دورية أكاديمية
Linkage to Gaucher mutations in the Ashkenazi population: effect of drift on decay of linkage disequilibrium and evidence for heterozygote selection.
| العنوان: | Linkage to Gaucher mutations in the Ashkenazi population: effect of drift on decay of linkage disequilibrium and evidence for heterozygote selection. |
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| المؤلفون: | Boas FE; Stanford University School of Medicine, Stanford, California 94305, USA. boas@stanford.edu |
| المصدر: | Blood cells, molecules & diseases [Blood Cells Mol Dis] 2000 Aug; Vol. 26 (4), pp. 348-59. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Academic Press Country of Publication: United States NLM ID: 9509932 Publication Model: Print Cited Medium: Print ISSN: 1079-9796 (Print) Linking ISSN: 10799796 NLM ISO Abbreviation: Blood Cells Mol Dis Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: <1996-> : Orlando, FL : Academic Press Original Publication: La Jolla, Calif. : Blood Cells Foundation, 1995- |
| مواضيع طبية MeSH: | Gaucher Disease/*genetics , Glucosylceramidase/*genetics , Jews/*genetics, Gaucher Disease/enzymology ; Gene Frequency ; Genetic Linkage ; Genetics, Population ; Heterozygote ; Humans ; Linkage Disequilibrium ; Mutation ; Probability ; Selection, Genetic ; Time Factors |
| مستخلص: | The two most common Gaucher disease mutations in the Ashkenazi population, 1226A-->G and 84G-->GG in the glucocerebrosidase gene, are tightly linked to a marker in the nearby pyruvate kinase gene. This paper develops a simulation of the Ashkenazi population that considers the effects of selection and drift on the mutant allele frequency and the recombinant haplotype frequency over time. Although the fraction of mutants that are linked to the original marker decays exponentially on average, this expected value is not very likely to occur. Instead, due to random loss of the recombinant haplotype, a mutation has a significant probability of retaining complete linkage disequilibrium long after its origin, so there may be large errors in estimating the age of a mutation based on linkage data. The simulations show that the 1226G mutation probably originated between 40 and 1000 generations ago (1000 to 25,000 years ago), and the 84GG mutation probably originated between 50 and 4800 generations ago (1300 to 120,000 years ago). The recent origin of the 1226G mutation and its high current allele frequency provide strong evidence for heterozygote selection. New techniques and results developed in this paper have general applicability toward analyzing linkage disequilibrium near other mutations. For example, they potentially explain the unexpected pattern of linkage disequilibrium seen around the DeltaF508 mutation of the cystic fibrosis transmembrane conductance regulator gene. (Copyright 2000 Academic Press.) |
| المشرفين على المادة: | EC 3.2.1.45 (Glucosylceramidase) |
| تواريخ الأحداث: | Date Created: 20001024 Date Completed: 20001222 Latest Revision: 20101118 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1006/bcmd.2000.0314 |
| PMID: | 11042036 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1079-9796 |
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| DOI: | 10.1006/bcmd.2000.0314 |