| 1. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 2. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 3. |
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| 4. |
- Kugelberg, Elisabeth, et al.
(författare)
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The Tandem Inversion Duplication in Salmonella enterica : Selection Drives Unstable Precursors to Final Mutation Types
- 2010
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Ingår i: Genetics. - : Oxford University Press (OUP). - 0016-6731 .- 1943-2631. ; 185:1, s. 65-80
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Tidskriftsartikel (refereegranskat)abstract
- During growth under selection, mutant types appear that are rare in unselected populations. Stress-induced mechanisms may cause these structures or selection may favor a series of standard events that modify common preexisting structures. One such mutation is the short junction (SJ) duplication with long repeats separated by short sequence elements: AB*(CD)*(CD)*E (* = a few bases). Another mutation type, described here, is the tandem inversion duplication (TID), where two copies of a parent sequence flank an inverse-order segment: AB(CD)(E'D'C'B')(CD) E. Both duplication types can amplify by unequal exchanges between direct repeats (CD), and both are rare in unselected cultures but common after prolonged selection for amplification. The observed TID junctions are asymmetric (aTIDs) and may arise from a symmetrical precursor (sTID)-ABCDE(E'D'C'B'A')ABCDE-when sequential deletions remove each palindromic junction. Alternatively, one deletion can remove both sTID junctions to generate an SJ duplication. It is proposed that sTID structures form frequently under all growth conditions, but are usually lost due to their instability and fitness cost. Selection for increased copy number helps retain the sTID and favors deletions that remodel junctions, improve fitness, and allow higher amplification. Growth improves with each step in formation of an SJ or aTID amplification, allowing selection to favor completion of the mutation process.
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| 5. |
- Weile, Jochen, et al.
(författare)
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A framework for exhaustively mapping functional missense variants
- 2017
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Ingår i: Molecular Systems Biology. - : WILEY. - 1744-4292 .- 1744-4292. ; 13:12
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Tidskriftsartikel (refereegranskat)abstract
- Although we now routinely sequence human genomes, we can confidently identify only a fraction of the sequence variants that have a functional impact. Here, we developed a deep mutational scanning framework that produces exhaustive maps for human missense variants by combining random codon mutagenesis and multiplexed functional variation assays with computational imputation and refinement. We applied this framework to four proteins corresponding to six human genes: UBE2I (encoding SUMO E2 conjugase), SUMO1 (small ubiquitin-like modifier), TPK1 (thiamin pyrophosphokinase), and CALM1/2/3 (three genes encoding the protein calmodulin). The resulting maps recapitulate known protein features and confidently identify pathogenic variation. Assays potentially amenable to deep mutational scanning are already available for 57% of human disease genes, suggesting that DMS could ultimately map functional variation for all human disease genes.
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