Medium-Chain Acyl-CoA Dehydrogenase (MCAD) Deficiency: The Prevalent Mutation G985 (K304E) Is Subject to a Strong Founder Effect from Northwestern Europe
| Autor: | Patrick Willems, Jan Hendrickx, Vibeke Winter, Alberto Ponzone, Katrine Schneiderman, Marion Mack, Teresa Parrella, Yuan Tsang Chen, Niels Gregersen, Stephen G. Kahler, Jia Huan Ding, Brage S. Andresen, Peter Bross, Wen Zhang, Riccardo Ponzone, Charles R. Roe, Thomas Deufel, Steen Kølvraa, Lars Bolund, Diana Curtis |
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| Rok vydání: | 1993 |
| Předmět: |
Canada
Heterozygote TaqI DNA Mutational Analysis Acyl-CoA Dehydrogenase Lipid Metabolism Inborn Errors White People chemistry.chemical_compound Acyl-CoA Dehydrogenases Gene Frequency Genetics Humans Point Mutation Allele frequency Genetics (clinical) biology MCAD deficiency Point mutation Homozygote Haplotype Australia Acyl CoA dehydrogenase Founder effect United States Europe Haplotypes chemistry G985 mutation Mutation (genetic algorithm) G985 allele frequency biology.protein Human medicine Restriction fragment length polymorphism Polymorphism Restriction Fragment Length |
| Zdroj: | Gregersen, N, Winter, V, Curtis, D, Deufel, T, Mack, M, Hendrickx, J, Willems, P J, Ponzone, A, Parrella, T, Ponzone, R, Ding, J H, Zhang, W, Chen, Y T, Kahler, S, Roe, C R, Kølvraa, S, Schneiderman, K, Andresen, B S, Bross, P & Bolund, L 1993, ' Medium-chain Acyl-CoA dehydrogenase (MCAD) Deficiency : The prevalent mutation G985 (K304E) is subject to a strong founder effect from northwestern Europe ', Human Heredity, vol. 43, no. 6, pp. 342-350 . https://doi.org/10.1159/000154157 Human heredity |
| ISSN: | 1423-0062 0001-5652 1280-1291 |
| DOI: | 10.1159/000154157 |
| Popis: | Medium-chain acyl CoA dehydrogenase (MCAD) deficiency is a potentially fatal inherited defect of fatty acid P-oxidation. Approximately 90% of the disease-causing alleles in diagnosed patients are due to a single base mutation, an A (adenine) to G (guanine) transition at position 985 of MCAD cDNA (G985). In a limited number of cases it was found that this mutation was always associated with a particular haplotype, defined by three intragenic restriction fragment length polymorphisms, indicating a founder effect [Kolvraa et al.; Hum Genet 1991;87:425-429]. In addition, recent studies of American patients and their ancestors suggested the existence of a founder from northern Europe [Yokota et al.; Am J Hum Genet 1991;49:1280-1291]. In the present study we document (1) that the G985 heterozygous frequency in the Caucasian population of North Carolina in the USA is 1/84, which is 5- to 10-fold higher than in non-Caucasian Americans; (2) that there exists a 100% association of the G985 mutation in 17 families with MCAD-deficient patients to a certain haplotype, defined by the restriction endonucleases BanII, PstI and TaqI; (3) that MCAD deficiency due to the G985 mutation is more frequent in the Netherlands, Ireland, England, Belgium and Denmark than in other western European countries, and (4) that the frequency distribution of G985 mutation carriers is 1/68-1/101 in newborns in the United Kingdom and Denmark, and 1/333 in Italy, These results support the notion of a founder effect in northwestern Europe. |
| Databáze: | OpenAIRE |
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