Evidence for selective advantage of pathogenic FGFR2 mutations in the male germ line.
Observed mutation rates in humans appear higher in male than female gametes and often increase with paternal age. This bias, usually attributed to the accumulation of replication errors or inefficient repair processes, has been difficult to study directly. Here, we describe a sensitive method to qua...
| Main Authors: | , , , , |
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| Format: | Journal article |
| Language: | English |
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2003
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| _version_ | 1826262080345341952 |
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| author | Goriely, A Mcvean, G Röjmyr, M Ingemarsson, B Wilkie, A |
| author_facet | Goriely, A Mcvean, G Röjmyr, M Ingemarsson, B Wilkie, A |
| author_sort | Goriely, A |
| collection | OXFORD |
| description | Observed mutation rates in humans appear higher in male than female gametes and often increase with paternal age. This bias, usually attributed to the accumulation of replication errors or inefficient repair processes, has been difficult to study directly. Here, we describe a sensitive method to quantify substitutions at nucleotide 755 of the fibroblast growth factor receptor 2 (FGFR2) gene in sperm. Although substitution levels increase with age, we show that even high levels originate from infrequent mutational events. We propose that these FGFR2 mutations, although harmful to embryonic development, are paradoxically enriched because they confer a selective advantage to the spermatogonial cells in which they arise. |
| first_indexed | 2024-03-06T19:30:42Z |
| format | Journal article |
| id | oxford-uuid:1d5e718d-d73d-4b65-9a56-1851b9411bc8 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:30:42Z |
| publishDate | 2003 |
| record_format | dspace |
| spelling | oxford-uuid:1d5e718d-d73d-4b65-9a56-1851b9411bc82022-03-26T11:10:24ZEvidence for selective advantage of pathogenic FGFR2 mutations in the male germ line.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:1d5e718d-d73d-4b65-9a56-1851b9411bc8EnglishSymplectic Elements at Oxford2003Goriely, AMcvean, GRöjmyr, MIngemarsson, BWilkie, AObserved mutation rates in humans appear higher in male than female gametes and often increase with paternal age. This bias, usually attributed to the accumulation of replication errors or inefficient repair processes, has been difficult to study directly. Here, we describe a sensitive method to quantify substitutions at nucleotide 755 of the fibroblast growth factor receptor 2 (FGFR2) gene in sperm. Although substitution levels increase with age, we show that even high levels originate from infrequent mutational events. We propose that these FGFR2 mutations, although harmful to embryonic development, are paradoxically enriched because they confer a selective advantage to the spermatogonial cells in which they arise. |
| spellingShingle | Goriely, A Mcvean, G Röjmyr, M Ingemarsson, B Wilkie, A Evidence for selective advantage of pathogenic FGFR2 mutations in the male germ line. |
| title | Evidence for selective advantage of pathogenic FGFR2 mutations in the male germ line. |
| title_full | Evidence for selective advantage of pathogenic FGFR2 mutations in the male germ line. |
| title_fullStr | Evidence for selective advantage of pathogenic FGFR2 mutations in the male germ line. |
| title_full_unstemmed | Evidence for selective advantage of pathogenic FGFR2 mutations in the male germ line. |
| title_short | Evidence for selective advantage of pathogenic FGFR2 mutations in the male germ line. |
| title_sort | evidence for selective advantage of pathogenic fgfr2 mutations in the male germ line |
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