| 1. |
- Kimberling, W. J., et al.
(författare)
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Linkage of Usher syndrome type I gene (USH1B) to the long arm of chromosome 11
- 1992
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Ingår i: Genomics. - 0888-7543 .- 1089-8646. ; 14:4, s. 988-994
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Tidskriftsartikel (refereegranskat)abstract
- Usher syndrome is the most commonly recognized cause of combined visual and hearing loss in technologically developed countries. There are several different types and all are inherited in an autosomal recessive manner. There may be as many as five different genes responsible for at least two closely related phenotypes. The nature of the gene defects is unknown, and positional cloning strategies are being employed to identify the genes. This is a report of the localization of one gene for Usher syndrome type I to chromosome 11q, probably distal to marker D11S527. Another USH1 gene had been previously localized to chromosome 14q, and this second localization establishes the existence of a new and independent locus for Usher syndrome.
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| 2. |
- Kimberling, William J., et al.
(författare)
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Localization of Usher syndrome type II to chromosome 1q
- 1990
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Ingår i: Genomics. - : Elsevier BV. - 0888-7543 .- 1089-8646. ; 7:2, s. 245-249
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Tidskriftsartikel (refereegranskat)abstract
- Usher syndrome is characterized by congenital hearing loss, progressive visual impairment due to retinitis pigmentosa, and variable vestibular problems. The two subtypes of Usher syndrome, types I and II, can be distinguished by the degree of hearing loss and by the presence or absence of vestibular dysfunction. Type I is characterized by a profound hearing loss and totally absent vestibular responses, while type II has a milder hearing loss and normal vestibular function. Fifty-five members of eight type II Usher syndrome families were typed for three DNA markers in the distal region of chromosome 1q: D1S65 (pEKH7.4), REN (pHRnES1.9), and D1S81 (pTHH33). Statistically significant linkage was observed for Usher syndrome type II with a maximum multipoint lod score of 6.37 at the position of the marker THH33, thus localizing the Usher type II (USH2) gene to 1q. Nine families with type I Usher syndrome failed to show linkage to the same three markers. The statistical test for heterogeneity of linkage between Usher syndrome types I and II was highly significant, thus demonstrating that they are due to mutations at different genetic loci.
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| 3. |
- Lagerström-Fermér, Maria, et al.
(författare)
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Amelogenin signal peptide mutation : correlation between mutations in the amelogenin gene (AMGX) and manifestations of X-linked amelogenesis imperfecta
- 1995
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Ingår i: Genomics. - : Elsevier BV. - 0888-7543 .- 1089-8646. ; 26:1, s. 159-162
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Tidskriftsartikel (refereegranskat)abstract
- Formation of tooth enamel is a poorly understood biological process. In this study we describe a 9-bp deletion in exon 2 of the amelogenin gene (AMGX) causing X-linked hypoplastic amelogenesis imperfecta, a disease characterized by defective enamel. The mutation results in the loss of 3 amino acids and exchange of 1 in the signal peptide of the amelogenin protein. This deletion in the signal peptide probably interferes with translocation of the amelogenin protein during synthesis, resulting in the thin enamel observed in affected members of the family. We compare this mutation to a previously reported mutation in the amelogenin gene that causes a different disease phenotype. The study illustrates that molecular analysis can help explain the various manifestations of a tooth disorder and thereby provide insights into the mechanisms of tooth enamel formation.
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| 4. |
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| 5. |
- Syvänen, Ann-Christine, et al.
(författare)
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A primer-guided nucleotide incorporation assay in the genotyping of apolipoprotein E
- 1990
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Ingår i: Genomics. - 0888-7543 .- 1089-8646. ; 8:4, s. 684-692
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Tidskriftsartikel (refereegranskat)abstract
- We describe a new technique by which single base changes in human genes can be conveniently detected. In this method the DNA fragment of interest is first amplified using the polymerase chain reaction with an oligonucleotide primer biotinylated at its 5'-end. The amplified 5'-biotinylated DNA is immobilized on an avidin matrix and rendered single-stranded. The variable nucleotide in the immobilized DNA is identified by a one-step primer extension reaction directed by a detection step primer, which anneals to the DNA immediately upstream of the site of variation. In this reaction a single labeled nucleoside triphosphate complementary to the nucleotide at the variable site is incorporated. The method is highly sensitive, allowing the use of nucleoside triphosphates labeled with radioisotopes of low specific activity (3H) as well as nonradioactive markers (digoxigenin). The procedure consists of few and simple operations and is thus applicable to the analysis of large numbers of samples. Here we applied it to the analysis of the three-allelic polymorphism of the human apolipoprotein E gene. We were able to correctly identify all possible combinations of the three apo E alleles.
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| 6. |
- Syvänen, Ann-Christine, et al.
(författare)
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Convenient and quantitative determination of the frequency of a mutant allele using solid-phase minisequencing : application to aspartylglucosaminuria in Finland
- 1992
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Ingår i: Genomics. - 0888-7543 .- 1089-8646. ; 12:3, s. 590-595
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Tidskriftsartikel (refereegranskat)abstract
- Aspartylglucosaminuria (AGU) is a recessively inherited lysosomal disease caused by inadequate aspartylglucosaminidase (AGA) activity. The disease is prevalent in the genetically isolated Finnish population. We have used a new method, solid-phase minisequencing, to determine the frequency of two missense mutations in the AGA gene in this population. In samples from 70% of the Finnish AGU families, we found that the two nucleotide changes were always associated, and they were identified in 98% of the AGU alleles analyzed. Thus, the high prevalence of AGU in the Finnish population is the consequence of a founder effect of one ancient mutation. The identification of asymptomatic carriers by the minisequencing test proved to be unequivocal. The method also allowed quantification of a mutated nucleotide sequence present in less than 1% of a sample. The frequency of AGU carriers in this population was 1/36 when estimated by quantifying the mutated AGU allele in a pooled leukocyte sample from 1350 normal Finnish individuals.
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| 7. |
- Almén, Markus Sällman, et al.
(författare)
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Genome wide analysis reveals association of a FTO gene variant with epigenetic changes
- 2012
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Ingår i: Genomics. - : Elsevier BV. - 0888-7543 .- 1089-8646. ; 99:3, s. 132-137
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Tidskriftsartikel (refereegranskat)abstract
- Variants of the FTO gene show strong association with obesity, but the mechanisms behind this association remain unclear. We determined the genome wide DNA methylation profile in blood from 47 female preadolescents. We identified sites associated with the genes KARS, TERF2IP, DEXI, MSI1,STON1 and BCAS3 that had a significant differential methylation level in the carriers of the FTO risk allele (rs9939609). In addition, we identified 20 differentially methylated sites associated with obesity. Our findings suggest that the effect of the FTO obesity risk allele may be mediated through epigenetic changes. Further, these sites might prove to be valuable biomarkers for the understanding of obesity and its comorbidites.
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| 8. |
- Behboudi, A, et al.
(författare)
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Functional significance of absence : The chromosomal segment harboring the Tp53 gene is missing in the T55 rat radiation hybrid mapping panel
- 2002
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Ingår i: Genomics. - : Academic Press. - 0888-7543 .- 1089-8646. ; 79:6, s. 844-848
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Tidskriftsartikel (refereegranskat)abstract
- The T55 rat radiation hybrid (RH) mapping panel has been reported to retain the entire rat genome at retention frequencies between 22% and 37%. However, we found that a small segment of rat chromosome 10 harboring at least four different genes, including Tp53, was completely absent from the panel (retention frequency = 0%). Two other markers located in the vicinity exhibited much reduced retention (2–6%). RH clones are generated by transferring highly fragmented DNA into a recipient cell. There might be a strong selection against the transfer and retention of chromosome segments harboring an intact Tp53, as the action of this gene might prevent proliferation and establishment of the RH clone. Our finding further suggests that unexpected low retention or absence of chromosome segments in an RH panel may represent indications that the segments harbor genes with important functions in cell proliferation control.
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| 9. |
- Behboudi, Afrouz, 1967, et al.
(författare)
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The functional significance of absence: the chromosomal segment harboring Tp53 is absent from the T55 rat radiation hybrid mapping panel.
- 2002
-
Ingår i: Genomics. - : Elsevier BV. - 0888-7543 .- 1089-8646. ; 79:6, s. 844-8
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Tidskriftsartikel (refereegranskat)abstract
- The T55 rat radiation hybrid (RH) mapping panel has been reported to retain the entire rat genome at retention frequencies between 22% and 37%. However, we found that a small segment of rat chromosome 10 harboring at least four different genes, including Tp53, was completely absent from the panel (retention frequency = 0%). Two other markers located in the vicinity exhibited much reduced retention (2-6%). RH clones are generated by transferring highly fragmented DNA into a recipient cell. There might be a strong selection against the transfer and retention of chromosome segments harboring an intact Tp53, as the action of this gene might prevent proliferation and establishment of the RH clone. Our finding further suggests that unexpected low retention or absence of chromosome segments in an RH panel may represent indications that the segments harbor genes with important functions in cell proliferation control.
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| 10. |
- Biermann, Jana, et al.
(författare)
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A 17-marker panel for global genomic instability in breast cancer.
- 2020
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Ingår i: Genomics. - : Elsevier BV. - 0888-7543 .- 1089-8646. ; 112:2, s. 1151-1161
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Tidskriftsartikel (refereegranskat)abstract
- Genomic instability is a hallmark of cancer that plays a pivotal role in breast cancer development and evolution. A number of existing prognostic gene expression signatures for breast cancer are based on proliferation-related genes. Here, we identified a 17-marker panel associated with genome stability. A total of 136 primary breast carcinomas were stratified by genome stability. Matched gene expression profiles showed an innate segregation based on genome stability. We identified a 17-marker panel stratifying the training and validation cohorts into high- and low-risk patients. The 17 genes associated with genomic instability strongly impacted clinical outcome in breast cancer. Pathway analyses determined chromosome organisation, cell cycle regulation, and RNA processing as the underlying biological processes, thereby offering options for drug development and treatment tailoring. Our work supports the applicability of the 17-marker panel to improve clinical outcome prediction for breast cancer patients based on a signature accounting for genomic instability.
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| 11. |
- Bjarnadóttir, Thóra K., et al.
(författare)
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Comprehensive repertoire and phylogenetic analysis of the G-protein-coupled receptors in human and mouse
- 2006
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Ingår i: Genomics. - : Elsevier BV. - 0888-7543 .- 1089-8646. ; 88:3, s. 263-273
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Tidskriftsartikel (refereegranskat)abstract
- Understanding differences in the repertoire of orthologous gene pairs is vital for interpretation of pharmacological and physiological experiments if conclusions are conveyed between species. Here we present a comprehensive dataset for G protein-coupled receptors (GPCRs) in both human and mouse with a phylogenetic road map. We performed systematic searches applying several search tools such as BLAST, BLAT, and Hidden Markov models and searches in literature data. We aimed to gather a full-length version of each human or mouse GPCR in only one copy referring to a single chromosomal position. Moreover, we performed detailed phylogenetic analysis of the transmembrane regions of the receptors to establish accurate orthologous pairs. The results show the identity of 495 mouse and 400 human functional nonolfactory GPCRs. Overall, 329 of the receptors are found in one-to-one orthologous pairs, while 119 mouse and 31 human receptors originate from species-specific expansions or deletions. The average percentage similarity of the orthologue pairs is 85%, while it varies between the main GRAFS families from an average of 59 to 94%. The orthologous pairs for the lipid-binding GPCRs had the lowest levels of conservation, while the biogenic amines had highest levels of conservation. Moreover, we searched for expressed sequence tags (ESTs) and identified more than 17,000 ESTs matching GPCRs in mouse and human, providing information about their expression patterns. On the whole, this is the most comprehensive study of the gene repertoire that codes for human and mouse GPCRs. The datasets are available for downloading.
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| 12. |
- Bjarnadóttir, Thóra K., et al.
(författare)
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The human and mouse repertoire of the adhesion family of G-protein-coupled receptors
- 2004
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Ingår i: Genomics. - : Elsevier BV. - 0888-7543 .- 1089-8646. ; 84:1, s. 23-33
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Tidskriftsartikel (refereegranskat)abstract
- The adhesion G-protein-coupled receptors (GPCRs) (also termed LN-7TM or EGF-7TM receptors) are membrane-bound proteins with long N-termini containing multiple domains. Here, 2 new human adhesion-GPCRs, termed GPR133 and GPR144, have been found by searches done in the human genome databases. Both GPR133 and GPR144 have a GPS domain in their N-termini, while GPR144 also has a pentraxin domain. The phylogenetic analyses of the 2 new human receptors show that they group together without close relationship to the other adhesion-GPCRs. In addition to the human genes, mouse orthologues to those 2 and 15 other mouse orthologues to human were identified (GPR110, GPR111, GPR112, GPR113, GPR114, GPR115, GPR116, GPR123, GPR124, GPR125, GPR126, GPR128, LEC1, LEC2, and LEC3). Currently the total number of human adhesion-GPCRs is 33. The mouse and human sequences show a clear one-to-one relationship, with the exception of EMR2 and EMR3, which do not seem to have orthologues in mouse. EST expression charts for the entire repertoire of adhesion-GPCRs in human and mouse were established. Over 1600 ESTs were found for these receptors, showing widespread distribution in both central and peripheral tissues. The expression patterns are highly variable between different receptors, indicating that they participate in a number of physiological processes.
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| 13. |
- Cavalli, Marco, et al.
(författare)
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Allele-specific transcription factor binding in liver and cervix cells unveils many likely drivers of GWAS signals
- 2016
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Ingår i: Genomics. - : Elsevier BV. - 0888-7543 .- 1089-8646. ; 107:6, s. 248-254
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) point to regions with associated genetic variants but rarely to a specific gene and therefore detailed knowledge regarding the genes contributing to complex traits and diseases remains elusive. The functional role of GWAS-SNPs is also affected by linkage disequilibrium with many variants on the same haplotype and sometimes in the same regulatory element almost equally likely to mediate the effect. Using ChIP-seq data on many transcription factors, we pinpointed genetic variants in HepG2 and HeLa-S3 cell lines which show a genome-wide significant difference in binding between alleles. We identified a collection of 3713 candidate functional regulatory variants many of which are likely drivers of GWAS signals or genetic difference in expression. A recent study investigated many variants before finding the functional ones at the GALNT2 locus, which we found in our genome-wide screen in HepG2. This illustrates the efficiency of our approach.
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| 14. |
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| 15. |
- Chattopadhyay, Balaji, et al.
(författare)
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Novel genome reveals susceptibility of popular gamebird, the red-legged partridge (Alectoris rufa, Phasianidae), to climate change
- 2021
-
Ingår i: Genomics. - : Elsevier BV. - 0888-7543 .- 1089-8646.
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Tidskriftsartikel (refereegranskat)abstract
- We produced a high-quality de novo genome assembly of the red-legged partridge A. rufa, the first reference genome of its genus, by utilising novel 10× Chromium technology. The estimated genome size was 1.19 Gb with an overall genome heterozygosity of 0.0022; no runs of homozygosity were observed. In total, 21,589 protein coding genes were identified and assigned to 16,772 orthologs. Of these, 201 emerged as unique to Alectoris and were enriched for positive regulation of epithelial cell migration, viral genome integration and maturation. Using PSMC analysis, we inferred a major demographic decline commencing ~140,000 years ago, consistent with forest expansion and reduction of open habitats during the Eemian interglacial. Present-day populations exhibit the historically lowest genetic diversity. Besides implications for management and conservation, this genome also promises key insights into the physiology of these birds with a view to improving poultry husbandry practices.
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| 16. |
- Courseaux, A, et al.
(författare)
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Definition of the minimal MEN 1 candidate area based on a 5-Mb integrated map proximal to 11q13 : The european consortium on men1
- 1996
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Ingår i: Genomics. - : Elsevier BV. - 0888-7543 .- 1089-8646. ; 37:3, s. 345-353
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Tidskriftsartikel (refereegranskat)abstract
- Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder with a high penetrance characterized by tumors of the parathyroid glands, the endocrine pancreas, and the anterior pituitary. The MEN1 gene, a putative tumor suppressor gene, has been mapped to a 3- to 8-cM region in chromosome 11q13 but it remains elusive as yet. We have combined the efforts and resources from four laboratories to form the European Consortium on MEN1 with the aims of establishing the genetic and the physical maps of 11q13 and of further narrowing the MEN1 region. A 5-Mb integrated map of the region was established by fluorescence in situ hybridization on both metaphase chromosomes and DNA fibers, by hybridization to DNA from somatic cell hybrids containing various parts of human chromosome 11, by long-range restriction mapping, and by characterization of YACs and cosmids. Polymorphic markers were positioned and ordered by physical mapping and genetic linkage in 86 MEN1 families with 452 affected individuals. Two critical recombinants identified in two affected cases placed the MEN1 gene in an approximately 2-Mb region around PYGM, flanked by D11S1883 and D11S449.
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| 17. |
- De Bustos, Cecilia, et al.
(författare)
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Analysis of copy number variation in normal human population within a region containing complex segmental duplications on 22q11 using high resolution array-CGH
- 2006
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Ingår i: Genomics. - : Elsevier BV. - 0888-7543 .- 1089-8646. ; 88:2, s. 152-162
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Tidskriftsartikel (refereegranskat)abstract
- A previously detected copy number polymorphism (Ep CNP) in patients affected with neuroectodermal tumors led us to investigate its frequency and length in the normal population. For this purpose, a program called Sequence Allocator was developed and applied for the construction of an array that consisted of unique and duplicated fragments, allowing the assessment of copy number variation within regions of segmental duplications. The average resolution of this array was 11 kb and we determined the size of the Ep CNP to be 290 kb. Analysis of normal controls identified 7.7 and 7.1% gains in peripheral blood and lymphoblastoid cell line (LCL) DNA, respectively, while deletions were found only in the LCL group (7.1%). This array platform allows the detection of DNA copy number variation within regions of pronounced genomic complexity, which constitutes an improvement over available technologies.
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| 18. |
- Dhanya Raj, C.T., et al.
(författare)
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Whole genome sequence analysis and in-vitro probiotic characterization of Bacillus velezensis FCW2 MCC4686 from spontaneously fermented coconut water
- 2023
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Ingår i: Genomics. - : Elsevier. - 0888-7543 .- 1089-8646. ; 115:4
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Tidskriftsartikel (refereegranskat)abstract
- In this study, the probiotic potential of B. velezensis FCW2, isolated from naturally fermented coconut water, was investigated by in vitro and genomic characterization. Our findings highlight key features of the bacterium which includes, antibacterial activity, high adhesive potential, aggregation capacity, production of nutrient secondary metabolites. In vivo safety assessment revealed no adverse effects on zebrafish. WGS data of B. velezensis FCW2 revealed a complete circular genome of 4,147,426 nucleotides and a GC content of 45.87%. We have identified 4059 coding sequence (CDS) genes that encode proteins involved in stress resistance, adhesion and micronutrient production. The genes responsible for producing secondary metabolites, exopolysaccharides, and other beneficial nutrients were identified. The KEGG and COG databases revealed that genes mainly involved amino acid metabolism, carbohydrate utilization, vitamin and cofactor metabolism, and biological adhesion. These findings suggest that B. velezensis FCW2 could be a putative probiotic in the development of fermented foods.
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| 19. |
- Guo, Dongsheng, et al.
(författare)
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The LRIG gene family has three vertebrate paralogs widely expressed in human and mouse tissues and a homolog in ascidiacea
- 2004
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Ingår i: Genomics. - : Elsevier BV. - 0888-7543 .- 1089-8646. ; 84:1, s. 157-165
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Tidskriftsartikel (refereegranskat)abstract
- Human LRIG1 (formerly LIG1), human LRIG2, and mouse Lrig1 (also known as Lig-1) encode integral membrane proteins. The human genes are located at chromosomes 3p14 and 1p13, which are regions frequently deleted in human cancers. We have searched for additional members of the LRIG family and by molecular cloning identified human LRIG3 and its mouse ortholog Lrig3. Human LRIG3 is located at chromosome 12q13. In silico analysis of public databases revealed a mouse Lrig2 mRNA, three LRIG homologs in the puffer fish Fugu rubripes, and one LRIG homolog in the ascidian tunicate Ciona intestinalis. The human and mouse LRIG polypeptides have the same predicted domain organization: a signal peptide, 15 tandem leucine-rich repeats with cysteine-rich N- and C-flanking domains, three immunoglobulin-like domains, a transmembrane domain, and a cytoplasmic tail. The extracellular part—especially the IgC2.2 domain, the transmembrane domain, and the membrane-proximal part of the cytoplasmic tail—are the most conserved regions. Northern blot analysis and real-time RT-PCR revealed that the three LRIG paralogs are widely expressed in human and mouse tissues. In conclusion, the LRIG gene family was found to have three widely expressed mammalian paralogs, corresponding orthologs in fish, and a homolog in Ascidiacea.
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| 20. |
- Haitina, Tatjana, et al.
(författare)
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Fourteen novel human members of mitochondrial solute carrier family 25 (SLC25) widely expressed in the central nervous system
- 2006
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Ingår i: Genomics. - : Elsevier BV. - 0888-7543 .- 1089-8646. ; 88:6, s. 779-790
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Tidskriftsartikel (refereegranskat)abstract
- Members of the solute carrier family 25 (SLC25) are known to transport molecules over the mitochondrial membrane. In this paper we present 14 novel members of SLC25 family in human. These were provided with following gene symbols by the HGNC: SLC25A32, SLC25A33, SLC25A34. SLC25A35, SLC25A37, SLC25A38, SLC25A39, SLC25A40, SLC25A41, SLC25A42, SLC25A43, SLC25A44, SLC25A45, and SLC25A46. We also identified the orthologues for these genes in rat and mouse. Moreover, we found yeast orthologues for 9 of these genes and show that the predicted substrate binding residues are highly conserved in the human and yeast proteins. We performed a comprehensive tissue localization study for 9 of these genes on a panel of 30 rat tissues with quantitative real-time polymerse chain reaction. We detected their mRNA in a wide number of tissues, both in brain and in periphery. This study provides an overall roadmap of the repertoire of the SLC25 family in mammals. showing that there are at least 46 genes in the human genome coding for mitochondrial transporters.
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| 21. |
- Hardy, Matthew P., et al.
(författare)
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Characterization of the type I interferon locus and identification of novel genes
- 2004
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Ingår i: Genomics. - : Elsevier. - 0888-7543 .- 1089-8646. ; 84:2, s. 331-345
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Tidskriftsartikel (refereegranskat)abstract
- The human type I interferon (IFN) genes are clustered on human chromosome 9p21 and the mouse genes are located in the region of conserved synteny on mouse chromosome 4. We have identified two novel mouse Ifna genes (Ifna12, Ifna13) and Ifnl2 (IFN-like 2, a homologue of Limitin/IFN-like 1). Another type I IFN gene was designated Ifne1. Mouse Ifne1 was expressed in ovaries and uterus but not in tissues of hematopoietic origin. IFN-epsilon1 has general structural characteristics of a type I IFN. These studies represent the first detailed annotation of the mouse type I IFN locus, and the products of these novel genes may have important functions in reproduction and host defense.
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| 22. |
- Heidari, Erfan, et al.
(författare)
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Identification of novel loss of function variants in MBOAT7 resulting in intellectual disability.
- 2020
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Ingår i: Genomics. - : Elsevier BV. - 1089-8646 .- 0888-7543. ; 112:6, s. 4072-4077
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Tidskriftsartikel (refereegranskat)abstract
- The membrane bound O-acyltransferase domain-containing 7 (MBOAT7) gene codes for an enzyme involved in regulating arachidonic acid incorporation in lysophosphatidylinositol. Patients with homozygous nonsense mutations in MBOAT7 have intellectual disability (ID) accompanied with seizure and autism. Accumulating evidences obtained from human genetic studies have shown that MBOAT7 is also involved in fatty liver disease. Here we identified two novel homozygous variants in MBOAT7, NM_024298.5: c.1062C>A; p.(Tyr354*) and NM_024298.5: c.1135del; p.(Leu379Trpfs*9), in two unrelated Iranian families by means of whole exome sequencing. Sanger sequencing performed to confirm the identified variants and also investigate whether they co-segregate with the patients' phenotypes. To understand the functional consequences of these changes, we overexpressed recombinant wild type MBOAT7 and mutants in vitro and showed these mutations resulted in abolished protein synthesis and expression, indicating a complete loss of function. Albeit, we did not trace any liver diseases in our patients, but presence of globus pallidus signal changes in Magnetic Resonance Images might be indicative of metabolic changes as a result of loss of MBOAT7 expression in hepatic cells. These signal changes could also help as an important marker of MBOAT7 deficiency while analyzing the genomic data of patients with similar phenotypes.
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| 23. |
- Hellman, Urban, 1966-, et al.
(författare)
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Temporal correlation between transcriptional changes and increased synthesis of hyaluronan in experimental cardiac hypertrophy
- 2010
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Ingår i: Genomics. - : Elsevier BV. - 0888-7543 .- 1089-8646. ; 96:2, s. 73-81
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Tidskriftsartikel (refereegranskat)abstract
- The role of hyaluronan in cardiac growth has become evident, previously shown by increased myocardial levels of hyaluronan in a rat model of cardiac hypertrophy. To further investigate the role of hyaluronan and regulation of its synthesis in cardiac hypertrophy, quantitative measurements of myocardial hyaluronan concentration was correlated to gene transcription in hypertrophic cardiac tissue. Factor analysis was used to study this correlation over time. A subset of differentially expressed genes was identified with a transcriptional regulation correlating to the increased synthesis of hyaluronan, suggesting a common regulatory pathway. Four transcription factors, Myc, Fos, Junb and Egr1, were also up-regulated. Furthermore, the Ace gene was up-regulated, representing increase of angiotensin II, an inducer of these transcription factors and fetal genes in cardiac hypertrophy. This demonstrates a coordinated synthesis of hyaluronan and pro-hypertrophic gene expression, regulated by immediate early genes, with angiotensin II as a possible mediator.
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| 24. |
- Jacobsson, Josefin A., et al.
(författare)
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Identification of six putative human transporters with structural similarity to the drug transporter SLC22 family
- 2007
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Ingår i: Genomics. - : Elsevier BV. - 0888-7543 .- 1089-8646. ; 90:5, s. 595-609
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Tidskriftsartikel (refereegranskat)abstract
- The solute carrier family 22 (SLC22) is a large family of organic cation and anion transporters. These are transmembrane proteins expressed predominantly in kidneys and liver and mediate the uptake and excretion of environmental toxins, endogenous substances, and drugs from the body. Through a comprehensive database search we identified six human proteins not yet cloned or annotated in the reference sequence databases. Five of these belong to the SLC22 family, SLC22A20, SLC22A23, SLC22A24, SLC22A25, and SPNS3, and the sixth gene, SVOPL, is a paralog to the synaptic vesicle protein SVOP. We identified the orthologs for these genes in mouse and rat and additional homologous proteins and performed the first phylogenetic analysis on the entire SLC22 family in human, mouse, and rat. In addition, we performed a phylogenetic analysis which showed that SVOP and SV2A-C are, in a comparison with all vertebrate proteins, most similar to the SLC22 family. Finally, we performed a tissue localization study on 15 genes on a panel of 30 rat tissues using quantitative real-time polymerase chain reaction.
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| 25. |
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| 26. |
- Karsten, Stanislav L., et al.
(författare)
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Two distinct deletions in the IDS gene and the gene W : a novel type of mutation associated with the Hunter syndrome
- 1997
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Ingår i: Genomics. - : Elsevier BV. - 0888-7543 .- 1089-8646. ; 43:2, s. 123-129
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Tidskriftsartikel (refereegranskat)abstract
- A novel mutation has been identified in a patient with the Hunter syndrome (mucopolysaccharidosis type II), in whom the disorder is associated with two distinct deletions separated by 30 kb. The deletions were characterized by Southern blot and PCR analyses, and the nucleotide sequences at both junctions were determined. The first deletion, corresponding to a loss of 3152 bp of DNA, included exons 5 and 6 of the iduronate-2-sulfatase (IDS) gene. The second deletion was 3603 bp long and included exons 3 and 4 of geneW, which is located in the DXS466 locus telomeric of theIDSgene. Both deletions are the result of nonhomologous (illegitimate) recombination events between short direct repeats at the deletion breakpoints. An interesting finding was the presence of the heptamer sequence 5′-TACTCTA-3′ present at both deletion junctions, suggesting that this motif might be a hot spot for recombination. We propose that the double deletion is the result of homology-associated nonhomologous recombinations caused by the presence of large duplicated regions in Xq27.3–q28.
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| 27. |
- Lagerström, Malin C., et al.
(författare)
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Origin of the prolactin-releasing hormone (PRLH) receptors : Evidence of coevolution between PRLH and a redundant neuropeptide Y receptor during vertebrate evolution
- 2005
-
Ingår i: Genomics. - : Elsevier BV. - 0888-7543 .- 1089-8646. ; 85:6, s. 688-703
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Tidskriftsartikel (refereegranskat)abstract
- We present seven new vertebrate homologs of the prolactin-releasing hormone receptor (PRLHR) and show that these are found as two separate subtypes, PRLHR1 and PRLHR2. Analysis of a number of vertebrate sequences using phylogeny, pharmacology, and paralogon analysis indicates that the PRLHRs are likely to share a common ancestry with the neuropeptide Y (NPY) receptors. Moreover, a micromolar level of NPY was able to bind and inhibit completely the PRLH-evoked response in PRLHR1-expressing cells. We suggest that an ancestral PRLH peptide started coevolving with a redundant NPY binding receptor, which then became PRLHR, approximately 500 million years ago. The PRLHR1 subtype was shown to have a relatively high evolutionary rate compared to receptors with fixed peptide preference, which could indicate a drastic change in binding preference, thus supporting this hypothesis. This report suggests how gene duplication events can lead to novel peptide ligand/receptor interactions and hence spur the evolution of new physiological functions.
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| 28. |
- Lagman, David, et al.
(författare)
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Expansion of transducin subunit gene families in early vertebrate tetraploidizations
- 2012
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Ingår i: Genomics. - : Elsevier BV. - 0888-7543 .- 1089-8646. ; 100:4, s. 203-211
-
Tidskriftsartikel (refereegranskat)abstract
- Hundreds of gene families expanded in the early vertebrate tetraploidizations including many gene families in the phototransduction cascade. We have investigated the evolution of the heterotrimeric G-proteins of photoreceptors, the transducins, in relation to these events using both phylogenetic analyses and synteny comparisons. Three alpha subunit genes were identified in amniotes and the coelacanth, GNAT1-3; two of these were identified in amphibians and teleost fish, GNAT1 and GNAT2. Most tetrapods have four beta genes, GNB1-4, and teleosts have additional duplicates. Finally, three gamma genes were identified in mammals, GNGT1, GNG11 and GNGT2. Of these, GNGT1 and GNGT2 were found in the other vertebrates. In frog and zebrafish additional duplicates of GNGT2 were identified. Our analyses show all three transducin families expanded during the early vertebrate tetraploidizations and the beta and gamma families gained additional copies in the teleost-specific genome duplication. This suggests that the tetraploidizations contributed to visual specialisations.
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| 29. |
- Larsson, M., et al.
(författare)
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Expression profile viewer (ExProView) : A software tool for transcriptome analysis
- 2000
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Ingår i: Genomics. - : Elsevier BV. - 0888-7543 .- 1089-8646. ; 63:3, s. 341-353
-
Tidskriftsartikel (refereegranskat)abstract
- A software tool, Expression Profile Viewer (ExProView), for analysis of gene expression profiles derived from expressed sequence tags (ESTs) and SAGE (serial analysis of gene expression) is presented. The software visualizes a complete set of classified transcript data in a two-dimensional array of dots, a virtual chip, in which each dot represents a known gene as characterized in the transcript databases Expressed Gene Anatomy Database or UniGene. The virtual chip display can be changed between representations of different conceptual systems for gene/protein classification and grouping. Four alternative projections are currently available: (i) cellular role, (ii) subcellular compartment, (iii) chromosome localization, and (iv) total UniGene display. However, the chip can be adapted to any other desired layout. By selecting dots, further information about the represented genes is obtained from the local database and WWW links. The software thus provides a visualization of global mRNA expression at the descriptive level and guides in the exploration of patterns of functional expression, while maintaining direct access to detailed information on each individual gene. To evaluate the software, public EST and SAGE gene expression data obtained from the Cancer Genome Anatomy Project at the National Center for Biotechnology Information were analyzed and visualized. A demonstration of the software is available at http://www.biochem.kth. se/exproview/.
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| 30. |
- Larsson, Tomas A., 1978-, et al.
(författare)
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Neuropeptide Y-family peptides and receptors in the elephant shark, Callorhinchus milii confirm gene duplications before the gnathostome radiation
- 2009
-
Ingår i: Genomics. - : Elsevier BV. - 0888-7543 .- 1089-8646. ; 93:3, s. 254-260
-
Tidskriftsartikel (refereegranskat)abstract
- We describe here the repertoire of neuropeptide Y (NPY) peptides and receptors in the elephant shark Callorhinchus milii, belonging to the chondrichthyans that diverged from the rest of the gnathostome (jawed vertebrate) lineage about 450 million years ago and the first chondrichthyan with a genome project. We have identified two peptide genes that are orthologous to NPY and PYY (peptide YY) in other vertebrates, and seven receptor genes orthologous to the Y1, Y2, Y4, Y5, Y6, Y7 and Y8 subtypes found in tetrapods and teleost fishes. The repertoire of peptides and receptors seems to reflect the ancestral configuration in the predecessor of all gnathostomes, whereas other lineages such as mammals and teleosts have lost one or more receptor genes or have acquired 1-2 additional peptide genes. Both the peptides and receptors showed broad and overlapping mRNA expression which may explain why some receptor gene losses could take place in some lineages, but leaves open the question why all the known ancestral receptors have been retained in the elephant shark.
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| 31. |
- Lindberg, Johan, et al.
(författare)
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The plasticity of the mammalian transcriptome
- 2010
-
Ingår i: Genomics. - : Elsevier BV. - 0888-7543 .- 1089-8646. ; 95:1, s. 1-6
-
Forskningsöversikt (refereegranskat)abstract
- The dogmatic view of RNA as a mere necessity in the transfer of information between DNA and proteins has during recent years come into question. Novel approaches and new technology has revealed an unprecedented level of inherent complexity in the mammalian transcriptome. Here, the majority of nucleotides are expressed, in sharp contrast to the similar to 1.2% of the human genome harboring protein coding information. Also, >50% of genomic loci contain antisense and interleaved transcription, a conservative estimate since non-coding RNA is highly regulated between tissues and developmental stages, which has only been investigated to a limited extent. Subsequent focus on RNA with no coding potential has revealed numerous species with novel functions, and deep sequencing studies imply that many remain to be discovered. This review gives an overview of the plasticity and dynamics of the mammalian transcriptome and the prevailing interpretation of its effect on the complexity of species.
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| 32. |
- Liu, Zhengtao, et al.
(författare)
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Multi-omics network analysis on samples from sequential biopsies reveals vital role of proliferation arrest for Macrosteatosis related graft failure in rats after liver transplantation
- 2023
-
Ingår i: Genomics. - : Elsevier BV. - 0888-7543 .- 1089-8646. ; 115:6
-
Tidskriftsartikel (refereegranskat)abstract
- To investigate the molecular impact of graft MaS on post-transplant prognosis, based on multi-omics integrative analysis. Rats were fed by methionine-choline deficient diet (MCD) for MaS grafts. Samples were collected from grafts by sequential biopsies. Transcriptomic and metabolomic profilings were assayed. Post-transplant MaS status showed a close association with graft failure. Differentially expressed genes (DEGs) for in-vivo MaS were mainly enriched on pathways of cell cycle and DNA replication. Post-transplant MaS caused arrests of graft regeneration via inhibiting the E2F1 centered network, which was confirmed by an in vitro experiment. Data from metabolomics assays found insufficient serine/creatine which is located on one‑carbon metabolism was responsible for MaS-related GF. Pre-transplant MaS caused severe fibrosis in long-term survivors. DEGs for grafts from long-term survivors with pre-transplant MaS were mainly enriched in pathways of ECM-receptor interaction and focal adhesion. Transcriptional regulatory network analysis confirmed SOX9 as a key transcription factor (TF) for MaS-related fibrosis. Metabolomic assays found elevation of aromatic amino acid (AAA) was a major feature of fibrosis in long-term survivors. Graft MaS in vivo increased post-transplant GF via negative regulations on graft regeneration. Pre-transplant MaS induced severe fibrosis in long-term survivors via activations on ECM-receptor interaction and AAA metabolism.
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| 33. |
- Lopes, Miguel, et al.
(författare)
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Temporal profiling of cytokine-induced genes in pancreatic beta-cells by meta-analysis and network inference
- 2014
-
Ingår i: Genomics. - : Elsevier BV. - 0888-7543 .- 1089-8646. ; 103:4, s. 264-275
-
Tidskriftsartikel (refereegranskat)abstract
- Type I Diabetes (T1D) is an autoimmune disease where local release of cytokines such as IL-1 beta and IFN-gamma contributes to beta-cell apoptosis. To identify relevant genes regulating this process we performed a meta-analysis of 8 datasets of beta-cell gene expression after exposure to IL-1 beta and IFN-gamma. Two of these datasets are novel and contain time-series expressions in human islet cells and rat INS-1E cells. Genes were ranked according to their differential expression within and after 24 h from exposure, and characterized by function and prior knowledge in the literature. A regulatory network was then inferred from the human time expression datasets, using a time-series extension of a network inference method. The two most differentially expressed genes previously unknown in T1D literature (RIPK2 and ELF3) were found to modulate cytokine-induced apoptosis. The inferred regulatory network is thus supported by the experimental validation, providing a proof-of-concept for the proposed statistical inference approach.
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| 34. |
- López, Maria-Eugenia
(författare)
-
Detection of selection signatures in the genome of a farmed population of anadromous rainbow trout (Oncorhynchus mykiss)
- 2021
-
Ingår i: Genomics. - : Elsevier BV. - 0888-7543 .- 1089-8646. ; 113, s. 3395-3404
-
Tidskriftsartikel (refereegranskat)abstract
- Domestication processes and artificial selection are likely to leave signatures that can be detected at a molecular level in farmed rainbow trout (Oncorhynchus mykiss). These signatures of selection are genomic regions that contain functional genetic variants conferring a higher fitness to their bearers. We genotyped 749 rainbow trout from a commercial population using a rainbow trout Axiom 57 K SNP array panel and identified putative genomic regions under selection using the pcadapt, Composite Likelihood Ratio (CLR) and Integrated Haplotype Score (iHS) methods. After applying quality-control pipelines and statistical analyses, we detected 12, 96 and 16 SNPs putatively under selection, associated with 96, 781 and 115 candidate genes, respectively. Several of these candidate genes were associated with growth, early development, reproduction, behavior and immune system traits. In addition, some of the SNPs were found in interesting regions located in autosomal inversions on Omy05 and Omy20. These findings could represent a genome-wide map of selection signatures in farmed rainbow trout and could be important in explaining domestication and selection for genetic traits of commercial interest.
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| 35. |
- Malmgren, Helena, et al.
(författare)
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Identification of an alternative transcript fromthe human iduronate-2-sulfatase (IDS) gene
- 1995
-
Ingår i: Genomics. - : Elsevier BV. - 0888-7543 .- 1089-8646. ; 29:1, s. 291-293
-
Tidskriftsartikel (refereegranskat)abstract
- Iduronate-2-sulfatase (IDS) is involved in the degradation of heparan sulfate and dermatan sulfate in the lysosomes, and a deficiency in this enzyme results in Hunter syndrome. A 2.3-kb cDNA clone that contains the entire coding sequence of IDS has previously been reported. Here we describe the identification of a 1.4-kb transcript that may encode an IDS-like enzyme. The predicted protein is identical to the previously described enzyme, except for the absence of the 207-amino-acid COOH-terminal domain, which is replaced by 7 amino-acids. Our data suggest that there might exist an additional form of the IDS enzyme in humans. The results from this study may have implications for the pathogenesis of the Hunter syndrome.
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| 36. |
- Martín Hernández, Giselle De La Caridad, et al.
(författare)
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Chromosome-level genome assembly and transcriptome-based annotation of the oleaginous yeast Rhodotorula toruloides CBS 14
- 2021
-
Ingår i: Genomics. - : Elsevier BV. - 0888-7543 .- 1089-8646. ; 113, s. 4022-4027
-
Tidskriftsartikel (refereegranskat)abstract
- Rhodotorula toruloides is an oleaginous yeast with high biotechnological potential. In order to understand the molecular physiology of lipid synthesis in R. toruloides and to advance metabolic engineering, a high-resolution genome is required. We constructed a genome draft of R. toruloides CBS 14, using a hybrid assembly approach, consisting of short and long reads generated by Illumina and Nanopore sequencing, respectively. The genome draft consists of 23 contigs and 3 scaffolds, with a N50 length of 1,529,952 bp, thus largely representing chromosomal organization. The total size of the genome is 20,534,857 bp and the overall GC content is 61.83%. Transcriptomic data from different growth conditions was used to aid species-specific gene annotation. We annotated 9464 genes and identified 11,691 transcripts. Furthermore, we demonstrated the presence of a potential plasmid, an extrachromosomal circular structure of about 11 kb with a copy number about three times as high as the other chromosomes.
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| 37. |
- MotieGhader, Habib, et al.
(författare)
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mRNA and microRNA selection for breast cancer molecular subtype stratification using meta-heuristic based algorithms
- 2020
-
Ingår i: Genomics. - : Elsevier BV. - 0888-7543 .- 1089-8646. ; 112:5, s. 3207-3217
-
Tidskriftsartikel (refereegranskat)abstract
- Cancer subtype stratification, which may help to make a better decision in treating cancerous patients, is one of the most crucial and challenging problems in cancer studies. To this end, various computational methods such as Feature selection, which enhances the accuracy of the classification and is an NP-Hard problem, have been proposed. However, the performance of the applied methods is still low and can be increased by the state-of-the-art and efficient methods. We used 11 efficient and popular meta-heuristic algorithms including WCC, LCA, GA, PSO, ACO, ICA, LA, HTS, FOA, DSOS and CUK along with SVM classifier to stratify human breast cancer molecular subtypes using mRNA and micro-RNA expression data. The applied algorithms select 186 mRNAs and 116 miRNAs out of 9692 mRNAs and 489 miRNAs, respectively. Although some of the selected mRNAs and miRNAs are common in different algorithms results, six miRNAs including miR-190b, miR-18a, miR-301a, miR-34c-5p, miR-18b, and miR-129-5p were selected by equal or more than three different algorithms. Further, six mRNAs, including HAUS6, LAMA2, TSPAN33, PLEKHM3, GFRA3, and DCBLD2, were chosen through two different algorithms. We have reported these miRNAs and mRNAs as important diagnostic biomarkers to the stratification of breast cancer subtypes. By investigating the literature, it is also observed that most of our reported mRNAs and miRNAs have been proposed and introduced as biomarkers in cancer subtypes stratification.
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| 38. |
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| 39. |
- Nilsson, Sven, et al.
(författare)
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Rat–Mouse and Rat–Human Comparative Maps Based on Gene Homology and High-Resolution Zoo-FISH
- 2001
-
Ingår i: Genomics. - : Elsevier BV. - 0888-7543 .- 1089-8646. ; 74:3, s. 287-98
-
Tidskriftsartikel (refereegranskat)abstract
- The laboratory rat, Rattus norvegicus, and the laboratory mouse, Mus musculus, are key animal models in biomedical research. A deeper understanding of the genetic interrelationsships between Homo sapiens and these two rodent species is desirable for extending the usefulness of the animal models. We present comprehensive rat–human and rat–mouse comparative maps, based on 1090 gene homology assignments available for rat genes. Radiation hybrid, FISH, and zoo-FISH mapping data have been integrated to produce comparative maps that are estimated to comprise 83–100% of the conserved regions between rat and mouse and 66–82% of the conserved regions between rat and human. The rat–mouse zoo-FISH analysis, supported by data for individual genes, revealed nine previously undetected conserved regions compared to earlier reports. Since there is almost complete genome coverage in the rat–mouse comparative map, we conclude that it is feasible to make accurate predictions of gene positions in the rat based on gene locations in the mouse.
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| 40. |
- Nordström, Karin, et al.
(författare)
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Extensive duplications of phototransduction genes in early vertebrate evolution correlate with block (chromosome) duplications.
- 2004
-
Ingår i: Genomics. - : Elsevier BV. - 0888-7543 .- 1089-8646. ; 83:5, s. 852-72
-
Tidskriftsartikel (refereegranskat)abstract
- Many gene families in mammals have members that are expressed more or less uniquely in the retina or differentially in specific retinal cell types. We describe here analyses of nine such gene families with regard to phylogenetic relationships and chromosomal location. The families are opsins, G proteins (alpha, beta, and gamma subunits), phosphodiesterases type 6, cyclic nucleotide-gated channels, G-protein-coupled receptor kinases, arrestins, and recoverins. The results suggest that multiple new gene copies arose in all of these families very early in vertebrate evolution during a period with extensive gene duplications. Many of the new genes arose through duplications of large chromosome regions (blocks of genes) or even entire chromosomes, as shown by linkage with other gene families. Some of the phototransduction families belong to the same duplicated regions and were thus duplicated simultaneously. We conclude that gene duplications in early vertebrate evolution probably helped facilitate the specialization of the retina and the subspecialization of different retinal cell types.
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| 41. |
- Nordström, Karl J V, et al.
(författare)
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Critical evaluation of the FANTOM3 non-coding RNA transcripts
- 2009
-
Ingår i: Genomics. - : Elsevier BV. - 0888-7543 .- 1089-8646. ; 94:3, s. 169-176
-
Tidskriftsartikel (refereegranskat)abstract
- We studied the genomic positions of 38,129 putative ncRNAs from the RIKEN dataset in relation to protein-coding genes. We found that the dataset has 41% sense, 6% antisense, 24% intronic and 29% intergenic transcripts. Interestingly, 17,678 (47%) of the FANTOM3 transcripts were found to potentially be internally primed from longer transcripts. The highest fraction of these transcripts was found among the intronic transcripts and as many as 77% or 6929 intronic transcripts were both internally primed and unspliced. We defined a filtered subset of 8535 transcripts that did not overlap with protein-coding genes, did not contain ORFs longer than 100 residues and were not internally primed. This dataset contains 53% of the FANTOM3 transcripts associated to known ncRNA in RNAdb and expands previous similar efforts with 6523 novel transcripts. This bioinformatic filtering of the FANTOM3 non-coding dataset has generated a lead dataset of transcripts without signs of being artefacts, providing a suitable dataset for investigation with hybridization-based techniques.
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| 42. |
- Näslund, Kalle, et al.
(författare)
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Genome-wide prediction of human VNTRs
- 2005
-
Ingår i: Genomics. - : Elsevier BV. - 0888-7543 .- 1089-8646. ; 85:1, s. 24-35
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Tidskriftsartikel (refereegranskat)abstract
- Polymorphic minisatellites, also known as variable number of tandem repeats (VNTRs), are tandem repeat regions that show variation in the number of repeat units among chromosomes in a population. Currently, there are no general methods for predicting which minisatellites have a high probability of being polymorphic, given their sequence characteristics. An earlier approach has focused on potentially highly polymorphic and hypervariable minisatellites, which make up only a small fraction of all minisatellites in the human genome. We have developed a model, based on available minisatellite and VNTR sequence data, that predicts the probability that a minisatellite (unit size > or = 6 bp) identified by the computer program Tandem Repeats Finder is polymorphic (VNTR). According to the model, minisatellites with high copy number and high degree of sequence similarity are most likely to be VNTRs. This approach was used to scan the draft sequence of the human genome for VNTRs. A total of 157,549 minisatellite repeats were found, of which 29,224 are predicted to be VNTRs. Contrary to previous results, VNTRs appear to be widespread and abundant throughout the human genome, with an estimated density of 9.1 VNTRs/Mb.
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| 43. |
- Odeberg, Jacob, et al.
(författare)
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Cloning and characterization of ZNF189, a novel human Krüppel-like zinc finger gene localized to chromosome 9q22-q31.
- 1998
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Ingår i: Genomics. - : Elsevier BV. - 0888-7543 .- 1089-8646. ; 50, s. 233-
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Tidskriftsartikel (refereegranskat)abstract
- A 3-kb-long cDNA encoding a Krüppel-like human zinc finger protein was isolated and mapped to chromosome 9q22-q31. The ZNF189 gene encodes a protein with 16 zinc fingers at its C-terminus and belongs to the Krüppel-associated box (KRAB)-containing group of zinc finger proteins. Four differently spliced cDNA transcripts, differing at the 5' coding region where a KRAB A repressor domain is encoded, were isolated. In addition, Northern blot analysis indicates the presence of two additional unidentified splice variants. Comparison of cDNA and genomic sequences shows that the ZNF189 gene spans approximately 11 kb and is organized into at least four exons, the large 3'-end exon coding for the complete zinc finger domain and the 3' untranslated region. ZNF189 is expressed in all tissues and cell types currently investigated, at varying levels, but with a tissue- or cell-type-restricted expression pattern for the different splice variants. ZNF189 is conserved in the genome of several mammalian species. Direct sequencing of the ZNF189 gene in microdissected tumor biopsies of sporadic basal cell carcinoma and squamous cell carcinoma reveals no mutations in the coding sequence or at exon/intron boundaries.
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| 44. |
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| 45. |
- Owman, Christer, et al.
(författare)
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Cloning of cDNA encoding a putative chemoattractant receptor
- 1996
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Ingår i: Genomics. - : Elsevier BV. - 1089-8646 .- 0888-7543. ; 37:2, s. 187-194
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Tidskriftsartikel (refereegranskat)abstract
- Based on polymerase chain reaction (PCR) utilizing degenerate primers directed to the second and sixth transmembrane domains of several G-protein-coupled neurotransmitter receptors and screening of a human B-lymphoblast cDNA library, we isolated a cDNA whose predicted amino acid sequence shows considerable homology with human chemoattractant receptors, e.g., 30% overall identity with the C5a anaphylatoxin receptors. The coding region consists of 1056 bp corresponding to 352 amino acid residues and giving an approximate molecular weight of 43 kDa. Northern blot analysis showed hybridizing transcripts in spleen, thymus, and lymph nodes, as well as in bone marrow and peripheral blood leukocytes. Message was also found in lymphoid tumor cell lines. Chromosome mapping with FISH/DAPI technique showed the corresponding gene to reside on human chromosome 14q11.2-q12. In accordance with the Genome Database Nomenclature the receptor was designated CMKRL1 ("chemoattractant receptor-like 1"). Stably transfected mammalian cells (CHO cells and LVIP2.0Zc reporter cells) expressing high levels of corresponding receptor RNA were analyzed for changes in cAMP concentration and cellular calcium fluxes. Chemokines tested to date (GRO-a, MCP-1, MCP-3, MIP-1a, MIP-1b, C5a, RANTES, and LTB4) have failed to elicit any reproducible response. Although the ligand for CMKRL1 could thus not be identified among chemotactic peptides, the high expression in lymphoid cells and tissues suggests that the receptor may function in the regulation of the inflammatory system.
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| 46. |
- Pavelin, Jon, et al.
(författare)
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The nedd-8 activating enzyme gene underlies genetic resistance to infectious pancreatic necrosis virus in Atlantic salmon
- 2021
-
Ingår i: Genomics. - : Elsevier. - 0888-7543 .- 1089-8646. ; 113:6, s. 3842-3850
-
Tidskriftsartikel (refereegranskat)abstract
- Genetic resistance to infectious pancreatic necrosis virus (IPNV) in Atlantic salmon is a rare example of a trait where a single locus (QTL) explains almost all of the genetic variation. Genetic marker tests based on this QTL on salmon chromosome 26 have been widely applied in selective breeding to markedly reduce the incidence of the disease. In the current study, whole genome sequencing and functional annotation approaches were applied to characterise genes and variants in the QTL region. This was complemented by an analysis of differential expression between salmon fry of homozygous resistant and homozygous susceptible genotypes challenged with IPNV. These analyses pointed to the NEDD-8 activating enzyme 1 (nae1) gene as a putative functional candidate underlying the QTL effect. The role of nae1 in IPN resistance was further assessed via CRISPR-Cas9 knockout of the nae1 gene and chemical inhibition of the nae1 protein activity in Atlantic salmon cell lines, both of which resulted in highly significant reduction in productive IPNV replication. In contrast, CRISPR-Cas9 knockout of a candidate gene previously purported to be a cellular receptor for the virus (cdh1) did not have a major impact on productive IPNV replication. These results suggest that nae1 is the causative gene underlying the major QTL affecting resistance to IPNV in salmon, provide further evidence for the critical role of neddylation in hostpathogen interactions, and highlight the value in combining high-throughput genomics approaches with targeted genome editing to understand the genetic basis of disease resistance.
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| 47. |
- Penha-Gonçalves, Carlos, et al.
(författare)
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Type 1 diabetes and the control of dexamethazone-induced apoptosis in mice maps to the same region on chromosome 6
- 1995
-
Ingår i: Genomics. - : Elsevier. - 0888-7543 .- 1089-8646. ; 28:3, s. 398-404
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Tidskriftsartikel (refereegranskat)abstract
- Quantitative trait loci mapping was used to identify the chromosomal location of genes that contribute to increase the resistance to apoptosis induced in immature CD4+8+ thymocytes. An F2 intercross of the nonobese diabetic (NOD) mouse (displaying an apoptosis-resistance phenotype) and the C57BL/6 mouse (displaying a nonresistance phenotype) was phenotypically analyzed and genotyped for 32 murine microsatellite polymorphisms. Maximum likelihood methods identified a region on the distal part of chromosome 6 that is linked to dexamethazone-induced apoptosis (lod score = 3.46) and accounts for 14% of the phenotypic variation. This chromosomal region contains the diabetes susceptibility locus Idd6, suggesting that the apoptosis-resistance phenotype constitutes a pathogenesis factor in IDDM of NOD mice.
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| 48. |
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| 49. |
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| 50. |
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