| 1. |
- Groenen, M. A., et al.
(author)
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Analyses of pig genomes provide insight into porcine demography and evolution
- 2012
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 491:7424, s. 393-398
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Journal article (peer-reviewed)abstract
- For 10,000 years pigs and humans have shared a close and complex relationship. From domestication to modern breeding practices, humans have shaped the genomes of domestic pigs. Here we present the assembly and analysis of the genome sequence of a female domestic Duroc pig (Sus scrofa) and a comparison with the genomes of wild and domestic pigs from Europe and Asia. Wild pigs emerged in South East Asia and subsequently spread across Eurasia. Our results reveal a deep phylogenetic split between European and Asian wild boars approximately 1 million years ago, and a selective sweep analysis indicates selection on genes involved in RNA processing and regulation. Genes associated with immune response and olfaction exhibit fast evolution. Pigs have the largest repertoire of functional olfactory receptor genes, reflecting the importance of smell in this scavenging animal. The pig genome sequence provides an important resource for further improvements of this important livestock species, and our identification of many putative disease-causing variants extends the potential of the pig as a biomedical model.
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| 2. |
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| 3. |
- Langerak, A. W., et al.
(author)
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EuroClonality/BIOMED-2 guidelines for interpretation and reporting of Ig/TCR clonality testing in suspected lymphoproliferations
- 2012
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In: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 26:10, s. 2159-2171
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Research review (peer-reviewed)abstract
- PCR-based immunoglobulin (Ig)/T-cell receptor (TCR) clonality testing in suspected lymphoproliferations has largely been standardized and has consequently become technically feasible in a routine diagnostic setting. Standardization of the pre-analytical and post-analytical phases is now essential to prevent misinterpretation and incorrect conclusions derived from clonality data. As clonality testing is not a quantitative assay, but rather concerns recognition of molecular patterns, guidelines for reliable interpretation and reporting are mandatory. Here, the EuroClonality (BIOMED-2) consortium summarizes important pre- and post-analytical aspects of clonality testing, provides guidelines for interpretation of clonality testing results, and presents a uniform way to report the results of the Ig/TCR assays. Starting from an immunobiological concept, two levels to report Ig/TCR profiles are discerned: the technical description of individual (multiplex) PCR reactions and the overall molecular conclusion for B and T cells. Collectively, the EuroClonality (BIOMED-2) guidelines and consensus reporting system should help to improve the general performance level of clonality assessment and interpretation, which will directly impact on routine clinical management (standardized best-practice) in patients with suspected lymphoproliferations.
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| 4. |
- Jonker, R.M., et al.
(author)
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Genetic consequences of breaking migratory traditions in barnacle geese Branta leucopsis
- 2013
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In: Molecular Ecology. - : John Wiley & Sons. - 0962-1083 .- 1365-294X. ; 22:23, s. 5835-5847
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Journal article (peer-reviewed)abstract
- Cultural transmission of migratory traditions enables species to deal with their environment based on experiences from earlier generations. Also, it allows a more adequate and rapid response to rapidly changing environments. When individuals break with their migratory traditions, new population structures can emerge that may affect gene flow. Recently, the migratory traditions of the Barnacle Goose Branta leucopsis changed, and new populations differing in migratory distance emerged. Here, we investigate the population genetic structure of the Barnacle Goose to evaluate the consequences of altered migratory traditions. We used a set of 358 single nucleotide polymorphism (SNP) markers to genotype 418 individuals from breeding populations in Greenland, Spitsbergen, Russia, Sweden and the Netherlands, the latter two being newly emerged populations. We used discriminant analysis of principal components, FST, linkage disequilibrium and a comparison of geneflow models using MIGRATE-N to show that there is significant population structure, but that relatively many pairs of SNPs are in linkage disequilibrium, suggesting recent admixture between these populations. Despite the assumed traditions of migration within populations, we also show that genetic exchange occurs between all populations. The newly established nonmigratory population in the Netherlands is characterized by high emigration into other populations, which suggests more exploratory behaviour, possibly as a result of shortened parental care. These results suggest that migratory traditions in populations are subject to change in geese and that such changes have population genetic consequences. We argue that the emergence of nonmigration probably resulted from developmental plasticity.
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| 5. |
- van Krieken, J. H., et al.
(author)
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Guideline on the requirements of external quality assessment programs in molecular pathology
- 2013
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In: Virchows Archiv. - : Springer Science and Business Media LLC. - 0945-6317 .- 1432-2307. ; 462:1, s. 27-37
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Journal article (peer-reviewed)abstract
- Molecular pathology is an integral part of daily diagnostic pathology and used for classification of tumors, for prediction of prognosis and response to therapy, and to support treatment decisions. For these reasons, analyses in molecular pathology must be highly reliable and hence external quality assessment (EQA) programs are called for. Several EQA programs exist to which laboratories can subscribe, but they vary in scope, number of subscribers, and execution. The guideline presented in this paper has been developed with the purpose to harmonize EQA in molecular pathology. It presents recommendations on how an EQA program should be organized, provides criteria for a reference laboratory, proposes requirements for EQA test samples, and defines the number of samples needed for an EQA program. Furthermore, a system for scoring of the results is proposed as well as measures to be taken for poorly performing laboratories. Proposals are made regarding the content requirements of an EQA report and how its results should be communicated. Finally, the need for an EQA database and a participant manual are elaborated. It is the intention of this guideline to improve EQA for molecular pathology in order to provide more reliable molecular analyses as well as optimal information regarding patient selection for treatment.
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| 6. |
- Kraus, Robert H. S., et al.
(author)
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Genome wide SNP discovery, analysis and evaluation in mallard (Anas platyrhynchos)
- 2011
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In: BMC Genomics. - 1471-2164 .- 1471-2164. ; 12, s. 150-
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Journal article (peer-reviewed)abstract
- Background: Next generation sequencing technologies allow to obtain at low cost the genomic sequence information that currently lacks for most economically and ecologically important organisms. For the mallard duck genomic data is limited. The mallard is, besides a species of large agricultural and societal importance, also the focal species when it comes to long distance dispersal of Avian Influenza. For large scale identification of SNPs we performed Illumina sequencing of wild mallard DNA and compared our data with ongoing genome and EST sequencing of domesticated conspecifics. This is the first study of its kind for waterfowl. Results: More than one billion base pairs of sequence information were generated resulting in a 16x coverage of a reduced representation library of the mallard genome. Sequence reads were aligned to a draft domesticated duck reference genome and allowed for the detection of over 122,000 SNPs within our mallard sequence dataset. In addition, almost 62,000 nucleotide positions on the domesticated duck reference showed a different nucleotide compared to wild mallard. Approximately 20,000 SNPs identified within our data were shared with SNPs identified in the sequenced domestic duck or in EST sequencing projects. The shared SNPs were considered to be highly reliable and were used to benchmark non-shared SNPs for quality. Genotyping of a representative sample of 364 SNPs resulted in a SNP conversion rate of 99.7%. The correlation of the minor allele count and observed minor allele frequency in the SNP discovery pool was 0.72. Conclusion: We identified almost 150,000 SNPs in wild mallards that will likely yield good results in genotyping. Of these, similar to 101,000 SNPs were detected within our wild mallard sequences and similar to 49,000 were detected between wild and domesticated duck data. In the similar to 101,000 SNPs we found a subset of similar to 20,000 SNPs shared between wild mallards and the sequenced domesticated duck suggesting a low genetic divergence. Comparison of quality metrics between the total SNP set (122,000 + 62,000 = 184,000 SNPs) and the validated subset shows similar characteristics for both sets. This indicates that we have detected a large amount (similar to 150,000) of accurately inferred mallard SNPs, which will benefit bird evolutionary studies, ecological studies (e. g. disentangling migratory connectivity) and industrial breeding programs.
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| 7. |
- Kraus, Robert H. S., et al.
(author)
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Genome wide SNP discovery, analysis and evaluation in mallard (Anas platyrhynchos)
- 2011
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In: BMC Genomics. - : BioMed Central Ltd.. - 1471-2164. ; 12
-
Journal article (peer-reviewed)abstract
- Background: Next generation sequencing technologies allow to obtain at low cost the genomic sequence information that currently lacks for most economically and ecologically important organisms. For the mallard duck genomic data is limited. The mallard is, besides a species of large agricultural and societal importance, also the focal species when it comes to long distance dispersal of Avian Influenza. For large scale identification of SNPs we performed Illumina sequencing of wild mallard DNA and compared our data with ongoing genome and EST sequencing of domesticated conspecifics. This is the first study of its kind for waterfowl. Results: More than one billion base pairs of sequence information were generated resulting in a 16x coverage of a reduced representation library of the mallard genome. Sequence reads were aligned to a draft domesticated duck reference genome and allowed for the detection of over 122,000 SNPs within our mallard sequence dataset. In addition, almost 62,000 nucleotide positions on the domesticated duck reference showed a different nucleotide compared to wild mallard. Approximately 20,000 SNPs identified within our data were shared with SNPs identified in the sequenced domestic duck or in EST sequencing projects. The shared SNPs were considered to be highly reliable and were used to benchmark non-shared SNPs for quality. Genotyping of a representative sample of 364 SNPs resulted in a SNP conversion rate of 99.7%. The correlation of the minor allele count and observed minor allele frequency in the SNP discovery pool was 0.72. Conclusion: We identified almost 150,000 SNPs in wild mallards that will likely yield good results in genotyping. Of these, similar to 101,000 SNPs were detected within our wild mallard sequences and similar to 49,000 were detected between wild and domesticated duck data. In the similar to 101,000 SNPs we found a subset of similar to 20,000 SNPs shared between wild mallards and the sequenced domesticated duck suggesting a low genetic divergence. Comparison of quality metrics between the total SNP set (122,000 + 62,000 = 184,000 SNPs) and the validated subset shows similar characteristics for both sets. This indicates that we have detected a large amount (similar to 150,000) of accurately inferred mallard SNPs, which will benefit bird evolutionary studies, ecological studies (e. g. disentangling migratory connectivity) and industrial breeding programs.
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| 8. |
- Rubin, Carl-Johan, et al.
(author)
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Strong signatures of selection in the domestic pig genome
- 2012
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In: 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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Journal article (peer-reviewed)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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| 9. |
- Beauchamp, Jonathan P, et al.
(author)
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Molecular Genetics and Economics
- 2011
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In: Journal of Economic Perspectives. - : American Economic Association. - 0895-3309. ; 25:4, s. 57-82
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Journal article (peer-reviewed)abstract
- The costs of comprehensively genotyping human subjects have fallen to the point where major funding bodies, even in the social sciences, are beginning to incorporate genetic and biological markers into major social surveys. How, if at all, should economists use and combine molecular genetic and economic data from these surveys? What challenges arise when analyzing genetically informative data? To illustrate, we present results from a “genome-wide association study” of educational attainment. We use a sample of 7,500 individuals from the Framingham Heart Study; our dataset contains over 360,000 genetic markers per person. We get some initially promising results linking genetic markers to educational attainment, but these fail to replicate in a second large sample of 9,500 people from the Rotterdam Study. Unfortunately such failure is typical in molecular genetic studies of this type, so the example is also cautionary. We discuss a number of methodological challenges that face researchers who use molecular genetics to reliably identify genetic associates of economic traits. Our overall assessment is cautiously optimistic: this new data source has potential in economics. But researchers and consumers of the genoeconomic literature should be wary of the pitfalls, most notably the difficulty of doing reliable inference when faced with multiple hypothesis problems on a scale never before encountered in social science.
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| 10. |
- Cree, I. A., et al.
(author)
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Guidance for laboratories performing molecular pathology for cancer patients
- 2014
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In: Journal of Clinical Pathology. - : BMJ. - 0021-9746 .- 1472-4146. ; 67:11, s. 923-931
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Journal article (peer-reviewed)abstract
- Molecular testing is becoming an important part of the diagnosis of any patient with cancer. The challenge to laboratories is to meet this need, using reliable methods and processes to ensure that patients receive a timely and accurate report on which their treatment will be based. The aim of this paper is to provide minimum requirements for the management of molecular pathology laboratories. This general guidance should be augmented by the specific guidance available for different tumour types and tests. Preanalytical considerations are important, and careful consideration of the way in which specimens are obtained and reach the laboratory is necessary. Sample receipt and handling follow standard operating procedures, but some alterations may be necessary if molecular testing is to be performed, for instance to control tissue fixation. DNA and RNA extraction can be standardised and should be checked for quality and quantity of output on a regular basis. The choice of analytical method(s) depends on clinical requirements, desired turnaround time, and expertise available. Internal quality control, regular internal audit of the whole testing process, laboratory accreditation, and continual participation in external quality assessment schemes are prerequisites for delivery of a reliable service. A molecular pathology report should accurately convey the information the clinician needs to treat the patient with sufficient information to allow for correct interpretation of the result. Molecular pathology is developing rapidly, and further detailed evidence-based recommendations are required for many of the topics covered here.
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