allele frequency
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2022 ◽  
Yoshiteru Tabata ◽  
Yoshiyuki Matsuo ◽  
Yosuke Fujii ◽  
Atsufumi Ohta ◽  
Kiichi Hirota

Introduction: Precision medicine is a phrase used to describe personalized medical care tailored to specific patients based on their clinical presentation and genetic makeup. However, despite the fact that several single nucleotide polymorphisms (SNPs) have been reported to be associated with increased susceptibility to particular anesthetic agents and the occurrence of perioperative complications, genomic profiling and thus precision medicine has not been widely applied in perioperative management. Methods: We validated six SNP loci known to affect perioperative outcomes in Japanese patients using genomic DNA from saliva specimens and nanopore sequencing of each SNP loci to facilitate allele frequency calculations and then compared the nanopore results to those produced using the conventional dideoxy sequencing method. Results: Nanopore sequencing reads clustered into the expected genotypes in both homozygous and heterozygous cases. In addition, the nanopore sequencing results were consistent with those obtained using conventional dideoxy sequencing and the workflow provided reliable allele frequency estimation, with a total analysis time of less than 4 h. Conclusion: Thus, our results suggest that nanopore sequencing may be a promising and versatile tool for SNP genotyping, allowing for rapid and feasible risk prediction of perioperative outcomes.

2022 ◽  
Vol 12 ◽  
Paul Galewski ◽  
Andrew Funk ◽  
J. Mitchell McGrath

Understanding the genetic basis of polygenic traits is a major challenge in agricultural species, especially in non-model systems. Select and sequence (SnS) experiments carried out within existing breeding programs provide a means to simultaneously identify the genomic background of a trait while improving the mean phenotype for a population. Using pooled whole genome sequencing (WGS) of selected and unselected bulks derived from a synthetic outcrossing sugar beet population EL57 (PI 663212), which segregates for seedling rhizoctonia resistance, we identified a putative genomic background involved in conditioning a resistance phenotype. Population genomic parameters were estimated to measure fixation (He), genome divergence (FST), and allele frequency changes between bulks (DeltaAF). We report on the genome wide patterns of variation resulting from selection and highlight specific genomic features associated with resistance. Expected heterozygosity (He) showed an increased level of fixation in the resistant bulk, indicating a greater selection pressure was applied. In total, 1,311 biallelic loci were detected as significant FST outliers (p < 0.01) in comparisons between the resistant and susceptible bulks. These loci were detected in 206 regions along the chromosomes and contained 275 genes. We estimated changes in allele frequency between bulks resulting from selection for resistance by leveraging the allele frequencies of an unselected bulk. DeltaAF was a more stringent test of selection and recovered 186 significant loci, representing 32 genes, all of which were also detected using FST. Estimates of population genetic parameters and statistical significance were visualized with respect to the EL10.2 physical map and produced a candidate gene list that was enriched for function in cell wall metabolism and plant disease resistance, including pathogen perception, signal transduction, and pathogen response. Specific variation associated with these genes was also reported and represents genetic markers for validation and prediction of resistance to Rhizoctonia. Select and sequence experiments offer a means to characterize the genetic base of sugar beet, inform selection within breeding programs, and prioritize candidate variation for functional studies.

2022 ◽  
Yunyun Fang ◽  
Jingjing Zhang ◽  
Linlin Ji ◽  
Chaoyu Zhu ◽  
Yuanyuan Xiao ◽  

Abstract Objective: To investigate the relationship between glucagon-like peptide-1 receptor (GLP1R) gene polymorphisms and susceptibility to early-onset type 2 diabetes (EOD).Methods: Samples from 316 type 2 diabetes (T2DM) patients with EOD (n = 137) and late-onset T2DM (n = 179) and 145 non-diabetic individuals were analyzed. Multiplex PCR combined with resequencing HI-Reseq technology was used to detect single nucleotide polymorphisms (SNPs) of the GLP1R gene, and the allele frequency, genotype distribution, and clinical parameters were analyzed between each diabetes subgroup and the control group.Results: Sixteen SNPs were identified in the exonic region of the GLP1R gene according to the minor allele frequency (MAF > 0.05) in the participants. Among these, the GLP1R rs3765467 (G→A) mutation was statistically associated with EOD. Compared with that of the GG carriers, carriers of genotype AA at rs3765467 had a decreased risk of EOD after adjusting for sex and body mass index. In the dominant model, the frequencies of the rs3765467 AA+GA genotype were significantly decreased in the EOD group, and carriers of genotype AA+GA at rs3765467 had a decreased risk of EOD after adjusting for sex and body mass index. Moreover, fasting c peptide levels were significantly higher in GA+AA genotype carriers than that in GG genotype carriers.Conclusion: The GLP1R rs3765467 polymorphism was significantly associated with the age at T2DM diagnosis, and thus may be used as a marker to screen and detect individuals at risk of developing EOD.The name of the clinical trials registry: Exploration of early warning indicators for diabetic chronic complications. The approval number is 2016-004.The approval date is June 12, 2016.

2022 ◽  
Cedric Mariac ◽  
Kevin Bethune ◽  
Sinara Oliveira de Aquino ◽  
Mohamed Abdelrahman ◽  
Adeline Barnaud ◽  

In-solution based capture is becoming a method of choice for sequencing targeted sequence. We assessed and optimized a capture protocol in 20 different species from 6 different plant genus using kits from 20,000 to 200,000 baits targeting from 300 to 32,000 genes. We evaluated both the effectiveness of the capture protocol and the fold enrichment in targeted sequences. We proposed a protocol with multiplexing up to 96 samples in a single hybridization and showed it was an efficient and cost-effective strategy. We also extended the use of capture to pools of 100 samples and proved the efficiency of the method to assess allele frequency. Using a set of various organisms with different genome sizes, we demonstrated a correlation between the percentage of on-target reads vs. the relative size of the targeted sequences. Altogether, we proposed methods, strategies, cost-efficient protocols and statistics to better evaluate and more effectively use hybridization capture.

N. Kovalyuk ◽  
N. Altukhova ◽  
M. Glushchenko ◽  
A. Solovykh

Purpose: to determine the potential of the Russian subpopulation of the Holstein breed in relation to selection by loci of beta-and kappa-casein.Materials and methods. For loci CSN2 and CSN3, 1,539 Holstein cattle were genotyped, including 1,242 cows and heifers and 297 sires, and information on CSN2 and CSN3 genotypes of 297 US bulls was analyzed (World Wide Sires, Ltd).Results. It has been established that in the last two years there has been an increase in the percentage of sires in WWS with CSN2 genotypes A2A2 and CSN3 genotypes BB. Thus, sires allele frequency in the 2019 catalog was 0.51 and 0.29, respectively; and in the 2021 catalog was 0.68 and 0.31, respectively.Genotyped sires of domestic breeding organizations, which are mostly foreign origin, were characterized by predominance of the A2 allele CSN2; in this group the frequency of the allele was 0.63. However, the CSN3 B allele in the group of sires belonging to domestic organizations was found with a frequency of 0.34, which is 1.6 times lower than that of sires of American origin.In the genotyped group of Holstein cows and heifers (n = 1242) belonging to 3 large farms in the Krasnodar Krai, the gene frequency CSN2 allele A2 was minimal (0.57), and the CSN3 allele B (0.40) was higher than the allele frequency in the sires group of domestic breeding enterprises.Conclusion. At present, Russian breeding enterprises and farms are lagging behind in these indicators, however, by conducting targeted selection in accordance with the indicated trend, by selecting the appropriate breeding bulls, it is possible in the next generation to increase the proportion of animals carrying valuable genotypes.

2022 ◽  
Abhay Singh ◽  
Nuria Mencia-Trinchant ◽  
Elizabeth A. Griffiths ◽  
Alaa Altahan ◽  
Mahesh Swaminathan ◽  

PURPOSE Hematologic toxic effects of peptide receptor radionuclide therapy (PRRT) can be permanent. Patients with underlying clonal hematopoiesis (CH) may be more inclined to develop hematologic toxicity after PRRT. However, this association remains understudied. MATERIALS AND METHODS We evaluated pre- and post-PRRT blood samples of patients with neuroendocrine tumors. After initial screening, 13 cases of interest were selected. Serial blood samples were obtained on 4 of 13 patients. Genomic DNA was analyzed using a 100-gene panel. A variant allele frequency cutoff of 1% was used to call CH. RESULT Sixty-two percent of patients had CH at baseline. Persistent cytopenias were noted in 64% (7 of 11) of the patients. Serial sample analysis demonstrated that PRRT exposure resulted in clonal expansion of mutant DNA damage response genes ( TP53, CHEK2, and PPM1D) and accompanying cytopenias in 75% (3 of 4) of the patients. One patient who had a normal baseline hemogram and developed persistent cytopenias after PRRT exposure showed expansion of mutant PPM1D (variant allele frequency increased to 20% after exposure from < 1% at baseline). In the other two patients, expansion of mutant TP53, CHEK2, and PPM1D clones was also noted along with cytopenia development. CONCLUSION The shifts in hematopoietic clonal dynamics in our study were accompanied by emergence and persistence of cytopenias. These cytopenias likely represent premalignant state, as PPM1D-, CHEK2-, and TP53-mutant clones by themselves carry a high risk for transformation to therapy-related myeloid neoplasms. Future studies should consider CH screening and longitudinal monitoring as a key risk mitigation strategy for patients with neuroendocrine tumors receiving PRRT.

2021 ◽  
Jeremy D Lange ◽  
Heloise Bastide ◽  
Justin B Lack ◽  
John E Pool

Population genetics seeks to illuminate the forces shaping genetic variation, often based on a single snapshot of genomic variation. However, utilizing multiple sampling times to study changes in allele frequencies can help clarify the relative roles of neutral and non-neutral forces on short time scales. This study compares whole-genome sequence variation of recently collected natural population samples of Drosophila melanogaster against a collection made approximately 35 years prior from the same locality - encompassing roughly 500 generations of evolution. The allele frequency changes between these time points would suggest a relatively small local effective population size on the order of 10,000, significantly smaller than the global effective population size of the species. Some loci display stronger allele frequency changes than would be expected anywhere in the genome under neutrality - most notably the tandem paralogs Cyp6a17 and Cyp6a23, which are impacted by structural variation associated with resistance to pyrethroid insecticides. We find a genome-wide excess of outliers for high genetic differentiation between old and new samples, but a larger number of adaptation targets may have affected SNP-level differentiation versus window differentiation. We also find evidence for strengthening latitudinal allele frequency clines: northern-associated alleles have increased in frequency by an average of nearly 2.5% at SNPs previously identified as clinal outliers, but no such pattern is observed at random SNPs. This project underscores the scientific potential of using multiple sampling time points to investigate how evolution operates in natural populations, by quantifying how genetic variation has changed over ecologically relevant timescales.

2021 ◽  
Vol 12 ◽  
Jialei Chen ◽  
Jing He ◽  
Jing Luo ◽  
Shixun Zhong

Objective: The etiology of sudden sensorineural hearing loss (SSNHL) is still unknown. It has been demonstrated that normal endolymph metabolism is essential for inner ear function and that epithelial sodium channels (ENaC) may play an important role in the regulation of endolymphatic Na+. This study aimed to explore the potential association between αENaC p. Ala663Thr gene polymorphism and SSNHL.Methods: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to examine the genotype and allele frequency of the αENaC p. Ala663Thr polymorphism in 20 cases of low-frequency SSNHL (LF-SSNHL), 19 cases of high-frequency SSNHL (HF-SSNHL), 31 cases of all frequency SSNHL (AF-SSNHL), 42 cases of profound deafness SSNHL (PD-SSNHL), and 115 normal controls.Results: The T663 allele was found to be significantly associated with an increased risk of LF-SSNHL (p = 0.046, OR = 2.16, 95% CI = 1.01–4.62). The TT genotype and T663 allele, on the other hand, conferred a protective effect for PD-SSNHL (AA vs. TT: p = 0.012, OR = 0.25, 95% CI = 0.08–0.74; A vs. T: p = 0.001, OR = 0.36, 95% CI = 0.21–0.61). However, there was no statistically significant difference in genotype or allele frequency between the two groups (HF-SSNHL and AF-SSNHL) and the control group.Conclusion: The αENaC p. Ala663Thr gene polymorphism plays different roles in different types of SSNHL.

2021 ◽  
Peter Czuppon ◽  
Sylvain Billiard

Under gametophytic self-incompatibility (GSI), plants are heterozygous at the self-incompatibility locus (S-locus) and can only be fertilized by pollen with a different allele at that locus. The last century has seen a heated debate about the correct way of modeling the allele diversity in a GSI population that was never formally resolved. Starting from an individual-based model, we derive the deterministic dynamics as proposed by Fisher (1958), and compute the stationary S-allele frequency distribution. We find that the stationary distribution proposed by Wright (1964) is close to our theoretical prediction, in line with earlier numerical confirmation. Additionally, we approximate the invasion probability of a new S-allele, which scales inversely with the number of resident S-alleles. Lastly, we use the stationary allele frequency distribution to estimate the population size of a plant population from an empirically obtained allele frequency spectrum, which complements the existing estimator of the number of S-alleles. Our expression of the stationary distribution resolves the long-standing debate about the correct approximation of the number of S-alleles and paves the way to new statistical developments for the estimation of the plant population size based on S-allele frequencies.

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