scholarly journals Uncertainties in tumor allele frequencies limit power to infer evolutionary pressures

2017 ◽  
Vol 49 (9) ◽  
pp. 1288-1289 ◽  
Author(s):  
Javad Noorbakhsh ◽  
Jeffrey H Chuang
Keyword(s):  
Allele Frequencies ◽  
Limit Power

scholarly journals Reply: Uncertainties in tumor allele frequencies limit power to infer evolutionary pressures

2017 ◽  
Vol 49 (9) ◽  
pp. 1289-1291 ◽  
Author(s):  
Marc J Williams ◽  
Benjamin Werner ◽  
Chris P Barnes ◽  
Trevor A Graham ◽  
Andrea Sottoriva
Keyword(s):  
Allele Frequencies ◽  
Limit Power

scholarly journals Uncertainties in tumor allele frequencies limit power to infer evolutionary pressures

2017 ◽  
Author(s):  
Javad Noorbakhsh ◽  
Jeffrey H. Chuang
Keyword(s):  
Allele Frequency ◽  
Somatic Mutations ◽  
Cancer Genome ◽  
Allele Frequencies ◽  
The Cancer Genome Atlas ◽  
Neutral Evolution ◽  
Evolutionary Models ◽  
Cancer Genome Atlas ◽  
Limit Power ◽  
Genome Atlas

We read with great interest the paper by Williams, et. al.[1], who argued for neutral evolution in tumors by analyzing The Cancer Genome Atlas (TCGA) data. They supported this conclusion by showing high R2 values for fits to a neutral evolution model predicting M ∝ 1 / f, where M is the number of somatic mutations with allele frequency ≥ f. However, we believe a conclusion of neutrality must be treated cautiously, as high R2 values are consistent with many evolutionary models.

scholarly journals Inbreeding of Bottlenecked Butterfly Populations: Estimation Using the Likelihood of Changes in Marker Allele Frequencies

Genetics ◽  
1999 ◽  
Vol 151 (3) ◽  
pp. 1053-1063 ◽  
Author(s):  
Ilik J Saccheri ◽  
Ian J Wilson ◽  
Richard A Nichols ◽  
Michael W Bruford ◽  
Paul M Brakefield
Keyword(s):  
Linkage Disequilibrium ◽  
Probability Distribution ◽  
Reproductive Success ◽  
Genetic Markers ◽  
Allele Frequencies ◽  
Demographic Parameters ◽  
Bicyclus Anynana ◽  
Marker Allele ◽  
Wide Applicability ◽  
Per Gene

Abstract Polymorphic enzyme and minisatellite loci were used to estimate the degree of inbreeding in experimentally bottlenecked populations of the butterfly, Bicyclus anynana (Satyridae), three generations after founding events of 2, 6, 20, or 300 individuals, each bottleneck size being replicated at least four times. Heterozygosity fell more than expected, though not significantly so, but this traditional measure of the degree of inbreeding did not make full use of the information from genetic markers. It proved more informative to estimate directly the probability distribution of a measure of inbreeding, σ2, the variance in the number of descendants left per gene. In all bottlenecked lines, σ2 was significantly larger than in control lines (300 founders). We demonstrate that this excess inbreeding was brought about both by an increase in the variance of reproductive success of individuals, but also by another process. We argue that in bottlenecked lines linkage disequilibrium generated by the small number of haplotypes passing through the bottleneck resulted in hitchhiking of particular marker alleles with those haplotypes favored by selection. In control lines, linkage disequilibrium was minimal. Our result, indicating more inbreeding than expected from demographic parameters, contrasts with the findings of previous (Drosophila) experiments in which the decline in observed heterozygosity was slower than expected and attributed to associative overdominance. The different outcomes may both be explained as a consequence of linkage disequilibrium under different regimes of inbreeding. The likelihood-based method to estimate inbreeding should be of wide applicability. It was, for example, able to resolve small differences in σ2 among replicate lines within bottleneck-size treatments, which could be related to the observed variation in reproductive viability.

scholarly journals The Epidemiology and Genetics of Hyperuricemia and Gout across Major Racial Groups: A Literature Review and Population Genetics Secondary Database Analysis

2021 ◽  
Vol 11 (3) ◽  
pp. 231
Author(s):  
Faven Butler ◽  
Ali Alghubayshi ◽  
Youssef Roman
Keyword(s):  
Literature Review ◽  
Risk Allele ◽  
Statistical Significance ◽  
Elevated Serum ◽  
The United States ◽  
Allele Frequencies ◽  
Racial Groups ◽  
1000 Genomes Project ◽  
1000 Genomes ◽  
Risk Alleles

Gout is an inflammatory condition caused by elevated serum urate (SU), a condition known as hyperuricemia (HU). Genetic variations, including single nucleotide polymorphisms (SNPs), can alter the function of urate transporters, leading to differential HU and gout prevalence across different populations. In the United States (U.S.), gout prevalence differentially affects certain racial groups. The objective of this proposed analysis is to compare the frequency of urate-related genetic risk alleles between Europeans (EUR) and the following major racial groups: Africans in Southwest U.S. (ASW), Han-Chinese (CHS), Japanese (JPT), and Mexican (MXL) from the 1000 Genomes Project. The Ensembl genome browser of the 1000 Genomes Project was used to conduct cross-population allele frequency comparisons of 11 SNPs across 11 genes, physiologically involved and significantly associated with SU levels and gout risk. Gene/SNP pairs included: ABCG2 (rs2231142), SLC2A9 (rs734553), SLC17A1 (rs1183201), SLC16A9 (rs1171614), GCKR (rs1260326), SLC22A11 (rs2078267), SLC22A12 (rs505802), INHBC (rs3741414), RREB1 (rs675209), PDZK1 (rs12129861), and NRXN2 (rs478607). Allele frequencies were compared to EUR using Chi-Square or Fisher’s Exact test, when appropriate. Bonferroni correction for multiple comparisons was used, with p < 0.0045 for statistical significance. Risk alleles were defined as the allele that is associated with baseline or higher HU and gout risks. The cumulative HU or gout risk allele index of the 11 SNPs was estimated for each population. The prevalence of HU and gout in U.S. and non-US populations was evaluated using published epidemiological data and literature review. Compared with EUR, the SNP frequencies of 7/11 in ASW, 9/11 in MXL, 9/11 JPT, and 11/11 CHS were significantly different. HU or gout risk allele indices were 5, 6, 9, and 11 in ASW, MXL, CHS, and JPT, respectively. Out of the 11 SNPs, the percentage of risk alleles in CHS and JPT was 100%. Compared to non-US populations, the prevalence of HU and gout appear to be higher in western world countries. Compared with EUR, CHS and JPT populations had the highest HU or gout risk allele frequencies, followed by MXL and ASW. These results suggest that individuals of Asian descent are at higher HU and gout risk, which may partly explain the nearly three-fold higher gout prevalence among Asians versus Caucasians in ambulatory care settings. Furthermore, gout remains a disease of developed countries with a marked global rising.

scholarly journals Estimation of Cry3Bb1 resistance allele frequency in field populations of western corn rootworm using a genetic marker

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alan Willse ◽  
Lex Flagel ◽  
Graham Head
Keyword(s):  
Allele Frequency ◽  
Western Corn Rootworm ◽  
Allele Frequencies ◽  
Chromosome 8 ◽  
Corn Belt ◽  
Corn Rootworm ◽  
Resistance Allele ◽  
Response To Selection ◽  
The Us ◽  
Causal Allele

Abstract Following the discovery of western corn rootworm (WCR; Diabrotica virgifera virgifera) populations resistant to the Bacillus thuringiensis (Bt) protein Cry3Bb1, resistance was genetically mapped to a single locus on WCR chromosome 8 and linked SNP markers were shown to correlate with the frequency of resistance among field-collected populations from the US Corn Belt. The purpose of this paper is to further investigate the relationship between one of these resistance-linked markers and the causal resistance locus. Using data from laboratory bioassays and field experiments, we show that one allele of the resistance-linked marker increased in frequency in response to selection, but was not perfectly linked to the causal resistance allele. By coupling the response to selection data with a genetic model of the linkage between the marker and the causal allele, we developed a model that allowed marker allele frequencies to be mapped to causal allele frequencies. We then used this model to estimate the resistance allele frequency distribution in the US Corn Belt based on collections from 40 populations. These estimates suggest that chromosome 8 Cry3Bb1 resistance allele frequency was generally low (&lt;10%) for 65% of the landscape, though an estimated 13% of landscape has relatively high (&gt;25%) resistance allele frequency.

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