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At least 919 records · Page 51Linked to original sources
PubMed1994

Genome analysis of the moss Physcomitrella patens (Hedw.) B.S.G.

A wild-type (WT) strain of the moss Physcomitrella patens (Hedw.) B.S.G., two mutants derived from it (PC22 and P24), and a somatic hybrid, PC22(+)P24, were analysed. Staining of metaphases revealed 54 +/- 2 chromosomes in the somatic hybrid and 27 chromosomes in the wild type and the two mutants. Using flow cytometry (FCM), DNA contents were calculated to be 0.6 pg (WT, PC22), 1.2 pg (P24), and 1.6 pg (PC22(+)P24) per nucleus, respectively. Southern hybridization provided evidence for at least one family of highly repetitive DNA and, furthermore, revealed different amounts of repetitive DNA in the four genotypes. However, these sequences cannot account for the 100% increase in the nuclear DNA amount in mutant P24, relative to wild type. In FCM analyses every moss genotype generated just one single peak of fluorescence, indicating an arrest in the cell cycle during the daytime. Thermal denaturation of wild-type DNA revealed a G+C content of 34.6% for total DNA and 38.6% for plastid DNA. A cDNA library of 1.2 x 10(6) independent clones was established, from which sequences homologous to cab and rbcS, respectively, were isolated. These genes show significant homologies to those of higher plants, and, likewise, comprise multigene families. No restriction fragment length polymorphisms could be detected between the four moss genotypes using these cDNA probes.

Base Composition↗
PubMed1996

Genomic analysis of Mycobacterium bovis and other members of the Mycobacterium tuberculosis complex by isoenzyme analysis and pulsed-field gel electrophoresis.

Initially, multilocus enzyme electrophoresis was used to examine genetic relationships among 63 isolates of Mycobacterium bovis and 13 other members of the M. tuberculosis complex. The isolates were divided into five electrophoretic types, with a mean genetic diversity of 0.1. The strains were genetically homogenous, indicating that members of the complex were closely related. This supported the suggestion that they should be considered as subspecies of a single species. Pulsed-field gel electrophoresis (PFGE) was then used to differentiate these isolates, as well as 59 additional isolates of M. bovis from different parts of the world. PFGE differentiated these strains into 63 patterns (53 patterns for M. bovis). Isolates of M. bovis from Western Australia (n = 46) were more homogenous than isolates from other regions. Eight strains were identified in that state, and one predominantly bovine strain was isolated from two human beings and a feral pig. Although M. bovis isolates from different parts of the world had distinct DNA patterns, some were very similar. PFGE is a highly discriminatory technique for epidemiological studies of bovine tuberculosis. For example, it allowed differentiation between isolates of M. bovis cultured from animals in separate outbreaks of tuberculosis, it suggested the transmission of infection between certain properties, and it demonstrated the existence of multiple infections with different strains at certain farms.

Animals↗
PubMed2006

Functional genome analysis indicates loss of 17beta-hydroxysteroid dehydrogenase type 2 enzyme in the zebrafish.

Among the family of 17beta-hydroxysteroid dehydrogenases, the type 2 (17beta-HSD 2) is the main enzyme responsible for inactivation of estrogens and androgens, catalyzing the oxidation of the C17 hydroxyl group. 17beta-HSD 2 has been studied only in mammals, its occurrence and function in other vertebrates hardly known. We investigated the presence of homologs in non-mammalian species and found sequences of 17beta-HSD 2 and its closest homolog 11beta-HSD 2 in zebrafish (Danio rerio), Takifugu rubripes, Tetraodon nigroviridis, Xenopus tropicalis and chicken databases. Furthermore, we cloned zebrafish 17beta-HSD 2 from ovarian tissue and found high expression also in the testis of adult fish and throughout embryogenesis. The enzyme, though, is inactive likely due to a non-sense N-terminal region including a dysfunctional cofactor binding motif. Replacement of the affected part by the corresponding human 17beta-HSD 2 sequence fully restored enzymatic activity. Comparison of all retrieved 17beta-HSD 2 sequences indicates that this functional loss may have occurred only in zebrafish, where steroid inactivation at position C17 seems to pursue without the protein studied. The closely related 11beta-HSD 2 is unlikely to substitute for 17beta-HSD 2 since in our hands it did not catalyze the respective oxidation of testosterone or estradiol.

17-Hydroxysteroid Dehydrogenases↗
PubMed2005

Functional genomic analysis of global regulator NolR in Sinorhizobium meliloti.

NolR is a regulator of nodulation genes present in species belonging to the genera Rhizobium and Sinorhizobium. The expression of the nolR gene in Sinorhizobium meliloti AK631 was investigated in relation to stage of growth, availability of nutrients, and different environmental stimuli using the nolR::lacZ fusion report system. It has been shown that the nolR gene is regulated in a population-density-dependent fashion and influenced by a number of environmental stimuli, including nutrients, pH, and oxygen. Exploration of the physiological functions of NolR under various laboratory conditions has shown that NolR is required for the optimal growth of the bacteria on solid media, optimal survival of the bacteria in carbon-starved minimal medium, and after heat shock challenge. NolR also is involved in recipient-induced conjugative transfer of a plasmid. Proteome analysis of strain AK631 and its Tn5-induced nolR-deficient mutant EK698 revealed that a functional NolR induced significant differences in the accumulation of 20 polypeptides in peptide mass fingerprinting early-log-phase cultures and 48 polypeptides in stationary-phase cultures. NolR acted mainly as a repressor in the early-log-phase cultures, whereas it acted as both repressor and activator in the stationary-phase cultures. The NolR protein and 59 NolR-associated proteins have been identified by peptide mass fingerprinting. The NolR protein was differentially expressed only in the NolR+ wild-type strain AK631 but not in its NolR- derivative EK698, confirming that no functional NolR was produced in the mutant. The NolR-associated proteins have diverse functions in amino acid metabolism, carbohydrate metabolism, lipid metabolism, nucleotide metabolism, energy metabolism, metabolism of Co-factors, and cellular adaptation and transportation. These results further support our previous proposal that the NolR is a global regulatory protein which is required for the optimization of nodulation, bacterial growth and survival, and conjugative transfer of a plasmid.

Bacterial Proteins↗
PubMed1998

Genomic analysis of the viral population in genital secretions early after infection of simian immunodeficiency viruses in macaque monkeys.

To clarify the change in the viral population during passage from the vaginal cavity to blood circulation and vice versa, we examined the viral clones detected in cells in vaginal washes (VWCs) early after inoculation and after systemic infection with polyclonal SIV. In two intravaginally inoculated monkeys, the viral clones found in VWCs at 18 days p.i. were shown to be some of those contained in the inoculum, whereas the viral population in the peripheral blood mononuclear cells (PBMCs) was a monotype. This gradual decrease of viral clones suggested the possible existence of two barriers, one at the genital tract and the other between the genital tract and the blood. Later, at one month p.i., the viral clones in VWCs became rather restricted, whereas those in PBMCs diverged from a single clone to several clones. This suggested that different mechanisms affect the viral populations in PBMCs and VWCs. In order to examine how the viral population was affected by passage from the blood to the vaginal cavity, a monkey was intravenously inoculated and the viral clones in VWCs were analyzed at 14 days p.i., at a time of the heterogeneous population in PBMCs. The viral population in VWCs was found to be a single clone and this clone was a minor type in PBMCs, suggesting that the major clone in PBMCs was not always secreted to the vaginal cavity.

Animals↗
PubMed2005

Paracoccidioides brasiliensis translation and protein fate machineries revealed by functional genome analysis.

The translational and post-translational modification machineries of Paracoccidioides brasiliensis were assessed by means of comparative analyses of PbAESTs (P. brasiliensis assembled expressed sequence tags) with sequences deposited on different databases. Of the 79 sequences corresponding to cytosolic ribosomal proteins, we were able to find 78 in the P. brasiliensis transcriptome. Nineteen of the 27 Saccharomyces cerevisiae genes related to translation initiation were also found. All eukaryotic elongation factors were detected in P. brasiliensis transcriptome, with eEF1A as one of the most expressed genes. Translation termination is performed, in eukaryotes, by factors 1 and 3 (eRF1, eRF3). In P. brasiliensis transcriptome it was possible to identify eRF3, but not eRF1. Sixteen PbAESTs showing aminoacyl-tRNA synthetase-predicted activities were found in our analyses, but no cysteinyl-, leucyl-, asparagyl- and arginyl-tRNA synthetases were detected. Among the mitochondrial ribosomal proteins, we have found 20 and 18 orthologs to S. cerevisiae large and small ribosomal subunit proteins, respectively. We have also found three PbAESTs similar to Neurospora crassa mitochondrial ribosomal genes, with no similarity with S. cerevisiae genes. Although orthologs to S. cerevisiae mitochondrial EF-Tu, EF-G and RF1 have been found in P. brasiliensis transcriptome, no sequences corresponding to functional EF-Ts were detected. In addition, 64 and 28 PbAESTs associated to protein modification and degradation, respectively, were found. These results suggest that these machineries are well conserved in P. brasiliensis, when compared to other organisms.

Expressed Sequence Tags↗
PubMed2001

Full-length genomic analysis of hepatitis B virus isolates in a patient progressing from hepatitis to hepatocellular carcinoma.

In hepatitis B virus (HBV)-endemic countries, the majority of hepatocellular carcinoma (HCC) arises in HBV carriers. High frequency of mutations at nucleotides 1762(A-->T) and 1764(G-->A) in the core promoter region have been described in HCC. Due to the differences in genetic backgrounds, environmental risk factors and random cellular insertion sites, it is difficult to analyze the possible roles of HBV variants detected in different HCC patients. In a follow-up cohort study, an HBsAg-positive asymptomatic carrier was diagnosed HCC within 4 years. Eleven full-length HBV isolates, three from the first serum sample obtained 4 years pre-HCC, and eight from serum sample, peri-tumor and tumor tissue post-HCC of this individual were sequenced and used to transfect HepG2 cells. When sequences were compared between pre- and post-HCC isolates, no single mutation common to all post-HCC isolates that differed from pre-HCC isolates was found. Among all 11 isolates, there were 20 predicted amino acid substitutions shared by two or more post-HCC isolates. These were located in the S(5), X(4), core(4), polymerase(4), pre-S1(2) and pre-S2(1) proteins. Possible roles of amino acid substitutions and enhanced replication efficiency in cells transfected by post-HCC isolates are discussed.

Amino Acid Substitution↗
PubMed2005

Paracoccidioides brasiliensis RNA biogenesis apparatus revealed by functional genome analysis.

The RNA biogenesis machinery of Paracoccidioides brasiliensis was assessed by comparative analyses of PbAESTs (P. brasiliensis assembled expressed sequence tags (ESTs)) with sequences from Saccharomyces cerevisiae MIPS database. PbAESTs related to almost all categories of S. cerevisiae RNA biogenesis were found. Two of the 12 S. cerevisiae RNA Pol II core subunits, Rpb3 and Rpb7, were found, probably reflecting the growth phase from which the cDNA libraries used in ESTs generation were constructed, as well as the low abundance of some of these transcripts. We have also found orthologs to TATA-box-binding protein (TBP), and at least one subunit of each TBP-associated factors (TFII) in P. brasiliensis transcriptome, except TFIIB. Genes associated to the chromatin remodeling complex, as well as transcription factors probably involved in the control of genes associated to a sexual cycle and virulence, were also identified. With respect to the pre-mRNA processing, 65 PbAEST orthologs to S. cerevisiae basal splicing machinery and 21 orthologs of 5'- and 3'-end formation processes were found. Components involved in RNA interference were detected, suggesting that this gene expression regulation mechanism is probably used by P. brasiliensis. Twelve PbAESTs related to Pol I and Pol III machineries were assigned as S. cerevisiae orthologs. Finally, 25 and 10 PbAESTs associated to rRNA and tRNA processing, respectively, were detected. Taken together, our results enable us to depict, for the first time, a global view of transcription and RNA processing in P. brasiliensis.

Expressed Sequence Tags↗
PubMed2003

A functional genomic analysis of cell morphology using RNA interference.

BACKGROUND: The diversity of metazoan cell shapes is influenced by the dynamic cytoskeletal network. With the advent of RNA-interference (RNAi) technology, it is now possible to screen systematically for genes controlling specific cell-biological processes, including those required to generate distinct morphologies. RESULTS: We adapted existing RNAi technology in Drosophila cell culture for use in high-throughput screens to enable a comprehensive genetic dissection of cell morphogenesis. To identify genes responsible for the characteristic shape of two morphologically distinct cell lines, we performed RNAi screens in each line with a set of double-stranded RNAs (dsRNAs) targeting 994 predicted cell shape regulators. Using automated fluorescence microscopy to visualize actin filaments, microtubules and DNA, we detected morphological phenotypes for 160 genes, one-third of which have not been previously characterized in vivo. Genes with similar phenotypes corresponded to known components of pathways controlling cytoskeletal organization and cell shape, leading us to propose similar functions for previously uncharacterized genes. Furthermore, we were able to uncover genes acting within a specific pathway using a co-RNAi screen to identify dsRNA suppressors of a cell shape change induced by Pten dsRNA. CONCLUSIONS: Using RNAi, we identified genes that influence cytoskeletal organization and morphology in two distinct cell types. Some genes exhibited similar RNAi phenotypes in both cell types, while others appeared to have cell-type-specific functions, in part reflecting the different mechanisms used to generate a round or a flat cell morphology.

Animals↗
PubMed2006

Genomic analysis of the Opi- phenotype.

Most of the phospholipid biosynthetic genes of Saccharomyces cerevisiae are coordinately regulated in response to inositol and choline. Inositol affects the intracellular levels of phosphatidic acid (PA). Opi1p is a repressor of the phospholipid biosynthetic genes and specifically binds PA in the endoplasmic reticulum. In the presence of inositol, PA levels decrease, releasing Opi1p into the nucleus where it represses transcription. The opi1 mutant overproduces and excretes inositol into the growth medium in the absence of inositol and choline (Opi(-) phenotype). To better understand the mechanism of Opi1p repression, the viable yeast deletion set was screened to identify Opi(-) mutants. In total, 89 Opi(-) mutants were identified, of which 7 were previously known to have the Opi(-) phenotype. The Opi(-) mutant collection included genes with roles in phospholipid biosynthesis, transcription, protein processing/synthesis, and protein trafficking. Included in this set were all nonessential components of the NuA4 HAT complex and six proteins in the Rpd3p-Sin3p HDAC complex. It has previously been shown that defects in phosphatidylcholine synthesis (cho2 and opi3) yield the Opi(-) phenotype because of a buildup of PA. However, in this case the Opi(-) phenotype is conditional because PA can be shuttled through a salvage pathway (Kennedy pathway) by adding choline to the growth medium. Seven new mutants present in the Opi(-) collection (fun26, kex1, nup84, tps1, mrpl38, mrpl49, and opi10/yol032w) were also suppressed by choline, suggesting that these affect PC synthesis. Regulation in response to inositol is also coordinated with the unfolded protein response (UPR). Consistent with this, several Opi(-) mutants were found to affect the UPR (yhi9, ede1, and vps74).

Gene Expression Regulation, Fungal↗
PubMed2002

Genomic analysis of smooth muscle cells in 3-dimensional collagen matrix.

The proliferation, differentiation, and protein synthesis of vascular smooth muscle cells (SMCs) play important roles in vascular remodeling. Here, we compared the genetic programming and signaling of SMCs in collagen matrix as a three-dimensional (3-D) environment and on a two-dimensional (2-D) surface. By using DNA microarrays with 9600 genes, we showed that 77 genes were expressed more than twofold and 22 genes were less than one-half in 3-D matrix, when compared with the 2-D condition. The higher expression level of cyclin-dependent kinase inhibitor 1 (p21) in 3-D matrix suggests that p21 may be responsible for the lower proliferation rate in 3-D matrix. The expression level of collagen I was higher in 3-D matrix, suggesting that SMCs in 3-D matrix have increased matrix synthesis. In addition, SMCs in 3-D matrix had less stress fibers and focal adhesions, and a lower level of tyrosine phosphorylation of focal adhesion kinase (FAK). Overexpression of FAK attenuated the expression of p21 and collagen I in 3-D matrix, suggesting that FAK functions as a molecular switch for cell cycle regulation and matrix synthesis. The information generated in this study helps to elucidate the molecular basis of the modulation of SMC phenotypes by the extracellular matrix.

Cell Culture Techniques↗
PubMed2005

Genomic analysis of a spontaneous model of breast cancer metastasis to bone reveals a role for the extracellular matrix.

A clinically relevant model of spontaneous breast cancer metastasis to multiple sites, including bone, was characterized and used to identify genes involved in metastatic progression. The metastatic potential of several genetically related tumor lines was assayed using a novel real-time quantitative RT-PCR assay of tumor burden. Based on this assay, the tumor lines were categorized as nonmetastatic (67NR), weakly metastatic to lymph node (168FARN) or lung (66cl4), or highly metastatic to lymph node, lung, and bone (4T1.2 and 4T1.13). In vitro assays that mimic stages of metastasis showed that highly metastatic tumors lines were more adhesive, invasive, and migratory than the less metastatic lines. To identify metastasis-related genes in this model, each metastatic tumor was array profiled against the nonmetastatic 67NR using 15,000 mouse cDNA arrays. A significant proportion of genes relating to the extracellular matrix had elevated expression in highly metastatic tumors. The role of one of these genes, POEM, was further investigated in the model. In situ hybridization showed that POEM expression was specific to the tumor epithelium of highly metastatic tumors. Decreased POEM expression in 4T1.2 tumors significantly inhibited spontaneous metastasis to the lung, bone, and kidney. Taken together, our data support a role for the extracellular matrix in metastatic progression and describe, for the first time, a role for POEM in this process.

Animals↗
PubMed2006

Genomic analysis and marker development for the Tsn1 locus in wheat using bin-mapped ESTs and flanking BAC contigs.

The wheat Tsn1 gene confers sensitivity to the host-selective toxin Ptr ToxA produced by the tan spot fungus (Pyrenophora tritici-repentis). The long-term goal of this research is to isolate Tsn1 using a positional cloning approach. Here, we evaluated 54 ESTs (expressed sequence tags) physically mapped to deletion bin 5BL 0.75-0.76, which is a gene-rich region containing Tsn1. Twenty-three EST loci were mapped as either PCR-based single-stranded conformational polymorphism or RFLP markers in a low-resolution wheat population. The genetic map corresponding to the 5BL 0.75-0.76 deletion bin spans 18.5 cM and contains 37 markers for a density of 2 markers/cM. The EST-based genetic map will be useful for tagging other genes, establishing colinearity with rice, and anchoring sequence ready BAC contigs of the 5BL 0.75-0.76 deletion bin. High-resolution mapping showed that EST-derived markers together with previously developed AFLP-derived markers delineated Tsn1 to a 0.8 cM interval. Flanking markers were used to screen the Langdon durum BAC library and contigs of 205 and 228 kb flanking Tsn1 were assembled, sequenced, and anchored to the genetic map. Recombination frequency averaged 760 kb/cM across the 228 kb contig, but no recombination was observed across the 205 kb contig resulting in an expected recombination frequency of more than 10 Mb/cM. Therefore, chromosome walking within the Tsn1 region may be difficult. However, the sequenced BACs allowed the identification of one microsatellite in each contig for which markers were developed and shown to be highly suitable for marker-assisted selection of Tsn1.

Chromosome Walking↗
PubMed2005

Functional genomics analysis of foliar condensed tannin and phenolic glycoside regulation in natural cottonwood hybrids.

Regulation of leaf condensed tannins (CT) and salicylate-derived phenolic glycosides (PG) in fast- and slow-growing cottonwood backcrosses was analyzed by metabolic profiling and cDNA microarray hybridization. Seven hybrid lines of Populus fremontii L. and P. angustifolia James exhibiting growth/CT-PG phenotypes ranging from fast/low (Lines 18 and 1979) to slow/high (Lines 1012 and RL2) and intermediate (Lines NUL, 3200 and RM5) were investigated. Methanol-extractable leaf metabolites were analyzed by gas chromatography-mass spectrometry, and the results evaluated by principal component analysis. The hybrid lines formed separate clusters based on their primary metabolite profiles, with cluster arrangement also reflecting differences in CT-PG phenotype. Nitrogen (N) supply was manipulated to alter CT-PG partitioning and to obtain molecular insights into how primary metabolism interfaces with CT-PG accumulation. Three backcross lines (RM5, 1012, 18) exhibiting differential CT-PG responses to a 10-day hydroponic N-deprivation treatment were chosen for metabolite and gene expression analyses. The fast- growing Line 18 showed a minimal CT-PG response to N deprivation, and a reduction in photosynthetic gene expression. Line 1012 exhibited a strong phenylpropanoid response to N deprivation, including a doubling in phenylalanine ammonia-lyase (PAL) gene expression, and a shift from CT accumulation in the absence of stress toward PG accumulation under N-deprivation conditions. Amino acid concentrations were depressed in Lines 18 and 1012, as was expression of nitrate-sensitive genes coding for transketolase (TK), and malate dehydrogenase (MDH). Genes associated with protein synthesis and fate were down-regulated in Line 1012 but not in Line 18. Line RM5 exhibited a comparatively large increase in CT in response to N deprivation, but did not sustain decreases in amino acid concentrations, or changes in PAL, TK or MDH gene expression. Molecular characterization of the variable CT-PG responses shows promise for the identification and future testing of candidate genes for CT-PG trait selection or manipulation.

Gas Chromatography-Mass Spectrometry↗
PubMed2025

Comprehensive genomic analysis of antibiotic resistance plasmids in animal-associated Staphylococcus aureus in France.

UNLABELLED: In Staphylococcus aureus, an animal pathogen and zoonotic agent, plasmids play a pivotal role in the acquisition and spread of antibiotic resistance genes (ARGs). This study investigated the plasmid content of 329 S. aureus isolates from livestock and companion animals collected in France between 2010 and 2021. Plasmids (n = 211) were identified from 139 isolates. The major families identified-rep7a, rep20, and rep10-were associated with specific resistance genes (str, cat, blaZ, erm(C)) and exhibited widespread horizontal transfer across different S. aureus sequence types (STs) and animal hosts. In temporal analysis, the rep7a/str and rep7a/cat plasmids circulating in horses were progressively replaced by a rep7a plasmid carrying both str and cat genes. The study also highlighted the presence of mosaic plasmids, which combined elements from different bacterial species/genera, confirming the broad host range of S. aureus plasmids and their ability to acquire ARGs from diverse sources. Moreover, the occurrence of hybrid plasmids (carrying multiple rep genes) underscores the plasticity of these vectors of ARGs. This study emphasizes the need to investigate the mechanisms driving the spread and persistence of antibiotic-resistant plasmids in S. aureus, with a view to developing strategies aimed at combating antibiotic resistance. IMPORTANCE: The spread of antibiotic resistance in Staphylococcus aureus is a growing concern, particularly in animals that can serve as reservoirs for resistant strains. This study highlights the crucial role of plasmids in transmitting resistance genes among different animal hosts and S. aureus lineages. The characterization of 329 isolates collected over 10 years revealed how certain plasmid families are associated with specific resistance genes and how they evolve over time. The occurrence of mosaic and hybrid plasmids further underscores the ability of S. aureus to acquire resistance from diverse bacterial sources. These findings provide key insights into the mechanisms shaping antibiotic resistance in this pathogen and emphasize the fact that understanding plasmid-driven resistance is essential for developing effective interventions to limit the spread of multidrug-resistant S. aureus in both veterinary and human medicine.

Animals↗
PubMed2006

Genomic analysis of a heterogeneous Mendelian phenotype: multiple novel alleles for inherited hearing loss in the Palestinian population.

Recessively inherited phenotypes are frequent in the Palestinian population, as the result of a historical tradition of marriages within extended kindreds, particularly in isolated villages. In order to characterise the genetics of inherited hearing loss in this population, we worked with West Bank schools for the deaf to identify children with prelingual, bilateral, severe to profound hearing loss not attributable to infection, trauma or other known environmental exposure. Of 156 families enrolled, hearing loss in 17 families (11 per cent) was due to mutations in GJB2 (connexin 26), a smaller fraction of GJB2-associated deafness than in other populations. In order to estimate how many different genes might be responsible for hearing loss in this population, we evaluated ten families for linkage to all 36 known human autosomal deafness-related genes, fully sequencing hearing-related genes at any linked sites in informative relatives. Four families harboured four novel alleles of TMPRSS3 (988DeltaA = 352stop), otoancorin (1067A > T = D356V) and pendrin (716T > A = V239D and 1001G > T = 346stop). In each family, all affected individuals were homozygous for the critical mutation. Each allele was specific to one or a few families in the cohort; none were widespread. Since epidemiological tests of association of mutations with deafness were not feasible for such rare alleles, we used functional and bioinformatics approaches to evaluate their consequences. In six other families, hearing loss was not linked to any known gene, suggesting that these families harbour novel genes responsible for this phenotype. We conclude that inherited hearing loss is highly heterogeneous in this population, with most extended families acting as genetic isolates in this context. We also conclude that the same genes are responsible for hearing loss in this population as elsewhere, so that gene discovery in these families informs the genetics of hearing loss worldwide.

Arabs↗
PubMed1998

Genomic analysis of the Tapasin gene, located close to the TAP loci in the MHC.

The Tapasin molecule is a member of the immunoglobulin (Ig) superfamily required for the association of TAP transporters and MHC class I heterodimers in the endoplasmic reticulum. In this study, the Tapasin gene was precisely mapped in relation to the MHC. The gene was centromeric of the HLA-DP locus between the HSET and HKE1.5 genes and within 500 kbp of the TAP1 and TAP2 genes. A homologous mouse EST was mapped to a syntenic position on chromosome 17, centromeric of the H-2 K locus. Similarly, the rat Tapasin gene was shown to be in an equivalent location with respect to the RT1.A locus. The localization of Tapasin, TAP, LMP and class I genes within such a short distance of each other on the chromosome implies some regulatory or functional significance. We determined the Tapasin gene sequence for comparison of its structure to that of other Ig superfamily members, such as MHC class I genes. The IgC domain was encoded by a separate exon. However, the positions of the other introns were not characteristic of other Ig superfamily genes, indicating that Tapasin has a distinct phylogeny.

ATP Binding Cassette Transporter, Subfamily B, Mem↗