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Even if one or few loci are sufficient to confer drug resistance, genetic changes at other loci – such as compensatory mutations – could modify fitness and thus rescue probability.
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Since the EDNRB 30G>A polymorphism is a silent mutation (22) that does not modify the amino acid sequence of the protein, we imagined that this mutation could modify the transcription of the gene and/or the stability of the mRNA either directly or by a linkage disequilibrium with a mutation located in the regulating region of the gene.
These observations raised the hypothesis that cis-regulatory variation could modify the penetrance of germline mutations in BRCA2, by varying the level of expression of the remaining wild-type allele, if different levels of haploinsufficiency are important.
This disease results from a mutation in the UROS gene, and recent work has suggested that an accompanying gain-of-function mutation in ALAS2 could modify the disease severity [ 95].
Therefore the mutation of Hsp90b1 could modify the expression of Hspa5. Figure 7(A B) presents the results obtained by RTqPCR and Western blot.
Thus, we assume that K113N mutation in DsbG could modify the CXXC activity in a DsbC-like way.
We asked whether a Mrg15 mutation (alone or in combination with Cap-H2 mutations) could also modify the y 1 8/y 82f29-transvecting alleles.
Thus, it was of interest to test whether a single-nucleotide mutation of Gne gene could modify ST3Gal5 expression pattern.
Mutations that affect PARK2 splicing could modify the levels of correctly spliced transcripts, alter their localization, and lead to a loss of function of some of them and/or gain of function of others in time- and cell-specific manner.
In this study, we set out to identify and characterize cis-regulatory variation responsible for DAE in BRCA2 and to determine whether the penetrance of BRCA2 mutations could be modified by the variable level of expression of the remaining wild-type allele in heterozygous mutation carriers.
To evaluate the biological significance of this quantitative decrease in Shh signaling, we investigated whether knockout of BBS function could modify another cilia-related mutation, a hypomorphic allele of Ift88 known as orpk (oak ridge polycystic kidney).
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