| 1. |
- Alvarez-Castro, Jose, et al.
(författare)
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Estimation and interpretation of genetic effects with epistasis using the NOIA model.
- 2012
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Ingår i: Methods in Molecular Biology. - Totowa, NJ : Humana Press. - 1064-3745 .- 1940-6029. ; 871, s. 191-204
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Tidskriftsartikel (refereegranskat)abstract
- We introduce this communication with a brief outline of the historical landmarks in genetic modeling, especially concerning epistasis. Then, we present methods for the use of genetic modeling in QTL analyses. In particular, we summarize the essential expressions of the natural and orthogonal interactions (NOIA) model of genetic effects. Our motivation for reviewing that theory here is twofold. First, this review presents a digest of the expressions for the application of the NOIA model, which are often mixed with intermediate and additional formulae in the original articles. Second, we make the required theory handy for the reader to relate the genetic concepts to the particular mathematical expressions underlying them. We illustrate those relations by providing graphical interpretations and a diagram summarizing the key features for applying genetic modeling with epistasis in comprehensive QTL analyses. Finally, we briefly review some examples of the application of NOIA to real data and the way it improves the interpretability of the results.
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| 2. |
- Besnier, Francois, et al.
(författare)
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Fine mapping and replication of QTL in outbred chicken advanced intercross lines
- 2011
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Ingår i: Genetics Selection Evolution. - Paris : Springer Science and Business Media LLC. - 0999-193X .- 1297-9686. ; 43, s. 3-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Linkage mapping is used to identify genomic regions affecting the expression of complex traits. However, when experimental crosses such as F2 populations or backcrosses are used to map regions containing a Quantitative Trait Locus (QTL), the size of the regions identified remains quite large, i.e. 10 or more Mb. Thus, other experimental strategies are needed to refine the QTL locations. Advanced Intercross Lines (AIL) are produced by repeated intercrossing of F2 animals and successive generations, which decrease linkage disequilibrium in a controlled manner. Although this approach is seen as promising, both to replicate QTL analyses and fine-map QTL, only a few AIL datasets, all originating from inbred founders, have been reported in the literature.METHODS: We have produced a nine-generation AIL pedigree (n = 1529) from two outbred chicken lines divergently selected for body weight at eight weeks of age. All animals were weighed at eight weeks of age and genotyped for SNP located in nine genomic regions where significant or suggestive QTL had previously been detected in the F2 population. In parallel, we have developed a novel strategy to analyse the data that uses both genotype and pedigree information of all AIL individuals to replicate the detection of and fine-map QTL affecting juvenile body weight.RESULTS: Five of the nine QTL detected with the original F2 population were confirmed and fine-mapped with the AIL, while for the remaining four, only suggestive evidence of their existence was obtained. All original QTL were confirmed as a single locus, except for one, which split into two linked QTL.CONCLUSIONS: Our results indicate that many of the QTL, which are genome-wide significant or suggestive in the analyses of large intercross populations, are true effects that can be replicated and fine-mapped using AIL. Key factors for success are the use of large populations and powerful statistical tools. Moreover, we believe that the statistical methods we have developed to efficiently study outbred AIL populations will increase the number of organisms for which in-depth complex traits can be analyzed.
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| 3. |
- Bjorvang, Richelle D., et al.
(författare)
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Follicular fluid and blood levels of persistent organic pollutants and reproductive outcomes among women undergoing assisted reproductive technologies
- 2022
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Ingår i: Environmental Research. - : Elsevier. - 0013-9351 .- 1096-0953. ; 208
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Tidskriftsartikel (refereegranskat)abstract
- Persistent organic pollutants (POPs) are industrial chemicals resistant to degradation and have been shown to have adverse effects on reproductive health in wildlife and humans. Although regulations have reduced their levels, they are still ubiquitously present and pose a global concern. Here, we studied a cohort of 185 women aged 21-43 years with a median of 2 years of infertility who were seeking assisted reproductive technology (ART) treatment at the Carl von Linne Clinic in Uppsala, Sweden. We analyzed the levels of 9 organochlorine pesticides (OCPs), 10 polychlorinated biphenyls (PCBs), 3 polybrominated diphenyl ethers (PBDEs), and 8 perfluoroalkyl substances (PFASs) in the blood and follicular fluid (FF) samples collected during ovum pick-up. Impact of age on chemical transfer from blood to FF was analyzed. Associations of chemicals, both individually and as a mixture, to 10 ART endpoints were investigated using linear, logistic, and weighted quantile sum regression, adjusted for age, body mass index, parity, fatty fish intake and cause of infertility. Out of the 30 chemicals, 20 were detected in more than half of the blood samples and 15 in FF. Chemical transfer from blood to FF increased with age. Chemical groups in blood crossed the blood-follicle barrier at different rates: OCPs > PCBs > PFASs. Hexachlorobenzene, an OCP, was associated with lower anti-Miillerian hormone, clinical pregnancy, and live birth. PCBs and PFASs were associated with higher antral follicle count and ovarian response as measured by ovarian sensitivity index, but also with lower embryo quality. As a mixture, similar findings were seen for the sum of PCBs and PFASs. Our results suggest that age plays a role in the chemical transfer from blood to FF and that exposure to POPs significantly associates with ART outcomes. We strongly encourage further studies to elucidate the underlying mechanisms of reproductive effects of POPs in humans.
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| 4. |
- Cedervall, Ylva, et al.
(författare)
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Timed Up-and-Go Dual-Task Testing in the Assessment of Cognitive Function : A Mixed Methods Observational Study for Development of the UDDGait Protocol
- 2020
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI. - 1661-7827 .- 1660-4601. ; 17:5
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Tidskriftsartikel (refereegranskat)abstract
- New methods to screen for and identify early-stage dementia disorders are highly sought after. The purpose of this pilot study is to develop a study protocol for a dual-task test aimed at aiding the early detection of dementia disorders. We used the Timed Up-and-Go (TUG) test, which is a mobility task involving starting in a sitting position, standing up, walking three meters to cross a line on the floor, turning around, walking back and sitting down again. We combined TUG with the verbal task of naming different animals. Pilot study participants were 43 individuals with and without established dementia diagnoses who attended a clinic for memory assessment. Video-recorded test performances were systematically analysed. Deviant test performances concerning the interplay between test administration and participants' responses to the assessment instructions were revealed and led to refinements being made to the final study protocol. Exploration of the dual-task test outcome measures in a sub-sample of 22 persons, ten with and twelve without dementia, indicated that step-length and number of named animals after the turning point of the dual-task test might constitute appropriate measures for examining this kind of sample. We concluded that the refined study protocol is feasible for testing individuals undergoing initial memory assessments and healthy controls. Follow-up studies with larger samples are being carried out and will bring new knowledge to this area of research. It may also provide an opportunity for further studies exploring possibilities for broad clinical implementation.
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| 5. |
- Elmgren Frykberg, Gunilla, 1957-, et al.
(författare)
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Impact of stroke on anterior-posterior force generation prior to seat-off during sit-to-walk
- 2012
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Ingår i: Gait & Posture. - : Elsevier BV. - 0966-6362 .- 1879-2219. ; 35:1, s. 56-60
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Tidskriftsartikel (refereegranskat)abstract
- Force generation during sit-to-walk (STW) post-stroke is a poorly studied area, although STW is a common daily transfer giving rise to a risk of falling in persons with disability. The purpose of this study was to describe and compare strategies for anterior-posterior (AP) force generation prior to seat-off during the STW transfer in both subjects with stroke and in matched controls. During STW at self-selected speed, AP force data were collected by 4 force plates, beneath the buttocks and feet from eight subjects with stroke '(>6 months after onset) and 8 matched controls. Subjects with post-stroke hemiparesis and matched controls generated a similar magnitude of total AP force impulses (F-1.71 = 0.67; p = 0.42) beneath buttocks and feet prior to seat-off during STW. However, there were significant group differences in AP force impulse generation beneath the stance buttock (i.e. the non-paretic buttock in the stroke group), with longer duration (F-1.71 = 8.78; p <0.005), larger net AP impulse (F-1.71 = 6.76; p < 0.05) and larger braking impulse (F-1.71 = 7.24; p <0.05) in the stroke group. The total braking impulse beneath buttocks and feet was about 4.5 times larger in the stroke group than in the control group (F-1.71 = 8.84; p < 0.005). An intra-and inter-limb dys-coordination with substantial use of braking impulses was demonstrated in the stroke group. This motor strategy differed markedly from the smooth force interaction in the control group. These results might be important in the development of treatment models related to locomotion post-stroke.
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| 6. |
- Husby, Arild, et al.
(författare)
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Genome-wide association mapping in a wild avian population identifies a link between genetic and phenotypic variation in a life-history trait
- 2015
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Ingår i: Proceedings of the Royal Society of London. Biological Sciences. - : The Royal Society. - 0962-8452 .- 1471-2954. ; 282:1806
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the genetic basis of traits involved in adaptation is a major challenge in evolutionary biology but remains poorly understood. Here, we use genome-wide association mapping using a custom 50 k single nucleotide polymorphism (SNP) array in a natural population of collared flycatchers to examine the genetic basis of clutch size, an important life-history trait in many animal species. We found evidence for an association on chromosome 18 where one SNP significant at the genome-wide level explained 3.9% of the phenotypic variance. We also detected two suggestive quantitative trait loci (QTLs) on chromosomes 9 and 26. Fitness differences among genotypes were generally weak and not significant, although there was some indication of a sex-by-genotype interaction for lifetime reproductive success at the suggestive QTL on chromosome 26. This implies that sexual antagonism may play a role in maintaining genetic variation at this QTL. Our findings provide candidate regions for a classic avian life-history trait that will be useful for future studies examining the molecular and cellular function of, as well as evolutionary mechanisms operating at, these loci.
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| 7. |
- LeBlanc, Neil, et al.
(författare)
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A novel combination of TaqMan RT-PCR and a suspension microarray assay for the detection and species identification of pestiviruses
- 2010
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Ingår i: Veterinary Microbiology. - : Elsevier BV. - 0378-1135 .- 1873-2542. ; 142:1-2, s. 81-86
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Tidskriftsartikel (refereegranskat)abstract
- The genus pestivirus contains four recognized species: classical swine fever virus, border disease virus, bovine viral diarrhoea virus types 1 and 2. All are economically important and globally distributed but classical swine fever is the most serious, concerning losses and control measures. It affects both domestic pigs and wild boars. Outbreaks of this disease in domestic pigs call for the most serious measures of disease control, including a stamping out policy in Europe. Since all the members of the pestivirus genus can infect swine, differential diagnosis using traditional methods poses some problems. Antibody tests may lack specificity due to cross-reactions, antigen capture ELISAs may have low sensitivity, and virus isolation may take several days or even longer time to complete. PCR-based tests overcome these problems for the most part, but in general lack the multiplexing capability to detect and differentiate all the pestiviruses simultaneously. The assay platform described here addresses all of these issues by combining the advantages of real-time PCR with the multiplexing capability of microarray technology. The platform includes a TaqMan real-time PCR designed for the universal detection of pestiviruses and a microarray assay that can use the amplicons produced in the real-time PCR to identify the specific pestivirus.
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| 8. |
- Mischenko, Kateryna, et al.
(författare)
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Assessing a multiple QTL search using the variance component model
- 2010
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Ingår i: Computational biology and chemistry (Print). - : Elseiver. - 1476-9271 .- 1476-928X. ; 34:1, s. 34-41
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Tidskriftsartikel (refereegranskat)abstract
- Development of variance component algorithms in genetics has previously mainly focused on animal breeding models or problems in human genetics with a simple data structure. We study alternative methods for constrained likelihood maximization in quantitative trait loci (QTL) analysis for large complex pedigrees. We apply a forward selection scheme to include several QTL and interaction effects, as well as polygenic effects, with up to five variance components in the model. We show that the implemented active set and primal-dual schemes result in accurate solutions and that they are robust. In terms of computational speed, a comparison of two approaches for approximating the Hessian of the log-likelihood shows that the method using an average information matrix is the method of choice for the five-dimensional problem. The active set method, with the average information method for Hessian computation, exhibits the fastest convergence with an average of 20 iterations per tested position, where the change in variance components <0.0001 was used as convergence criterion.
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| 9. |
- Nelson, Ronald, et al.
(författare)
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Genetics of Interactive Behavior in Silver Foxes (Vulpes vulpes)
- 2017
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Ingår i: Behavior Genetics. - : Springer Science and Business Media LLC. - 0001-8244 .- 1573-3297. ; 47:1, s. 88-101
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Tidskriftsartikel (refereegranskat)abstract
- Individuals involved in a social interaction exhibit different behavioral traits that, in combination, form the individual's behavioral responses. Selectively bred strains of silver foxes (Vulpes vulpes) demonstrate markedly different behaviors in their response to humans. To identify the genetic basis of these behavioral differences we constructed a large F2 population including 537 individuals by cross-breeding tame and aggressive fox strains. 98 fox behavioral traits were recorded during social interaction with a human experimenter in a standard four-step test. Patterns of fox behaviors during the test were evaluated using principal component (PC) analysis. Genetic mapping identified eight unique significant and suggestive QTL. Mapping results for the PC phenotypes from different test steps showed little overlap suggesting that different QTL are involved in regulation of behaviors exhibited in different behavioral contexts. Many individual behavioral traits mapped to the same genomic regions as PC phenotypes. This provides additional information about specific behaviors regulated by these loci. Further, three pairs of epistatic loci were also identified for PC phenotypes suggesting more complex genetic architecture of the behavioral differences between the two strains than what has previously been observed.
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| 10. |
- Nelson, Ronald, et al.
(författare)
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MAPfastR : Quantitative trait loci mapping in outbred line crosses
- 2013
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Ingår i: G3. - : Oxford University Press (OUP). - 2160-1836. ; 3, s. 2147-2149
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Tidskriftsartikel (refereegranskat)abstract
- MAPfastR is a software package developed to analyze quantitative trait loci data from inbred and outbred line-crosses. The package includes a number of modules for fast and accurate quantitative trait loci analyses. It has been developed in the R language for fast and comprehensive analyses of large datasets. MAPfastR is freely available at: http://www.computationalgenetics.se/?page_id=7
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