uu.seUppsala University Publications
Change search
Refine search result
1 - 22 of 22
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 1. Bains, Ripudaman K.
    et al.
    Kovacevic, Mirna
    Plaster, Christopher A.
    Tarekegn, Ayele
    Bekele, Endashaw
    Bradman, Neil N.
    Thomas, Mark G.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Molecular diversity and population structure at the Cytochrome P450 3A5 gene in Africa2013In: BMC Genetics, ISSN 1471-2156, E-ISSN 1471-2156, Vol. 14, p. 34-Article in journal (Refereed)
    Abstract [en]

    Background: Cytochrome P450 3A5 (CYP3A5) is an enzyme involved in the metabolism of many therapeutic drugs. CYP3A5 expression levels vary between individuals and populations, and this contributes to adverse clinical outcomes. Variable expression is largely attributed to four alleles, CYP3A5*1 (expresser allele); CYP3A5*3 (rs776746), CYP3A5*6 (rs10264272) and CYP3A5*7 (rs41303343) (low/non-expresser alleles). Little is known about CYP3A5 variability in Africa, a region with considerable genetic diversity. Here we used a multi-disciplinary approach to characterize CYP3A5 variation in geographically and ethnically diverse populations from in and around Africa, and infer the evolutionary processes that have shaped patterns of diversity in this gene. We genotyped 2538 individuals from 36 diverse populations in and around Africa for common low/non-expresser CYP3A5 alleles, and re-sequenced the CYP3A5 gene in five Ethiopian ethnic groups. We estimated the ages of low/non-expresser CYP3A5 alleles using a linked microsatellite and assuming a step-wise mutation model of evolution. Finally, we examined a hypothesis that CYP3A5 is important in salt retention adaptation by performing correlations with ecological data relating to aridity for the present day, 10,000 and 50,000 years ago. Results: We estimate that similar to 43% of individuals within our African dataset express CYP3A5, which is lower than previous independent estimates for the region. We found significant intra-African variability in CYP3A5 expression phenotypes. Within Africa the highest frequencies of high-activity alleles were observed in equatorial and Niger-Congo speaking populations. Ethiopian allele frequencies were intermediate between those of other sub-Saharan African and non-African groups. Re-sequencing of CYP3A5 identified few additional variants likely to affect CYP3A5 expression. We estimate the ages of CYP3A5*3 as similar to 76,400 years and CYP3A5*6 as similar to 218,400 years. Finally we report that global CYP3A5 expression levels correlated significantly with aridity measures for 10,000 [Spearmann's Rho= -0.465, p=0.004] and 50,000 years ago [Spearmann's Rho= -0.379, p=0.02]. Conclusions: Significant intra-African diversity at the CYP3A5 gene is likely to contribute to multiple pharmacogenetic profiles across the continent. Significant correlations between CYP3A5 expression phenotypes and aridity data are consistent with a hypothesis that the enzyme is important in salt-retention adaptation.

  • 2.
    Berlin, Sofia
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolution, Genomics and Systematics, Evolutionary Biology.
    Quintela, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Evolution, Population and Conservation Biology.
    Höglund, Jacob
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Evolution, Population and Conservation Biology.
    A multilocus assay reveals high nucleotide diversity and limited differentiation among Scandinavian willow grouse (Lagopus lagopus)2008In: BMC Genetics, ISSN 1471-2156, E-ISSN 1471-2156, Vol. 9, p. 89-Article in journal (Refereed)
    Abstract [en]

    Background: There is so far very little data on autosomal nucleotide diversity in birds, except for data from the domesticated chicken and some passerines species. Estimates of nucleotide diversity reported so far in birds have been high (similar to 10(-3)) and a likely explanation for this is the generally higher effective population sizes compared to mammals. In this study, the level of nucleotide diversity has been examined in the willow grouse, a non-domesticated bird species from the order Galliformes, which also holds the chicken. The willow grouse (Lagopus lagopus) has an almost circumpolar distribution but is absent from Greenland and the north Atlantic islands. It primarily inhabits tundra, forest edge habitats and sub-alpine vegetation. Willow grouse are hunted throughout its range, and regionally it is a game bird of great cultural and economical importance.

    Results: We sequenced 18 autosomal protein coding loci from approximately 15-18 individuals per population. We found a total of 127 SNP's, which corresponds to 1 SNP every 51 bp. 26 SNP's were amino acid replacement substitutions. Total nucleotide diversity (pi(t)) was between 1.30 x 10(-4) and 7.66 x 10(-3) (average pi(t) = 2.72 x 10(-3) +/- 2.06 x 10(-3)) and silent nucleotide diversity varied between 4.20 x 10(-4) and 2.76 x 10(-2) (average pi(S) = 9.22 x 10(-3) +/- 7.43 x 10(-4)). The synonymous diversity is approximately 20 times higher than in humans and two times higher than in chicken. Non-synonymous diversity was on average 18 times lower than the synonymous diversity and varied between 0 and 4.90 x 10(-3) (average pi(a) = 5.08 x 10(-4) +/- 7.43 x 10(3)), which suggest that purifying selection is strong in these genes. F-ST values based on synonymous SNP's varied between -5.60 x 10(-4) and 0.20 among loci and revealed low levels of differentiation among the four localities, with an overall value of F-ST = 0.03 (95% CI: 0.006 -0.057) over 60 unlinked loci. Non-synonymous SNP's gave similar results. Low levels of linkage disequilibrium were observed within genes, with an average r(2) = 0.084 +/- 0.110, which is expected for a large outbred population with no population differentiation. The mean per site per generation recombination parameter (rho) was comparably high (0.028 +/- 0.018), indicating high recombination rates in these genes.

    Conclusion: We found unusually high levels of nucleotide diversity in the Scandinavian willow grouse as well as very little population structure among localities with up to 1647 km distance. There are also low levels of linkage disequilibrium within the genes and the population recombination rate is high, which is indicative of an old panmictic population, where recombination has had time to break up any haplotype blocks. The non-synonymous nucleotide diversity is low compared with the silent, which is in agreement with effective purifying selection, possibly due to the large effective population size.

  • 3.
    Besnier, Francois
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, The Linnaeus Centre for Bioinformatics.
    Carlborg, Örjan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, The Linnaeus Centre for Bioinformatics.
    A genetic algorithm based method for stringent haplotyping of family data2009In: BMC Genetics, ISSN 1471-2156, E-ISSN 1471-2156, Vol. 10, article id 57Article in journal (Refereed)
    Abstract [en]

    Background: The linkage phase, or haplotype, is an extra level of information that in addition to genotype and pedigree can be useful for reconstructing the inheritance pattern of the alleles in a pedigree, and computing for example Identity By Descent probabilities. If a haplotype is provided, the precision of estimated IBD probabilities increases, as long as the haplotype is estimated without errors. It is therefore important to only use haplotypes that are strongly supported by the available data for IBD estimation, to avoid introducing new errors due to erroneous linkage phases.

    Results: We propose a genetic algorithm based method for haplotype estimation in family data that includes a stringency parameter. This allows the user to decide the error tolerance level when inferring parental origin of the alleles. This is a novel feature compared to existing methods for haplotype estimation. We show that using a high stringency produces haplotype data with few errors, whereas a low stringency provides haplotype estimates in most situations, but with an increased number of errors.

    Conclusion: By including a stringency criterion in our haplotyping method, the user is able to maintain the error rate at a suitable level for the particular study; one can select anything from haplotyped data with very small proportion of errors and a higher proportion of non-inferred haplotypes, to data with phase estimates for every marker, when haplotype errors are tolerable. Giving this choice makes the method more flexible and useful in a wide range of applications as it is able to fulfil different requirements regarding the tolerance for haplotype errors, or uncertain marker-phases.

  • 4.
    Brunberg, Emma
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Andersson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Cothran, Gus
    Sandberg, Kaj
    Mikko, Sofia
    Lindgren, Gabriella
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    A missense mutation in PMEL17 is associated with the Silver coat color in the horse2006In: BMC Genetics, ISSN 1471-2156, E-ISSN 1471-2156, Vol. 7, p. 46-Article in journal (Refereed)
    Abstract [en]

    Background: The Silver coat color, also called Silver dapple, in the horse is characterized by dilution of the black pigment in the hair. This phenotype shows an autosomal dominant inheritance. The effect of the mutation is most visible in the long hairs of the mane and tail, which are diluted to a mixture of white and gray hairs. Herein we describe the identification of the responsible gene and a missense mutation associated with the Silver phenotype.

    Results: Segregation data on the Silver locus (Z) were obtained within one half-sib family that consisted of a heterozygous Silver colored stallion with 34 offspring and their 29 non-Silver dams. We typed 41 genetic markers well spread over the horse genome, including one single microsatellite marker (TKY284) close to the candidate gene PMEL17 on horse chromosome 6 (ECA6q23). Significant linkage was found between the Silver phenotype and TKY284 (theta = 0, z = 9.0). DNA sequencing of PMEL17 in Silver and non-Silver horses revealed a missense mutation in exon 11 changing the second amino acid in the cytoplasmic region from arginine to cysteine (Arg618Cys). This mutation showed complete association with the Silver phenotype across multiple horse breeds, and was not found among non-Silver horses with one clear exception; a chestnut colored individual that had several Silver offspring when mated to different non-Silver stallions also carried the exon 11 mutation. In total, 64 Silver horses from six breeds and 85 non-Silver horses from 14 breeds were tested for the exon 11 mutation. One additional mutation located in intron 9, only 759 bases from the missense mutation, also showed complete association with the Silver phenotype. However, as one could expect to find several non-causative mutations completely associated with the Silver mutation, we argue that the missense mutation is more likely to be causative.

    Conclusion: The present study shows that PMEL17 causes the Silver coat color in the horse and enable genetic testing for this trait.

  • 5. Ching, Yung-Hao
    et al.
    Munroe, Robert J.
    Moran, Jennifer L.
    Barker, Anna K.
    Mauceli, Evan
    Fennell, Tim
    diPalma, Frederica
    Lindblad-Toh, Kerstin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Abcunas, Lindsay M.
    Gilmour, Joyanna F.
    Harris, Tanya P.
    Kloet, Susan L.
    Luo, Yunhai
    McElwee, John L.
    Mu, Weipeng
    Park, Hyo K.
    Rogal, David L.
    Schimenti, Kerry J.
    Shen, Lishuang
    Shindo, Mami
    Shou, James Y.
    Stenson, Erin K.
    Stover, Patrick J.
    Schimenti, John C.
    High resolution mapping and positional cloning of ENU-induced mutations in the Rw region of mouse chromosome 52010In: BMC Genetics, ISSN 1471-2156, E-ISSN 1471-2156, Vol. 11, p. 106-Article in journal (Refereed)
    Abstract [en]

    Background: Forward genetic screens in mice provide an unbiased means to identify genes and other functional genetic elements in the genome. Previously, a large scale ENU mutagenesis screen was conducted to query the functional content of a similar to 50 Mb region of the mouse genome on proximal Chr 5. The majority of phenotypic mutants recovered were embryonic lethals. Results: We report the high resolution genetic mapping, complementation analyses, and positional cloning of mutations in the target region. The collection of identified alleles include several with known or presumed functions for which no mutant models have been reported (Tbc1d14, Nol14, Tyms, Cad, Fbxl5, Haus3), and mutations in genes we or others previously reported (Tapt1, Rest, Ugdh, Paxip1, Hmx1, Otoe, Nsun7). We also confirmed the causative nature of a homeotic mutation with a targeted allele, mapped a lethal mutation to a large gene desert, and localized a spermiogenesis mutation to a region in which no annotated genes have coding mutations. The mutation in Tbc1d14 provides the first implication of a critical developmental role for RAB-GAP-mediated protein transport in early embryogenesis. Conclusion: This collection of alleles contributes to the goal of assigning biological functions to all known genes, as well as identifying novel functional elements that would be missed by reverse genetic approaches.

  • 6.
    Cortés, Andrés J.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Plant Ecology and Evolution.
    Carolina Chavarro, M.
    Madrinan, Santiago
    This, Dominique
    Blair, Matthew W.
    Molecular ecology and selection in the drought-related Asr gene polymorphisms in wild and cultivated common bean (Phaseolus vulgaris L.)2012In: BMC Genetics, ISSN 1471-2156, E-ISSN 1471-2156, Vol. 13, p. 58-Article in journal (Refereed)
    Abstract [en]

    Background: The abscisic acid (ABA) pathway plays an important role in the plants' reaction to drought stress and ABA-stress response (Asr) genes are important in controlling this process. In this sense, we accessed nucleotide diversity at two candidate genes for drought tolerance (Asr1 and Asr2), involved in an ABA signaling pathway, in the reference collection of cultivated common bean (Phaseolus vulgaris L.) and a core collection of wild common bean accessions. Results: Our wild population samples covered a range of mesic (semi-arid) to very dry (desert) habitats, while our cultivated samples presented a wide spectrum of drought tolerance. Both genes showed very different patterns of nucleotide variation. Asr1 exhibited very low nucleotide diversity relative to the neutral reference loci that were previously surveyed in these populations. This suggests that strong purifying selection has been acting on this gene. In contrast, Asr2 exhibited higher levels of nucleotide diversity, which is indicative of adaptive selection. These patterns were more notable in wild beans than in cultivated common beans indicting that natural selection has played a role over long time periods compared to farmer selection since domestication. Conclusions: Together these results suggested the importance of Asr1 in the context of drought tolerance, and constitute the first steps towards an association study between genetic polymorphism of this gene family and variation in drought tolerance traits. Furthermore, one of our major successes was to find that wild common bean is a reservoir of genetic variation and selection signatures at Asr genes, which may be useful for breeding drought tolerance in cultivated common bean.

  • 7. Dedukh, Dmitry
    et al.
    Mazepa, Glib
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Population and Conservation Biology.
    Shabanov, Dmitry
    Rosanov, Juriy
    Litvinchuk, Spartak
    Borkin, Leo
    Saifitdinova, Alsu
    Krasikova, Alla
    Cytological maps of lampbrush chromosomes of European water frogs (Pelophylax esculentus complex) from the Eastern Ukraine2013In: BMC Genetics, ISSN 1471-2156, E-ISSN 1471-2156, Vol. 14, p. 26-Article in journal (Refereed)
    Abstract [en]

    Background: Hybridogenesis (hemiclonal inheritance) is a kind of clonal reproduction in which hybrids between parental species are reproduced by crossing with one of the parental species. European water frogs (Pelophylax esculentus complex) represent an appropriate model for studying interspecies hybridization, processes of hemiclonal inheritance and polyploidization. P. esculentus complex consists of two parental species, P. ridibundus (the lake frog) and P. lessonae (the pool frog), and their hybridogenetic hybrid - P. esculentus (the edible frog). Parental and hybrid frogs can reproduce syntopically and form hemiclonal population systems. For studying mechanisms underlying the maintenance of water frog population systems it is required to characterize the karyotypes transmitted in gametes of parental and different hybrid animals of both sexes. Results: In order to obtain an instrument for characterization of oocyte karyotypes in hybrid female frogs, we constructed cytological maps of lampbrush chromosomes from oocytes of both parental species originating in Eastern Ukraine. We further identified certain molecular components of chromosomal marker structures and mapped coilin-rich spheres and granules, chromosome associated nucleoli and special loops accumulating splicing factors. We recorded the dissimilarities between P. ridibundus and P. lessonae lampbrush chromosomes in the length of orthologous chromosomes, number and location of marker structures and interstitial (TTAGGG)(n)-repeat sites as well as activity of nucleolus organizer. Satellite repeat RrS1 was mapped in centromere regions of lampbrush chromosomes of the both species. Additionally, we discovered transcripts of RrS1 repeat in oocytes of P. ridibundus and P. lessonae. Moreover, G-rich transcripts of telomere repeat were revealed in association with terminal regions of P. ridibundus and P. lessonae lampbrush chromosomes. Conclusions: The constructed cytological maps of lampbrush chromosomes of P. ridibundus and P. lessonae provide basis to define the type of genome transmitted within individual oocytes of P. esculentus females with different ploidy and from various population systems.

  • 8. Galeano, C.H.
    et al.
    Cortés, Andres J.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Plant Ecology and Evolution.
    Fernandez, A.C.
    Soler, A.
    Franco-Herrera, N.
    Makunde, G.
    Vanderleyden, J.
    Blair, M.W.
    Gene-based single nucleotide polymorphism markers for genetic and association mapping in common bean2012In: BMC Genetics, ISSN 1471-2156, E-ISSN 1471-2156, Vol. 12, article id 48Article in journal (Refereed)
    Abstract [en]

    Background: In common bean, expressed sequence tags (ESTs) are an underestimated source of gene-based markers such as insertion-deletions (Indels) or single-nucleotide polymorphisms (SNPs). However, due to the nature of these conserved sequences, detection of markers is difficult and portrays low levels of polymorphism. Therefore, development of intron-spanning EST-SNP markers can be a valuable resource for genetic experiments such as genetic mapping and association studies. 

    Results: In this study, a total of 313 new gene-based markers were developed at target genes. Intronic variation was deeply explored in order to capture more polymorphism. Introns were putatively identified after comparing the common bean ESTs with the soybean genome, and the primers were designed over intron-flanking regions. The intronic regions were evaluated for parental polymorphisms using the single strand conformational polymorphism (SSCP) technique and Sequenom MassARRAY system. A total of 53 new marker loci were placed on an integrated molecular map in the DOR364 x G19833 recombinant inbred line (RIL) population. The new linkage map was used to build a consensus map, merging the linkage maps of the BAT93 x JALO EEP558 and DOR364 x BAT477 populations. A total of 1,060 markers were mapped, with a total map length of 2,041 cM across 11 linkage groups. As a second application of the generated resource, a diversity panel with 93 genotypes was evaluated with 173 SNP markers using the MassARRAY-platform and KASPar technology. These results were coupled with previous SSR evaluations and drought tolerance assays carried out on the same individuals. This agglomerative dataset was examined, in order to discover marker-trait associations, using general linear model (GLM) and mixed linear model (MLM). Some significant associations with yield components were identified, and were consistent with previous findings. 

    Conclusions: In short, this study illustrates the power of intron-based markers for linkage and association mapping in common bean. The utility of these markers is discussed in relation with the usefulness of microsatellites, the molecular markers by excellence in this crop.

  • 9. Guo, Jiazhong
    et al.
    Jorjani, Hossein
    Carlborg, Örjan
    SLU.
    A genome-wide association study using international breeding-evaluation data identifies major loci affecting production traits and stature in the Brown Swiss cattle breed.2012In: BMC Genetics, ISSN 1471-2156, E-ISSN 1471-2156, Vol. 13Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The genome-wide association study (GWAS) is a useful approach to identify genes affecting economically important traits in dairy cattle. Here, we report the results from a GWAS based on high-density SNP genotype data and estimated breeding values for nine production, fertility, body conformation, udder health and workability traits in the Brown Swiss cattle population that is part of the international genomic evaluation program.

    RESULT: GWASs were performed using 50 k SNP chip data and deregressed estimated breeding values (DEBVs) for nine traits from between 2061 and 5043 bulls that were part of the international genomic evaluation program coordinated by Interbull Center. The nine traits were milk yield (MY), fat yield (FY), protein yield (PY), lactating cow's ability to recycle after calving (CRC), angularity (ANG), body depth (BDE), stature (STA), milk somatic cell score (SCS) and milk speed (MSP). Analyses were performed using a linear mixed model correcting for population confounding. A total of 74 SNPs were detected to be genome-wide significantly associated with one or several of the nine analyzed traits. The strongest signal was identified on chromosome 25 for milk production traits, stature and body depth. Other signals were on chromosome 11 for angularity, chromosome 24 for somatic cell score, and chromosome 6 for milking speed. Some signals overlapped with earlier reported QTL for similar traits in other cattle populations and were located close to interesting candidate genes worthy of further investigations.

    CONCLUSIONS: Our study shows that international genetic evaluation data is a useful resource for identifying genetic factors influencing complex traits in livestock. Several genome wide significant association signals could be identified in the Brown Swiss population, including a major signal on BTA25. Our findings report several associations and plausible candidate genes that deserve further exploration in other populations and molecular dissection to explore the potential economic impact and the genetic mechanisms underlying these production traits in cattle.

  • 10.
    Li, Sen
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Jakobsson, Mattias
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Estimating demographic parameters from large-scale population genomic data using Approximate Bayesian Computation2012In: BMC Genetics, ISSN 1471-2156, E-ISSN 1471-2156, Vol. 13, p. 22-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The Approximate Bayesian Computation (ABC) approach has been used to infer demographic parameters for numerous species, including humans. However, most applications of ABC still use limited amounts of data, from a small number of loci, compared to the large amount of genome-wide population-genetic data which have become available in the last few years.

    RESULTS: We evaluated the performance of the ABC approach for three 'population divergence' models - similar to the 'isolation with migration' model - when the data consists of several hundred thousand SNPs typed for multiple individuals by simulating data from known demographic models. The ABC approach was used to infer demographic parameters of interest and we compared the inferred values to the true parameter values that was used to generate hypothetical "observed" data. For all three case models, the ABC approach inferred most demographic parameters quite well with narrow credible intervals, for example, population divergence times and past population sizes, but some parameters were more difficult to infer, such as population sizes at present and migration rates. We compared the ability of different summary statistics to infer demographic parameters, including haplotype and LD based statistics, and found that the accuracy of the parameter estimates can be improved by combining summary statistics that capture different parts of information in the data. Furthermore, our results suggest that poor choices of prior distributions can in some circumstances be detected using ABC. Finally, increasing the amount of data beyond some hundred loci will substantially improve the accuracy of many parameter estimates using ABC.

    CONCLUSIONS: We conclude that the ABC approach can accommodate realistic genome-wide population genetic data, which may be difficult to analyze with full likelihood approaches, and that the ABC can provide accurate and precise inference of demographic parameters from these data, suggesting that the ABC approach will be a useful tool for analyzing large genome-wide datasets.

  • 11.
    Markljung, Ellen
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Braunschweig, Martin H.
    Jørgensen, Claus B.
    Fredholm, Merete
    Karlskov-Mortensen, Peter
    Bruun, Camilla S.
    Sawera, Milena
    Cho, In-Cheol
    Hedebro-Velander, Ingela
    Josell, Åsa
    Lundström, Kerstin
    von Seth, Gertrud
    Andersson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Genome-wide identification of quantitative trait loci in a cross between Hampshire and Landrace II: meat quality traits2008In: BMC Genetics, ISSN 1471-2156, E-ISSN 1471-2156, Vol. 9, p. 22-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Meat quality traits are important in pig breeding programs, but they are difficult to include in a traditional selection program. Marker assisted selection (MAS) of meat quality traits is therefore of interest in breeding programs and a Quantitative Trait Locus (QTL) analysis is the key to identifying markers that can be used in MAS. In this study, Landrace and Hampshire intercross and backcross families were used to investigate meat quality traits. Hampshire pigs are commonly used as the sire line in commercial pig breeding. This is the first time a pedigree including Hampshire pigs has been used for a QTL analysis of meat quality traits. RESULTS: In total, we analyzed 39 meat quality traits and identified eight genome-wide significant QTL peaks in four regions: one on chromosome 3, two on chromosome 6 and one on chromosome 16. At least two of the QTLs do not appear to have been detected in previous studies. On chromosome 6 we identified QTLs for water content in M. longissimus dorsi (LD), drip loss in LD and post mortem pH decline in LD. On chromosomes 3 and 16 we identified previously undetected QTLs for protein content in LD and for freezing and cooking loss respectively. CONCLUSION: We identified at least two new meat quality trait QTLs at the genome-wide significance level. We detected two QTLs on chromosome 6 that possibly coincide with QTLs detected in other studies. We were also able to exclude the C1843T mutation in the ryanodine receptor (RYR1) as a causative mutation for one of the chromosome 6 QTLs in this cross.

  • 12.
    Meyer-Lucht, Yvonne
    et al.
    Leibniz-Institute for Zoo- and Wildlife Research.
    Otten, Celine
    Leibniz-Institute for Zoo- and Wildlife Research.
    Puettker, Thomas
    Leibniz-Institute for Zoo- and Wildlife Research.
    Sommer, Simone
    Leibniz-Institute for Zoo- and Wildlife Research.
    Selection, diversity and evolutionary patterns of the MHC class II DAB in free-ranging Neotropical marsupials2008In: BMC Genetics, ISSN 1471-2156, E-ISSN 1471-2156, Vol. 9, p. 39-Article in journal (Refereed)
    Abstract [en]

    Background: Research on the genetic architecture and diversity of the MHC has focused mainly on eutherian mammals, birds and fish. So far, studies on model marsupials used in laboratory investigations indicated very little or even no variation in MHC class II genes. However, natural levels of diversity and selection are unknown in marsupials as studies on wild populations are virtually absent. We used two endemic South American mouse opossums, Gracilinanus microtarsus and Marmosops incanus, to investigate characteristic features of MHC selection. This study is the first investigation of MHC selection in free-ranging Neotropical marsupials. In addition, the evolutionary history of MHC lineages within the group of marsupials was examined.

    Results: G. microtarsus showed extensive levels of MHC diversity within and among individuals as 47 MHC-DAB alleles and high levels of sequence divergence were detected at a minimum of four loci. Positively selected codon sites were identified, of which most were congruent with human antigen binding sites. The diversity in M. incanus was rather low with only eight observed alleles at presumably two loci. However, these alleles also revealed high sequence divergence. Again, positive selection was identified on specific codon sites, all congruent with human ABS and with positively selected sites observed in G. microtarsus. In a phylogenetic comparison alleles of M. incanus interspersed widely within alleles of G. microtarsus with four alleles being present in both species.

    Conclusion: Our investigations revealed extensive MHC class II polymorphism in a natural marsupial population, contrary to previous assumptions. Furthermore, our study confirms for the first time in marsupials the presence of three characteristic features common at MHC loci of eutherian mammals, birds and fish: large allelic sequence divergence, positive selection on specific sites and trans-specific polymorphism.

  • 13. Nassir, Rami
    et al.
    Kosoy, Roman
    Tian, Chao
    White, A
    Butler, M
    Silva, Gabriel
    Kittles, Rick
    Alarcon-Riquelme, Marta E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Gregersen, K
    Belmont, W
    De La Vega, M
    Seldin, Michael F.
    An ancestry informative marker set for determining continental origin: validation and extension using human genome diversity panels2009In: BMC Genetics, ISSN 1471-2156, E-ISSN 1471-2156, Vol. 10, p. 39-Article in journal (Refereed)
    Abstract [en]

    Background: Case-control genetic studies of complex human diseases can be confounded by population stratification. This issue can be addressed using panels of ancestry informative markers (AIMs) that can provide substantial population substructure information. Previously, we described a panel of 128 SNP AIMs that were designed as a tool for ascertaining the origins of subjects from Europe, Sub-Saharan Africa, Americas, and East Asia. Results: In this study, genotypes from Human Genome Diversity Panel populations were used to further evaluate a 93 SNP AIM panel, a subset of the 128 AIMS set, for distinguishing continental origins. Using both model-based and relatively model-independent methods, we here confirm the ability of this AIM set to distinguish diverse population groups that were not previously evaluated. This study included multiple population groups from Oceana, South Asia, East Asia, Sub-Saharan Africa, North and South America, and Europe. In addition, the 93 AIM set provides population substructure information that can, for example, distinguish Arab and Ashkenazi from Northern European population groups and Pygmy from other Sub-Saharan African population groups. Conclusion: These data provide additional support for using the 93 AIM set to efficiently identify continental subject groups for genetic studies, to identify study population outliers, and to control for admixture in association studies.

  • 14.
    Nettelblad, Carl
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Scientific Computing. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computational Science.
    Inferring haplotypes and parental genotypes in larger full sib-ships and other pedigrees with missing or erroneous genotype data2012In: BMC Genetics, ISSN 1471-2156, E-ISSN 1471-2156, Vol. 13, p. 85:1-13Article in journal (Refereed)
  • 15. Rönnegård, Lars
    et al.
    Besnier, Francois
    Carlborg, Örjan
    SLU.
    Modelling dominance in a flexible intercross analysis.2009In: BMC Genetics, ISSN 1471-2156, E-ISSN 1471-2156, Vol. 10Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The aim of this paper is to develop a flexible model for analysis of quantitative trait loci (QTL) in outbred line crosses, which includes both additive and dominance effects. Our flexible intercross analysis (FIA) model accounts for QTL that are not fixed within founder lines and is based on the variance component framework. Genome scans with FIA are performed using a score statistic, which does not require variance component estimation.

    RESULTS: Simulations of a pedigree with 800 F2 individuals showed that the power of FIA including both additive and dominance effects was almost 50% for a QTL with equal allele frequencies in both lines with complete dominance and a moderate effect, whereas the power of a traditional regression model was equal to the chosen significance value of 5%. The power of FIA without dominance effects included in the model was close to those obtained for FIA with dominance for all simulated cases except for QTL with overdominant effects. A genome-wide linkage analysis of experimental data from an F2 intercross between Red Jungle Fowl and White Leghorn was performed with both additive and dominance effects included in FIA. The score values for chicken body weight at 200 days of age were similar to those obtained in FIA analysis without dominance.

    CONCLUSION: We have extended FIA to include QTL dominance effects. The power of FIA was superior, or similar, to standard regression methods for QTL effects with dominance. The difference in power for FIA with or without dominance is expected to be small as long as the QTL effects are not overdominant. We suggest that FIA with only additive effects should be the standard model to be used, especially since it is more computationally efficient.

  • 16.
    Rönnegård, Lars
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, The Linnaeus Centre for Bioinformatics.
    Carlborg, Örjan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, The Linnaeus Centre for Bioinformatics.
    Separation of base allele and sampling term effects gives new insights in variance component QTL analysis2007In: BMC Genetics, ISSN 1471-2156, E-ISSN 1471-2156, Vol. 8, p. 1-Article in journal (Refereed)
    Abstract [en]

    Background

    Variance component (VC) models are commonly used for Quantitative Trait Loci (QTL) mapping in outbred populations. Here, the QTL effect is given as a random effect and a critical part of the model is the relationship between the phenotypic values and the random effect. In the traditional VC model, each individual has a unique QTL effect and the relationship between these random effects is given as a covariance structure (known as the identity-by-descent (IBD) matrix).

    Results

    We present an alternative notation of the variance component model, where the elements of the random effect are independent base generation allele effects and sampling term effects. The relationship between the phenotypic vales and the random effect is given by an incidence matrix, which results in a novel, but statistically equivalent, version of the traditional VC model. A general algorithm to estimate this incidence matrix is presented. Since the model is given in terms of base generation allele effects and sampling term effects, these effects can be estimated separately using best linear unbiased prediction (BLUP). From simulated data, we showed that biallelic QTL effects could be accurately clustered using the BLUP obtained from our model notation when markers are fully informative, and that the accuracy increased with the size of the QTL effect. We also developed a measure indicating whether a base generation marker homozygote is a QTL heterozygote or not, by comparing the variances of the sampling term BLUP and the base generation allele BLUP. A ratio greater than one gives strong support for a QTL heterozygote.

    Conclusion

    We developed a simple presentation of the VC QTL model for identification of base generation allele effects in QTL linkage analysis. The base generation allele effects and sampling term effects were separated in our model notation. This clarifies the assumptions of the model and should also enhance the development of genome scan methods.

  • 17.
    Seroussi, Eyal
    et al.
    Volcani Ctr, Agr Res Org, Dept Anim Sci, Rishon Letsiyon.
    Pitel, Frederique
    Univ Toulouse, INRA, GenPhySE, INPT, ENVT, Castanet Tolosan.
    Leroux, Sophie
    Univ Toulouse, INRA, GenPhySE, INPT, ENVT, Castanet Tolosan.
    Morisson, Mireille
    Univ Toulouse, INRA, GenPhySE, INPT, ENVT, Castanet Tolosan.
    Bornelöv, Susanne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Miyara, Shoval
    Volcani Ctr, Agr Res Org, Dept Anim Sci, Rishon Letsiyon.
    Yosefi, Sara
    Volcani Ctr, Agr Res Org, Dept Anim Sci, Rishon Letsiyon.
    Cogburn, Larry A.
    Univ Delaware, Dept Anim & Food Sci, Newark.
    Burt, David W.
    Univ Edinburgh, Roslin Inst, Midlothian.; Univ Edinburgh, Royal (Dick) Sch Vet Studies, Midlothian.
    Andersson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Texas A&M Univ, Coll Vet Med & Biomed Sci, Dept Vet Integrat Biosci, College Stn, Texas.; Swedish Univ Agr Sci, Dept Anim Breeding & Genet, Uppsala.
    Friedman-Einat, Miriam
    Volcani Ctr, Agr Res Org, Dept Anim Sci, Rishon Letsiyon.
    Correction to: Mapping of leptin and its syntenic genes to chicken chromosome 1p2017In: BMC Genetics, ISSN 1471-2156, E-ISSN 1471-2156, Vol. 18, no 113Article in journal (Other academic)
  • 18.
    Seroussi, Eyal
    et al.
    Agr Res Org, Volcani Ctr, Dept Anim Sci, POB 15159, IL-7528809 Rishon Letsiyon, Israel..
    Pitel, Frederique
    Univ Toulouse, INRA, INPT, ENVT,GenPhySE, F-31326 Castanet Tolosan, France..
    Leroux, Sophie
    Univ Toulouse, INRA, INPT, ENVT,GenPhySE, F-31326 Castanet Tolosan, France..
    Morisson, Mireille
    Univ Toulouse, INRA, INPT, ENVT,GenPhySE, F-31326 Castanet Tolosan, France..
    Bornelöv, Susanne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Miyara, Shoval
    Agr Res Org, Volcani Ctr, Dept Anim Sci, POB 15159, IL-7528809 Rishon Letsiyon, Israel..
    Yosefi, Sara
    Agr Res Org, Volcani Ctr, Dept Anim Sci, POB 15159, IL-7528809 Rishon Letsiyon, Israel..
    Cogburn, Larry A.
    Univ Delaware, Dept Anim & Food Sci, Newark, DE 19716 USA..
    Burt, David W.
    Univ Edinburgh, Sch Vet Studies, Roslin Inst & Royal Dick, Roslin EH25 9RG, Midlothian, Scotland..
    Andersson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Texas A&M Univ, Coll Vet Med & Biomed Sci, Dept Vet Integrat Biosci, College Stn, TX 77843 USA.;Swedish Univ Agr Sci, Dept Anim Breeding & Genet, SE-75007 Uppsala, Sweden..
    Friedman-Einat, Miriam
    Agr Res Org, Volcani Ctr, Dept Anim Sci, POB 15159, IL-7528809 Rishon Letsiyon, Israel..
    Mapping of leptin and its syntenic genes to chicken chromosome 1p2017In: BMC Genetics, ISSN 1471-2156, E-ISSN 1471-2156, Vol. 18, article id 77Article in journal (Refereed)
    Abstract [en]

    Background: Misidentification of the chicken leptin gene has hampered research of leptin signaling in this species for almost two decades. Recently, the genuine leptin gene with a GC-rich (similar to 70%) repetitive-sequence content was identified in the chicken genome but without indicating its genomic position. This suggests that such GC-rich sequences are difficult to sequence and therefore substantial regions are missing from the current chicken genome assembly.

    Results: A radiation hybrid panel of chicken-hamster Wg3hCl2 cells was used to map the genome location of the chicken leptin gene. Contrary to our expectations, based on comparative genome mapping and sequence characteristics, the chicken leptin was not located on a microchromosome, which are known to contain GC-rich and repetitive regions, but at the distal tip of the largest chromosome (1p). Following conserved synteny with other vertebrates, we also mapped five additional genes to this genomic region (ARF5, SND1, LRRC4, RBM28, and FLNC), bridging the genomic gap in the current Galgal5 build for this chromosome region. All of the short scaffolds containing these genes were found to consist of GC-rich (54 to 65%) sequences comparing to the average GC-content of 40% on chromosome 1. In this syntenic group, the RNA-binding protein 28 (RBM28) was in closest proximity to leptin. We deduced the full-length of the RBM28 cDNA sequence and profiled its expression patterns detecting a negative correlation (R = -0.7) between the expression of leptin and of RBM28 across tissues that expressed at least one of the genes above the average level. This observation suggested a local regulatory interaction between these genes. In adipose tissues, we observed a significant increase in RBM28 mRNA expression in breeds with lean phenotypes.

    Conclusion: Mapping chicken leptin together with a cluster of five syntenic genes provided the final proof for its identification as the true chicken ortholog. The high GC-content observed for the chicken leptin syntenic group suggests that other similar clusters of genes in GC-rich genomic regions are missing from the current genome assembly (Galgal5), which should be resolved in future assemblies of the chicken genome.

  • 19.
    Sjöstrand, Agnès E.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Sjödin, Per
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Jakobsson, Mattias
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Private haplotypes can reveal local adaptation2014In: BMC Genetics, ISSN 1471-2156, E-ISSN 1471-2156, Vol. 15, p. 61-Article in journal (Refereed)
    Abstract [en]

    Background: Genome-wide scans for regions that demonstrate deviating patterns of genetic variation have become common approaches for finding genes targeted by selection. Several genomic patterns have been utilized for this purpose, including deviations in haplotype homozygosity, frequency spectra and genetic differentiation between populations. Results: We describe a novel approach based on the Maximum Frequency of Private Haplotypes - MFPH - to search for signals of recent population-specific selection. The MFPH statistic is straightforward to compute for phased SNP-and sequence-data. Using both simulated and empirical data, we show that MFPH can be a powerful statistic to detect recent population-specific selection, that it performs at the same level as other commonly used summary statistics (e.g. F-ST, iHS and XP-EHH), and that MFPH in some cases capture signals of selection that are missed by other statistics. For instance, in the Maasai, MFPH reveals a strong signal of selection in a region where other investigated statistics fail to pick up a clear signal that contains the genes DOCK3, MAPKAPK3 and CISH. This region has been suggested to affect height in many populations based on phenotype-genotype association studies. It has specifically been suggested to be targeted by selection in Pygmy groups, which are on the opposite end of the human height spectrum compared to the Maasai. Conclusions: From the analysis of both simulated and publicly available empirical data, we show that MFPH represents a summary statistic that can provide further insight concerning population-specific adaptation.

  • 20.
    Strand, Tanja
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Population and Conservation Biology.
    Wang, Biao
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Population and Conservation Biology.
    Meyer-Lucht, Yvonne
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Population and Conservation Biology.
    Höglund, Jacob
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Population and Conservation Biology.
    Evolutionary history of black grouse major histocompatibility complex class IIB genes revealed through single locus sequence-based genotyping2013In: BMC Genetics, ISSN 1471-2156, E-ISSN 1471-2156, Vol. 14, p. 29-Article in journal (Refereed)
    Abstract [en]

    Background: Gene duplications are frequently observed in the Major Histocompatibility Complex (MHC) of many species, and as a consequence loci belonging to the same MHC class are often too similar to tell apart. In birds, single locus genotyping of MHC genes has proven difficult due to concerted evolution homogenizing sequences at different loci. But studies on evolutionary history, mode of selection and heterozygosity correlations on the MHC cannot be performed before it is possible to analyse duplicated genes separately. In this study we investigate the architecture and evolution of the MHC class IIB genes in black grouse. We developed a sequence-based genotyping method for separate amplification of the two black grouse MHC class IIB genes BLB1 and BLB2. Based on this approach we are able to study differences in structure and selection between the two genes in black grouse and relate these results to the chicken MHC structure and organization. Results: Sequences were obtained from 12 individuals and separated into alleles using the software PHASE. We compared nucleotide diversity measures and employed selection tests for BLB1 and BLB2 to explore their modes of selection. Both BLB1 and BLB2 are transcribed and display classic characteristics of balancing selection as predicted for expressed MHC class IIB genes. We found evidence for both intra- and interlocus recombination or gene conversion, as well as indication for positive but differential selection at both loci. Moreover, the two loci appear to be linked. Phylogenetic analyses revealed orthology of the black grouse MHC class IIB genes to the respective BLB loci in chicken. Conclusions: The results indicate that the duplication of the BLB gene occurred before the species divergence into black grouse, chicken and pheasant. Further, we conclude that BLB1 and BLB2 in black grouse are subjected to homogenizing concerted evolution due to interlocus genetic exchange after species divergence. The loci are in linkage disequilibrium, which is in line with the theory of tightly coevolving genes within the MHC under the minimal essential MHC hypothesis. Our results support the conclusion that MHC form and function in birds derived from studies on the domesticated chicken are not artefacts of the domestication process.

  • 21.
    Tengvall, Katarina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Kozyrev, Sergey
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Kierczak, Marcin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Bergvall, Kerstin
    Swedish Univ Agr Sci, Dept Clin Sci, Uppsala, Sweden..
    Farias, Fabiana H. G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Ardesjö-Lundgren, Brita
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Swedish Univ Agr Sci, Dept Anim Breeding & Genet, Uppsala, Sweden..
    Olsson, Mia
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Murén, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala Univ, Dept Med Biochem & Microbiol, Sci Life Lab, Uppsala, Sweden..
    Hagman, Ragnvi
    Swedish Univ Agr Sci, Dept Clin Sci, Uppsala, Sweden..
    Leeb, Tosso
    Univ Bern, Inst Genet, Bern, Switzerland..
    Pielberg, Gerli
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Hedhammar, Åke
    Swedish Univ Agr Sci, Dept Clin Sci, Uppsala, Sweden..
    Andersson, Göran
    Swedish Univ Agr Sci, Dept Anim Breeding & Genet, Uppsala, Sweden..
    Lindblad-Toh, Kerstin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Broad Inst MIT & Harvard, Cambridge, MA USA..
    Multiple regulatory variants located in cell type-specific enhancers within the PKP2 locus form major risk and protective haplotypes for canine atopic dermatitis in German shepherd dogs2016In: BMC Genetics, ISSN 1471-2156, E-ISSN 1471-2156, Vol. 17, article id 97Article in journal (Refereed)
    Abstract [en]

    Background: Canine atopic dermatitis (CAD) is a chronic inflammatory skin disease triggered by allergic reactions involving IgE antibodies directed towards environmental allergens. We previously identified a similar to 1.5 Mb locus on canine chromosome 27 associated with CAD in German shepherd dogs (GSDs). Fine-mapping indicated association closest to the PKP2 gene encoding plakophilin 2. Results: Additional genotyping and association analyses in GSDs combined with control dogs from five breeds with low-risk for CAD revealed the top SNP 27: 19,086,778 (p = 1.4 x 10(-7)) and a rare similar to 48 kb risk haplotype overlapping the PKP2 gene and shared only with other high-risk CAD breeds. We selected altogether nine SNPs (four top-associated in GSDs and five within the similar to 48 kb risk haplotype) that spanned similar to 280 kb forming one risk haplotype carried by 35 % of the GSD cases and 10 % of the GSD controls (OR = 5.1, p = 5.9 x 10(-5)), and another haplotype present in 85 % of the GSD cases and 98 % of the GSD controls and conferring a protective effect against CAD in GSDs (OR = 0.14, p = 0.0032). Eight of these SNPs were analyzed for transcriptional regulation using reporter assays where all tested regions exerted regulatory effects on transcription in epithelial and/or immune cell lines, and seven SNPs showed allelic differences. The DNA fragment with the top-associated SNP 27: 19,086,778 displayed the highest activity in keratinocytes with 11-fold induction of transcription by the risk allele versus 8-fold by the control allele (p(difference) = 0.003), and also mapped close (similar to 3 kb) to an ENCODE skin-specific enhancer region. Conclusions: Our experiments indicate that multiple CAD-associated genetic variants located in cell type-specific enhancers are involved in gene regulation in different cells and tissues. No single causative variant alone, but rather multiple variants combined in a risk haplotype likely contribute to an altered expression of the PKP2 gene, and possibly nearby genes, in immune and epithelial cells, and predispose GSDs to CAD.

  • 22.
    Väli, Ulo
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolution, Genomics and Systematics, Evolutionary Biology.
    Brandström, Mikael
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolution, Genomics and Systematics, Evolutionary Biology.
    Johansson, Malin
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolution, Genomics and Systematics, Evolutionary Biology.
    Ellegren, Hans
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolution, Genomics and Systematics, Evolutionary Biology.
    Insertion-deletion polymorphisms (indels) as genetic markers in natural populations2008In: BMC Genetics, ISSN 1471-2156, E-ISSN 1471-2156, Vol. 9, p. 8-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: We introduce the use of short insertion-deletion polymorphisms (indels) for genetic analysis of natural populations. RESULTS: Sequence reads from light shot-gun sequencing efforts of different dog breeds were aligned to the dog genome reference sequence and gaps corresponding to indels were identified. One hundred candidate markers (4-bp indels) were selected and genotyped in unrelated dogs (n=7) and wolves (n=18). Eighty-one and 76 out of 94 could be validated as polymorphic loci in the respective sample. Mean indel heterozygosity in a diverse set of wolves was 19%, and 74% of the loci had a minor allele frequency of >10%. Indels found to be polymorphic in wolves were subsequently genotyped in a highly bottlenecked Scandinavian wolf population. Fifty-one loci turned out to be polymorphic, showing their utility even in a population with low genetic diversity. In this population, individual heterozygosity measured at indel and microsatellite loci, respectively were highly correlated. CONCLUSIONS: With an increasing amount of sequence information gathered from non-model organisms, we suggest that indels will come to form an important source of genetic markers, easy and cheap to genotype, for studies of natural populations.

1 - 22 of 22
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf