Origins of the fragile X syndrome mutation.
The fragile X syndrome is a common cause of mental impairment. In view of the low reproductive fitness of affected males, the high incidence of the syndrome has been suggested to be the result of a high rate of new mutations occurring exclusively in the male germline. Extensive family studies, howev...
| Main Authors: | , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
1993
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| _version_ | 1826290197802778624 |
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| author | Hirst, M Knight, S Christodoulou, Z Grewal, P Fryns, J Davies, K |
| author_facet | Hirst, M Knight, S Christodoulou, Z Grewal, P Fryns, J Davies, K |
| author_sort | Hirst, M |
| collection | OXFORD |
| description | The fragile X syndrome is a common cause of mental impairment. In view of the low reproductive fitness of affected males, the high incidence of the syndrome has been suggested to be the result of a high rate of new mutations occurring exclusively in the male germline. Extensive family studies, however, have failed to identify any cases of a new mutation. Alternatively, it has been suggested that a selective advantage of unaffected heterozygotes may, in part, explain the high incidence of the syndrome. Molecular investigations have shown that the syndrome is caused by the amplification of a CGG trinucleotide repeat in the FMR-1 gene which leads to the loss of gene expression. Further to this, genetic studies have suggested that there is evidence of linkage disequilibrium between the fragile X disease locus and flanking polymorphic markers. More recently, this analysis has been extended and has led to the observation that a large number of fragile X chromosomes appear to be lineage descendants of founder mutation events. Here, we present a study of the FRAXAC1 polymorphic marker in our patient cohort. We find that its allele distribution is strikingly different on fragile X chromosomes, confirming the earlier observations and giving further support to the suggestions of a fragile X founder effect. |
| first_indexed | 2024-03-07T02:40:30Z |
| format | Journal article |
| id | oxford-uuid:aa47d095-072d-49d1-bd9a-54423c794eb2 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T02:40:30Z |
| publishDate | 1993 |
| record_format | dspace |
| spelling | oxford-uuid:aa47d095-072d-49d1-bd9a-54423c794eb22022-03-27T03:14:09ZOrigins of the fragile X syndrome mutation.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:aa47d095-072d-49d1-bd9a-54423c794eb2EnglishSymplectic Elements at Oxford1993Hirst, MKnight, SChristodoulou, ZGrewal, PFryns, JDavies, KThe fragile X syndrome is a common cause of mental impairment. In view of the low reproductive fitness of affected males, the high incidence of the syndrome has been suggested to be the result of a high rate of new mutations occurring exclusively in the male germline. Extensive family studies, however, have failed to identify any cases of a new mutation. Alternatively, it has been suggested that a selective advantage of unaffected heterozygotes may, in part, explain the high incidence of the syndrome. Molecular investigations have shown that the syndrome is caused by the amplification of a CGG trinucleotide repeat in the FMR-1 gene which leads to the loss of gene expression. Further to this, genetic studies have suggested that there is evidence of linkage disequilibrium between the fragile X disease locus and flanking polymorphic markers. More recently, this analysis has been extended and has led to the observation that a large number of fragile X chromosomes appear to be lineage descendants of founder mutation events. Here, we present a study of the FRAXAC1 polymorphic marker in our patient cohort. We find that its allele distribution is strikingly different on fragile X chromosomes, confirming the earlier observations and giving further support to the suggestions of a fragile X founder effect. |
| spellingShingle | Hirst, M Knight, S Christodoulou, Z Grewal, P Fryns, J Davies, K Origins of the fragile X syndrome mutation. |
| title | Origins of the fragile X syndrome mutation. |
| title_full | Origins of the fragile X syndrome mutation. |
| title_fullStr | Origins of the fragile X syndrome mutation. |
| title_full_unstemmed | Origins of the fragile X syndrome mutation. |
| title_short | Origins of the fragile X syndrome mutation. |
| title_sort | origins of the fragile x syndrome mutation |
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