page |
| Alpha Thalassemia Minor - Heterozygous In the heterozygous state (--/), one parent contributes a normal gene while the other one a gene with both alpha chain loci deleted.(drawing modified from Harmening, 1999) | View Page |
| References Burtis, CA. & Ashwood, ER. Tietz Textbook of Clinical Chemistry 2nd ed. W. B. Saunders. 1994.Harmening, DM. Clinical Hematology and Fundamentals of Hemostatis 5th ed., F.A. Davis, 2008Lotspeich-Steininger, Stiene-Martin and Koepke, Clinical Hematology Principles, Procedures, Correlations, Lippincott 1992McKenzie, SB., Textbook of Hematology 2nd ed., Williams and Wilkins 1996.Miale, JB, Laboratory Medicine Hematology 6th ed., Mosby 1982.Nouwens, J and Spahn, M. Hemoglobin H Disease: A self-instructional unit 3rd ed., Educational Materials for Health Professionals, Inc. 1991.Doig, K. Rodak's Diagnostic Hematology 3rd ed. W.B.Sunders Co., 2007. | View Page |
| Chromosome 11 Beta Thalassemia Major Beta thalassemia major, B0/B0 (two gene mutations, deletions or combination) results in very few to no beta chains being produced.Hemoglobin A levels are at or near 0%.(drawing modified from Harmening, 1999) | View Page |
| Chromosome 11 Beta Thalassemia Silent Carrier B++s/B The silent carrier state of beta thalassemia, B++s/B, involves one minor beta chain deletion or mutation. This state produces such a small drop in the level of beta chain synthesis that the alpha to beta chain ratio remains at a near normal state.Hemoglobin A levels remain normal (98% or higher).(drawing modified from Harmening, 1999) | View Page |
| Normal Chromosome 11 Beta chain synthesis is controlled by two gene loci; one on each of chromosome 11. Chromosome 11 also carries the gene loci for delta chains, G-gamma and A-gamma chains and embryonic epsilon chains. Normal chromosome 11 is depicted in the image below. In the genotypic notation of beta thalassemia, a "+" represents a reduction in beta chain production whereas a "0" represents a complete deletion of a locus. The "+s" represents a silent carrier. Delta chain deletions may be present in combination with beta chain deletions.(drawing modified from Harmening, 1999) | View Page |
| Chromosome 11 Beta Thalassemia Minor B+/B In Beta thalassemia minor B+/B, one beta gene locus is partially deleted or inactive. With this deletion, only 85% to 95% of the normal level of Hb A is made.(drawing modified from Harmening, 1999) | View Page |
| Chromosome 11 Beta Thalassemia Minor B0/B In Beta thalassemia minor, B0/B, one beta gene locus is completely deleted or inactive.Hemoglobin A production is down to 70% - 85% in this state of beta thalassemia.(drawing modified from Harmening, 1999) | View Page |
| Chromosome 11 Delta-Beta Thalassemia Minor Occasionally, the beta chain gene deletion extends to include the locus for the delta chain gene. If this deletion occurs on only one chromosome of the pair, it creates delta-beta thalassemia minor. Delta-Beta 0/ BetaHb A and A2 will both be decreased and Hb F will be increased.(drawing modified from Harmening, 1999) | View Page |
| Chromosome 11 Beta Thalassemia Intermedia B+s/B+s In Beta thalassemia intermedia, B+s/B+s, both beta chain loci show a partial deletion or inactivation of the gene.Hemoglobin A is made to only 55% to 75% of its normal amount.(drawing modified from Harmening, 1999) | View Page |
| Chromosome 11 Beta Thalassemia Intermedia B0/B+s In Beta thalassemia intermedia B0/B+s, there is one completely deleted or inactive beta chain gene, while the other is partially deleted or inactive.This state also results in Hb A production of 55%-75% of normal.(drawing modified from Harmening, 1999) | View Page |
| Chromosome 11 Delta-Beta Thalassemia Intermedia Delta-beta thalassemia intermedia exists when both gene loci for beta and delta chains are deleted or inactive on one chromosome, while the other chromosome contains a beta chain gene that is partially deleted or inactive. Delta-Beta 0/ Beta+sIn this state the majority of hemoglobin will be Hb F, with very little Hb A and A2 present.(drawing modified from Harmening, 1999) | View Page |
| Chromosome 11 Delta-Beta Thalassemia Major Delta-beta thalassemia major, Delta-beta 0/ Delta-beta0, exists when both gene loci for beta and delta chains are completely deleted or inactive on both chromosomes. In this state, only Hb F can be made.(drawing modified from Harmening, 1999) | View Page |
| References Burtis CA, Ashwood ER. Tietz Textbook of Clinical Chemistry 2nd ed. WB Saunders; 1994.Doig, K. Rodak's Diagnostic Hematology. 3rd ed. WB Saunders Co; 2007.Harmening DM. Clinical Hematology and Fundamentals of Hemostatis. 5th ed. FA Davis; 2008Hoffman R, Benz EJ Jr., Shattil SJ, Furie B, Cohen HJ, Silberstein LE. Hematology Basic Principles and Practice, 2nd ed. Churchill Livingstone; 1995.McKenzie SB. Textbook of Hematology, 2nd ed. Williams and Wilkins; 1996.Miale JB, Laboratory Medicine Hematology, 6th ed. Mosby; 1982.Stiene-Martin EA, Lotspeich-Steininger CA, Koepke JA, Clinical Hematology Principles, Procedures, Correlations, 2nd ed. Lippincott; 1998. | View Page |