Strategies and cost–benefit of selecting for a polled sheep nucleus by using DNA testing

2019 ◽  
Vol 59 (8) ◽  
pp. 1428
Author(s):  
T. Granleese ◽  
S. A. Clark ◽  
N. Duijvesteijn ◽  
P. E. Bradley ◽  
J. H. J. van der Werf
Keyword(s):  
Allele Frequency ◽  
Genetic Gain ◽  
Single Gene ◽  
Cost Benefit ◽  
Economic Loss ◽  
Allele Frequencies ◽  
Production Traits ◽  
Dna Testing ◽  
Dominance Model ◽  
Female Candidates

The present study assessed the effectiveness and cost–benefit of several genotyping strategies for breeding poll Merino sheep in a closed nucleus with different initial allele frequencies and assuming a single-gene responsible for the horn or poll phenotype. We assumed that selection was based on phenotypes or genotypes for a single gene conferring polledness via a complete-dominance model. Under such a model, a complete fixation of the ‘polled allele’ (P) requires genotyping of the ewe-selection candidates. Testing a higher proportion of female candidates resulted in a faster fixation of the P-allele. Fixation ranged from 1 year of selection with a high starting P-allele frequency of 0.9, to 7 years for low starting P-allele frequencies of 0.3. When premiums of AU$50 or AU$100 were paid for rams with a PP genotype, breeding for PP genotypes was not profitable when the starting P-allele frequency was below 0.7. If the starting allele frequency was above 0.7, net profitability was positive over 10 years when premiums of AU$200 were paid for known PP-genotype rams. While fixing the P-allele, genetic gain for production traits was slowed down in the first 5 years of selection by up to 23% and 3% for initial P allele-frequencies of 0.3 and 0.9 respectively. Lost genetic gain due to fixing the P-allele, which can never be recovered in a closed nucleus, incurred 200–800% higher costs than the DNA testing costs. Rates of genetic gain recovered to pre-P-allele selection level rates of genetic gain once the P-allele was fixed. Testing a maximum of 25% ewe-selection candidates was the least expensive strategy across all starting allele frequencies and premiums. To avoid large losses of genetic gain in a closed nucleus with low P-allele starting frequencies, opening the nucleus should be considered to increase starting P-allele frequencies and also to potentially increase rates of genetic gain to offset the economic loss caused by P-selection.

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 (<10%) for 65% of the landscape, though an estimated 13% of landscape has relatively high (>25%) resistance allele frequency.

scholarly journals A simple method to estimate the in-house limit of detection for genetic mutations with low allele frequencies in whole-exome sequencing analysis by next-generation sequencing

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Takumi Miura ◽  
Satoshi Yasuda ◽  
Yoji Sato
Keyword(s):  
Next Generation Sequencing ◽  
Allele Frequency ◽  
Somatic Mutations ◽  
Limit Of Detection ◽  
Allele Frequencies ◽  
Genetic Mutations ◽  
Sequencing Data ◽  
Simple Method ◽  
Whole Exome ◽  
Generation Sequencing

Abstract Background Next-generation sequencing (NGS) has profoundly changed the approach to genetic/genomic research. Particularly, the clinical utility of NGS in detecting mutations associated with disease risk has contributed to the development of effective therapeutic strategies. Recently, comprehensive analysis of somatic genetic mutations by NGS has also been used as a new approach for controlling the quality of cell substrates for manufacturing biopharmaceuticals. However, the quality evaluation of cell substrates by NGS largely depends on the limit of detection (LOD) for rare somatic mutations. The purpose of this study was to develop a simple method for evaluating the ability of whole-exome sequencing (WES) by NGS to detect mutations with low allele frequency. To estimate the LOD of WES for low-frequency somatic mutations, we repeatedly and independently performed WES of a reference genomic DNA using the same NGS platform and assay design. LOD was defined as the allele frequency with a relative standard deviation (RSD) value of 30% and was estimated by a moving average curve of the relation between RSD and allele frequency. Results Allele frequencies of 20 mutations in the reference material that had been pre-validated by droplet digital PCR (ddPCR) were obtained from 5, 15, 30, or 40 G base pair (Gbp) sequencing data per run. There was a significant association between the allele frequencies measured by WES and those pre-validated by ddPCR, whose p-value decreased as the sequencing data size increased. By this method, the LOD of allele frequency in WES with the sequencing data of 15 Gbp or more was estimated to be between 5 and 10%. Conclusions For properly interpreting the WES data of somatic genetic mutations, it is necessary to have a cutoff threshold of low allele frequencies. The in-house LOD estimated by the simple method shown in this study provides a rationale for setting the cutoff.

scholarly journals Biased Estimation of the Recombination Fraction Using Half-Sib Families and Informative Offspring

Genetics ◽  
2001 ◽  
Vol 157 (3) ◽  
pp. 1357-1367 ◽  
Author(s):  
L Gomez-Raya
Keyword(s):  
Recombination Fraction ◽  
Allele Frequencies ◽  
Likelihood Method ◽  
Simultaneous Estimation ◽  
Sampling Variance ◽  
Production Traits ◽  
Lod Score ◽  
Absolute Value ◽  
Sib Families ◽  
Map Distance

Abstract A maximum-likelihood method to estimate the recombination fraction and its sampling variance using informative and noninformative half-sib offspring is derived. Estimates of the recombination fraction are biased up to 20 cM when noninformative offspring are discarded. In certain scenarios, the sampling variance can be increased or reduced up to fivefold due to the bias in estimating the recombination fraction and the LOD score can be reduced up to 5 units when discarding noninformative offspring. Comparison of the estimates of recombination fraction, map distance, and LOD score when constructing a genetic map with 251 two-point linkage analyses and six families of Norwegian cattle was carried out to evaluate the implications of discarding noninformative offspring in practical situations. The average discrepancies in absolute value (average difference when using and neglecting noninformative offspring) were 0.0146, 1.64 cM, and 2.61 for the recombination fraction, map distance, and the LOD score, respectively. A method for simultaneous estimation of allele frequencies in the dam population and a transmission disequilibrium parameter is proposed. This method might account for the bias in estimating allele frequencies in the dam population when the half-sib offspring is selected for production traits.

scholarly journals The Dynamics of Gynodioecy in Plantago lanceolatu L. II. Mode of Action and Frequencies of Restorer Alleles

Genetics ◽  
1997 ◽  
Vol 147 (3) ◽  
pp. 1317-1328
Author(s):  
Anita A de Haan ◽  
Hans P Koelewijn ◽  
Maria P J Hundscheid ◽  
Jos M M Van Damme
Keyword(s):  
Cytoplasmic Male Sterility ◽  
Male Sterility ◽  
Allele Frequency ◽  
Mode Of Action ◽  
Male Fertility ◽  
Fertility Restoration ◽  
Plantago Lanceolata ◽  
Allele Frequencies ◽  
Male Sterile ◽  
Male Fertility Restoration

Male fertility in Plantago lanceolata is controlled by the interaction of cytoplasmic and nuclear genes. Different cytoplasmic male sterility (CMS) types can be either male sterile or hermaphrodite, depending on the presence of nuclear restorer alleles. In three CMS types of P. lanceolata (CMSI, CMSIIa, and CMSIIb) the number of loci involved in male fertility restoration was determined. In each CMS type, male fertility was restored by multiple genes with either dominant or recessive action and capable either of restoring male fertility independently or in interaction with each other (epistasis). Restorer allele frequencies for CMSI, CMSIIa and CMSIIb were determined by crossing hermaphrodites with “standard” male steriles. Segregation of male steriles vs. non-male steriles was used to estimate overall restorer allele frequency. The frequency of restorer alleles was different for the CMS types: restorer alleles for CMSI were less frequent than for CMSIIa and CMSIIb. On the basis of the frequencies of male steriles and the CMS types an “expected” restorer allele frequency could be calculated. The correlation between estimated and expected restorer allele frequency was significant.

scholarly journals Allele frequency divergence reveals ubiquitous influence of positive selection in Drosophila

2021 ◽  
Author(s):  
Jason Bertram
Keyword(s):  
Allele Frequency ◽  
Evolutionary Biology ◽  
Polymorphic Locus ◽  
Purifying Selection ◽  
Allele Frequencies ◽  
Intermediate Allele ◽  
Genome Wide ◽  
Signature Of Selection ◽  
Basic Objective ◽  
Genomic Regions

Resolving the role of natural selection is a basic objective of evolutionary biology. It is generally difficult to detect the influence of selection because ubiquitous non-selective stochastic change in allele frequencies (genetic drift) degrades evidence of selection. As a result, selection scans typically only identify genomic regions that have undergone episodes of intense selection. Yet it seems likely such episodes are the exception; the norm is more likely to involve subtle, concurrent selective changes at a large number of loci. We develop a new theoretical approach that uncovers a previously undocumented genome-wide signature of selection in the collective divergence of allele frequencies over time. Applying our approach to temporally-resolved allele frequency measurements from laboratory and wild Drosophila populations, we quantify the selective contribution to allele frequency divergence and find that selection has substantial effects on much of the genome. We further quantify the magnitude of the total selection coefficient (a measure of the combined effects of direct and linked selection) at a typical polymorphic locus, and find this to be large (of order 1%) even though most mutations are not directly under selection. We find that selective allele frequency divergence is substantial at intermediate allele frequencies, which we argue is most parsimoniously explained by positive --- not purifying --- selection. Thus, in these populations most mutations are far from evolving neutrally in the short term (tens of generations), including mutations with neutral fitness effects, and the result cannot be explained simply as a purging of deleterious mutations.

scholarly journals Accurate allele frequencies from ultra-low coverage pool-seq samples in evolve-and-resequence experiments

2018 ◽  
Author(s):  
Susanne Tilk ◽  
Alan Bergland ◽  
Aaron Goodman ◽  
Paul Schmidt ◽  
Dmitri Petrov ◽  
...  
Keyword(s):  
Allele Frequency ◽  
Model Organism ◽  
Software Tool ◽  
Allele Frequencies ◽  
Model Organisms ◽  
Sequencing Data ◽  
High Coverage ◽  
Next Generation Sequencing Technology ◽  
Low Coverage ◽  
Pooled Samples

AbstractEvolve-and-resequence (E+R) experiments leverage next-generation sequencing technology to track the allele frequency dynamics of populations as they evolve. While previous work has shown that adaptive alleles can be detected by comparing frequency trajectories from many replicate populations, this power comes at the expense of high-coverage (>100x) sequencing of many pooled samples, which can be cost-prohibitive. Here, we show that accurate estimates of allele frequencies can be achieved with very shallow sequencing depths (<5x) via inference of known founder haplotypes in small genomic windows. This technique can be used to efficiently estimate frequencies for any number of bi-allelic SNPs in populations of any model organism founded with sequenced homozygous strains. Using both experimentally-pooled and simulated samples of Drosophila melanogaster, we show that haplotype inference can improve allele frequency accuracy by orders of magnitude for up to 50 generations of recombination, and is robust to moderate levels of missing data, as well as different selection regimes. Finally, we show that a simple linear model generated from these simulations can predict the accuracy of haplotype-derived allele frequencies in other model organisms and experimental designs. To make these results broadly accessible for use in E+R experiments, we introduce HAF-pipe, an open-source software tool for calculating haplotype-derived allele frequencies from raw sequencing data. Ultimately, by reducing sequencing costs without sacrificing accuracy, our method facilitates E+R designs with higher replication and resolution, and thereby, increased power to detect adaptive alleles.

scholarly journals Single nucleotide polymorphism of the β-lactoglobulin gene in sheep breeds reared in Bulgaria

2020 ◽  
Vol 23 (3) ◽  
pp. 295-303
Author(s):  
D. Gencheva
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Polymorphic Locus ◽  
Association Studies ◽  
Allele Frequencies ◽  
Production Traits ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Sheep Population ◽  
Sheep Breeds ◽  
Β Lactoglobulin

In the present study, single nucleotide polymorphism in exon II of the β-lactoglobulin gene was investigated in four Bulgarian sheep breeds: Bulgarian Dairy Synthetic Population sheep (BDSP), Copper-red Shumen sheep (CRSH), Stara Zagora sheep (STZG) and Pleven Blackhead sheep (PLBH). Two genetic variants of β-LG gene (A and B) have been identified through PCR-RFLP assay. A 103 bp fragment of the polymorphic β-LG locus were amplified and digested with endonuclease enzyme RsaI. The obtained restriction fragments revealed three genotypes: AA, AB and BB, observed in 31%, 65.5% and 3.5% of the BDSP population and in 48%, 28% and 24% of CRSH sheep population, respectively, with departure from the Hardy-Weinberg equilibrium (P<0.05) in these groups. The allele frequencies demonstrated a prevalence of the A allele (0.638 and 0.620) over the B allele (0.362 and 0.380) in both populations. On the contrary, the distribution of allele frequencies in STZG and PLBH was 0.240 and 0.100 for allele A, respectively and 0.760 and 0.900 for allele B. Therefore, the homozygous BB genotype in these sheep populations was more frequently encountered (0.520 and 0.800) than the heterozygous AB genotype (0.480 and 0.200), with HWE correspondence (P>0.1). The homozygous genotype AA was absent in STZG and PLBH sheep populations. The greatest Nei’s genetic distance calculated by UPGMA method was found between the populations BDSPand PLBH (0.5334), while the closest relationship (0.0006) was established between CRSH and BDSP. The results obtained from the present investigation confirmed the presence of the SNP polymorphism in exon II of the β-lactoglobulin gene. Therefore, the genetic variability established in this polymorphic locus could be applied in further association studies with milk production traits in sheep.

scholarly journals Mutation Rate Model Used in the DNA VIEW Program

2020 ◽  
Vol 10 (10) ◽  
pp. 3585 ◽  
Author(s):  
Tomasz Krajka
Keyword(s):  
Computer Simulation ◽  
Allele Frequency ◽  
Mutation Rate ◽  
Allele Frequencies ◽  
Rate Model ◽  
Dna Database ◽  
Mutation Model ◽  
Population Allele Frequency ◽  
Frequency Changes

The first problem considered in this paper is the problem of correctness of a mutation model used in the DNA VIEW program. To this end, we theoretically predict population allele frequency changes in time according to this and similar models (we determine the limit frequencies of alleles—they are uniformly distributed). Furthermore, we evaluate the speed of the above changes using computer simulation applied to our DNA database. Comparing uniformly distributed allele frequencies with these existing in the population (for example, using entropy), we conclude that this mutation model is not correct. The evolution does not follow this direction (direction of uniformly distributed frequencies). The second problem relates to the determination of the extent to which an incorrect mutation model can disturb DNA VIEW program results. We show that in typical computations (simple paternity testing without maternal mutation) this influence is negligible, but in the case of maternal mutation, this should be taken into account. Furthermore, we show that this model is inconsistent from a theoretical viewpoint. Equivalent methods result in different error levels.

Spermatogonial Stem Cell Transplantation: Insights and Outlook for Domestic Animals

2019 ◽  
Vol 7 (1) ◽  
pp. 385-401 ◽  
Author(s):  
Mariana I. Giassetti ◽  
Michela Ciccarelli ◽  
Jon M. Oatley
Keyword(s):  
Genetic Gain ◽  
Selective Breeding ◽  
Production Systems ◽  
Population Expansion ◽  
Testicular Tissue ◽  
Domestic Animal ◽  
Livestock Production ◽  
Production Traits ◽  
Current State ◽  
Animal Populations

The demand for food will increase to an unprecedented level over the next 30 years owing to human population expansion, thus necessitating an evolution that improves the efficiency of livestock production. Genetic gain to improve production traits of domestic animal populations is most effectively achieved via selective use of gametes from animals deemed to be elite, and this principle has been the basis of selective breeding strategies employed by humans for thousands of years. In modern-day animal agriculture, artificial insemination (AI) has been the staple of selective breeding programs, but it has inherent limitations for applications in beef cattle and pig production systems. In this review, we discuss the potential and current state of development for a concept termed Surrogate Sires as a next-generation breeding tool in livestock production. The scheme capitalizes on the capacity of spermatogonial stem cells to regenerate sperm production after isolation from donor testicular tissue and transfer into the testes of a recipient male that lacks endogenous germline, thereby allowing the surrogate male to produce offspring with the donor haplotype via natural mating. This concept provides an effective selective breeding tool to achieve genetic gain that is conducive for livestock production systems in which AI is difficult to implement.

Association of susceptibility to multiple sclerosis in Southern Han Chinese with HLA-DRB1, -DPB1 alleles and DRB1-DPB1 haplotypes: distinct from other populations

2009 ◽  
Vol 15 (12) ◽  
pp. 1422-1430 ◽  
Author(s):  
Xiao-Mu Wu ◽  
Chaodong Wang ◽  
Kun-Nan Zhang ◽  
Ai-Yu Lin ◽  
Jun-ichi Kira ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Allele Frequency ◽  
Odds Ratio ◽  
Class Ii ◽  
Hla Class Ii ◽  
Allele Frequencies ◽  
Carriage Rate ◽  
Southern Chinese ◽  
Haplotype Frequencies ◽  
Effect Method

Association of HLA class II with multiple sclerosis (MS) has been widely studied in both Western and Oriental populations. However, such an association is not well documented in Chinese. The objective of this study was to examine the association between the susceptibility to conventional MS in Southern Chinese with HLA-DRB1,-DPB1 alleles and putative DRB1-DPB1 haplotypes. Genotyping of HLA-DRB1 and -DPB1 alleles was performed in 60 patients with conventional MS and 95 controls. Allele frequencies were compared between patients and controls to identify MSassociated alleles. Relative predisposing effect method was used to compare haplotype frequencies in patients and controls and to identify possible predisposing DRB1-DPB1 haplotypes, which were further examined for differences in haplotype carriage rates between the two groups. We found that the allele frequency of DRB1*1501 was not different between patients (18.3%) and controls (21.1%) ( p = 0.837). In contrast, frequency of the DPB1*0501 allele was significantly higher in patients (90%) than in controls (67.4%) (odds ratio = 4.36, p = 0.0013, pcorr = 0.025). DRB1-DPB1 linkage haplotype in patients (8.33%) was significantly higher than in controls (0%) ( p < 0.0001) and the carriage rate of this haplotype was significantly increased in patients (15%) as compared with controls (0%) ( p = 0.00013, pcorr = 0.003). Combined, these results suggest that HLA-DRB1*1501 is not associated with susceptibility to conventional MS in Southern Chinese. Instead, both the DPB1*0501 allele and the DRB1*1602- DPB1*0501 haplotype are strong predisposing factors for conventional MS in this population. Our results establish that the HLA profiles of MS in Southern Chinese are distinct from other populations.

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