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1. Stimuli-Responsive Non-viral Nanoparticles for Gene Delivery

Author

Reichel, Liên S., Traeger, Anja, Michel, Martin C., Editor-in-Chief, Barrett, James E., Editorial Board Member, Centurión, David, Editorial Board Member, Flockerzi, Veit, Editorial Board Member, Meier, Kathryn Elaine, Editorial Board Member, Page, Clive P., Editorial Board Member, Seifert, Roland, Editorial Board Member, Wang, KeWei, Editorial Board Member, Schäfer-Korting, Monika, editor, and Schubert, Ulrich S., editor

Published
2024
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15. Genetic analysis of avian influenza A viruses isolated from domestic waterfowl in live-bird markets of Hanoi, Vietnam, preceding fatal H5N1 human infections in 2004

Author

Jadhao, Samadhan J., Nguyen, Doan C., Uyeki, Timothy M., Shaw, Michael, Maines, Taronna, Rowe, Thomas, Smith, Catherine, Huynh, Lien P. T., Nghiem, Ha K., Nguyen, Diep H. T., Nguyen, Hang K. L., Nguyen, Hanh H. T., Hoang, Long T., Nguyen, Tung, Phuong, Lien S., Klimov, Alexander, Tumpey, Terrence M., Cox, Nancy J., Donis, Ruben O., Matsuoka, Yumiko, and Katz, Jacqueline M.

Published
2009
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17. Consistent scaling of inbreeding depression in space and time in a house sparrow metapopulation

Author

Niskanen, A. K. (Alina K.), Billing, A. M. (Anna M.), Holand, H. (Håkon), Hagen, I. J. (Ingerid J.), Araya-Ajoy, Y. G. (Yimen G.), Husby, A. (Arild), Rønning, B. (Bernt), Myhre, A. M. (Ane Marlene), Ranke, P. S. (Peter Sjolte), Kvalnes, T. (Thomas), Pärn, H. (Henrik), Ringsby, T. H. (Thor Harald), Lien, S. (Sigbjørn), Sæther, B.-E. (Bernt-Erik), Muff, S. (Stefanie), and Jensen, H. (Henrik)

Subjects
house sparrow, metapopulation, SNP pedigree, individual fitness, inbreeding depression
Abstract

Inbreeding may increase the extinction risk of small populations. Yet, studies using modern genomic tools to investigate inbreeding depression in nature have been limited to single populations, and little is known about the dynamics of inbreeding depression in subdivided populations over time. Natural populations often experience different environmental conditions and differ in demographic history and genetic composition, characteristics that can affect the severity of inbreeding depression. We utilized extensive long-term data on more than 3,100 individuals from eight islands in an insular house sparrow metapopulation to examine the generality of inbreeding effects. Using genomic estimates of realized inbreeding, we discovered that inbred individuals had lower survival probabilities and produced fewer recruiting offspring than noninbred individuals. Inbreeding depression, measured as the decline in fitness-related traits per unit inbreeding, did not vary appreciably among populations or with time. As a consequence, populations with more resident inbreeding (due to their demographic history) paid a higher total fitness cost, evidenced by a larger variance in fitness explained by inbreeding within these populations. Our results are in contrast to the idea that effects of inbreeding generally depend on ecological factors and genetic differences among populations, and expand the understanding of inbreeding depression in natural subdivided populations.

Published
2020

18. A genome‐wide linkage map for the house sparrow (Passer domesticus) provides insights into the evolutionary history of the avian genome

Author

Hagen, I. J. (Ingerid J.), Lien, S. (Sigbjørn), Billing, A. M. (Anna M.), Elgvin, T. O. (Tore O.), Trier, C. (Cassandra), Niskanen, A. K. (Alina K.), Tarka, M. (Maja), Slate, J. (Jon), Sætre, G.-P. (Glenn-Peter), Jensen, H. (Henrik), Hagen, I. J. (Ingerid J.), Lien, S. (Sigbjørn), Billing, A. M. (Anna M.), Elgvin, T. O. (Tore O.), Trier, C. (Cassandra), Niskanen, A. K. (Alina K.), Tarka, M. (Maja), Slate, J. (Jon), Sætre, G.-P. (Glenn-Peter), and Jensen, H. (Henrik)

Abstract

The house sparrow is an important model species for studying physiological, ecological and evolutionary processes in wild populations. Here, we present a medium density, genome wide linkage map for house sparrow (Passer domesticus) that has aided the assembly of the house sparrow reference genome, and that will provide an important resource for ongoing mapping of genes controlling important traits in the ecology and evolution of this species. Using a custom house sparrow 10 K iSelect Illumina SNP chip we have assigned 6,498 SNPs to 29 autosomal linkage groups, based on a mean of 430 informative meioses per SNP. The map was constructed by combining the information from linkage with that of the physical position of SNPs within scaffold sequences in an iterative process. Averaged between the sexes; the linkage map had a total length of 2,004 cM, with a longer map for females (2,240 cM) than males (1,801 cM). Additionally, recombination rates also varied along the chromosomes. Comparison of the linkage map to the reference genomes of zebra finch, collared flycatcher and chicken, showed a chromosome fusion of the two avian chromosomes 8 and 4A in house sparrow. Lastly, information from the linkage map was utilized to conduct analysis of linkage disequilibrium (LD) in eight populations with different effective population sizes (Ne) in order to quantify the background level LD. Together, these results aid the design of future association studies, facilitate the development of new genomic tools and support the body of research that describes the evolution of the avian genome.

Published
2020

21. Recurrent and novel fusions detected by targeted RNA sequencing as part of the diagnostic workflow of soft tissue and bone tumours

Author

Rafael Zago Baltazar, Sofie Claerhout, Sara Vander Borght, Lien Spans, Raphael Sciot, Patrick Schöffski, Daphne Hompes, Friedl Sinnaeve, Hazem Wafa, Marleen Renard, Mari FCM van den Hout, Astrid Vernemmen, Louis Libbrecht, An‐Katrien De Roo, Filomena Mazzeo, Cédric van Marcke, Karen Deraedt, Claire Bourgain, and Isabelle Vanden Bempt

Subjects
RNA‐seq, soft tissue tumours, bone tumours, sarcomas, FISH, Pathology, RB1-214
Abstract

Abstract The identification of gene fusions has become an integral part of soft tissue and bone tumour diagnosis. We investigated the added value of targeted RNA‐based sequencing (targeted RNA‐seq, Archer FusionPlex) to our current molecular diagnostic workflow of these tumours, which is based on fluorescence in situ hybridisation (FISH) for the detection of gene fusions using 25 probes. In a series of 131 diagnostic samples targeted RNA‐seq identified a gene fusion, BCOR internal tandem duplication or ALK deletion in 47 cases (35.9%). For 74 cases, encompassing 137 FISH analyses, concordance between FISH and targeted RNA‐seq was evaluated. A positive or negative FISH result was confirmed by targeted RNA‐seq in 27 out of 49 (55.1%) and 81 out of 88 (92.0%) analyses, respectively. While negative concordance was high, targeted RNA‐seq identified a canonical gene fusion in seven cases despite a negative FISH result. The 22 discordant FISH‐positive analyses showed a lower percentage of rearrangement‐positive nuclei (range 15–41%) compared to the concordant FISH‐positive analyses (>41% of nuclei in 88.9% of cases). Six FISH analyses (in four cases) were finally considered false positive based on histological and targeted RNA‐seq findings. For the EWSR1 FISH probe, we observed a gene‐dependent disparity (p = 0.0020), with 8 out of 35 cases showing a discordance between FISH and targeted RNA‐seq (22.9%). This study demonstrates an added value of targeted RNA‐seq to our current diagnostic workflow of soft tissue and bone tumours in 19 out of 131 cases (14.5%), which we categorised as altered diagnosis (3 cases), added precision (6 cases), or augmented spectrum (10 cases). In the latter subgroup, four novel fusion transcripts were found for which the clinical relevance remains unclear: NAB2::NCOA2, YAP1::NUTM2B, HSPA8::BRAF, and PDE2A::PLAG1. Overall, targeted RNA‐seq has proven extremely valuable in the diagnostic workflow of soft tissue and bone tumours.

Published
2024
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38. Cumulin and FSH cooperate to regulate inhibin B and activin B production by human granulosa-lutein cells in vitro

Author

Richani, D, Constance, K, Lien, S, Agapiou, D, Stocker, WA, Hedger, MP, Ledger, WL, Thompson, JG, Robertson, DM, Mottershead, DG, Walton, KL, Harrison, CA, Gilchrist, RB, Richani, D, Constance, K, Lien, S, Agapiou, D, Stocker, WA, Hedger, MP, Ledger, WL, Thompson, JG, Robertson, DM, Mottershead, DG, Walton, KL, Harrison, CA, and Gilchrist, RB

Abstract

The oocyte-secreted factors bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9) interact functionally, and it is hypothesized that this interaction may be mediated by formation of a GDF9:BMP15 heterodimer termed cumulin. GDF9 and BMP15 regulate folliculogenesis and ovulation rate and have been shown to regulate inhibin and activin, local regulators of folliculogenesis. The objective of this study was to determine whether cumulin regulates granulosa cell inhibin and activin production and whether this requires cooperation with FSH. Human granulosa-lutein (hGL) cells collected from patients undergoing in vitro fertilization were cultured with or without FSH with various forms of recombinant cumulin (native and cysteine mutants, with or without the prodomains), and cysteine mutant GDF9 or BMP15. Messenger RNA expression of the subunits of inhibins/activins (INHA, INHBA, INHBB) and secretion of inhibin A, inhibin B, and activin B were measured. Mature forms and proforms of cumulin stimulated comparable INHBB mRNA expression and secretion of inhibin B and activin B, whereas GDF9 or BMP15 exhibited no effect. Cumulin, but not GDF9 or BMP15, interacted synergistically with FSH to increase INHBB mRNA and inhibin B expression. FSH markedly stimulated INHA, which encodes the α subunit of inhibin A/B, and suppressed activin B. Cumulin with or without FSH did not significantly alter inhibin A. Together these data demonstrate that cumulin, but not GDF9 or BMP15, exerts paracrine control of FSH-induced regulation of inhibin B and activin B. The prodomains of cumulin may have a minimal role in its actions on granulosa cells.

Published
2019

39. Strong selection pressures maintain divergence on genomic islands in Atlantic cod (Gadus morhua L.) populations

Author

Rodriguez-Ramilo, ST, Baranski, M, Moghadam, H, Grove, H, Lien, S, Goddard, ME, Meuwissen, THE, Sonesson, AK, Rodriguez-Ramilo, ST, Baranski, M, Moghadam, H, Grove, H, Lien, S, Goddard, ME, Meuwissen, THE, and Sonesson, AK

Abstract

BACKGROUND: Two distinct populations have been extensively studied in Atlantic cod (Gadus morhua L.): the Northeast Arctic cod (NEAC) population and the coastal cod (CC) population. The objectives of the current study were to identify genomic islands of divergence and to propose an approach to quantify the strength of selection pressures using whole-genome single nucleotide polymorphism (SNP) data. After applying filtering criteria, information on 93 animals (9 CC individuals, 50 NEAC animals and 34 CC × NEAC crossbred individuals) and 3,123,434 autosomal SNPs were used. RESULTS: Four genomic islands of divergence were identified on chromosomes 1, 2, 7 and 12, which were mapped accurately based on SNP data and which extended in size from 11 to 18 Mb. These regions differed considerably between the two populations although the differences in the rest of the genome were small due to considerable gene flow between the populations. The estimates of selection pressures showed that natural selection was substantially more important than genetic drift in shaping these genomic islands. Our data confirmed results from earlier publications that suggested that genomic islands are due to chromosomal rearrangements that are under strong selection and reduce recombination between rearranged and non-rearranged segments. CONCLUSIONS: Our findings further support the hypothesis that selection and reduced recombination in genomic islands may promote speciation between these two populations although their habitats overlap considerably and migrations occur between them.

Published
2019

43. Comprehensive linkage map of bovine chromosome 11

Author

Casas, E., Bennett, G. L., Bottema, C. D. K., Crawford, A., Kalm, E., Kappes, S. M., Kister, A., Lewin, H. A., Lien, S., Morris, C. A., Olsaker, I., Pitchford, W. S., Schmutz, S. M., Thomsen, H., and Xu, N.

Published
2001

44. Comprehensive linkage map of bovine chromosome 27

Author

Casas, E., Sonstegard, T. S., Barendse, W., Bennett, G. L., Bottema, C. D. K., Crawford, A., Grosz, M. D., Kalm, E., Kappes, S. M., Kister, A., Li, Y., Lien, S., Morris, C. A., Olsaker, I., Pitchford, W. S., Schmutz, S. M., Thomsen, H., and Xu, N.

Published
2001

48. Bovine chromosome 4 workshop: consensus and comprehensive linkage maps

Author

Casas, E, Barendse, W, Beever, J E, Burns, B M, Davis, S K, Erhardt, G, Förster, M, Gomez-Raya, L, Kalm, E, Kappes, S M, Klungland, H, Lewin, H A, Lien, S, Olsaker, I, Reinsch, N, Schwerin, M, Song, Y, Taylor, J F, Thomsen, H, Våge, D I, Wu, X, Xu, N, and Yeh, C-C

Published
1999

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