Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dystrophin is the protein whose defect underlies Duchenne Muscular Dystrophy, DMD, a common (1:3500 male births) and fatal condition in which muscle tissue deteriorates leading to death in the second or third decade of life. Dystrophin is coded for by the largest human gene, and one of the most complex. It is translated from at least 7 distinct promoters, with the largest transcripts (which are the ones involved in DMD) containing 79 exons over >2.5 Mbp [K.F. O'Brien, L.M. Kunkel, Dystrophin and muscular dystrophy: past, present, and future, Mol. Genet. Metab. 74 (2001) 75-88, H.M. Sadoulet-Puccio, L.M. Kunkel, Dystrophin and its isoforms, Brain Pathol. 6 (1996) 25-35]. Exacerbating this complexity, it has recently been shown that dystrophin is subject to extensive alternative RNA processing, potentially producing a wide variety dystrophin variants [M. Sironi, R. Cagliani, U. Pozzoli, A. Bardoni, G.P. Comi, R. Giorda, N. Bresolin, The dystrophin gene is alternatively spliced throughout its coding sequence FEBS Lett 517 (2002) 163-166]. The structure of the dystrophin protein is highly modular, with the most common module being a motif termed the spectrin type repeat, or STR, of which there are 24. Each STR is roughly coded for by two exons, and the most common type of multiple exon-skipping events start and end at introns in the middle of STRs [R.G. Roberts, A.J. Coffey, M. Bobrow, D.R. Bentley, Exon structure of the human dystrophin gene Genomics 16 (1993) 536-538, M. Koenig, L.M. Kunkel, Detailed analysis of the repeat domain of dystrophin reveals four potential hinge segments that may confer flexibility, J. Biol. Chem. 265 (1990) 4560-4566]. This would produce fractional STR modules, however, the concept of STRs as proteins domains makes the viability of such fractional motifs questionable. However, certain of these events produce pairs of potentially complementary fractional domain that might reassemble into a hybrid STR motif. We have constructed model fragment corresponding to one such exon-skipping event, and show that the hybrid STR so produced is viable, and furthermore that some of the properties of the protein containing it differ substantially of the native, un-skipped parent.
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PMID:Hybrid spectrin type repeats produced by exon-skipping in dystrophin. 1671 78

The dramatic changes in human population structure over the last 200 years have resulted in significant levels of outbreeding, which, in turn, is predicted to lead to increased levels of individual genetic diversity (genome-wide heterozygosity, h). To investigate possible effects of these large demographic changes on global health, we studied the effect of h, measured as relative heterozygosity, h(R), on 15 disease-related traits in four groups of individuals with widely differing ancestral histories (ranging from outbred to inbred) from the Dalmatian islands in Croatia. Higher levels of h(R), estimated using 1184 STR/indel markers, were found in the outbred group (P < 0.0001) and were associated with lower blood pressure (BP) and total/LDL cholesterol (P = 0.01 and 0.01, respectively) after controlling for other factors, with BP showing a strong sex effect (males P > 0.5 and females P = 0.002). These findings, if replicated, suggest that h(R) be considered as a genetic risk factor in genetic epidemiological studies on common disease traits. They are consistent with the well-known effects of heterosis (hybrid vigour) described when outcrossing animals and plants. Outbreeding resulting from urbanization and migration from traditional population subgroups may be leading to increasing h(R) and may have beneficial effects on a range of traits associated with human health and disease. Other traits, such as age at menarche, IQ and lifespan, which have been changing during the decades of urbanization, may also have been influenced by demographic factors.
Hum Mol Genet 2007 Jan 15
PMID:Effects of genome-wide heterozygosity on a range of biomedically relevant human quantitative traits. 1722 Jan 73

The paper presents allele frequencies at 15 STR loci (D3S1358, vWA, FGA, TH01, TPOX, CSFIPO, D5S818, D13S317, D7S820, D16S539, D2Sl338, D8S1179, D21S1l, D18S51, D19S433), used in forensic medicine, in Russian sample (n = 176) representing population of the European part of the Russian Federation. The combined power of discrimination (PD) and the combined power of exclusion (PE) for the 15 STR loci were 0.999 999 999 999 999 986 and 0.999 999 331 310 171 000, respectively. The data obtained for allele and genotype frequencies conformed to Hardy-Weinberg expectations. According to the presented data, loci D2S1338, D18S51, D21Sll and FGA are the most informative markers for Russians. The data obtained may be used as reference database for forensic medicine laboratories in Russian Federation.
Mol Biol (Mosk)
PMID:[Variability at 15 autosomal microsatellite DNA loci in Russian population]. 1738 Aug 85

This study examined the beta-adrenergic regulation of uncoupling protein (UCP) 2 and UCP3 gene expression in porcine tissues. In vitro experiments examined changes in UCP2 and UCP3 gene expression in middle (MSQ) and outer (OSQ) subcutaneous adipose tissues from crossbred neutered male pigs. Incubation of tissue slices (24 h) with 0 to 1000 nM isoproterenol increased UCP2 and UCP3 mRNA abundance in MSQ and OSQ, relative to 18S rRNA (P<0.05). For the in vivo experiment, nine randomly selected pigs (80 kg) were presented with a diet supplemented with 10.0 ppm ractopamine for 2 weeks. Another eight pigs were maintained on a control diet. Dietary ractopamine did not affect adipose UCP2 or UCP3 gene expression (P>0.05). However, UCP2 mRNA abundance was depressed in semitendinosus white (STW, P<0.05) and semitendinosus red (STR, P<0.001) by ractopamine feeding. Also, ractopamine decreased UCP3 mRNA abundance by 28% in STW (P<0.05). The in vitro data suggest that beta-adrenergic agonists directly affect adipose tissue UCP expression, although these adipose effects can be masked by the in vivo physiology. The in vivo data indicate that beta-adrenergic agonists may function in regulating UCP2 and UCP3 expression in selected muscles.
Comp Biochem Physiol A Mol Integr Physiol 2007 Jun
PMID:Beta-adrenergic regulation of uncoupling protein expression in swine. 1738 7

The mitochondria are the major cellular site of energy production and respiration. Recent research has focused on investigating the role of mitochondria in disease development and it has become increasingly evident that mitochondrial dysfunction contributes to a variety of human diseases. Mitochondrial DNA (mtDNA) quantity is very important for maintaining mitochondrial function and meeting the energy needs of the body. We have measured mitochondrial content in 1259 Mexican American individuals (from 42 extended families) and have shown that mtDNA quantity (a surrogate measure of mitochondrial integrity) has a large genetic component. We performed a genome scan and a genome-wide quantitative transcriptomic scan to identify QTLs influencing mitochondrial content. A variance components linkage-based genome scan utilizing 439 STR markers was used to localize a QTL for mitochondrial content on chromosome 10q (LOD = 3.83). Significant linkage to the mitochondrial genome was also detected for mitochondrial transmission (LOD = 3.39). For replication, we measured mitochondrial content in an independent Caucasian population (1088 individuals) finding evidence for linkage in these same regions. As part of the San Antonio Family Heart Study, we obtained genome-wide quantitative transcriptional profiles from 1240 individuals. Using lymphocyte samples, we quantitated 20 413 transcripts and examined correlations between the expression levels of these transcripts and mitochondrial content using the variance components method. Using regression analysis allowing for residual genetic components, we identified 829 transcripts (including many novel genes) influencing mitochondrial content that vary in their general biological actions, from cell signaling to cell trafficking and ion binding.
Hum Mol Genet 2007 Jun 15
PMID:Genetic determinants of mitochondrial content. 1746 76

The allele distributions for 15 STR loci included in the AmpFISTR SGM Plus and AmpFISTR Profiler Plus kits ("Applied Biosystems", USA) were determined in 261 healthy unrelated individuals belonging to five indigenous populations of South Siberia: in Buryats, Altaians, Tofalars, Sojots and Khakassians. No significant differences in allele frequencies were found between populations studied. Combined power of discrimination (PD) for the STR loci investigated were estimated for the populations under study.
Mol Biol (Mosk)
PMID:[Variability of fifteen autosomal microsatellite DNA loci in five populations of aboriginal South Siberians]. 1793 77

Plasma dopamine beta-hydroxylase activity (plDbetaH) is tightly regulated by the DBH gene and several genetic polymorphisms have been found to independently exert their influence. In the present investigation, association of four DBH polymorphisms, DBH-STR, rs1611115, rs1108580, and rs2519152 with plDbetaH was examined in blood samples from 100 unrelated individuals belonging to the state of West Bengal, Eastern India. Genotypes obtained after PCR amplification and restriction digestion were used for statistical analyses. plDbetaH was measured using a photometric assay and its correlation with the genetic polymorphisms was analyzed using analysis of variance and linear regression. Moderate linkage disequilibrium (LD) was observed between DBH-STR and rs1611115, while rs1108580 and rs2519152 were in strong LD. 'T' allele of rs1611115 showed strong negative correlation with plDbetaH, whereas DBH-STR, rs1108580 and rs2519152 had no major effect. Four haplotypes showed significant influence on plDbetaH. This is the first report on the effect of genetic polymorphisms on plDbetaH from the Indian sub-continent. rs1611115 was the only polymorphism that showed substantial control over plDbetaH. Other polymorphisms which did not show individual effects could possibly be part of larger haplotype blocks that carry the functional polymorphisms controlling plDbetaH.
Cell Mol Neurobiol 2008 May
PMID:Correlation of plasma dopamine beta-hydroxylase activity with polymorphisms in DBH gene: a study on Eastern Indian population. 1817 55

The present study was designed to determine if dietary protein can alter uncoupling protein (UCP) expression in swine, as has been shown in rats, and attempt to identify the mechanism. Eight pigs (approximately 50 kg body mass) were fed an 18% crude protein (CP) diet while another eight pigs were switched to a diet containing 12% crude protein (CP) and fed these diets until 110 kg body mass. The outer (OSQ) and middle (MSQ) subcutaneous adipose tissues, liver, leaf fat, longissimus (LM), red portion of the semitendinosus (STR) and the white portion of the ST (STW) were analyzed for gene expression by real-time PCR. Feeding of 12% CP did not alter growth or carcass composition, relative to 18% CP (P>0.05). Serum growth hormone, non-esterified fatty acids, triglycerides and urea nitrogen were reduced with the feeding of 12% CP (P<0.05). The UCP2 mRNA abundance was reduced in LM, STR, MSQ and OSQ with feeding of 12% CP (P<0.05), as was UCP3 mRNA abundance in MSQ and STW (P<0.01). Peroxisome proliferation activated receptor alpha (PPARalpha) and PPARgamma were reduced in MSQ and STR (P<0.05) with feeding 12% CP as was the PPARalpha regulated protein, acyl CoA oxidase (ACOX, P<0.05). These data suggest that feeding 12% CP relative to 18% CP reduces serum NEFA, which reduces PPARalpha and PPARgamma expression and consequently reduces UCP2 lipoperoxidation in OSQ and STR and also reduced UCP3 associated fatty acid transport in MSQ and STW.
Comp Biochem Physiol B Biochem Mol Biol 2008 Apr
PMID:Impact of dietary protein content on uncoupling protein mRNA abundance in swine. 1824 11

Renal cell carcinoma is the most common variant of the kidney cancer, which accounts approximately 75% patients with this disease. The majority of those tumors are characterized by inactivation of the VHL gene suppressor as a result of mutations, allelic deletions and/or methylation. We have conducted the complex molecular-genetic analysis of 64 samples obtained from patients with the clear cell renal cancer. VHL mutations were detected by single strand conformation polymorphism and subsequent sequencing, loss of heterozygosity was analyzed using two STR-markers, methylation was tested by methylsensitive polymerase chain reaction. All revealed variations were statistically analyzed in respect to the parameters of primary tumors in various groups of patients. Seventeen VHL somatic mutations were detected, 12 from which were described for the first time. Allelic deletions of VHL were found in 31.6%, and methylation--in 7.8% samples of the renal cancer. As a whole, VHL inactivating events were presented in 46.9% cases of disease, in 51.7% -among renal cancer patients with first stage. We have not observed any association of mutations, loss of heterozygosity and methylation with clinical-pathological parameters of disease. Results of this investigation specify for expediency of further studies of molecular genetics aberrations in the VHL gene. Perhaps, it would promote renal cancer molecular markers evaluation, for example, a determination of suppressor genes methylated in renal cancer.
Mol Biol (Mosk)
PMID:[Inactivation of the VHL gene in sporadic clear cell renal cancer]. 1838 22

The X-STRs are important tools in forensic application, particularly in complex cases of kinship testing. In deficiency paternity testing when alleged father cannot be typed, investigation of X-STR markers yields the desired information. Blood samples were collected from unrelated individual (118 females and 94 males) and 84 trios families (father, mother and daughter). DNA extraction from whole blood was performed with Phenol chloroform method. Five X-linked STR markers DXS6800, DXS7133, DXS6797, DXS981 and GATA165B12 were selected. The amplicons were analyzed through ABI 3100 Genetic Analyzer. Pentaplex PCR system was developed for multilocus amplification at the same time. For each locus 4-9 alleles were noted. Altogether, 32 alleles were observed from five markers. Eighty-four trios families were analysed to check the mutation rate and no mutation was observed. Stutter peaks were observed maximum at locus DXS6797 (12.44%) while the minimum at locus DXS7133 (4.5%). For sensitivity study, amplification of X chromosomal short tandem repeats loci was successfully performed using 0.15 ng quantity of DNA as template. In conclusion; this pentaplex represents a convenient method to study X chromosome markers. It works with reasonable amounts of DNA and is suitable for paternity cases.
Mol Biol Rep 2009 Sep
PMID:Development of pentaplex PCR and genetic analysis of X chromosomal STRs in Punjabi population of Pakistan. 1893 51


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