By applying a novel software tool, information on 4080 UniGene clusters was retrieved from three adult human skeletal muscle cDNA libraries, which were selected for being neither normalized nor ...subtracted. Reconstruction of a transcriptional profile of the corresponding tissue was attempted by a computational approach, classifying each transcript according to its level of expression. About 25% of the transcripts accounted for about 80% of the detected transcriptional activity, whereas most genes showed a low level of expression. This in silico transcriptional profile was then compared with data obtained by a SAGE study. A fairly good agreement between the two methods was observed. About 400 genes, highly expressed in skeletal muscle or putatively skeletal muscle-specific, may represent the minimal set of genes needed to determine the tissue specificity. These genes could be used as a convenient reference to monitor major changes in the transcriptional profile of adult human skeletal muscle in response to different physiological or pathological conditions, thus providing a framework for designing DNA microarrays and initiating biological studies.
To reconstruct the transcriptional profile of the human adult retina and the genomic map of the genes expressed in this tissue.
Original software was used for the retrieval and analysis of records ...from UniGene (http://www.ncbi.nlm.nih. gov/UniGene/) pertaining to selected cDNA libraries from adult human retina.
The 4974 genes reported so far to be expressed in retina were included in a catalog available on the Internet. For each entry, an estimation of the level of expression of the corresponding gene in the retina was provided. A high-resolution genomic map of the human retina was built up by inclusion of 3152 genes showing a precise and unique map assignment. The correspondence was established between 53 gene-orphan retinal diseases and clusters of genes expressed in the retina.
The in silico reconstruction of the transcriptional profile of the adult human retina provides preliminary information on the pattern of genomic expression in this tissue. The chromosomal location of many retinal genes, combined with their expression data, should speed up the identification of genes involved in retinal diseases.
Detecting seeded motifs in DNA sequences Pizzi, Cinzia; Bortoluzzi, Stefania; Bisognin, Andrea ...
Nucleic acids research,
01/2005, Letnik:
33, Številka:
15
Journal Article
Recenzirano
Odprti dostop
The problem of detecting DNA motifs with functional relevance in real biological sequences is difficult due to a number of biological, statistical and computational issues and also because of the ...lack of knowledge about the structure of searched patterns. Many algorithms are implemented in fully automated processes, which are often based upon a guess of input parameters from the user at the very first step. In this paper, we present a novel method for the detection of seeded DNA motifs, composed by regions with a different extent of variability. The method is based on a multi-step approach, which was implemented in a motif searching web tool (MOST). Overrepresented exact patterns are extracted from input sequences and clustered to produce motifs core regions, which are then extended and scored to generate seeded motifs. The combination of automated pattern discovery algorithms and different display tools for the evaluation and selection of results at several analysis steps can potentially lead to much more meaningful results than complete automation can produce. Experimental results on different yeast and human real datasets proved the methodology to be a promising solution for finding seeded motifs. MOST web tool is freely available at http://telethon.bio.unipd.it/bioinfo/MOST.
Arrhythmogenic right ventricular cardiomyopathy type 1 (ARVD1) is an autosomal dominant disorder characterised by progressive degeneration of right ventricular myocardium, arrhythmias and risk of ...sudden death. By linkage analysis, we previously mapped the involved gene to chromosome 14q24.3. In the present study we report on linkage analysis of one additional and unrelated family, which enabled to confirm previous locus assignment. Another family is reported, in which genetic and clinical data suggest linkage to the same locus. Direct sequencing of DNA from individuals belonging to established ARVD1 families failed to detect causative mutations in exonic sequences of four genes (POMT2, TGFbeta3, KIAAA1036 and KIAA0759) expressed in the heart and which defects could possibly induce plasma membrane instability or apoptosis, key features of ARVD pathogenesis.
Cardiac involvement in becker muscular dystrophy Melacini, Paola; Fanin, Marina; Danieli, Gian Antonio ...
Journal of the American College of Cardiology,
12/1993, Letnik:
22, Številka:
7
Journal Article
Recenzirano
Odprti dostop
Objectives. The purpose of this study was to assess the incidence of myocardial involvement and the relation of cardiac disease to the molecular defect at the deoxyribonucleic acid (DNA) or protein ...level in Becker muscular dystrophy.
Background. Dystrophin gene mutations produce clinical manifestations of disease in the heart and skeletal muscle of patients with Becker muscular dystrophy.
Methods. Thirty-one patients underwent electrocardiographic and echocardiographic examination and 24-h Holter monitoring. The diagnosis was established by neurologic examination, dystrophin immunohistochemical assays or Western blot on muscle biopsy, or both, and DNA analysis.
Results. Electrocardiographic and echocardiographic findings were abnormal in 68% and 62% of the patients, respectively. Right ventricular involvement was detected in 52%. Left ventricular impairment was observed either as an isolated phenomenon (10%) or in association with right ventricular dysfunction (29%). Right ventricular disease was manifested in the teenagers, and an impairment of the left ventricle was observed in older patients. Right ventricular end-diastolic volumes were significantly increased compared with those in a control group. The left ventricular ejection fraction was significantly lower in older patients than in control subjects or younger patients. Life-threatening ventricular arrhythmias were detected in four patients. No correlations were found between skeletal muscle disease, cardiac involvement and dystrophin abnormalities. In our patients, exon 49 deletion was invariably associated with cardiac involvement. Exon 48 deletion was associated with cardiac disease in all but two patients.
Conclusions. The cardiac manifestation of Becker muscular dystrophy is characterized by early right ventricular involvement associated or not with left ventricular impairment. Exon 49 deletion is associated with cardiac disease.
We present the Human Muscle Gene Map (HMGM), the first comprehensive and updated high-resolution expression map of human skeletal muscle. The 1078 entries of the map were obtained by merging data ...retrieved from UniGene with the RH mapping information on 46 novel muscle transcripts, which showed no similarity to any known sequence. In the map, distances are expressed in megabase pairs. About one-quarter of the map entries represents putative novel genes. Genes known to be specifically expressed in muscle account for <4% of the total. The genomic distribution of the map entries confirmed the previous finding that muscle genes are selectively concentrated in chromosomes 17, 19, and X. Five chromosomal regions are suspected to have a significant excess of muscle genes. Present data support the hypothesis that the biochemical and functional properties of differentiated muscle cells may result from the transcription of a very limited number of muscle-specific genes along with the activity of a large number of genes, shared with other tissues, but showing different levels of expression in muscle. The sequence data described in this paper have been submitted to the EMBL data library under accession nos. F23198-F23242.
We report here on characterization of a novel human gene on chromosome 2q32, containing several ankyrin repeats and ARM domains. The gene FLJ25415, including at least 31 exons and spanning about 90
...kb of a gene-rich genomic region, is present in the human genome as a single copy. It seems highly conserved along the mammalian phylogeny. By analysing FLJ25415 gene expression in different human tissues, we demonstrated a ubiquitously expression pattern with extensive alternative splicing. In silico prediction of promoter regions revealed the presence of a TATA box and some hypothetical transcription factor binding sites, such as TMF, C/EBPα, LE-1, and NF-ATp.
The increasing number of cDNA libraries from which human ESTs are obtained is clearing the way for in silico analysis of tissue-specific transcription patterns. The first collection of ...tissue-specific transcriptional profiles was made available online in 1991 at the website BODYMAP (Ref. 1). However, this collection is limited to the database of human sequences produced by one laboratory. Later, LENS (linking ESTs and their associated name space; Ref. 2) was created, linking and resolving the names and identifiers of clones and ESTs retrieved from UniGene (Ref. 3). LENS was the first site to use a public EST database and to allow the search by source tissue. Lists of ESTs occurring in a given human tissue can be obtained. If available, the cytogenetic band location corresponding to each EST is provided although the location data can be imprecise.
The reconstruction of the transcriptional profile of the adult human heart was attempted, by applying a bioinformatic and computational approach to UniGene data. A catalogue of 2077 expressed genes ...was produced. Over 1000 entries of the catalogue corresponded to putative novel genes. Highly expressed genes accounted for about 20% of the total. Almost all genes expressed in adult heart resulted to be active in at least one additional tissue and about 90% were found in over five additional tissues. A genomic map of 1364 genes expressed in heart, which also indicated chromosomal location, was produced, which could be conveniently used for the discovery of the determinants of gene-orphan heart diseases and for the detection of clusters of highly expressed genes. The catalogue and the genomic map of genes expressed in adult human heart are available on Internet at the sites: http://telethon.bio.unipd.it/GETProfiles/heart and http://telethon.bio.unipd.it/GETMaps/heart.
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