| 1. |
- Ahsan, Muhammad, et al.
(författare)
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Identification of candidate genes and mutations in QTL regions for chicken growth using bioinformatic analysis of NGS and SNP-chip data.
- 2013
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Ingår i: Frontiers in Genetics. - : Frontiers Media SA. - 1664-8021. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- Mapping of chromosomal regions harboring genetic polymorphisms that regulate complex traits is usually followed by a search for the causative mutations underlying the observed effects. This is often a challenging task even after fine mapping, as millions of base pairs including many genes will typically need to be investigated. Thus to trace the causative mutation(s) there is a great need for efficient bioinformatic strategies. Here, we searched for genes and mutations regulating growth in the Virginia chicken lines - an experimental population comprising two lines that have been divergently selected for body weight at 56 days for more than 50 generations. Several quantitative trait loci (QTL) have been mapped in an F2 intercross between the lines, and the regions have subsequently been replicated and fine mapped using an Advanced Intercross Line. We have further analyzed the QTL regions where the largest genetic divergence between the High-Weight selected (HWS) and Low-Weight selected (LWS) lines was observed. Such regions, covering about 37% of the actual QTL regions, were identified by comparing the allele frequencies of the HWS and LWS lines using both individual 60K SNP chip genotyping of birds and analysis of read proportions from genome resequencing of DNA pools. Based on a combination of criteria including significance of the QTL, allele frequency difference of identified mutations between the selected lines, gene information on relevance for growth, and the predicted functional effects of identified mutations we propose here a subset of candidate mutations of highest priority for further evaluation in functional studies. The candidate mutations were identified within the GCG, IGFBP2, GRB14, CRIM1, FGF16, VEGFR-2, ALG11, EDN1, SNX6, and BIRC7 genes. We believe that the proposed method of combining different types of genomic information increases the probability that the genes underlying the observed QTL effects are represented among the candidate mutations identified.
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| 2. |
- Alvarez-Castro, Jose, et al.
(författare)
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Modelling of genetic interactions improves prediction of hybrid patterns : a case study in domestic fowl
- 2012
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Ingår i: Genetical Research. - 0016-6723 .- 1469-5073. ; 94:5, s. 255-266
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Tidskriftsartikel (refereegranskat)abstract
- Summary A major challenge in complex trait genetics is to unravel how multiple loci and environmental factors together cause phenotypic diversity. Both first (F1) and second (F2) generation hybrids often display phenotypes that deviate from what is expected under intermediate inheritance. We have here studied two chicken F2 populations generated by crossing divergent chicken lines to assess how epistatic loci, identified in earlier quantitative trait locus (QTL) studies, contribute to hybrid deviations from the mid-parent phenotype. Empirical evidence suggests that the average phenotypes of the intercross birds tend to be lower than the midpoint between the parental means in both crosses. Our results confirm that epistatic interactions, despite a relatively small contribution to the phenotypic variance, play an important role in the deviation of hybrid phenotypes from the mid-parent values (i.e. multi-locus hybrid genotypes lead to lower rather than higher body weights). To a lesser extent, dominance also appears to contribute to the mid-parent deviation, at least in one of the crosses. This observation coincides with the hypothesis that hybridization tends to break up co-adapted gene complexes, i.e. generate Bateson-Dobzhansky-Muller incompatibilities.
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| 3. |
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| 4. |
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| 5. |
- Hill, Daniel, et al.
(författare)
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Microfluidic and Transducer Technologies for Lab on a Chip Applications
- 2010
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Ingår i: 2010 ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY (EMBC). - : IEEE conference proceedings. - 9781424441242 ; , s. 305-307
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Konferensbidrag (refereegranskat)abstract
- Point-of-care diagnostic devices typically require six distinct qualities: they must deliver at least the same sensitivity and selectivity, and for a cost per assay no greater than that of today's central lab technologies, deliver results in a short period of time (<15 min at GP; <2h in hospital), be portable or at least small in scale, and require no or extremely little sample preparation. State-of-the-art devices deliver information of several markers in the same measurement.
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| 6. |
- Johansson, Anna Maria, et al.
(författare)
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Genome-Wide Effects of Long-Term Divergent Selection
- 2010
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 6:11, s. e1001188-
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Tidskriftsartikel (refereegranskat)abstract
- To understand the genetic mechanisms leading to phenotypic differentiation, it is important to identify genomic regions under selection. We scanned the genome of two chicken lines from a single trait selection experiment, where 50 generations of selection have resulted in a 9-fold difference in body weight. Analyses of nearly 60,000 SNP markers showed that the effects of selection on the genome are dramatic. The lines were fixed for alternative alleles in more than 50 regions as a result of selection. Another 10 regions displayed strong evidence for ongoing differentiation during the last 10 generations. Many more regions across the genome showed large differences in allele frequency between the lines, indicating that the phenotypic evolution in the lines in 50 generations is the result of an exploitation of standing genetic variation at 100s of loci across the genome.
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| 7. |
- Pettersson, Mats, et al.
(författare)
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Dynamics of adaptive alleles in divergently selected body weight lines of chickens.
- 2013
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Ingår i: G3. - : Oxford University Press (OUP). - 2160-1836. ; 3:12
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Tidskriftsartikel (refereegranskat)abstract
- By studying genomic changes over time in populations subjected to strong artificial directional selection, we can gain insights to the dynamics of beneficial alleles originating from the founder population or emerging as novel mutations undergoing ongoing selection. The Virginia lines are a chicken resource population generated by long-term bi-directional, single-trait selection for juvenile body weight. We studied genome-wide allele frequency changes from generation 40 to 53 using genome-wide genotypes from directional and relaxed selection lines. Overall, there were small changes in allele frequencies at individual loci over the studied time period; but, on average, the changes were greater in lines with larger phenotypic changes. This is consistent with previous findings that much of the response to selection over the first 40 years of selection was attributable to utilization of standing genetic variation at many loci in the genome, indicating a mostly polygenic architecture for body weight. Over the course of the selection experiment, the largest phenotypic response to selection was observed in the high-weight selected line, and in this line we detected a single locus where the allele frequency changed rapidly during a late stage of the experiment. This locus likely contains a novel, beneficial mutation that appeared between generations 40 and 45 and was driven to fixation in 5 to 10 generations. This result illustrates the dependence of continued long-term selection response on standing genetic variation at many loci as well as strong, novel, beneficial mutations.
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| 8. |
- Pettersson, Mats, et al.
(författare)
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Replication and Explorations of High-Order Epistasis Using a Large Advanced Intercross Line Pedigree
- 2011
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 7:7, s. e1002180-
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Tidskriftsartikel (refereegranskat)abstract
- Dissection of the genetic architecture of complex traits persists as a major challenge in biology; despite considerable efforts, much remains unclear including the role and importance of genetic interactions. This study provides empirical evidence for a strong and persistent contribution of both second- and third-order epistatic interactions to long-term selection response for body weight in two divergently selected chicken lines. We earlier reported a network of interacting loci with large effects on body weight in an F(2) intercross between these high-and low-body weight lines. Here, most pair-wise interactions in the network are replicated in an independent eight-generation advanced intercross line (AIL). The original report showed an important contribution of capacitating epistasis to growth, meaning that the genotype at a hub in the network releases the effects of one or several peripheral loci. After fine-mapping of the loci in the AIL, we show that these interactions were persistent over time. The replication of five of six originally reported epistatic loci, as well as the capacitating epistasis, provides strong empirical evidence that the originally observed epistasis is of biological importance and is a contributor in the genetic architecture of this population. The stability of genetic interaction mechanisms over time indicates a non-transient role of epistasis on phenotypic change. Third-order epistasis was for the first time examined in this study and was shown to make an important contribution to growth, which suggests that the genetic architecture of growth is more complex than can be explained by two-locus interactions only. Our results illustrate the importance of designing studies that facilitate exploration of epistasis in populations for obtaining a comprehensive understanding of the genetics underlying a complex trait.
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| 9. |
- Rubin, Carl-Johan, et al.
(författare)
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Strong signatures of selection in the domestic pig genome
- 2012
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 109:48, s. 19529-19536
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Tidskriftsartikel (refereegranskat)abstract
- Domestication of wild boar (Sus scrofa) and subsequent selection have resulted in dramatic phenotypic changes in domestic pigs for a number of traits, including behavior, body composition, reproduction, and coat color. Here we have used whole-genome resequencing to reveal some of the loci that underlie phenotypic evolution in European domestic pigs. Selective sweep analyses revealed strong signatures of selection at three loci harboring quantitative trait loci that explain a considerable part of one of the most characteristic morphological changes in the domestic pig - the elongation of the back and an increased number of vertebrae. The three loci were associated with the NR6A1, PLAG1, and LCORL genes. The latter two have repeatedly been associated with loci controlling stature in other domestic animals and in humans. Most European domestic pigs are homozygous for the same haplotype at these three loci. We found an excess of derived nonsynonymous substitutions in domestic pigs, most likely reflecting both positive selection and relaxed purifying selection after domestication. Our analysis of structural variation revealed four duplications at the KIT locus that were exclusively present in white or white-spotted pigs, carrying the Dominant white, Patch, or Belt alleles. This discovery illustrates how structural changes have contributed to rapid phenotypic evolution in domestic animals and how alleles in domestic animals may evolve by the accumulation of multiple causative mutations as a response to strong directional selection.
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| 10. |
- Sandström, Niklas, 1981-, et al.
(författare)
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Lab-on-a-chip microsystems for point-of-care diagnostics
- 2010
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Ingår i: 1st International scientific conference on Microfluidics in bioanalytical research and diagnostics. ; , s. 34-35
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 11. |
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