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| 2. |
- Deans, Andrew R, et al.
(författare)
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Finding Our Way through Phenotypes.
- 2015
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Ingår i: PLoS Biology. - : Public Library of Science (PLoS). - 1545-7885. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Despite a large and multifaceted effort to understand the vast landscape of phenotypic data, their current form inhibits productive data analysis. The lack of a community-wide, consensus-based, human- and machine-interpretable language for describing phenotypes and their genomic and environmental contexts is perhaps the most pressing scientific bottleneck to integration across many key fields in biology, including genomics, systems biology, development, medicine, evolution, ecology, and systematics. Here we survey the current phenomics landscape, including data resources and handling, and the progress that has been made to accurately capture relevant data descriptions for phenotypes. We present an example of the kind of integration across domains that computable phenotypes would enable, and we call upon the broader biology community, publishers, and relevant funding agencies to support efforts to surmount today's data barriers and facilitate analytical reproducibility.
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| 3. |
- Figlioli, G, et al.
(författare)
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The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer
- 2019
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Ingår i: NPJ breast cancer. - : Springer Science and Business Media LLC. - 2374-4677. ; 5, s. 38-
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Tidskriftsartikel (refereegranskat)abstract
- Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors.
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| 4. |
- Höglund, Jacob, et al.
(författare)
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Blood transcriptomes and de novo identification of candidate loci for mating success in lekking great snipe (Gallinago media)
- 2017
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Ingår i: Molecular Ecology. - : Wiley. - 0962-1083 .- 1365-294X. ; 26:13, s. 3458-3471
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Tidskriftsartikel (refereegranskat)abstract
- We assembled the great snipe blood transcriptome using data from fourteen lekking males, in order to de novo identify candidate genes related to sexual selection, and determined the expression profiles in relation to mating success. The three most highly transcribed genes were encoding different haemoglobin subunits. All tended to be overexpressed in males with high mating success. We also called single nucleotide polymorphisms (SNPs) from the transcriptome data and found considerable genetic variation for many genes expressed during lekking. Among these, we identified 14 polymorphic candidate SNPs that had a significant genotypic association with mating success (number of females mated with) and/or mating status (mated or not). Four of the candidate SNPs were found in HBAA (encoding the haemoglobin a-chain). Heterozygotes for one of these and one SNP in the gene PABPC1 appeared to enjoy higher mating success compared to males homozygous for either of the alleles. In a larger data set of individuals, we genotyped 38 of the identified SNPs but found low support for consistent selection as only one of the zygosities of previously identified candidate SNPs and none of their genotypes were associated with mating status. However, candidate SNPs generally showed lower levels of spatial genetic structure compared to noncandidate markers. We also scored the prevalence of avian malaria in a subsample of birds. Males infected with avian malaria parasites had lower mating success in the year of sampling than noninfected males. Parasite infection and its interaction with specific genes may thus affect performance on the lek.
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| 5. |
- Karlsson, Maria, et al.
(författare)
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House sparrow Passer domesticus survival is not associated with MHC-I diversity, but possibly with specific MHC-I alleles
- 2015
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Ingår i: Journal of Avian Biology. - : Wiley. - 0908-8857 .- 1600-048X. ; 46:2, s. 167-174
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Tidskriftsartikel (refereegranskat)abstract
- The MHC (Major Histocompatibility Complex) plays an important role in the immune system of vertebrates. MHC genes are extremely polymorphic and this variation is considered to be maintained by selection from pathogens. We investigate whether MHC diversity (number of different alleles per individual) affects the survival and recruitment of nestling house sparrows. We hypothesize that individuals with higher MHC diversity can recognize and combat a wider range of pathogens, and therefore are more likely to survive and recruit into the breeding population. Additionally, we hypothesize that specific MHC class I alleles (MHC-I) could be associated with survival and recruitment. We screened MHC-I genotypes in 518 house sparrow chicks hatched on Lundy Island but we found no evidence for a relationship between nestling survival, post-fledging survival or recruitment success with MHC diversity. Then we investigated effects of specific MHC-I alleles in 195 individuals from a single cohort. Twenty-one MHC-I alleles were tested for relationships with nestling survival, post-fledging survival and recruitment, and we detected associations with survival for three different alleles. This pattern was, however, not different to what would be expected from random, so we could not conclude that particular MHC-I alleles are associated with survival in house sparrows on Lundy Island. Nonetheless, one of these alleles (1105) showed both a tendency for a higher probability of surviving in nestlings, and a significant association with survival in fledglings. We envision that allele 1105 could be an interesting candidate gene for testing associations with survival in house sparrows in the future.
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| 7. |
- Meziane, El Kahina, et al.
(författare)
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Bi-Functional Chicken Immunoglobulin-Like Receptors With a Single Extracellular Domain (ChIR-AB1): Potential Framework Genes Among a Relatively Stable Number of Genes Per Haplotype
- 2019
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Ingår i: Frontiers in Immunology. - : FRONTIERS MEDIA SA. - 1664-3224. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- The leukocyte receptor complex (LRC) in humans encodes many receptors with immunoglobulin-like (Ig-like) extracellular domains, including the killer Ig-like receptors (KIRs) expressed on natural killer (NK) cells among others, the leukocyte Ig-like receptors (LILRs) expressed on myeloid and B cells, and an Fc receptor (FcR), all of which have important roles in the immune response. These highly-related genes encode activating receptors with positively-charged residues in the transmembrane region, inhibitory receptors with immuno-tyrosine based motifs (ITIMs) in the cytoplasmic tail, and bi-functional receptors with both. The related chicken Ig-like receptors (ChIRs) are almost all found together on a microchromosome, with over 100 activating (A), inhibitory (B), and bi-functional (AB) genes, bearing either one or two extracellular Ig-like domains, interspersed over 500-1,000 kB in the genome of an individual chicken. Sequencing studies have suggested rapid divergence and little overlap between ChIR haplotypes, so we wished to begin to understand their genetics. We chose to use a hybridization technique, reference strand-mediated conformational analysis (RSCA), to examine the ChIR-AB1 family, with a moderate number of genes dispersed across the microchromosome. Using fluorescently-labeled references (FLR), we found that RSCA and sequencing of ChIR-AB1 extracellular exon gave two groups of peaks with mobility correlated with sequence relationship to the FLR. We used this system to examine widely-used and well-characterized experimental chicken lines, finding only one or a few simple ChIR haplotypes for each line, with similar numbers of peaks overall. We found much more complicated patterns from a broiler line from a commercial breeder and a flock of red junglefowl, but trios of parents and offspring from another commercial chicken line show that the complicated patterns are due to heterozygosity, indicating a relatively stable number of peaks within haplotypes of these birds. Some ChIR-AB1 peaks were found in all individuals from the commercial lines, and some of these were shared with red junglefowl and the experimental lines derived originally from egg-laying chickens. Overall, this analysis suggests that there are some simple features underlying the apparent complexity of the ChIR locus.
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| 8. |
- Razali, Haslina, et al.
(författare)
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A quantitative and qualitative comparison of illumina MiSeq and 454 amplicon sequencing for genotyping the highly polymorphic major histocompatibility complex (MHC) in a non‑model species
- 2017
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Ingår i: BMC Research Notes. - : Springer Science and Business Media LLC. - 1756-0500. ; 10:1, s. 346-356
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Tidskriftsartikel (refereegranskat)abstract
- Background: High-throughput sequencing enables high-resolution genotyping of extremely duplicated genes.454 amplicon sequencing (454) has become the standard technique for genotyping the major histocompatibilitycomplex (MHC) genes in non-model organisms. However, illumina MiSeq amplicon sequencing (MiSeq), which offersa much higher read depth, is now superseding 454. The aim of this study was to quantitatively and qualitativelyevaluate the performance of MiSeq in relation to 454 for genotyping MHC class I alleles using a house sparrow (Passerdomesticus) dataset with pedigree information. House sparrows provide a good study system for this comparison astheir MHC class I genes have been studied previously and, consequently, we had prior expectations concerning thenumber of alleles per individual.Results: We found that 454 and MiSeq performed equally well in genotyping amplicons with low diversity, i.e. ampliconsfrom individuals that had fewer than 6 alleles. Although there was a higher rate of failure in the 454 dataset inresolving amplicons with higher diversity (6–9 alleles), the same genotypes were identified by both 454 and MiSeq in98% of cases.Conclusions: We conclude that low diversity amplicons are equally well genotyped using either 454 or MiSeq,but the higher coverage afforded by MiSeq can lead to this approach outperforming 454 in amplicons with higherdiversity.
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| 9. |
- Wielstra, Ben, et al.
(författare)
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A genomic footprint of hybrid zone movement in crested newts.
- 2017
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Ingår i: Evolution letters. - : Oxford University Press (OUP). - 2056-3744. ; 1:2, s. 93-101
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Tidskriftsartikel (refereegranskat)abstract
- Speciation typically involves a stage in which species can still exchange genetic material. Interspecific gene flow is facilitated by the hybrid zones that such species establish upon secondary contact. If one member of a hybridizing species pair displaces the other, their hybrid zone would move across the landscape. Although theory predicts that moving hybrid zones quickly stagnate, hybrid zones tracked over one or a few decades do not always follow such a limitation. This suggests that hybrid zones have the potential to traverse considerable distances over extended periods of time. When hybrid zones move, introgression is predicted to result in biased gene flow of selectively neutral alleles, from the receding species into the advancing species. We test for such a genomic footprint of hybrid zone movement in a pair of crested newt species (genus Triturus) for which we have a priori support for westward hybrid zone movement. We perform a multilocus phylogeographical survey and conduct Bayesian clustering analysis, estimation of ancestry and heterozygosity, and geographical cline analysis. In a 600 km wide area east of the present day hybrid zone a genomic footprint constitutes empirical evidence consistent with westward hybrid zone movement. The crested newt case suggests that hybrid zone movement can occur over an extensive span of time and space. Inferring hybrid zone movement provides fundamental insight into historical biogeography and the speciation process, and we anticipate that hybrid zones will prove to be far more mobile than currently appreciated.
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