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- Ahsan, Muhammad, et al.
(författare)
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Genetic analysis and replication of QTL effects on chicken body weight using a multi-locus introgression line
- 2013
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Ingår i: Journal of Data Mining in Genomics and Proteomics. - 2153-0602. ; 4, s. 83-83
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Quantitative Trait Loci (QTL) mapping is a useful initial step to dissect the geneticarchitecture of complex biological traits. Intercrosses between divergently selected lines ofanimals is a powerful approach to map loci that affect such traits individually or throughinteractions. The drawback with the approach is a low mapping resolution and consequentlyfurther fine mapping is needed for detailed studies of the mapped loci. We have earliermapped a network of four interacting loci that through reciprocal epistatic capacitationexplains nearly half of the difference in body weight between the Virginia High WeightSelected (HWS) and Low Weight Selected (LWS) chicken lines that after 50 generationsdisplay a 12-fold difference in weight at 56 days of age. The network has been replicated andfine-mapped in an eight-generation Advance Intercross Line (AIL) and its large effect onweight confirmed. A three-locus introgression line has been bred, where the LWS haplotypesat the three loci in the network with the strongest effects on weight have been simultaneouslyintrogressed into the HWS background. Here we describe the first results from a haplotypebasedassociation analysis in this multi-locus introgression line that again replicate the effectsof the introgressed loci on body-weight in the Virginia chicken lines, but also indicate anallelic heterogeneity at the loci within the founder-lines. Further analyses are in progress toevaluate the epistatic effects of the loci in this population as well as the functionalcontribution of the allelic heterogeneity.
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- 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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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Quantitative trait loci (QTL) mapping is a first step to identify chromosomal regions harboring genetic polymorphisms that regulate complex traits. Searching causative mutations for observed effects is sometimes a daunting task as even after fine mapping of the QTL, millions of base pairs including many genes will typically need to be explored. There is thus a great need for efficient bioinformatics strategies to trace the causative mutation(s). Here, we searched for gene transcripts along with mutations regulating body weight at 56 days traits in the Virginia chicken lines – an experimental population comprising two lines that have been divergently selected for 56 days body weight for more than 50 generations. Several QTL regions 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 (AIL). Candidate transcripts and mutations were here sought in the parts of the QTL regions where the highest genetic divergence between the High-Weight selected (HWS) and Low-Weight selected (LWS) lines was observed. Such regions, 47 Mbp or 35% of the actual QTL regions, were identified by comparing the allele frequencies in the genomes of the HWS and LWS lines using both individual 60K SNP chip genotyping of birds and analysis of read proportions with 12X ABI SOLID genome resequencing of DNA pools. Gene transcripts in the target segments, obtained using the Ensembl genome browser 67, were analyzed with DAVID bioinformatic database to investigate their role in any growth-related functions. Single nucleotide polymorphisms (SNPs) in target segments obtained from resequencing data were analyzed with Variant Effect Predictor (VEP) tool to find their location and functional consequences in gene transcripts. Non-synonymous SNPs (nsSNPs) were scored for their effects on protein function with PASE software (Li et al., submitted). Finally, we present most important candidate gene transcripts from each QTL segment for further functional validation. For example, the cysteine rich transmembrane BMP regulator 1 (chordin-like) gene has growth factor binding and cell growth functions. It carries a nsSNP with high allele frequency difference (0.97) between lines, PASE (0.67) and conservation scores (0.63). Another candidate, glucagon is involved in anorexia and appetite regulation carrying a CpG mutation with high allele frequency difference (0.87) between lines.
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| 5. |
- 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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- Albert, Frank W., et al.
(författare)
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Genetic architecture of tameness in a rat model of animal domestication
- 2009
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Ingår i: Genetics. - : Oxford University Press (OUP). - 0016-6731 .- 1943-2631. ; 182:2, s. 541-554
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Tidskriftsartikel (refereegranskat)abstract
- A common feature of domestic animals is tameness - i.e., they tolerate and are unafraid of human presence and handling. To gain insight into the genetic basis of tameness and aggression, we studied an intercross between two lines of rats (Rattus norvegicus) selected over >60 generations for increased tameness and increased aggression against humans, respectively. We measured 45 traits, including tameness and aggression, anxiety-related traits, organ weights, and levels of serum components in >700 rats from an intercross population. Using 201 genetic markers, we identified two significant quantitative trait loci (QTL) for tameness. These loci overlap with QTL for adrenal gland weight and for anxiety-related traits and are part of a five-locus epistatic network influencing tameness. An additional QTL influences the occurrence of white coat spots, but shows no significant effect on tameness. The loci described here are important starting points for finding the genes that cause tameness in these rats and potentially in domestic animals in general.
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| 7. |
- Albert, F. W., et al.
(författare)
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Targeted resequencing of a genomic region influencing tameness and aggression reveals multiple signals of positive selection
- 2011
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Ingår i: Heredity. - : Springer Science and Business Media LLC. - 0018-067X .- 1365-2540. ; 107:3, s. 205-214
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Tidskriftsartikel (refereegranskat)abstract
- The identification of the causative genetic variants in quantitative trait loci (QTL) influencing phenotypic traits is challenging, especially in crosses between outbred strains. We have previously identified several QTL influencing tameness and aggression in a cross between two lines of wild-derived, outbred rats (Rattus norvegicus) selected for their behavior towards humans. Here, we use targeted sequence capture and massively parallel sequencing of all genes in the strongest QTL in the founder animals of the cross. We identify many novel sequence variants, several of which are potentially functionally relevant. The QTL contains several regions where either the tame or the aggressive founders contain no sequence variation, and two regions where alternative haplotypes are fixed between the founders. A re-analysis of the QTL signal showed that the causative site is likely to be fixed among the tame founder animals, but that several causative alleles may segregate among the aggressive founder animals. Using a formal test for the detection of positive selection, we find 10 putative positively selected regions, some of which are close to genes known to influence behavior. Together, these results show that the QTL is probably not caused by a single selected site, but may instead represent the joint effects of several sites that were targets of polygenic selection.
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- Alexander, Michelle, et al.
(författare)
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Mitogenomic analysis of a 50-generation chicken pedigree reveals a rapid rate of mitochondrial evolution and evidence for paternal mtDNA inheritance
- 2015
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Ingår i: Biology Letters. - : The Royal Society. - 1744-9561 .- 1744-957X. ; 11:10
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Tidskriftsartikel (refereegranskat)abstract
- Mitochondrial genomes represent a valuable source of data for evolutionary research, but studies of their short-term evolution have typically been limited to invertebrates, humans and laboratory organisms. Here we present a detailed study of 12 mitochondrial genomes that span a total of 385 transmissions in a well-documented 50-generation pedigree in which two lineages of chickens were selected for low and high juvenile body weight. These data allowed us to test the hypothesis of time-dependent evolutionary rates and the assumption of strict maternal mitochondrial transmission, and to investigate the role of mitochondrial mutations in determining phenotype. The identification of a non-synonymous mutation in ND4L and a synonymous mutation in CYTB, both novel mutations in Gallus, allowed us to estimate a molecular rate of 3.13 x 10(-7) mutations/site/year (95% confidence interval 3.75 x 10(-8)-1.12 x 10(-6)). This is substantially higher than avian rate estimates based upon fossil calibrations. Ascertaining which of the two novel mutations was present in an additional 49 individuals also revealed an instance of paternal inheritance of mtDNA. Lastly, an association analysis demonstrated that neither of the point mutations was strongly associated with the phenotypic differences between the two selection lines. Together, these observations reveal the highly dynamic nature of mitochondrial evolution over short time periods.
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- 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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