Determining whether individual mutations are deleterious, or even adaptive, would require functional analysis; however, the rate
of nonsynonymous mutations suggests that continued progression of this epidemic could afford an opportunity for viral adaptation (Fig. 4H), underscoring the need for rapid containment.
Synonymous /
nonsynonymous substitution mutation analyses revealed that the majority of nucleotide mutations yielded synonymous amino acids, indicating the presence of purifying selection pressure across the polyprotein with pockets of positive selection also being detected.
Synonymous and
nonsynonymous rate variation in nuclear genes of mammals Yang, Z. and R. Nielsen.
While the authors only look
at nonsynonymous and synonymous variants, they've done a lot of work to comprehensively investigate evolutionary models with their data.
They investigated the unfolded
nonsynonymous site frequency spectra using 13 different selection models, including some complex two - parameter and three - parameter models.
Methods.: Dogs of various breeds, affected or unaffected with primary glaucoma, were genotyped for the Gly661Arg variant of ADAMTS10, as well as 7
other nonsynonymous single nucleotide polymorphisms (SNPs) in other genes in the beagle POAG locus that segregate with disease.
However, the catalog of 395 mutations, including 50
fixed nonsynonymous changes with 8 at positions with high levels of conservation across ebolaviruses, provides a starting point for such studies (table S4).
This seems laborious to me, since there were 1,120
nonsynonymous SNVs, of which 437 (39 %) were valid and only 32 (< 3 %) were absent in the normal and therefore somatic.
Another regrettable limitation of this approach is that it doesn't offer a complete picture of the somatic mutations
beyond nonsynonymous - coding events.
Instead, the authors
identified nonsynonymous coding variants in met WGS data, and validated them by PCR / 3730 sequencing in the met, tumor, and normal samples.
One mouse was sequenced to 15x coverage, and among the handful of
somatic nonsynonymous mutations found, one was recurrent, not only in the APL mice, but also in the same gene in human tumors.
Yet each one tells a different story: (a), how novel - to - dbSNP variants were rare; (b),
how nonsynonymous variant frequencies are shifted to lower values relative to those of synonymous variants, (c), how this shift in allele frequencies is more pronounced for damaging nsSNPs, consistent with natural selection, and (d), how the sizes of observed indels are enriched for non-frameshift events divisible by 3.
Helgason H A
rare nonsynonymous sequence variant in C3 is associated with high risk of age - related macular degeneration
The coding regions of these four genes were previously sequenced and led to the identification of only two
nonsynonymous polymorphisms in exon 32 of C3 and in exon 1 of Vav1 (7).
Three
nonsynonymous SNPs in the hemochromatosis gene (HFE) are genotyped, and I'm heterozygous for one of them.
The Mendelian disease variants occur largely in exon 5, but the IAMDGC's study uncovered a number of rare variants of the same class (
nonsynonymous changes disrupting cysteine residues) in other exons in AMD cases.
Then they sorted the mutations by type, focusing on 15,259
nonsynonymous mutations, which alter amino acids and thus a gene's function.
The top row shows the type of mutation (green, synonymous; pink,
nonsynonymous; gray, intergenic), with genomic locations indicated above.
They reveal 341 fixed substitutions (35
nonsynonymous, 173 synonymous, and 133 noncoding) between the 2014 EBOV and all previously published EBOV sequences, with an additional 55 single - nucleotide polymorphisms (SNPs; 15 nonsynonymous, 25 synonymous, and 15 noncoding), fixed within individual patients, within the West African outbreak.
Deep - sequence coverage allowed identification of 263 iSNVs (73
nonsynonymous, 108 synonymous, 70 noncoding, and 12 frameshift) in the Sierra Leone patients (6).
(G) Proportion of
nonsynonymous changes observed on different time scales (green, synonymous; pink, nonsynonymous).
Mutations as missing data: inferences on the ages and distributions of
nonsynonymous and synonymous mutations Nielsen, R. 2001.
The age of
nonsynonymous and synonymous mutations in animal mtDNA and implications for the mildly deleterious theory.
Some 32 somatic, protein - altering (
nonsynonymous) mutations were identified, of which 11 could be detected in the primary tumor sample from 9 years earlier.
The age of
nonsynonymous and synonymous mutations in animal mtDNA and implications for the mildly deleterious theory Nielsen, R. and D. M. Weinreich.
Estimating synonymous and
nonsynonymous substitution rates under realistic evolutionary models Yang Z. and R. Nielsen.
Mutations as missing data: inferences on the ages and distributions of
nonsynonymous and synonymous mutations.
The current issue of PLoS Genetics has an interesting article on the distribution of fitness effects (DFE) among new amino acid changing (
nonsynonymous) mutations.
By sequencing the exomes of multiple individuals, isolating what we'd call «tier 1» variants —
Nonsynonymous, nonsense, splice site, or frameshift - indel — and then removing all known common variants from public databases, Dr. Shendure and colleagues can reduce 20,000 gene candidates down to a handful.
That's how many validated, somatic,
nonsynonymous mutations we found in this AML genome.
Another way to go is bioinformatic analysis of individual protein - altering (
nonsynonymous) mutations to score their probable effect on the protein.
In addition, rare variants in the CNTNAP2 gene, including deletions and
nonsynonymous changes, are also suggested to play a role in autism, ID, DD and language impairment.
None of
the nonsynonymous SNPs were found associated with primary glaucoma in American cocker spaniels.