Mendelian Disorders in Humans — Thalassemia

A Mendelian disorder, by definition, is a genetic disorder caused by a mutation or other structural alteration affecting just a SINGLE gene, and whose characteristic pattern of transmission through the successive generations of an affected family therefore follows the same basic principles of dominance, recessiveness and segregation that Mendel originally worked out from his pea-breeding experiments (§4.3-4.4) — a Mendelian disorder can, depending on the specific gene and chromosome involved, be transmitted as autosomal dominant, autosomal recessive, or X-linked (either dominant or recessive, though X-linked recessive is by far the most commonly encountered pattern, §4.14), and the precise transmission pattern followed by a disorder within any given family can typically be worked out directly by constructing and carefully reading that family's own pedigree chart (§4.16).

Thalassemia is one of the single most medically and demographically important Mendelian disorders affecting the Indian population, and it carries particular regional significance for West Bengal and the wider eastern-Indian region, which report among the highest population carrier rates for the disease found anywhere in the country — making an understanding of its genetics a matter of direct practical, and not merely academic, importance. Thalassemia is fundamentally an autosomal RECESSIVE blood disorder in which the normal synthesis of one of the two distinct types of polypeptide chain (either the alpha-globin chain or the beta-globin chain) that together make up the complete, functional haemoglobin molecule is significantly reduced, or in more severe cases absent altogether — a mechanism that is importantly and instructively different from that of sickle-cell anaemia, a separate genetic blood disorder in which the relevant globin chain continues to be produced in a perfectly normal AMOUNT, but the chain itself is structurally ABNORMAL because of a specific mutation altering its amino-acid sequence. In thalassemia, this reduced or absent synthesis of one globin-chain type creates a serious internal IMBALANCE between the relative amounts of alpha-globin and beta-globin chains being produced within the developing red blood cell, and it is precisely this imbalance, rather than any structural fault in the haemoglobin molecule itself, that leads to the premature destruction of red blood cells and the resulting severe, often transfusion-dependent, anaemia characteristic of the more serious forms of the disease. …