Allelic heterogeneity

Allelic heterogeneity is observed in osteogenesis imperfecta (choice A), but allelic heterogeneity causes variable expression in patients and is not the principle described here. 

Allelic heterogeneity occurs when different alleles of the same gene produce clinically similar conditions. 

Park, W.J., Meyers, G.A., Li, X., Theda, C., Day, D., Orlow, S.J., Jones, M.C., and Jabs, E.W. (1995) Novel FGFR2 mutations in Crouzon and Jackson-Weiss syndromes show allelic heterogeneity and phenotypic variability. Hum Mol Genet 4 1229-1233. 

We also noticed that 11 out of 28 sample sets showed significant association for different haplotypes, using global P values, as evidence of association ( Table 2.1-1). One possibility is that multiple causal variants are contained in different haplotypes in different populations or subpopulations. Another possibility is that a single disease mutation has occurred on multiple haplotypic backgrounds. This could contribute to the allelic heterogeneity that we observed in the meta-analysis. 

In summary, different SNPs and haplotypes in the G72/G30 region showed BD and/or SZ association in different studies. Strong between-study heterogeneities were observed for almost all the five SNPs that were analyzed in the meta-analysis. All these data suggest potential strong allelic heterogeneity at the G72/G30 locus. As usual, the conclusions from meta-analyses must be read with caution because of possible publication bias toward positive reports. 

We are thus led to consider allelic heterogeneity, the existence of different susceptibility variants in the same gene. This is a primary reason for what are often termed inconsistent findings in psychiatric... 

Whatley SD, Puy H, Morgan RR, Robreau AM, Roberts AG, Nordmann Y, Elder GH, Deybach JC. Variegate porphyria in 41. Western Europe identification of PPOX gene mutations in 104 families, extent of allelic heterogeneity, and absence of correlation between phenotype and type of mutation. Am. J. Hum. Genet. 42. 1999 65 984-994. 

All the autosomal dominant acute porphyrias show extensive allelic heterogeneity. More than 200... 

Brody LC, Mitchell GA, Obie C. Michaud J, Steel G, et al. 1992. Ornithine delta-aminotransferase mutations in gyrate atrophy. Allelic heterogeneity and functional consequences. J Biol Chem 267 3302-3307. 

To our knowledge, no published reports specify which of the esterases found in other mouse tissues are excreted in the urine. Of the five somatic esterase loci for which all strains employed in this study have been typed, nonblockers are isogenic at all of them. Nonblockers and blockers show allelic differences at four loci and are completely isogenic at Es-2 (Heiniger and Dorey, 1980). Significant differences in migration of Peak 2 in blockers but not in nonblockers may be related to this allelic heterogeneity. 

Phenotype tests, primarily at chemical and biochemical levels (metabolites and enzymes) are emphasized. Genetic information is provided to indicate how much genetic and allelic heterogeneity may be associated with the phenotype. A later edition of this book may expand into the area of mutation detection and DNA diagnostics, but at present the phenotype tests are robust and remain powerful. 

Amour R, Driss A Murayama K et al. (2005) Allelic heterogeneity of GNE gene mutation in two Tunisian families with autosomal recessive inclusion body myopathy. Neuromuscul Disord 15, 361-363. 

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