Multiple alleles

Tirona, R. G., Leake, B. F., Merino, G., Kim, R. B., Polymorphisms in OATP-C identification of multiple allelic variants associated with altered transport activity among European-and African-Americans, J. Bid. Chem. 2001, 276, 35669-35675. 

CYP2C9 Multiple allelic variants of CYP2C9 may account for the occurrence of poor metabolizers and increased efficacy of warfarin (84)... 

Individual mice express a combinatorial pattern of MUPs (typically at least 7-12 isoforms) reflecting multiple allelic variants and multiple expressed loci (Robertson et al. 1997). Among wild mice, individuals each express a different pattern even when captured from the same population (Payne, Malone, Humphries, Bradbrook, Veggerby, Beynon and Hurst 2001 Beynon et al. 2002), with the exception of very closely related animals that have inherited the same haplotypes from their parents (a 25% chance among outbred sibs, similar to MHC type sharing). The extreme heterogeneity in the sequence of MUPs is mostly confined to strands B, C and D and the intervening turns of the 8-barrel structure (Beynon et al. 2002). 

It is clear from family studies that apo(a) gene polymorphism is a consequence of the autosomal codominant Mendelian inheritance of multiple alleles operating at a single chromosomal locus (G7, U4, U6). In families where this simple inheritance pattern was not followed, the existence of a null allele has been postulated (U4, U6). A null allele frequency of 6% was estimated for the subjects... 

IFN-a Family. There are 14 human genes that comprise the IFN-a family. These genes generally encode mature polypeptides with either 165 or 166 amino acids and have a 15% to 25% variation in primary amino-acid sequence. Minor variants consisting of one or two amino-acid differences account for multiple alleles. Thirteen separate proteins are expressed from these 14 genes (Table 7.1), each with a different profile of antiviral and antiproliferative activity [40,41]. Evidence for cell specificity of IFN-a subtypes has been reported. For example, IFN-al has greater antiproliferative effects on B-cell neoplasms, whereas IFN-a2 is more specific for other malignancies [42]. When assayed on human cells, IFN-al has less antiviral activity than IFN-a2 [43]. Nevertheless, IFN-al has potent antiviral activity in bovine-, feline-, and primate-derived cells [44]. Fur-... 

P. A. (1993). A comparison of the multiple alleles of xylS carried by TOL plasmids pWW53and pDKl and its implications for their evolutionary relationship. Journal of General Microbiology, 139. 557—68. 

No functional polymorphisms have been reported in human CAR, the major nuclear receptor that mediates CYP2B6 induction. However, PXR, which also plays a significant role in CYP2B6 induction, exists as multiple allelic variants, some of which alter transactivation function of this receptor (122,123). 

Kritzik M, Tarantino MD, Nugent DJ, Santoso S, Kunicki TJ Nucleotide polymorphisms in the (z2 goie define multiple alleles whidi are associated with differences in platelet 0(2Pl. Blood 90a 27, 1997 (abstract)... 

Another category of multiple molecular forms can arise when enzymes are ofigomeric and consist of molecules made up of subunits. The association of different types of subunits in various combinations gives rise to a range of active enzyme molecules. When the subunits are derived from different structural genes, either multiple loci or multiple alleles, the hybrid molecules so formed are called hybrid isoenzymes. The ability to form hybrid isoenzymes is evidence of considerable structural similarities between the different subunits. Hybrid isoenzymes can be formed in vitro, but they are also formed in vivo in cells in which the different types of constituent subunits are present in the same sub-ceUular compartment. 

Short tandem repeat (STR) or microsatellite loci consist of DNA sequence motifs that have core repeats of two to seven base pairs. Examples include the dinucleotide 5 CACACACA 3 and the tetranucleotide 5 TTTATTTATTTA 3". Thousands of STRs are scattered throughout the genome. Because they are flanked by unique sequences, each can be specifically amplified with the polymerase chain reaction (PGR) for analysis. In populations of individuals, multiple alleles may be present based on differences in the number of repeated motifs at the locus. STRs have many characteristics that make them ideal for identity testing (1) They can be analyzed in fluorescent automated systems (2) alleles can be assigned in a definitive manner following analysis (3) STR loci are almost always transmitted in families in a Mendelian fashion (4) the loci may have 10 or more alleles, often with... 

Approximately 25% of all human genes occur among individuals in a population in multiple allelic forms referred to as polymorphisms. For example, the ABO locus, an important factor in blood transfusions, consists of three different alleles (alternative states of a gene) called A, B, and O. Individuals can be homozygous or heterozygous for any pair of A, B, and O alleles. The HLA family... 

B27. Bonderman, P. W., and Bonderman, D. P., Family segregating for multiple alleles of cholinesterase a laboratory study. Clin. Biochem. 6, 256-265 (1973). 

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