| 1. |
- Andres, Olga, et al.
(författare)
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A microarray system for Y chromosomal and mitochondrial single nucleotide polymorphism analysis in chimpanzee populations
- 2008
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Ingår i: Molecular Ecology Notes. - : Wiley. - 1471-8278 .- 1471-8286 .- 1755-098X .- 1755-0998. ; 8:3, s. 529-539
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Tidskriftsartikel (refereegranskat)abstract
- Chimpanzee populations are diminishing as a consequence of human activities, and as a result this species is now endangered. In the context of conservation programmes, genetic data can add vital information, for instance on the genetic diversity and structure of threatened populations. Single nucleotide polymorphisms (SNP) are biallelic markers that are widely used in human molecular studies and can be implemented in efficient microarray systems. This technology offers the potential of robust, multiplexed SNP genotyping at low reagent cost in other organisms than humans, but it is not commonly used yet in wild population studies. Here, we describe the characterization of new SNPs in Y-chromosomal intronic regions in chimpanzees and also identify SNPs from mitochondrial genes, with the aim of developing a microarray system that permits the simultaneous study of both paternal and maternal lineages. Our system consists of 42 SNPs for the Y chromosome and 45 SNPs for the mitochondrial genome. We demonstrate the applicability of this microarray in a captive population where genotypes accurately reflected its large pedigree. Two wild-living populations were also analysed and the results show that the microarray will be a useful tool alongside microsatellite markers, since it supplies complementary information about population structure and ecology. SNP genotyping using microarray technology, therefore, is a promising approach and may become an essential tool in conservation genetics to help in the management and study of captive and wild-living populations. Moreover, microarrays that combine SNPs from different genomic regions could replace microsatellite typing in the future.
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| 2. |
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| 3. |
- Davies, John R., et al.
(författare)
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An inherited variant in the gene coding for vitamin D-binding protein and survival from cutaneous melanoma: a BioGenoMEL study
- 2014
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Ingår i: Pigment Cell & Melanoma Research. - : Wiley. - 1755-148X .- 1755-1471. ; 27:2, s. 234-243
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Tidskriftsartikel (refereegranskat)abstract
- An association between low serum vitamin D levels and poorer melanoma survival has been reported. We have studied inheritance of a polymorphism of the GC gene, rs2282679, coding for the vitamin D-binding protein, which is associated with lower serum levels of vitamin D, in a meta-analysis of 3137 melanoma patients. The aim was to investigate evidence for a causal relationship between vitamin D and outcome (Mendelian randomization). The variant was not associated with reduced overall survival (OS) in the UK cohort, per-allele hazard ratio (HR) for death 1.23 (95% confidence interval (CI) 0.93, 1.64). In the smaller cohorts, HR in OS analysis was 1.07 (95% CI 0.88, 1.3) and for all cohorts combined, HR for OS was 1.09 (95% CI 0.93, 1.29). There was evidence of increased melanoma-specific deaths in the seven cohorts for which these data were available. The lack of unequivocal findings despite the large sample size illustrates the difficulties of implementing Mendelian randomization.
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| 4. |
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| 5. |
- Grujic, Mirjana, et al.
(författare)
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Protective role of mouse mast cell tryptase Mcpt6 in melanoma.
- 2020
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Ingår i: Pigment Cell & Melanoma Research. - : Wiley. - 1755-1471 .- 1755-148X. ; 33:4, s. 579-590
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Tidskriftsartikel (refereegranskat)abstract
- Tryptase-positive mast cells populate melanomas, but it is not known whether tryptase impacts on melanoma progression. Here we addressed this and show that melanoma growth is significantly higher in tryptase-deficient (Mcpt6-/- ) versus wild-type mice. Histochemical analysis showed that mast cells were frequent in the tumor stroma of both wild-type and Mcpt6-/- mice, and also revealed their presence within the tumor parenchyma. Confocal microscopy analysis revealed that tryptase was taken up by the tumor cells. Further, tryptase-positive granules were released from mast cells and were widely distributed within the tumor tissue, suggesting that tryptase could impact on the tumor microenvironment. Indeed, gene expression analysis showed that the absence of Mcpt6 caused decreased expression of numerous genes, including Cxcl9, Tgtp2, and Gbp10, while the expression of 5p-miR3098 was enhanced. The levels of CXCL9 were lower in serum from Mcpt6-/- versus wild-type mice. In further support of a functional impact of tryptase on melanoma, recombinant tryptase (Mcpt6) was taken up by cultured melanoma cells and caused reduced proliferation. Altogether, our results indicate a protective role of mast cell tryptase in melanoma growth.
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| 6. |
- Gunnarsson, Ulrika, et al.
(författare)
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The Dark brown plumage color in chickens is caused by an 8.3 kb deletion upstream of SOX10.
- 2011
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Ingår i: Pigment cell & melanoma research. - 1755-148X .- 1755-1471.
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Tidskriftsartikel (refereegranskat)abstract
- The Dark brown mutation in chickens reduces expression of black eumelanin and enhances expression of red pheomelanin but only in certain parts of the plumage. Here we present genetic evidence that an 8.3 kb deletion upstream of the SOX10 transcription start site is the causal mutation underlying the Dark brown phenotype. The SOX10 transcription factor has a well-established role in melanocyte biology and is essential for melanocyte migration and survival. Previous studies have demonstrated that the mouse homolog of a highly conserved element within the deleted region is a SOX10 enhancer. The mechanism of action of this mutation remains to be established but one possible scenario is that the deletion leads to reduced SOX10 expression which in turn down-regulates expression of key enzymes in pigment synthesis such as tyrosinase. Lower tyrosinase activity leads to a shift towards a more pheomelanistic (reddish) plumage color, which is the characteristic feature of the Dark brown phenotype.
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| 7. |
- Hellström, Anders R., et al.
(författare)
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Sex-linked barring in chickens is controlled by the CDKN2A/B tumour suppressor locus
- 2010
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Ingår i: Pigment Cell and Melanoma Research. - : Blackwell Publishing Group. - 1755-1471 .- 1755-148X. ; 23:4, s. 521-530
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Tidskriftsartikel (refereegranskat)abstract
- Sex-linked barring, a common plumage colour found in chickens, is characterized by black and white barred feathers. Previous studies have indicated that the white bands are caused by an absence of melanocytes in the feather follicle during the growth of this region. Here we show that Sex-linked barring is controlled by the CDKN2A/B locus, which encodes the INK4b and ARF transcripts. We identified two non-coding mutations in CDKN2A that showed near complete association with the phenotype. Also identified were two missense mutations at highly conserved sites, V9D and R10C, and every bird tested with a confirmed Sex-linked barring phenotype carried one of these missense mutations. Further work is required to determine if one of these or a combined effect of two or more CDKN2A mutations is causing Sex-linked barring. This novel finding provides the first evidence that the tumour suppressor locus CDKN2A/B can affect pigmentation phenotypes and sheds new light on the functional significance of this gene.
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| 8. |
- Hoiom, Veronica, et al.
(författare)
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MC1R variation and melanoma risk in the Swedish population in relation to clinical and pathological parameters
- 2009
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Ingår i: Pigment Cell & Melanoma Research. - 1755-148X .- 1755-1471. ; 22:2, s. 196-204
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Tidskriftsartikel (refereegranskat)abstract
- The genetic background of cutaneous malignant melanoma (CMM) includes both germ line aberrations in high-penetrance genes, like CDKN2A, and allelic variation in low-penetrance genes like the melanocortin-1 receptor gene, MC1R. Red-hair colour associated MC1R alleles (RHC) have been associated with red hair, fair skin and risk of CMM. We investigated MC1R and CDKN2A variation in relation to phenotype, clinical factors and CMM risk in the Swedish population. The study cohort consisted of sporadic primary melanoma patients, familial melanoma patients and a control group. An allele-dose dependent increase in melanoma risk for carriers of variant MC1R alleles (after adjusting for phenotype), with an elevated risk among familial CMM patients, was observed. This elevated risk was found to be significantly associated with an increased frequency of dysplastic nevi (DN) among familial patients compared to sporadic patients. MC1R variation was found to be less frequent among acral lentiginous melanomas (ALM) and dependent on tumour localisation. No association was found between CDKN2A gene variants and general melanoma risk. Two new variants in the POMC gene were identified in red haired individuals without RHC alleles.
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| 9. |
- Li, Jingyi, et al.
(författare)
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A missense mutation in TYRP1 causes the chocolate plumage color in chicken and alters melanosome structure
- 2019
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Ingår i: Pigment Cell & Melanoma Research. - : WILEY. - 1755-1471 .- 1755-148X. ; 32:3, s. 381-390
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Tidskriftsartikel (refereegranskat)abstract
- The chocolate plumage color in chickens is due to a sex-linked recessive mutation, choc, which dilutes eumelanin pigmentation. Because TYRP1 is sex-linked in chickens, and TYRP1 mutations determine brown coat color in mammals, TYRP1 appeared as the obvious candidate gene for the choc mutation. By combining gene mapping with gene capture, a complete association was identified between the chocolate phenotype and a missense mutation leading to a His214Asn change in the ZnA zinc-binding domain of the protein. A diagnostic test confirmed complete association by screening 428 non-chocolate chickens of various origins. This is the first TYRP1 mutation described in the chicken. Electron microscopy analysis showed that melanosomes were more numerous in feather follicles of chocolate chickens but exhibited an abnormal structure characterized by a granular content and an irregular shape. A similar altered morphology was observed on melanosomes of another TYRP1 mutant in birds, the roux mutation of the quail.
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| 10. |
- Nathan, Vaishnavi, et al.
(författare)
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Germline variants in oculocutaneous albinism genes and predisposition to familial cutaneous melanoma
- 2019
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Ingår i: Pigment Cell and Melanoma Research. - : Wiley. - 1755-1471 .- 1755-148X. ; 32:6, s. 854-863
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Tidskriftsartikel (refereegranskat)abstract
- Approximately 1%–2% of cutaneous melanoma (CM) is classified as strongly familial. We sought to investigate unexplained CM predisposition in families negative for the known susceptibility genes using next-generation sequencing of affected individuals. Segregation of germline variants of interest within families was assessed by Sanger sequencing. Several heterozygous variants in oculocutaneous albinism (OCA) genes: TYR, OCA2, TYRP1 and SLC45A2, were present in our CM cohort. OCA is a group of autosomal recessive genetic disorders, resulting in pigmentation defects of the eyes, hair and skin. Missense variants classified as pathogenic for OCA were present in multiple families and some fully segregated with CM. The functionally compromised TYR p.T373K variant was present in three unrelated families. In OCA2, known pathogenic variants: p.V443I and p.N489D, were present in three families and one family, respectively. We identified a likely pathogenic SLC45A2 frameshift variant that fully segregated with CM in a family of four cases. Another four-case family harboured cosegregating variants (p.A24T and p.R153C) of uncertain functional significance in TYRP1. We conclude that rare, heterozygous variants in OCA genes confer moderate risk for CM.
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| 11. |
- Nilsson Sköld, Helen, 1970, et al.
(författare)
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Rapid color change in fish and amphibians - function, regulation, and emerging applications.
- 2013
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Ingår i: Pigment Cell & Melanoma Research. - : Wiley. - 1755-1471 .- 1755-148X. ; 26:1, s. 29-38
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Forskningsöversikt (refereegranskat)abstract
- Physiological color change is important for background matching, thermoregulation as well as signaling and is in vertebrates mediated by synchronous intracellular transport of pigmented organelles in chromatophores. We describe functions of and animal situations where color change occurs. A summary of endogenous and external factors that regulate this color change in fish and amphibians is provided, with special emphasis on extracellular stimuli. We describe not only color change in skin, but also highlight studies on color change that occurs using chromatophores in other areas such as iris and on the inside of the body. In addition, we discuss the growing field that applies melanophores and skin color in toxicology and as biosensors, and point out research areas with future potential.
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| 12. |
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| 13. |
- Orfanidis, Kyriakos, et al.
(författare)
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Evaluation of tubulin β-3 as a novel senescence-associated gene in melanocytic malignant transformation.
- 2017
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Ingår i: Pigment Cell & Melanoma Research. - : Blackwell Munksgaard. - 1755-1471 .- 1755-148X. ; 30:2, s. 243-254
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Tidskriftsartikel (refereegranskat)abstract
- Malignant melanoma might develop from melanocytic nevi in which the growth-arrested state has been broken. We analyzed the gene expression of young and senescent human melanocytes in culture and compared the gene expression data with a dataset from nevi and melanomas. A concordant altered gene expression was identified in 84 genes when comparing the growth-arrested samples with proliferating samples. TUBB3, which encodes the microtubule protein tubulin β-3, showed a decreased expression in senescent melanocytes and nevi and was selected for further studies. Depletion of tubulin β-3 caused accumulation of cells in the G2/M phase and decreased proliferation and migration. Immunohistochemical assessment of tubulin β-3 in benign lesions revealed strong staining in the superficial part of the intradermal components, which faded with depth. In contrast, primary melanomas exhibited staining without gradient in a disordered pattern and strong staining of the invasive front. Our results describe an approach to find clinically useful diagnostic biomarkers to more precisely identify cutaneous malignant melanoma and present tubulin β-3 as a candidate marker. This article is protected by copyright. All rights reserved.
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| 14. |
- Saleiban, Amina, et al.
(författare)
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miR-20b regulates expression of proteinase-activated receptor-1 (PAR-1) thrombin receptor in melanoma cells
- 2014
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Ingår i: Pigment Cell & Melanoma Research. - : Wiley. - 1755-1471 .- 1755-148X. ; 27:3, s. 431-441
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Tidskriftsartikel (refereegranskat)abstract
- The proteinase-activated receptor 1 (PAR-1) plays a central role in melanoma progression and its expression level is believed to correlate with the degree of cancer invasiveness. Here, we show that PAR-1 is post-transcriptionally regulated by miR-20b microRNA in human melanoma cells. PAR-1 was found to be expressed in metastatic melanoma cells but was barely detectable in primary melanoma. By transducing primary melanoma cells with a lentivirus containing a 3-UTR construct of PAR-1 mRNA, we could show that endogenous melanoma microRNAs interacted with PAR-1 3-UTR and silenced a fused luciferase reporter. Transfection of an inhibitor against miR-20b into primary melanoma cells reversed this process. Finally, transfection of miR-20b mimic into metastatic melanoma cells caused downregulation of the luciferase reporter. We conclude that miR-20b regulates expression of melanoma PAR-1 receptor, which may explain the differential expression of PAR-1 observed in human melanoma.
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| 15. |
- Sanna, Adriana, et al.
(författare)
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Tumor genetic heterogeneity analysis of chronic sun-damaged melanoma
- 2020
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Ingår i: Pigment Cell & Melanoma Research. - : Wiley. - 1755-148X .- 1755-1471. ; 33:3, s. 480-489
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Tidskriftsartikel (refereegranskat)abstract
- Chronic sun-damaged (CSD) melanoma represents 10%-20% of cutaneous melanomas and is characterized by infrequent BRAF V600E mutations and high mutational load. However, the order of genetic events or the extent of intra-tumor heterogeneity (ITH) in CSDhigh melanoma is still unknown. Ultra-deep targeted sequencing of 40 cancer-associated genes was performed in 72 in situ or invasive CMM, including 23 CSDhigh cases. In addition, we performed whole exome and RNA sequencing on multiple regions of primary tumor and multiple in-transit metastases from one CSDhigh melanoma patient. We found no significant difference in mutation frequency in melanoma-related genes or in mutational load between in situ and invasive CSDhigh lesions, while this difference was observed in CSDlow lesions. In addition, increased frequency of BRAF V600K, NF1, and TP53 mutations (p < .01, Fisher's exact test) was found in CSDhigh melanomas. Sequencing of multiple specimens from one CSDhigh patient revealed strikingly limited ITH with >95% shared mutations. Our results provide evidence that CSDhigh and CSDlow melanomas are distinct molecular entities that progress via different genetic routes.
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| 16. |
- Schwochow, Doreen, et al.
(författare)
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The feather pattern autosomal barring in chicken is strongly associated with segregation at the MC1R locus
- 2021
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Ingår i: Pigment Cell & Melanoma Research. - : John Wiley & Sons. - 1755-1471 .- 1755-148X. ; 34:6, s. 1015-1028
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Tidskriftsartikel (refereegranskat)abstract
- Color patterns within individual feathers are common in birds but little is known about the genetic mechanisms causing such patterns. Here, we investigate the genetic basis for autosomal barring in chicken, a horizontal striping pattern on individual feathers. Using an informative backcross, we demonstrate that the MC1R locus is strongly associated with this phenotype. A deletion at SOX10, underlying the dark brown phenotype on its own, affects the manifestation of the barring pattern. The coding variant L133Q in MC1R is the most likely causal mutation for autosomal barring in this pedigree. Furthermore, a genetic screen across six different breeds showing different patterning phenotypes revealed that the most striking shared characteristics among these breeds were that they all carried the MC1R alleles Birchen or brown. Our data suggest that the presence of activating MC1R mutations enhancing pigment synthesis is an important mechanism underlying pigmentation patterns on individual feathers in chicken. We propose that MC1R and its antagonist ASIP play a critical role for determining within-feather pigmentation patterns in birds by acting as activator and inhibitor possibly in a Turing reaction-diffusion model.
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| 17. |
- Sturm, Richard A., et al.
(författare)
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Genetics of human iris colour and patterns
- 2009
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Ingår i: Pigment Cell & Melanoma Research. - 1755-1471 .- 1755-148X. ; 22:5, s. 544-562
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Tidskriftsartikel (refereegranskat)abstract
- P>The presence of melanin pigment within the iris is responsible for the visual impression of human eye colouration with complex patterns also evident in this tissue, including Fuchs' crypts, nevi, Wolfflin nodules and contraction furrows. The genetic basis underlying the determination and inheritance of these traits has been the subject of debate and research from the very beginning of quantitative trait studies in humans. Although segregation of blue-brown eye colour has been described using a simple Mendelian dominant-recessive gene model this is too simplistic, and a new molecular genetic perspective is needed to fully understand the biological complexities of this process as a polygenic trait. Nevertheless, it has been estimated that 74% of the variance in human eye colour can be explained by one interval on chromosome 15 that contains the OCA2 gene. Fine mapping of this region has identified a single base change rs12913832 T/C within intron 86 of the upstream HERC2 locus that explains almost all of this association with blue-brown eye colour. A model is presented whereby this SNP, serving as a target site for the SWI/SNF family member HLTF, acts as part of a highly evolutionary conserved regulatory element required for OCA2 gene activation through chromatin remodelling. Major candidate genes possibly effecting iris patterns are also discussed, including MITF and PAX6.
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| 18. |
- Sundström, Elisabeth, et al.
(författare)
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Identification of a melanocyte-specific, microphthalmia-associated transcription factor-dependent regulatory element in the intronic duplication causing hair greying and melanoma in horses
- 2012
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Ingår i: Pigment Cell & Melanoma Research. - 1755-1471 .- 1755-148X. ; 25:1, s. 28-36
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Tidskriftsartikel (refereegranskat)abstract
- Greying with age in horses is an autosomal dominant trait, characterized by hair greying, high incidence of melanoma and vitiligo-like depigmentation. Previous studies have revealed that the causative mutation for this phenotype is a 4.6-kb intronic duplication in STX17 (Syntaxin 17). By using reporter constructs in transgenic zebrafish, we show that a construct containing two copies of the duplicated sequence acts as a strong enhancer in neural crest cells and has subsequent melanophore-specific activity during zebrafish embryonic development whereas a single copy of the duplicated sequence acts as a weak enhancer, consistent with the phenotypic manifestation of the mutation in horses. We further used luciferase assays to investigate regulatory regions in the duplication, to reveal tissue-specific activities of these elements. One region upregulated the reporter gene expression in a melanocyte-specific manner and contained two microphthalmia-associated transcription factor (MITF) binding sites, essential for the activity. Microphthalmia-associated transcription factor regulates melanocyte development, and these binding sites are outstanding candidates for mediating the melanocyte-specific activity of the element. These results provide strong support for the causative nature of the duplication and constitute an explanation for the melanocyte-specific effects of the Grey allele.
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| 19. |
- Verma, Deepti, et al.
(författare)
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Inflammasome polymorphisms confer susceptibility to sporadic malignant melanoma
- 2012
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Ingår i: Pigment Cell & Melanoma Research. - : Blackwell Publishing. - 1755-1471 .- 1755-148X. ; 25:4, s. 506-513
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants of NLRP3 and NLRP1 are known to modulate levels of pro-inflammatory cytokine interleukin (IL)-1 beta. The purpose of this study was to investigate the association of NLRP3/NLRP1 polymorphisms with susceptibility and clinical features of malignant melanoma in a Swedish casecontrol study. Common variants in NLRP3/NLRP1 were investigated in sporadic malignant melanoma patients and healthy controls followed by analysis using logistic regression. NLRP3 variant (rs35829419) was significantly more common in male patients than in controls (OR, 2.22; CI, 1.273.86). Upon stratification, significant association with nodular melanoma was observed (OR, 2.89; CI, 1.336.30), which intensified in male patients (OR 4.03, CI 1.4011.59). The NLRP1 variant (rs12150220) was significantly more common in fair-skinned female patients (OR, 1.85; CI, 1.043.33) and showed strong associations with nodular melanoma (OR, 6.03; CI, 1.3325). Our data suggest that NLRP3/NLRP1 polymorphisms are associated with melanoma susceptibility; these findings warrant validation in other independent populations.
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| 20. |
- Vogel, Celia J., et al.
(författare)
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Cooperative induction of apoptosis in NRAS mutant melanoma by inhibition of MEK and ROCK
- 2015
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Ingår i: Pigment Cell & Melanoma Research. - : Wiley. - 1755-1471 .- 1755-148X. ; 28:3
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Tidskriftsartikel (refereegranskat)abstract
- No effective targeted therapy is currently available for NRAS mutant melanoma. Experimental MEK inhibition is rather toxic and has only limited efficacy in clinical trials. At least in part, this is caused by the emergence of drug resistance, which is commonly seen for single agent treatment and shortens clinical responses. Therefore, there is a dire need to identify effective companion drug targets for NRAS mutant melanoma. Here, we show that at concentrations where single drugs had little effect, ROCK inhibitors GSK269962A or Fasudil, in combination with either MEK inhibitor GSK1120212 (Trametinib) or ERK inhibitor SCH772984 cooperatively caused proliferation inhibition and cell death in vitro. Simultaneous inhibition of MEK and ROCK caused induction of Bim(EL), PARP, and Puma, and hence apoptosis. In vivo, MEK and ROCK inhibition suppressed growth of established tumors. Our findings warrant clinical investigation of the effectiveness of combinatorial targeting of MAPK/ERK and ROCK in NRAS mutant melanoma.
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| 21. |
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| 22. |
- Wäster, Petra, et al.
(författare)
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Extracellular vesicles released by melanocytes after UVA irradiation promote intercellular signaling via miR21
- 2020
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Ingår i: Pigment Cell & Melanoma Research. - : WILEY. - 1755-1471 .- 1755-148X. ; 33:4, s. 542-555
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Tidskriftsartikel (refereegranskat)abstract
- Skin pigmentation is controlled by complex crosstalk between melanocytes and keratinocytes and is primarily induced by exposure to ultraviolet (UV) irradiation. Several aspects of UVA-induced signaling remain to be explored. In skin cells, UVA induces plasma membrane damage, which is repaired by lysosomal exocytosis followed by instant shedding of extracellular vesicles (EVs) from the plasma membrane. The released EVs are taken up by neighboring cells. To elucidate the intercellular crosstalk induced by UVA irradiation, EVs were purified from UVA-exposed melanocytes and added to keratinocytes. Transcriptome analysis of the keratinocytes revealed the activation of TGF-beta and IL-6/STAT3 signaling pathways and subsequent upregulation of microRNA (miR)21. EVs induced phosphorylation of ERK and JNK, reduced protein levels of PDCD4 and PTEN, and augment antiapoptotic signaling. Consequently, keratinocyte proliferation and migration were stimulated and UV-induced apoptosis was significantly reduced. Interestingly, melanoma cells and melanoma spheroids also generate increased amounts of EVs with capacity to stimulate proliferation and migration upon UVA. In conclusion, we present a novel intercellular crosstalk mediated by UVA-induced lysosome-derived EVs leading to the activation of proliferation and antiapoptotic signaling via miR21.
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| 23. |
- Zheng, Guoqiao, et al.
(författare)
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Association between tumor characteristics and second primary cancers with cutaneous melanoma survival : A nationwide cohort study
- 2020
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Ingår i: Pigment Cell and Melanoma Research. - : Wiley. - 1755-1471 .- 1755-148X. ; 33:4, s. 625-632
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Tidskriftsartikel (refereegranskat)abstract
- The increased survival in malignant cutaneous melanoma (melanoma) is probably due to early diagnosis combined with improved treatment most recently. National health campaigns and screening programs for melanoma detection were started in Sweden several decades ago. We want to assess the influence of tumor characteristics, based on the TNM classification, and of second primary cancers on overall survival in melanoma. We used the Swedish Cancer Registry to assess all-cause survival in melanoma from 2003 to 2015. Hazard ratios (HRs) were estimated using multivariable Cox regression models. A total of 19,773 melanoma patients were diagnosed with TNM data. Survival showed a strong improving trend over time (p-trend <.001). T1a was the most common classification (48.0% of all), while higher T class was associated systematically with worse survival (p-trend <.001). For distant metastases, the HR was 3.17, accounting for 0.9% of the patients. Any types of second primary cancers, other than melanoma, were associated with an HR of 2.00, accounted for 6.7% of all cases. Even if melanoma survival in Sweden ranks among the best national rates, the large percentage of patients with advanced tumors (T3b, T4a, and T4b, 17%) and 21% of deaths with T1a call for improved preventive and follow-up strategies.
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| 24. |
- Naurin, Sara, et al.
(författare)
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A microarray for large-scale genomic and transcriptional analyses of the zebra finch (Taeniopygia guttata) and other passerines
- 2008
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Ingår i: Molecular Ecology Notes. - : Wiley. - 1471-8278 .- 1755-098X. ; 8:2, s. 275-281
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Tidskriftsartikel (refereegranskat)abstract
- The microarray technology has revolutionized biological research in the last decade. By monitoring the expression of many genes simultaneously, microarrays can elucidate gene function, as well as scan entire genomes for candidate genes encoding complex traits. However, because of high costs of sequencing and design, microarrays have largely been restricted to a few model species. Cross-species microarray (CSM) analyses, where microarrays are used for other species than the one they were designed for, have had varied success. We have conducted a CSM analysis by hybridizing genomic DNA from the common whitethroat (Sylvia communis) on a newly developed Affymetrix array designed for the zebra finch (Taeniopygia guttata), the Lund-zf array. The results indicate a very high potential for the zebra finch array to act as a CSM utility in other passerine birds. When hybridizing zebra finch genomic DNA, 98% of the gene representatives had higher signal intensities than the background cut-off, and for the common whitethroat, we found the equivalent proportion to be as high as 96%. This was surprising given the fact that finches and warblers diverged 25-50 million years ago, but may be explained by a relatively low sequence divergence between passerines (89-93%). Passerine birds are widely used in studies of ecology and evolution, and a zebra finch array that can be used for many species may have a large impact on future research directions.
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| 25. |
- Lindell, Johan, et al.
(författare)
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Simple identification of mitochondrial lienages in contact zones based on lineage-selective primers
- 2008
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Ingår i: Molecular Ecology Resources. - : Wiley. - 1755-098X .- 1755-0998. ; 8:1, s. 66-73
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Tidskriftsartikel (refereegranskat)abstract
- A variety of research projects focus on genetic variation among and within maternal lineages as encompassed by mitochondrial DNA (mtDNA). While mtDNA often differs substantially between species, large differences may also be found within species. The evaluation of such divergent lineages, for example in intraspecific contact zones (hybrid zones), commonly involves sequencing numerous individuals. Large-scale sequencing is both expensive and labour-intensive. Based on sequences from 15 individuals, we devised a simple and quick polymerase chain reaction assay for identification of divergent mtDNA lineages in a secondary contact zone of the side-blotched lizard (Uta stansburiana). The application uses lineage-selective primers to amplify a lineage-diagnostic product, and is based on each group of mtDNA haplotypes being a monophyletic assemblage of haplotypes sharing the same maternal ancestry, deeply divergent from the other group. The assay was tested on a larger sample (n = 147) of specimens from the contact zone, confirming its usefulness in quick and reliable identification of mtDNA lineages. This approach can be modified for other species, provided diagnostic lineage variation is available, and may also be performed in simple laboratory settings while conducting fieldwork.
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| 26. |
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| 27. |
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| 28. |
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| 29. |
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| 30. |
- Haas, Fredrik, et al.
(författare)
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Identification of 20 polymorphic microsatellite loci in European crow (Corvus corone) from existing passerine loci
- 2008
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Ingår i: Molecular Ecology Notes. - : Wiley. - 1471-8278 .- 1755-098X. ; 8:4, s. 846-850
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Tidskriftsartikel (refereegranskat)abstract
- The European crow (Corvus corone) occurs in two subspecies (or species) with distinct plumage coloration: the black carrion crow (C. c. corone) and the grey and black hooded crow (C. c. cornix). We tested 42 passerine microsatellite loci for amplification in the European crow and identified 20 loci that were both polymorphic and easy to score. In 50 individuals sampled in the Danish part of the species' pan-European hybrid zone, the number of alleles ranged between two and 21. One locus deviated from Hardy-Weinberg equilibrium and had a high estimated null allele frequency. These 20 loci were highly successful in amplifying polymorphic products also in other crow populations and in another Corvidae species, the rook (Corvus frugilegus).
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| 31. |
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| 32. |
- Karlsson, Oskar, et al.
(författare)
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Retention of the cyanobacterial neurotoxin beta-N-methylamino-l-alanine in melanin and neuromelanin-containing cells : a possible link between Parkinson-dementia complex and pigmentary retinopathy
- 2009
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Ingår i: Pigment cell & melanoma research. - 1755-1471. ; 22:1, s. 120-130
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Tidskriftsartikel (refereegranskat)abstract
- beta-N-methylamino-l-alanine (BMAA), a neurotoxic amino acid produced by cyanobacteria, has been suggested to be involved in the etiology of a neurodegenerative disease complex which includes Parkinson-dementia complex (PDC). In PDC, neuromelanin-containing neurons in substantia nigra are degenerated. Many PDC patients also have an uncommon pigmentary retinopathy. The aim of this study was to investigate the distribution of (3)H-BMAA in mice and frogs, with emphasis on pigment-containing tissues. Using autoradiography, a distinct retention of (3)H-BMAA was observed in melanin-containing tissues such as the eye and neuromelanin-containing neurons in frog brain. Analysis of the binding of (3)H-BMAA to Sepia melanin in vitro demonstrated two apparent binding sites. In vitro-studies with synthetic melanin revealed a stronger interaction of (3)H-BMAA with melanin during synthesis than the binding to preformed melanin. Long-term exposure to BMAA may lead to bioaccumulation in melanin- and neuromelanin-containing cells causing high intracellular levels, and potentially changed melanin characteristics via incorporation of BMAA into the melanin polymer. Interaction of BMAA with melanin may be a possible link between PDC and pigmentary retinopathy.
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| 33. |
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| 34. |
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| 35. |
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| 36. |
- Stromberg, Sara, et al.
(författare)
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Transcriptional profiling of melanocytes from patients with vitiligo vulgaris
- 2008
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Ingår i: Pigment Cell & Melanoma Research. - 1755-1471. ; 21:2, s. 162-171
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Tidskriftsartikel (refereegranskat)abstract
- Vitiligo is a complex, polygenic disorder characterized by patchy loss of skin pigmentation due to abnormal melanocyte function. Both genetic and environmental etiological factors have been proposed for vitiligo and lack of molecular markers renders difficulties to predict development and progression of the disease. Identification of dysregulated genes has the potential to unravel biological pathways involved in vitiligo pathogenesis, facilitating discovery of potential biomarkers and novel therapeutic approaches. In this study, we characterized the transcriptional profile of melanocytes from vitiligo patients. Oligonucleotide microarrays containing similar to 16 000 unique genes were used to analyse mRNA expression in melanocytes from vitiligo patients and age-matched healthy controls. In total, 859 genes were identified as differentially expressed. A substantial number of these genes were involved in (i) melanocyte development, (ii) intracellular processing and trafficking of tyrosinase gene family proteins, (iii) packing and transportation of melanosomes, (iv) cell adhesion and (v) antigen processing and presentation. In conclusion, our results show a significantly different transcription profile in melanocytes from vitiligo patients compared with controls. Several genes of potential importance for the pathogenesis and development of vitiligo were identified. Our data indicate that autoimmunity involving melanocytes may be a secondary event in vitiligo patients caused by abnormal melanocyte function.
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| 37. |
- Bourlat, Sarah, et al.
(författare)
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Feeding ecology of Xenoturbella bocki (phylum Xenoturbellida) revealed by genetic barcoding
- 2008
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Ingår i: Molecular Ecology Resources. - 1755-098X. ; 8, s. 18-22
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Tidskriftsartikel (refereegranskat)abstract
- The benthic marine worm Xenoturbella is frequently contaminated with molluscan DNA, which had earlier caused confusion resulting in a suggested bivalve relationship. In order to find the source of the contaminant, we have used molluscan sequences derived from Xenoturbella and compared them to barcodes obtained from several individuals of the nonmicroscopic molluscs sharing the same environment as Xenoturbella. Using cytochrome oxidase 1, we found the contaminating sequences to be 98% similar to the bivalve Ennucula tenuis. Using the highly variable D1-D2 region of the large ribosomal subunit in Xenoturbella, we found three distinct species of contaminating molluscs, one of which is 99% similar to the bivalve Abra nitida, one of the most abundant bivalves in the Gullmarsfjord where Xenoturbella was found, and another 99% similar to the bivalve Nucula sulcata. These data clearly show that Xenoturbella only contains molluscan DNA originating from bivalves living in the same environment, refuting former hypotheses of a bivalve relationship. In addition, these data suggest that Xenoturbella feeds specifically on bivalve prey from multiple species, possibly in the form of eggs and larvae.
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