| 1. |
- Brawand, David, et al.
(författare)
-
The genomic substrate for adaptive radiation in African cichlid fish
- 2014
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 513:7518, s. 375-381
-
Tidskriftsartikel (refereegranskat)abstract
- Cichlid fishes are famous for large, diverse and replicated adaptive radiations in the Great Lakes of East Africa. To understand themolecular mechanisms underlying cichlid phenotypic diversity, we sequenced the genomes and transcriptomes of five lineages of African cichlids: the Nile tilapia (Oreochromis niloticus), an ancestral lineage with low diversity; and four members of the East African lineage: Neolamprologus brichardi/pulcher (older radiation, Lake Tanganyika), Metriaclima zebra (recent radiation, Lake Malawi), Pundamilia nyererei (very recent radiation, Lake Victoria), and Astatotilapia burtoni (riverine species around Lake Tanganyika). We found an excess of gene duplications in the East African lineage compared to tilapia and other teleosts, an abundance of non-coding element divergence, accelerated coding sequence evolution, expression divergence associated with transposable element insertions, and regulation by novel microRNAs. In addition, we analysed sequence data from sixty individuals representing six closely related species from Lake Victoria, and show genome-wide diversifying selection on coding and regulatory variants, some of which were recruited from ancient polymorphisms. We conclude that a number of molecular mechanisms shaped East African cichlid genomes, and that amassing of standing variation during periods of relaxed purifying selection may have been important in facilitating subsequent evolutionary diversification.
|
|
| 2. |
- Genereux, Diane P., et al.
(författare)
-
A comparative genomics multitool for scientific discovery and conservation
- 2020
-
Ingår i: Nature. - : NATURE RESEARCH. - 0028-0836 .- 1476-4687. ; 587:7833, s. 240-245
-
Tidskriftsartikel (refereegranskat)abstract
- A whole-genome alignment of 240 phylogenetically diverse species of eutherian mammal-including 131 previously uncharacterized species-from the Zoonomia Project provides data that support biological discovery, medical research and conservation. The Zoonomia Project is investigating the genomics of shared and specialized traits in eutherian mammals. Here we provide genome assemblies for 131 species, of which all but 9 are previously uncharacterized, and describe a whole-genome alignment of 240 species of considerable phylogenetic diversity, comprising representatives from more than 80% of mammalian families. We find that regions of reduced genetic diversity are more abundant in species at a high risk of extinction, discern signals of evolutionary selection at high resolution and provide insights from individual reference genomes. By prioritizing phylogenetic diversity and making data available quickly and without restriction, the Zoonomia Project aims to support biological discovery, medical research and the conservation of biodiversity.
|
|
| 3. |
- Lagerwall, Jan P. F., et al.
(författare)
-
Cellulose nanocrystal-based materials : from liquid crystal self-assembly and glass formation to multifunctional thin films
- 2014
-
Ingår i: NPG Asia materials. - : Springer Science and Business Media LLC. - 1884-4049 .- 1884-4057. ; 6
-
Forskningsöversikt (refereegranskat)abstract
- Cellulose nanocrystals (CNCs), produced by the acid hydrolysis of wood, cotton or other cellulose-rich sources, constitute a renewable nanosized raw material with a broad range of envisaged uses: for example, in composites, cosmetics and medical devices. The intriguing ability of CNCs to self-organize into a chiral nematic (cholesteric) liquid crystal phase with a helical arrangement has attracted significant interest, resulting in much research effort, as this arrangement gives dried CNC films a photonic band gap. The films thus acquire attractive optical properties, creating possibilities for use in applications such as security papers and mirrorless lasing. In this critical review, we discuss the sensitive balance between glass formation and liquid crystal self-assembly that governs the formation of the desired helical structure. We show that several as yet unclarified observations-some constituting severe obstacles for applications of CNCs-may result from competition between the two phenomena. Moreover, by comparison with the corresponding self-assembly processes of other rod-like nanoparticles, for example, carbon nanotubes and fd virus particles, we outline how further liquid crystal ordering phenomena may be expected from CNCs if the suspension parameters can be better controlled. Alternative interpretations of some unexpected phenomena are provided, and topics for future research are identified, as are new potential application strategies.
|
|
| 4. |
- Letko, Anna, et al.
(författare)
-
Genome-Wide Analyses for Osteosarcoma in Leonberger Dogs Reveal the CDKN2A/B Gene Locus as a Major Risk Locus
- 2021
-
Ingår i: Genes. - : MDPI. - 2073-4425 .- 2073-4425. ; 12:12
-
Tidskriftsartikel (refereegranskat)abstract
- Dogs represent a unique spontaneous cancer model. Osteosarcoma (OSA) is the most common primary bone tumor in dogs (OMIA 001441-9615), and strongly resembles human forms of OSA. Several large- to giant-sized dog breeds, including the Leonberger, have a greatly increased risk of developing OSA. We performed genome-wide association analysis with high-density imputed SNP genotype data from 273 Leonberger cases with a median age of 8.1 [3.1-13.5] years and 365 controls older than eight years. This analysis revealed significant associations at the CDKN2A/B gene locus on canine chromosome 11, mirroring previous findings in other dog breeds, such as the greyhound, that also show an elevated risk for OSA. Heritability (h(SNP)(2)) was determined to be 20.6% (SE = 0.08; p-value = 5.7 x 10(-4)) based on a breed prevalence of 20%. The 2563 SNPs across the genome accounted for nearly all the h(SNP)(2) of OSA, with 2183 SNPs of small effect, 316 SNPs of moderate effect, and 64 SNPs of large effect. As with many other cancers it is likely that regulatory, non-coding variants underlie the increased risk for cancer development. Our findings confirm a complex genetic basis of OSA, moderate heritability, and the crucial role of the CDKN2A/B locus leading to strong cancer predisposition in dogs. It will ultimately be interesting to study and compare the known genetic loci associated with canine OSA in human OSA.
|
|
| 5. |
|
|
| 6. |
- Noh, Hyun Ji, et al.
(författare)
-
Integrating evolutionary and regulatory information with multispecies approach implicates genes and pathways in obsessive-compulsive disorder
- 2017
-
Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- Obsessive-compulsive disorder is a severe psychiatric disorder linked to abnormalities in glutamate signaling and the cortico-striatal circuit. We sequenced coding and regulatory elements for 608 genes potentially involved in obsessive-compulsive disorder in human, dog, and mouse. Using a new method that prioritizes likely functional variants, we compared 592 cases to 560 controls and found four strongly associated genes, validated in a larger cohort. NRXN1 and HTR2A are enriched for coding variants altering postsynaptic protein-binding domains. CTTNBP2 (synapse maintenance) and REEP3 (vesicle trafficking) are enriched for regulatory variants, of which at least six (35%) alter transcription factor-DNA binding in neuroblastoma cells. NRXN1 achieves genome-wide significance (p = 6.37 x 10(-11)) when we include 33,370 population-matched controls. Our findings suggest synaptic adhesion as a key component in compulsive behaviors, and show that targeted sequencing plus functional annotation can identify potentially causative variants, even when genomic data are limited.
|
|
| 7. |
- Noh, Hyun Ji, et al.
(författare)
-
The Antarctic Weddell seal genome reveals evidence of selection on cardiovascular phenotype and lipid handling
- 2022
-
Ingår i: Communications Biology. - : Springer Nature. - 2399-3642. ; 5:1
-
Tidskriftsartikel (refereegranskat)abstract
- The Weddell seal (Leptonychotes weddellii) thrives in its extreme Antarctic environment. We generated the Weddell seal genome assembly and a high-quality annotation to investigate genome-wide evolutionary pressures that underlie its phenotype and to study genes implicated in hypoxia tolerance and a lipid-based metabolism. Genome-wide analyses included gene family expansion/contraction, positive selection, and diverged sequence (acceleration) compared to other placental mammals, identifying selection in coding and non-coding sequence in five pathways that may shape cardiovascular phenotype. Lipid metabolism as well as hypoxia genes contained more accelerated regions in the Weddell seal compared to genomic background. Top-significant genes were SUMO2 and EP300; both regulate hypoxia inducible factor signaling. Liver expression of four genes with the strongest acceleration signals differ between Weddell seals and a terrestrial mammal, sheep. We also report a high-density lipoprotein-like particle in Weddell seal serum not present in other mammals, including the shallow-diving harbor seal. The Antarctic Weddell inhabits one of the most extreme environments on Earth. Comparative genomics with close relatives reveals the specific genetic adaptations for cardiovascular and fat metabolism that enable it to thrive.
|
|
| 8. |
- Park, Ji Hyun, et al.
(författare)
-
Macroscopic Control of Helix Orientation in Films Dried from Cholesteric Liquid-Crystalline Cellulose Nanocrystal Suspensions
- 2014
-
Ingår i: ChemPhysChem. - : Wiley. - 1439-4235 .- 1439-7641. ; 15:7, s. 1477-1484
-
Tidskriftsartikel (refereegranskat)abstract
- The intrinsic ability of cellulose nanocrystals (CNCs) to self-organize into films and bulk materials with helical order in a cholesteric liquid crystal is scientifically intriguing and potentially important for the production of renewable multifunctional materials with attractive optical properties. A major obstacle, however, has been the lack of control of helix direction, which results in a defect-rich, mosaic-like domain structure. Herein, a method for guiding the helix during film formation is introduced, which yields dramatically improved uniformity, as confirmed by using polarizing optical and scanning electron microscopy. By raising the CNC concentration in the initial suspension to the fully liquid crystalline range, a vertical helix orientation is promoted, as directed by the macroscopic phase boundaries. Further control of the helix orientation is achieved by subjecting the suspension to a circular shear flow during drying.
|
|
| 9. |
- Park, Kwang-Hyun, et al.
(författare)
-
RNA activation-independent DNA targeting of the Type III CRISPR-Cas system by a Csm complex
- 2017
-
Ingår i: EMBO Reports. - : Wiley-VCH Verlagsgesellschaft. - 1469-221X .- 1469-3178. ; 18:5, s. 826-840
-
Tidskriftsartikel (refereegranskat)abstract
- The CRISPR-Cas system is an adaptive and heritable immune response that destroys invading foreign nucleic acids. The effector complex of the Type III CRISPR-Cas system targets RNA and DNA in a transcription-coupled manner, but the exact mechanism of DNA targeting by this complex remains elusive. In this study, an effector Csm holocomplex derived from Thermococcus onnurineus is reconstituted with a minimalistic combination of Csm1(1)2(1)3(3)4(1)5(1), and shows RNA targeting and RNA-activated single-stranded DNA (ssDNA) targeting activities. Unexpectedly, in the absence of an RNA transcript, it cleaves ssDNA containing a sequence complementary to the bound crRNA guide region in a manner dependent on the HD domain of the Csm1 subunit. This nuclease activity is blocked by a repeat tag found in the host CRISPR loci. The specific cleavage of ssDNA without a target RNA suggests a novel ssDNA targeting mechanism of the Type III system, which could facilitate the efficient and complete degradation of foreign nucleic acids.
|
|
| 10. |
- Tang, Ruqi, et al.
(författare)
-
Candidate genes and functional noncoding variants identified in a canine model of obsessive-compulsive disorder
- 2014
-
Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 15:3, s. R25-
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Obsessive-compulsive disorder (OCD), a severe mental disease manifested in time-consuming repetition of behaviors, affects 1 to 3% of the human population. While highly heritable, complex genetics has hampered attempts to elucidate OCD etiology. Dogs suffer from naturally occurring compulsive disorders that closely model human OCD, manifested as an excessive repetition of normal canine behaviors that only partially responds to drug therapy. The limited diversity within dog breeds makes identifying underlying genetic factors easier. Results: We use genome-wide association of 87 Doberman Pinscher cases and 63 controls to identify genomic loci associated with OCD and sequence these regions in 8 affected dogs from high-risk breeds and 8 breed-matched controls. We find 119 variants in evolutionarily conserved sites that are specific to dogs with OCD. These case-only variants are significantly more common in high OCD risk breeds compared to breeds with no known psychiatric problems. Four genes, all with synaptic function, have the most case-only variation: neuronal cadherin (CDH2), catenin alpha2 (CTNNA2), ataxin-1 (ATXN1), and plasma glutamate carboxypeptidase (PGCP). In the 2 Mb gene desert between the cadherin genes CDH2 and DSC3, we find two different variants found only in dogs with OCD that disrupt the same highly conserved regulatory element. These variants cause significant changes in gene expression in a human neuroblastoma cell line, likely due to disrupted transcription factor binding. Conclusions: The limited genetic diversity of dog breeds facilitates identification of genes, functional variants and regulatory pathways underlying complex psychiatric disorders that are mechanistically similar in dogs and humans.
|
|
