Estimating mutation rates using abnormal human hemoglobins

Estimates of mutation rates in human populations vary widely. Considering the numerous potential sources of error, which include illegitimacy, the existence of genocopies and/or phenocopies, variation in expressivity, and incomplete penetrance, the extent of variation among estimates is not surprising. When mutational events are defined in detail at the level of DNA sequence, one can estimate rates at which nucleotide substitutions give rise to the abnormal phenotypes under consideration. The vast body of data now available on globin-gene sequence and organization, as well as on abnormalities in amino acid sequences of globin chains, renders certain dominantly inherited hemoglobinopathies especially well suited to analyses of mutation rates. Using cases of unstable β-chain disease and Hb M disease that appeared among children of unaffected parents, rates at which these conditions arise by new mutation were estimated, as were rates of substitution per α- or β-gene nucleotide and per α gene (423 nucleotides) or β gene (438 nucleotides). These estimates, and the differences between them and others calculated using sporadic cases of various phenotypically defined conditions, are discussed in relation to the biases to which they are subject

Biology · Expressivity · Gene · Mutation · Mutation rate · Penetrance · Phenocopy · Phenotype · Sequence (biology) · Folate and B Vitamins Research · Genetics · Hemoglobinopathies and Related Disorders · Iron Metabolism and Disorders

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