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)

Allele frequencies of four VNTR regions (loci D1S80, D17S30, APOB and IGHJ) were determined in 120 unrelated Russian individuals living in Moscow. The high level of length polymorphism was discovered among alleles of these VNTRs. The genotype distribution of these hypervariable regions was established on the basis of experimental data. The comparative analysis showed the likeness between the allele distributions of these VNTRs among Russians and other groups of Caucasians living in Europe and North America.
Mol Biol (Mosk)
PMID:[Analysis of the distribution of alleles of four hypervariable tandem repeats among unrelated Russian individuals living in Moscow, using the polymerase chain reaction]. 790 27

The effects of comprehensive LNA substitution in PCR primers for amplification of human genomic DNA targets are presented in this report. Previous research with LNA in other applications has shown interesting properties for molecular hybridization including enhanced specificity in allele-specific PCR. Here we systematically modified PCR primers and conditions for the human genomic DNA targets APOB and PAH, along with a beta-globin amplification control, to study whether the number and position of LNA residues improves or diminishes amplification sensitivity and specificity. It was observed that the design rules for LNA substitution in PCR primers are complex and depend upon number, position and sequence context. Technical advantages were seen when compared to DNA controls for the best LNA primer designs, which were typically one to a few centrally located LNA residues. LNA advantages include increased maximum annealing temperature (Tmax) and increased signal with limiting primer or Taq DNA polymerase. Several well-characterized designs exhibited different efficiencies with different brands of hot-start enzymes. Many shorter LNA primers were found to be functional compared to same-length non-functional native DNA controls. These results show that LNA-substituted PCR primers have potential for use in difficult PCR techniques, such as multiplex amplification at higher Tmax, once firm LNA primer design rules are established.
Mol Cell Probes 2003 Oct
PMID:Design considerations and effects of LNA in PCR primers. 1458 Apr

In ethnic Russians, MHC (HLA) was shown to be the major locus determining the predisposition to type 1 diabetes mellitus (T1DM). To map the regions linked to T1DM, families with concordant or discordant sib pairs were selected from the Russian population of Moscow. With these families, linkage to T1DM was demonstrated for CTLA4 (IDDM12, 2q32.1-q33), which codes for a T-cell surface antigen, and PDCD2 (IDDM8, 6q25-q27), which is homologous to the mouse programmed cell death activator gene. With polymorphic microsatellites, regions 3q21-q25 (IDDM9) and 10p12.2 (IDDM10) were also linked to T1DM. Case/control and family studies of the polymorphic markers from region 11p13 revealed a new T1DM-associated locus in the vicinity of the catalase gene (CAT); linkage to this locus was not reported earlier for other populations. Diabetic polyneuropathy (DPN) proved to be associated with single-nucleotide polymorphisms Ala(-9)Val (SOD2), Arg213Gly (SOD3), and T(-262)C (CAT) and with a polymorphic microsatellite of the NOS2 promoter. Hence oxidative stress, which results from hyperglycemia, increased mitochondrial production of superoxide radicals, and insufficient activities of antioxidative enzymes, was assumed to play an important part in DPN development in T1DM. Diabetic nephropathy (DN) showed no association with the antioxidative enzyme genes. However, the association was observed for the insertion/deletion (I/D) polymorphism of ACE and the ecNOS34a/4b polymorphism of NOS3, two genes involved in controlling vascular tonicity, and for the I/D polymorphism of APOB and the epsilon 2/epsilon 3/epsilon 4 polymorphism of APOE, two genes involved in lipid transport. In addition, polymorphic microsatellites of chromosome 3q21-q25 proved to be closely associated with DN. The tightest association was established for D3S1550, carriers of allele 12 or genotype 12/14 having high risk of DN (OR = 4.85 and 6.25, respectively). Region 3q21-q25 was assumed to contain a major gene determining DN development, while the other DN-associated genes mostly affect the progression of DN.
Mol Biol (Mosk)
PMID:[Genomics of type I diabetes mellitus and its late complications]. 1504 45

Single nucleotide polymorphisms (SNPs) and derived haplotypes within multiple genes may explain genetic variance in complex traits; however, this hypothesis has not been rigorously tested. In an earlier study we analyzed six genes and have now expanded this investigation to include 13. We studied 250 families including 1054 individuals and measured lipid phenotypes. We focused on low-density cholesterol (LDL), high-density cholesterol (HDL) and their ratio (LDL/HDL). A component analysis of the phenotypic variance relying on a standard genetic model' showed that the genetic variance on LDL explained 26%, on HDL explained 38% and on LDL/HDL explained 28% of the total variance, respectively. Genotyping of 93 SNPs in 13 lipid-relevant genes generated 230 haplotypes. The association of haplotypes in all the genes tested explained a major fraction of the genetic phenotypic variance component. For LDL, the association with haplotypes explained 67% and for HDL 58% of the genetic variance relative to the polygenic background. We conclude that these haplotypes explain most of the genetic variance in LDL, HDL and LDL/HDL in these representative German families. An analysis of the contribution to the genetic variance at each locus showed that APOE (50%), CETP (28%), LIPC (9%), APOB (8%) and LDLR (5%) influenced variation in LDL. LIPC (53%), CETP (25%), ABCA1 (10%), LPL (6%) and LDLR (6%) influenced the HDL variance. The LDL/HDL ratio was primarily influenced by APOE (36%), CETP (27%) and LIPC (31%). This expanded analysis substantially increases the explanation of genetic variance on these complex traits.
Hum Mol Genet 2004 May 15
PMID:Haplotypes and SNPs in 13 lipid-relevant genes explain most of the genetic variance in high-density lipoprotein and low-density lipoprotein cholesterol. 1504 81

Familial hypobetalipoproteinemia (FHBL), an autosomal dominant disorder, is defined as <5th percentile LDL-cholesterol or apolipoprotein (apo) B in the plasma. FHBL subjects are generally heterozygous and asymptomatic. Three genetic forms exist: (i) premature stop codon specifying mutations of APOB; (ii) FHBL linked to a susceptibility locus on the chromosome 3p21; and (iii) FHBL linked neither to APOB nor to the chromosome 3p21. In heterozygous apoB-defective FHBL, the hepatic VLDL export system is defective because apoB 100, the product of the normal allele, is produced at approximately 25% of normal rate, and truncated apoB is cleared too rapidly. The reduced capacity for hepatic triglyceride export increases hepatic fat three-fold. Indexes of adiposity and insulin action are similar to controls. 'Knock-in' mouse models of apoB truncations resemble human FHBL phenotypes. Liver fat in the chromosome 3p21-linked FHBL is normal. Elucidation of the genetic basis of the non-apoB FHBL could uncover attractive targets for lipid-lowering therapy. (See note added in proof.).
Cell Mol Life Sci 2005 Jun
PMID:Familial hypobetalipoproteinemia: genetics and metabolism. 1581 69

Activation-induced deaminase (AID) is essential for immunoglobulin gene diversification by the distinct processes of class switch recombination, somatic hypermutation and gene conversion. Most evidence indicates that AID triggers these reactions through the direct deamination of cytosine residues in the DNA. However, AID is predominantly cytoplasmic and the mechanism that directs it to the immunoglobulin loci remains elusive. Like its homolog APOBEC1, which requires at least one additional factor to efficiently edit APOB RNA, other proteins are likely to be required for the proper targeting of AID to the immunoglobulin loci. Here, we show that AID can interact with MDM2, an oncoprotein that shuttles between the nucleus and the cytoplasm and targets p53 for nuclear export and degradation. This interaction mapped to the carboxy-terminal region of AID that harbors a nuclear export sequence, suggesting that MDM2 may be involved in the nucleo-cytoplasmic trafficking of AID. We therefore assessed the role of MDM2 in immunoglobulin gene diversification by disrupting MDM2 in DT40, an avian B cell line that constitutively undergoes AID-dependent immunoglobulin gene diversification. The subcellular localization of AID was unaffected in MDM2-deficient DT40 cells. However, slight hyper-and hypo-conversion phenotypes were caused by MDM2-abrogation and overexpression, respectively. These observations suggested that MDM2 has the capacity to negatively regulate AID. Intriguingly, the same carboxy-terminal residues of AID were recently shown to be inessential for somatic hypermutation and immunoglobulin gene conversion but they were strictly required for class switch recombination.
Mol Immunol 2006 Mar
PMID:MDM2 can interact with the C-terminus of AID but it is inessential for antibody diversification in DT40 B cells. 1612 2

Congenital human cytomegalovirus (HCMV) infection affects 1% of children and is the most common infectious cause of sensorineural hearing loss. Due to the difficulty of diagnosing deafness and other neurological disorders in infants, affected individuals may not be recognized until much later when active infection has resolved and culture is no longer informative. To overcome this problem, congenital HCMV infection was diagnosed retrospectively by testing residual blood samples collected from newborns and dried on perinatal cards as part of the North Carolina Newborn Screening Program. We modified the Qiagen method for purifying DNA from dried blood spots to increase the sample size and recovery of the lysate. A multiplex, real-time TaqMan polymerase chain reaction assay on an ABI 7900 instrument measured a highly conserved segment of the HCMV polymerase gene and the APOB human control gene. HCMV DNA was detected in blood dried on perinatal cards from all seven infants with culture-proven congenital infection, and all 24 negative control cases lacked detectable HCMV DNA. Our findings suggest that it is possible to diagnose congenital HCMV infection using dried blood collected up to 20 months earlier. Further studies are warranted on patients with hearing loss or other neurological deficits to determine the percentage that is attributable to congenital HCMV infection.
J Mol Diagn 2006 May
PMID:Diagnosis of human congenital cytomegalovirus infection by amplification of viral DNA from dried blood spots on perinatal cards. 1664 11

In male mice heterozygous for a null apolipoprotein B (apoB), allele infertility was noticed. These data led us to investigate a possible role of APOB gene polymorphism and male infertility in humans. In this case-control study, we searched for an association between the insertion/deletion (I/D) polymorphism of the APOB gene and male infertility in 560 Slovene Caucasian men. The study group consisted of 310 infertile patients: 115 with azoospermia and 195 with oligoasthenoteratozoospermia (OAT) and a control group of 250 fertile men. We found a statistically significant difference in the genotype distribution between the two groups (chi2 = 6.315, P = 0.043). A separate analysis of azoospermic and OAT patients demonstrated that significant differences in genotype distribution were limited to the OAT group (chi2 = 7.011, P = 0.030). The presence of the D allele (DD or ID genotypes) conferred a 1.6 risk [chi2 = 6.089, P = 0.014, 95% confidence interval (95% CI) = 1.102-2.347] for male infertility in the OAT group of patients. We did not find a correlation between the I/D polymorphism genotypes and the clinical characteristics of infertile men: sperm concentration (P = 0.102), rapid progressive motility (P = 0.449), normal morphology (P = 0.085) and Johnsen score (P = 0.531). These data suggest that genetic variation in the signal peptide of the APOB gene (I/D polymorphism) might be a risk factor for the development of male infertility.
Mol Hum Reprod 2006 Dec
PMID:Association between the apolipoprotein B signal peptide gene insertion/deletion polymorphism and male infertility. 1707 10

Cytomegalovirus (CMV) is a significant cause of morbidity and mortality in immunocompromised patients. We compared the CMV pp65 antigenemia test with a less labor intensive quantitative polymerase chain reaction (PCR) assay in 109 whole blood samples predominantly from transplant patients and patients with AIDS. DNA was amplified on an Applied Biosystems 7900 instrument using a TaqMan probe targeting the CMV polymerase gene and the APOB human control gene. The DNA assay was linear over a 6-log range from 8 to 800,000 CMV genomes per reaction; coefficient of variation was 20%. CMV DNA was undetectable in 20 blood samples from healthy donors whereas it was detected in 55 of 109 patient samples. Results were concordant in a nonlinear fashion with those of the antigenemia test in 90/109 (83%). Evaluation of the discrepancies suggested that either PCR or antigenemia assays could be falsely negative when virus levels were quite low. A point mutation interfered with probe binding in 1 sample. A second real-time PCR targeting the immediate early gene was even more likely to be false negative. In summary, CMV viral load measurement targeting the polymerase gene is nearly equivalent to the antigenemia assay for detecting and monitoring active CMV infection in whole blood samples.
Diagn Mol Pathol 2007 Jun
PMID:Analytic validation of a quantitative real-time PCR assay to measure CMV viral load in whole blood. 1752 75

Familial hypobetalipoproteinemia (FHBL) is a co-dominant disorder characterized by reduced plasma levels of low density lipoprotein cholesterol (LDL-C) and its protein constituent apolipoprotein B (apoB), which may be due to mutations in APOB gene, mostly located in the coding region of this gene. We report two novel APOB gene mutations involving the acceptor splice site of intron 11 (c.1471-1G>A) and of intron 23 (c.3697-1G>C), respectively, which were identified in two patients with heterozygous FHBL associated with severe fatty liver disease. The effects of these mutations on APOB pre-mRNA splicing were assessed in COS-1 cells expressing the mutant APOB minigenes. The c.1471-1G>A APOB minigene generated two abnormal mRNAs. In one mRNA the entire intron 11 was retained; in the other mRNA exon 11 joined to exon 12, in which the first nucleotide was deleted due to the activation of a novel acceptor splice site. The predicted products of these mRNAs are truncated proteins of 546 and 474 amino acids, designated apoB-12.03 and apoB-10.45, respectively. The c.3697-1G>C APOB minigene generated a single abnormal mRNA in which exon 23 joined to exon 25, with the complete skipping of exon 24. This abnormal mRNA is predicted to encode a truncated protein of 1220 amino acids, designated apoB-26.89. These splice site mutations cause the formation of short truncated apoBs, which are not secreted into the plasma as lipoprotein constituents. This secretion defect is the major cause of severe fatty liver observed in carriers of these mutations.
Mol Genet Metab 2009 Feb
PMID:Functional analysis of two novel splice site mutations of APOB gene in familial hypobetalipoproteinemia. 1908 51


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