Human Transferrin Polymorphism

Abstract

The application of isoelectric focussing (IEF) has revealed a large amount of heterogeneity in the human transferrin (TF) system and has enhanced its potential value in anthropological and genetic studies. The average heterozygosity has been elevated from 0.05, observed by conventional methods of electrophoresis, to 0.29 detected by IEF. So far approximately 30,000 individuals from 122 population groups have been analyzed for TF subtypes to evaluate the magnitude of genetic variation at the TF locus. Possible environmental and biological factors, which may be operating to maintain the TF polymorphism, are discussed.

Screening Using Serum Percentage of Carbohydrate-Deficient Transferrin for Congenital Disorders of Glycosylation in Children with Suspected Metabolic Disease

“…Moreover, we have found several types of Tf polymorphisms that hampered efforts to reach a conclusive diagnosis in sick children. The most common polymorphism in human serum is Tf C (Ͼ99%), whereas TF B (lower pI) and D (higher pI) variants, which possess a different primary structure but a normal set of carbohydrate chains, occur less often (28 ). After neuraminidase treatment, all homozygote Tf variants present 1 band at the asialoTf level, whereas heterozygote variants show 2 bands, based on the particular subtype.…”

Development and Multicenter Evaluation of the N Latex CDT Direct Immunonephelometric Assay for Serum Carbohydrate-Deficient Transferrin

“…Another advantage of N Latex CDT over the indirect column-based immunoassays is that the CDT mAb is not influenced by transferrin genetic variants. Genetic variants, which are rare in white individuals but more common in other populations (8,35 ), may cause falsely low and high CDT values with the column-based immunoassays (28 ). For example, trisialotransferrin D in samples from individuals with C and D genetic variants will coelute with disialotransferrin C and thereby cause overestimation of CDT.…”

“…Amino acid sequence variation is observed in individuals with genetic variants B, C, and D (8 ), whereas transferrin glycoforms with variable carbohydrate content and/or branching of the maximum 2 N-linked oligosaccharide chains (N-glycans) are always present (4,7,9 ). Typically, the major serum transferrin glycoform, tetrasialotransferrin, contains 2 disialylated biantennary glycans.…”

A BF subtype “Fb1” is a marker gene of some mongoloid populations

“…As for Mongoloid populations, such specific alleles are typically illustrated by the Di S antigen of the Diego blood group (Layrisse et al, 1955), the Gmab3st haplotype of immunoglobulin heavy chain allotypes (Gin, for review see Matsumoto, 1988), the TFDChi allele of transferrin (for review see Kamboh and Ferrell, 1987), a set of rare mutant alleles of vitamin D binding protein (DBP, initially called groupspecific component, Gc, for review see Constans et al, 1985), and so on. The distribution of the rare variants such as TFDChi or DBP variants informs us anthropological relationship between populations, their exchanges, and their migrations (Constans et al, 1985).…”