scholarly journals Inbred lab mice are not isogenic: genetic variation within inbred strains used to infer the mutation rate per nucleotide site

Heredity ◽  
2020 ◽  
Vol 126 (1) ◽  
pp. 107-116
Author(s):  
Jobran Chebib ◽  
Benjamin C. Jackson ◽  
Eugenio López-Cortegano ◽  
Diethard Tautz ◽  
Peter D. Keightley
Keyword(s):  
Genetic Variation ◽  
Mutation Rate ◽  
Inbred Mice ◽  
Genetic Research ◽  
Inbred Strains ◽  
Genetics Research ◽  
Novel Approach ◽  
Nucleotide Mutation ◽  
Commercial Breeder ◽  
Mutation Rate Estimate

AbstractFor over a century, inbred mice have been used in many areas of genetics research to gain insight into the genetic variation underlying traits of interest. The generalizability of any genetic research study in inbred mice is dependent upon all individual mice being genetically identical, which in turn is dependent on the breeding designs of companies that supply inbred mice to researchers. Here, we compare whole-genome sequences from individuals of four commonly used inbred strains that were procured from either the colony nucleus or from a production colony (which can be as many as ten generations removed from the nucleus) of a large commercial breeder, in order to investigate the extent and nature of genetic variation within and between individuals. We found that individuals within strains are not isogenic, and there are differences in the levels of genetic variation that are explained by differences in the genetic distance from the colony nucleus. In addition, we employ a novel approach to mutation rate estimation based on the observed genetic variation and the expected site frequency spectrum at equilibrium, given a fully inbred breeding design. We find that it provides a reasonable per nucleotide mutation rate estimate when mice come from the colony nucleus (~7.9 × 10−9 in C3H/HeN), but substantially inflated estimates when mice come from production colonies.

Teaching the Teachers the Genetics of Learning: An Application of the Mixed Blessings Model

2021 ◽  
Author(s):  
Sally A. Larsen ◽  
Callie Little
Keyword(s):  
Genetic Variation ◽  
Teacher Perceptions ◽  
Genetic Information ◽  
Teaching Practice ◽  
Genetic Research ◽  
Genetic Influences ◽  
School Contexts ◽  
Genetics Research ◽  
New Directions ◽  
And Behavior

Decades of educational genetics research has highlighted that differences in academic achievement are partly explained by genetic variation between individuals. Consequently, there is ongoing discussion about whether genetic influences on educationally-related traits should be more widely acknowledged in schools and communicated specifically to teachers. Nonetheless, there is little research on how teachers might interpret such information, and how it might alter their perceptions of the students they teach, or their teaching practice. In this review we draw on the mixed blessings model proposed by Haslam and Kvaale (2015) as a framework for defining both positive and negative repercussions of disseminating the findings of educational genetic research to teachers. We discuss research examining teacher perceptions of student ability and behavior, and findings outlining perceptions of psychological disorders when genetic explanations are invoked. We conclude by proposing new directions for research designed to better understand interpretations of genetic information in school contexts.

scholarly journals De novo mutations across 1,465 diverse genomes reveal novel mutational insights and reductions in the Amish founder population

2019 ◽  
Author(s):  
Michael D. Kessler ◽  
Douglas P. Loesch ◽  
James A. Perry ◽  
Nancy L. Heard-Costa ◽  
Brian E. Cade ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Mutation Rate ◽  
De Novo ◽  
Population Level ◽  
Mutation Rates ◽  
Founder Population ◽  
Single Nucleotide ◽  
Genome Wide ◽  
Nucleotide Mutation ◽  
Rare Genetic Variation

Abstractde novo Mutations (DNMs), or mutations that appear in an individual despite not being seen in their parents, are an important source of genetic variation whose impact is relevant to studies of human evolution, genetics, and disease. Utilizing high-coverage whole genome sequencing data as part of the Trans-Omics for Precision Medicine (TOPMed) program, we directly estimate and analyze DNM counts, rates, and spectra from 1,465 trios across an array of diverse human populations. Using the resulting call set of 86,865 single nucleotide DNMs, we find a significant positive correlation between local recombination rate and local DNM rate, which together can explain up to 35.5% of the genome-wide variation in population level rare genetic variation from 41K unrelated TOPMed samples. While genome-wide heterozygosity does correlate weakly with DNM count, we do not find significant differences in DNM rate between individuals of European, African, and Latino ancestry, nor across ancestrally distinct segments within admixed individuals. However, interestingly, we do find significantly fewer DNMs in Amish individuals compared with other Europeans, even after accounting for parental age and sequencing center. Specifically, we find significant reductions in the number of T→C mutations in the Amish, which seems to underpin their overall reduction in DNMs. Finally, we calculate near-zero estimates of narrow sense heritability (h2), which suggest that variation in DNM rate is significantly shaped by non-additive genetic effects and/or the environment, and that a less mutagenic environment may be responsible for the reduced DNM rate in the Amish.SignificanceHere we provide one of the largest and most diverse human de novo mutation (DNM) call sets to date, and use it to quantify the genome-wide relationship between local mutation rate and population-level rare genetic variation. While we demonstrate that the human single nucleotide mutation rate is similar across numerous human ancestries and populations, we also discover a reduced mutation rate in the Amish founder population, which shows that mutation rates can shift rapidly. Finally, we find that variation in mutation rates is not heritable, which suggests that the environment may influence mutation rates more significantly than previously realized.

scholarly journals Estimating Mutation Rate: How to Count Mutations?

Genetics ◽  
2003 ◽  
Vol 164 (2) ◽  
pp. 797-805
Author(s):  
Yun-Xin Fu ◽  
Haying Huai
Keyword(s):  
Mutation Rate ◽  
Genetic Research ◽  
Accurate Estimate ◽  
General Strategy ◽  
Direct Estimate ◽  
Pairwise Correlation ◽  
Essential Parameter ◽  
Order Of Magnitude ◽  
Independent Mutation ◽  
Mutation Rate Estimate

Abstract Mutation rate is an essential parameter in genetic research. Counting the number of mutant individuals provides information for a direct estimate of mutation rate. However, mutant individuals in the same family can share the same mutations due to premeiotic mutation events, so that the number of mutant individuals can be significantly larger than the number of mutation events observed. Since mutation rate is more closely related to the number of mutation events, whether one should count only independent mutation events or the number of mutants remains controversial. We show in this article that counting mutant individuals is a correct approach for estimating mutation rate, while counting only mutation events will result in underestimation. We also derived the variance of the mutation-rate estimate, which allows us to examine a number of important issues about the design of such experiments. The general strategy of such an experiment should be to sample as many families as possible and not to sample much more offspring per family than the reciprocal of the pairwise correlation coefficient within each family. To obtain a reasonably accurate estimate of mutation rate, the number of sampled families needs to be in the same or higher order of magnitude as the reciprocal of the mutation rate.

scholarly journals Inherited histocompatibility changes in progeny of irradiated and unirradiated inbred mice

1965 ◽  
Vol 6 (3) ◽  
pp. 330-340 ◽  
Author(s):  
D. W. Bailey ◽  
H. I. Kohn
Keyword(s):  
Mutation Rate ◽  
Inbred Mice ◽  
Spontaneous Mutation ◽  
Inbred Strains ◽  
Mutant Mice ◽  
Antigen Specificity ◽  
Spontaneous Mutation Rate ◽  
Doubling Dose ◽  
X Irradiation ◽  
Hybrid Mice

(1) F1-hybrid mice derived from a cross of the highly inbred strains: C57BL/6 and BALB/c, were tested for inherited changes of histocompatibility by an orthotopic inter-exchange of tail-skin grafts. The fathers of tested mice received either 522 rads of gonadal X-irradiation, or received no irradiation 2 months prior to mating.(2) Thirty-two mice with altered histocompatibilities were found in a total of 2572 complete tests. All of those mutant mice (twenty-one) that produced an adequate number of offspring were shown to pass the incompatibility on to their progeny.(3) Mutants were classified as to whether they effected a gain, a loss or both a gain and a loss in antigen specificity as determined by whether they rejected skin of donor mice or their skin was rejected by host mice. Twenty-six were clearly of the gain type, five were most likely gain type and only one showed both a loss and a gain effect. There was no clearcut evidence that loss types had occurred. The preponderance of gain types was tentatively explained as an artifact of the system used for the assay.(4) Several of the detected mutants were probably from parents carrying mutations that originated in past generations, for some mutant mice occurred in clusters.(5) There was no apparent effect of paternal irradiation (522 rads) on mutation frequency. The induced mutation rate was estimated to be less than 2·6 × 10−5/ gamete/rad.(6) Independent data on isografts from F1 hybrids of proven non-carrier pedigreed parents provided an estimate of spontaneous mutation rate of 6·75 × 10−3/ gamete.(7) The estimate of doubling dose (greater than 260 rads) was consistent with the estimates for recessive lethals and visibles in mice.

Revitalizing Difference in the HapMap: Race and Contemporary Human Genetic Variation Research

2008 ◽  
Vol 36 (3) ◽  
pp. 471-477 ◽  
Author(s):  
Jennifer A. Hamilton
Keyword(s):  
Genetic Variation ◽  
Human Genome ◽  
Genetic Research ◽  
The United States ◽  
Genome Project ◽  
Human Genetic Variation ◽  
Early 21St Century ◽  
The Social ◽  
English Speaking ◽  
The Human Genome Project

In 2000, researchers from the Human Genome Project (HGP) proclaimed that the initial sequencing of the human genome definitively proved, among other things, that there was no genetic basis for race. The genetic fact that most humans were 99.9% the same at the level of their DNA was widely heralded and circulated in the English-speaking press, especially in the United States. This pronouncement seemed proof that long-term antiracist efforts to de-biologize race were legitimized by scientific findings. Yet, despite the seemingly widespread acceptance of the social construction of race, post-HGP genetic science has seen a substantial shift toward the use of race variables in genetic research and, according to a number of prominent scholars, is re-invoking the specter of earlier forms of racial science in some rather discomfiting ways. During the past seven years, the main thrust of human genetic research, especially in the realm of biomedicine, has shifted from a concern with the 99.9% of the shared genome — what is thought to make humans alike — towards an explicit focus on the 0.1% that constitutes human genetic variation. Here I briefly explore some of the potential implications of the conceptualization and practice of early 21st century genetic variation research, especially as it relates to questions of race.

scholarly journals Induction of a ragweed-specific allergic state in Ir-gene-restricted nonresponder mice.

1977 ◽  
Vol 146 (1) ◽  
pp. 302-307 ◽  
Author(s):  
N Chiorazzi ◽  
A S Tung ◽  
D H Katz
Keyword(s):  
Inbred Mice ◽  
Inbred Strains ◽  
Antibody Responses ◽  
Pollen Extract ◽  
Antibody Synthesis ◽  
Ige Antibody ◽  
Gene Concept ◽  
X Irradiation ◽  
Suppressive Mechanism ◽  
Ir Genes

Mice of the inbred strains, C57BL/6 and C57BL/10 (H-2b), are genetically incapable of developing IgE antibody responses to ragweed pollen extract (RE) or its dinitrophenylated derivative, DNP-RE. This nonresponsiveness has previously been thought to reflect the absence of a relevant H-2-linked Ir genes controlling responses of inbred mice to these antigens. However, pretreatment of H-2b mice with either low doses of ionizing X irradiation or cyclophosphamide abrogates the nonresponder status of such animals, apparently by removal of a suppressive mechanism normally inhibiting development of IgE responses to these antigens. The implications of these findings for mechanisms of genetic control of IgE antibody synthesis and the Ir-gene concept are discussed.

scholarly journals Insights into Dyslexia Genetics Research from the Last Two Decades

2021 ◽  
Vol 12 (1) ◽  
pp. 27
Author(s):  
Florina Erbeli ◽  
Marianne Rice ◽  
Silvia Paracchini
Keyword(s):  
Language Disorder ◽  
Association Studies ◽  
Neurodevelopmental Disorder ◽  
Molecular Genetic ◽  
Genetic Research ◽  
Twin Studies ◽  
Genome Wide Association Studies ◽  
Genetics Research ◽  
Genome Wide ◽  
Genetic Risks

Dyslexia, a specific reading disability, is a common (up to 10% of children) and highly heritable (~70%) neurodevelopmental disorder. Behavioral and molecular genetic approaches are aimed towards dissecting its significant genetic component. In the proposed review, we will summarize advances in twin and molecular genetic research from the past 20 years. First, we will briefly outline the clinical and educational presentation and epidemiology of dyslexia. Next, we will summarize results from twin studies, followed by molecular genetic research (e.g., genome-wide association studies (GWASs)). In particular, we will highlight converging key insights from genetic research. (1) Dyslexia is a highly polygenic neurodevelopmental disorder with a complex genetic architecture. (2) Dyslexia categories share a large proportion of genetics with continuously distributed measures of reading skills, with shared genetic risks also seen across development. (3) Dyslexia genetic risks are shared with those implicated in many other neurodevelopmental disorders (e.g., developmental language disorder and dyscalculia). Finally, we will discuss the implications and future directions. As the diversity of genetic studies continues to increase through international collaborate efforts, we will highlight the challenges in advances of genetics discoveries in this field.

scholarly journals Efficacy of Artemisinin Base Combination Therapy and Genetic Diversity of Plasmodium falciparum from Uncomplicated Ma-laria Falciparum Patient in District of Pesawaran, Province of Lampung, Indonesia

2019 ◽  
Author(s):  
Jhons Fatriyadi SUWANDI ◽  
Widya ASMARA ◽  
Hari KUSNANTO ◽  
Din SYAFRUDDIN ◽  
Supargiyono SUPARGIYONO
Keyword(s):  
Plasmodium Falciparum ◽  
Genetic Variation ◽  
Falciparum Malaria ◽  
Health Centre ◽  
Sequencing Data ◽  
Single Nucleotide ◽  
Pfmdr1 Gene ◽  
Pcr Product ◽  
Nucleotide Mutation ◽  
Reverse Primer

Background: Malaria is an infectious disease caused by Plasmodium sp., that still prevalence in some part of Indonesia. District of Pesawaran is one of malaria endemic area in the Province of Lampung. The purpose of this study was to evaluate the efficacy of the ACT treatment in the District of Pesawaran Province of Lampung, Indonesia from Dec 2012 to Jul 2013 and the genetic variation of the Plasmodium falciparum also studied. Methods: This study was observational analytic study of falciparum malaria patients treated with ACT and primaquine (DHP-PQ and AAQ-PQ) at Hanura Primary Health Centre (Puskesmas). DNA isolation was done with QIAmp DNA Mini Kit. Amplification of PfMDR1, MSP1, and MSP2 genes was done with appropriate forward and reverse primer and procedures optimized first. PCR Product of PfMDR1 gene was prepared for sequencing. Data analysis was done with MEGA 6 software. Results: The results of this research are DHP-PQ effectiveness was still wellness among falciparum malaria patients in District of Pesawaran, Province of Lampung, Indonesia. There is Single-nucleotide mutation of N86Y of PfMDR1 gene. The dominant alleles found are MAD20 and 3D7 alleles with Multiplicity of Infection (MOI) are low. Conclusion: Therapy of DHP-PQ as an antimalarial falciparum in Pesawaran District, Lampung, Indonesia is still good. The genetic variation found was the SNP on the N86Y PfMDR1 gene, with dominant allele MAD20 and 3D7.

scholarly journals RAPD ANALYSIS OF GENETIC VARIATION IN NATURAL POPULATIONS OF AEGILOPS SP. FROM SOUTH ADRIATIC

AGROFOR ◽  
2018 ◽  
Vol 3 (1) ◽  
Author(s):  
Miodrag DIMITRIJEVIĆ ◽  
Sofija PETROVIĆ ◽  
Borislav BANJAC ◽  
Goran BARAĆ
Keyword(s):  
Genetic Variation ◽  
Food Production ◽  
Rapd Markers ◽  
Rapd Analysis ◽  
Gene Diversity ◽  
Rapd Marker ◽  
Natural Populations ◽  
Genetic Structuring ◽  
Potential Source ◽  
Novel Approach

New challenges that food production is facing, requires novel approach inagricultural strategy. The scissors of growing demand for food and the limits of theEarth's resources are forcing plant breeders to run for the new borders, utilizing allthe available genetic variation in order to create fruitful and economically soundcultivars. Aegilops sp. (Poaceae) is a potential source of genetic variation for wheatimprovement. RAPD marker analysis was used in order to distinguish and evaluatedifferent genotypes of Aegilops sp. population samples from the collectiongathered during few years’ expeditions in South Adriatic, along the coastal, littoraland the inland parts of Montenegro. Ten randomly amplified polymorphic DNAmarkers (RAPDs) were tested: OPA-05, OPA-08, OPB-06, OPA-02, OPA-07,OPA-25, OPB-07, OPB-18, OPC-06, OPC-10 to examine genetic structuring on 18samples of 6 populations of different Aegilops sp. According to global AMOVA,75% of total gene diversity was attributable mostly to diversity within population(ΦPT =0.205 p=0.001), indicating that the groups of studied goat grass populationswere seemingly to differing genetically. In contrast, 25% of the variation camefrom variation among populations. According to PCoA, the distribution of 18 goatgrass accessions by Principal Coordinate Analysis shows 3 distinct groups. PCoaxis 1, PCo axis 2, and PCo axis 3 account for 20.8%, 18.2% and 14.1% of thevariation, respectively. The results showed that RAPD markers could be aconvenient tool for investigating genetic variation and for detecting geneticstructuring of populations. Genetic variability formed under natural selection wasentrenched.

scholarly journals Spontaneous rate of clonal mutations in Daphnia galeata

2020 ◽  
Author(s):  
Markus Pfenninger ◽  
Halina Binde Doria ◽  
Jana Nickel ◽  
Anne Thielsch ◽  
Klaus Schwenk ◽  
...  
Keyword(s):  
Mutation Rate ◽  
De Novo ◽  
Mutation Accumulation ◽  
Parental Genotype ◽  
De Novo Mutations ◽  
Daphnia Galeata ◽  
Short Term ◽  
Heritable Variation ◽  
Nucleotide Mutation ◽  
Ultimate Source

AbstractMutations are the ultimate source of heritable variation and therefore the fuel for evolution, but direct estimates exist only for few species. We estimated the spontaneous nucleotide mutation rate among clonal generations in the waterflea Daphnia galeata with a short term mutation accumulation approach. Individuals from eighteen mutation accumulation lines over five generations were deep genome sequenced to count de novo mutations that were not present in a pool of F1 individuals, representing the parental genotype. We identified 12 new nucleotide mutations in 90 clonal generational passages. This resulted in an estimated haploid mutation rate of 0.745 x 10-9 (95% c.f. 0.39 x 10-9 − 1.26 x 10-9), which is slightly lower than recent estimates for other Daphnia species. We discuss the implications for the population genetics of Cladocerans.

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