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Any such mutation event, we call a "potential TFBS creation event".
To explore whether this could represent a single ancestral mutation event, we examined haplotype sharing in the five Irish case samples in linkage disequilibrium (LD) blocks (termed Hap Block 1 and Hap Block 2) immediately 5′ and 3′ of the inferred duplication.
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For Z. lateralis and N. temporalis, which were recently introduced to French Polynesia and in which allele frequency changes were unlikely to have been altered by mutation events, we tested whether low allelic diversity in French Polynesian populations could be attributed to the loss of rare alleles.
To verify observed mutation events, we amplified microsatellite fragments twice for the parents and offspring involved in these cases.
To avoid laboratory-induced mutation events, we sequenced these samples directly from scab or vesicle material without virus isolation or propagation.
As an alternative to a series of gain-of-function mutation events, we suggest that the metastatic mesenchymal phenotype can arise from malignant myeloid cells either through cell hybrid formation or through direct transformation of tissue macrophages.
Out of those putative creation events, the vast majority (∼96%) was due to a single nucleotide mutation event and thus we focused on such creation events in our further analysis.
To determine whether all occurrences of RETR114H mutation descended from a single ancestral mutation event or arisen independently, we first constructed haplotypes with 21 RET region SNP genotypes from 224 controls and 430 HSCR patients of whom 25 were RETR114H mutation carriers (see Figure 1).
Through our additive combination of rare mutations into one event, we have found 15 mutational events causal on pathway level at the cut of FDR q value < 0.1.
We infer a shared signal as a single mutation event if the HSI > 0.98, and as convergent evolution if HSI < 0.9.
Polyploidy: Though we are still deciphering how pervasive this maximal chromosomal mutation event has been, the consensus is that polyploidy has affected eukaryotes significantly over their long history, with plants having been more significantly affected than animals.
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