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1.
P Roma R E Gregg C Bishop R Ronan L A Zech M V Meng C Glueck C Vergani G Giudici H B Brewer 《Journal of lipid research》1990,31(10):1753-1760
Familial hypoalphalipoproteinemia (hypoalpha), characterized by a decreased high density lipoprotein level, is associated with an increased incidence of premature cardiovascular disease. Restriction fragment length polymorphism analysis of genomic DNA has detected a polymorphism for the PstI restriction endonuclease near the apoA-I gene, with either a 2.2 or a 3.3 kb fragment. The latter has been previously found to occur with significantly higher frequency in probands of families with familial hypoalpha. ApoA-I was isolated from three unrelated subjects with familial hypoalpha and the 3.3 kb PstI polymorphism of the apoA-I gene, and from normal control subjects. The apoA-I from the hypoalpha subjects was structurally normal as determined by amino acid analysis and by two-dimensional gel electrophoresis. When normal apoA-I and hypoalpha apoA-I were simultaneously injected into either normal controls or hypoalpha subjects, both forms of apoA-I were catabolized at the same rate in the same subject, indicating that the hypoalpha apoA-I is also metabolically normal. Analysis of the kinetics of metabolism of apoA-I in the hypoalpha subjects, compared to the normal controls, revealed that the reduced plasma levels of apoA-I were due to an increased apoA-I fractional catabolic rate, and that the synthetic rate was normal. Based on these results, we conclude that the apoA-I gene in these hypoalpha subjects is normal, and the PstI polymorphism near the apoA-I gene, which is associated with familial hypoalpha, is likely to be a marker for a mutant gene closely linked to, but not in, the apoA-I gene. 相似文献
2.
Familial apolipoprotein A-I, C-III, and A-IV deficiency and premature atherosclerosis due to deletion of a gene complex on chromosome 11 总被引:7,自引:0,他引:7
J M Ordovas D K Cassidy F Civeira C L Bisgaier E J Schaefer 《The Journal of biological chemistry》1989,264(28):16339-16342
The defect in a kindred with marked plasma high density lipoprotein (HDL) deficiency and premature atherosclerosis was examined. The homozygous proband died of coronary artery atherosclerosis at age 45 and had undetectable levels of plasma apolipoproteins A-I and C-III, proteins of HDL. In family studies 10 heterozygotes were identified whose mean apoA-I, apoC-III, apoA-IV, and HDL cholesterol levels were 67, 57, 65, and 62% of normal. These subjects were noted to have restriction fragment length polymorphisms following DNA digestion with a number of enzymes including BamHI, EcoRI, HindIII, XmnI, PstI, and PvuII, following hybridization with a probe spanning 1.1 kilobases approximately 2.5 kilobases 5' to the apoA-I gene. Cloning and sequence analysis of the abnormal allele indicated that the defect is due to the complete deletion of the apoA-I, -C-III, and -A-IV gene complex on chromosome 11, with both ends of the deletion being located in areas of highly repetitive DNA. The data support the concept of an independent role for HDL in the pathogenesis of atherosclerosis. 相似文献
3.
D J Rader R E Gregg M S Meng J R Schaefer L A Zech M D Benson H B Brewer 《Journal of lipid research》1992,33(5):755-763
Apolipoprotein (apo) A-I is the major protein constituent of plasma high density lipoproteins (HDL). A kindred has been identified in which a glycine to arginine mutation at residue 26 in apoA-I is associated with hypoalphalipoproteinemia and hereditary systemic amyloidosis. We isolated the mutant protein, termed apoA-IIowa, from the plasma of an affected subject and studied its in vivo metabolism compared to that of normal apoA-I in two heterozygous apoA-IIowa subjects and two normal controls. Normal and mutant apoA-I were radioiodinated with 131I and 125I, respectively, reassociated with autologous plasma lipoproteins, and simultaneously injected into all subjects. Kinetic analysis of the plasma radioactivity curves demonstrated that the mutant apoA-IIowa was rapidly cleared from plasma (mean fractional catabolic rate [FCR] 0.559 day-1) compared with normal apoA-I (mean FCR 0.244 day-1) in all four subjects. The FCR of normal apoA-I was also substantially faster in the heterozygous apoA-IIowa subjects (mean FCR 0.281 days-1) than in the normal controls (mean FCR 0.203 days-1). Despite the rapid removal from plasma of apoA-IIowa, the cumulative urinary excretion of its associated radioactivity after 2 weeks (44%) of the injected dose) was substantially less than that associated with normal apoA-I (78% of injected dose), indicating extravascular sequestration of radiolabeled apoA-IIowa.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
4.
K Aalto-Set?l? J Viikari H K Akerblom V Kuusela K Kontula 《Journal of lipid research》1991,32(9):1477-1487
A number of restriction fragment length polymorphisms (RFLPs) of the apolipoprotein B (apoB) and apolipoprotein A-I/C-III(apoA-I/C-III) genes have been found to be associated with serum lipoprotein levels in many adult populations. In order to examine whether these genetic polymorphisms influence serum lipoprotein levels in childhood and adolescence, we determined the apoB XbaI and apoA-I/C-III SstI genotypes and serum lipoprotein concentrations in 307 healthy Finns aged 9 to 21 years. In the age groups of 9, 12, and 15 years, subjects homozygous for the X2 allele (the XbaI site present) of the apoB gene had mean serum low-density lipoprotein (LDL) cholesterol levels (3.69, 3.43, and 3.15 mmol/l, respectively) that were 12-20% higher than those in subjects homozygous for the absence of this allele (3.08, 3.02, and 2.80 mmol/l, respectively). This association was more significant in males than in females. At the age of 9 to 18 years, subjects carrying the S2 allele (SstI site present) of the apoA-I/C-III gene complex had an approximately 6-15% higher mean serum LDL-cholesterol level than those homozygous for its absence. The combined genotype X2+S2+ (the simultaneous presence of the X2 allele and the S2 allele) was associated with an even more marked elevation of serum LDL-cholesterol level than either allele alone. As an example, the serum LDL cholesterol concentration was 20% higher in 9-year-old subjects with at least one X2 and one S2 allele than in those without either allele (3.55 vs. 2.97 mmol/l, P less than 0.005). The S2 allele was found to be significantly more frequent in eastern than in western Finland, whereas no significant areal differences were seen in the occurrence of the X2 allele. In conclusion, genetic variations of the apoB and apoA-I/C-III gene loci influence serum lipoprotein concentrations already in childhood. 相似文献
5.
An analysis of the role of a retroendocytosis pathway in ABCA1-mediated cholesterol efflux from macrophages 总被引:2,自引:0,他引:2
Faulkner LE Panagotopulos SE Johnson JD Woollett LA Hui DY Witting SR Maiorano JN Davidson WS 《Journal of lipid research》2008,49(6):1322-1332
The ATP binding cassette transporter A-1 (ABCA1) is critical for apolipoprotein-mediated cholesterol efflux, an important mechanism employed by macrophages to avoid becoming lipid-laden foam cells, the hallmark of early atherosclerotic lesions. It has been proposed that lipid-free apolipoprotein A-I (apoA-I) enters the cell and is resecreted as a lipidated particle via a retroendocytosis pathway during ABCA1-mediated cholesterol efflux from macrophages. To determine the functional importance of such a pathway, confocal microscopy was used to characterize the internalization of a fully functional apoA-I cysteine mutant containing a thiol-reactive fluorescent probe in cultured macrophages. ApoA-I was also endogenously labeled with (35)S-methionine to quantify cellular uptake and to determine the metabolic fate of the internalized protein. It was found that apoA-I was specifically taken inside macrophages and that a small amount of intact apoA-I was resecreted from the cells. However, a majority of the label that reappeared in the media was degraded. We estimate that the mass of apoA-I retroendocytosed is not sufficient to account for the HDL produced by the cholesterol efflux reaction. Furthermore, we have demonstrated that lipid-free apoA-I-mediated cholesterol efflux from macrophages can be pharmacologically uncoupled from apoA-I internalization into cells. On the basis these findings, we present a model in which the ABCA1-mediated lipid transfer process occurs primarily at the membrane surface in macrophages, but still accounts for the observed specific internalization of apoA-I. 相似文献
6.
Asztalos BF Horvath KV Kajinami K Nartsupha C Cox CE Batista M Schaefer EJ Inazu A Mabuchi H 《Journal of lipid research》2004,45(3):448-455
Our purpose was to compare HDL subpopulations, as determined by nondenaturing two-dimensional gel electrophoresis followed by immunoblotting for apolipoprotein A-I (apoA-I), apoA-II, apoA-IV, apoCs, and apoE in heterozygous, compound heterozygous, and homozygous subjects for cholesteryl ester transfer protein (CETP) deficiency and controls. Heterozygotes, compound heterozygotes, and homozygotes had CETP masses that were 30, 63, and more than 90% lower and HDL-cholesterol values that were 64, 168, and 203% higher than those in controls, respectively. Heterozygotes had approximately 50% lower pre-beta-1 and more than 2-fold higher levels of alpha-1 and pre-alpha-1 particles than controls. Three of the five heterozygotes' alpha-1 particles also contained apoA-II, which was not seen in controls. Compound heterozygotes and homozygotes had very large particles not observed in controls and heterozygotes. These particles contained apoA-I, apoA-II, apoCs, and apoE. However, these subjects did not have decreased pre-beta-1 levels. Our data indicate that CETP deficiency results in the formation of very large HDL particles containing all of the major HDL apolipoproteins except for apoA-IV. We hypothesize that the HDL subpopulation profile of heterozygous CETP-deficient patients, especially those with high levels of alpha-1 containing apoA-I but no apoA-II, represent an improved anti-atherogenic state, although this might not be the case for compound heterozygotes and homozygotes with very large, undifferentiated HDL particles. 相似文献
7.
S Marcovina S Fantappie A Zoppo G Franceschini A L Catapano 《Journal of lipid research》1990,31(3):375-384
We have produced and characterized six murine monoclonal antibodies to human apolipoprotein A-I named A-I-9, A-I-12, A-I-15, A-I-16, A-I-19, and A-I-57. All monoclonal antibodies were specific for apolipoprotein A-I and bound between 55% and 100% of 125I-labeled high density lipoproteins (HDL) in a fluid phase radioimmunoassay. All antibodies possessed a higher affinity to apoA-I in HDL than to free, delipidated apoA-I. Two of them, particularly A-I-12 and A-I-15, which were directed to the same or very close epitopes on the molecule, recognized very poorly the delipidated protein. Binding of apoA-I to phospholipid restored the immunoreactivity of the monoclonal antibodies to the protein suggesting that lipids play an important role in determining the immunochemical structure of apoA-I. Using CNBr fragments and synthetic peptides, the epitopes for the antibodies were mapped as follows: A-I-19, CNBr fragment 1; A-I-12 and 15, CNBr fragment 2; A-I-9 and A-I-16, CNBr fragment 3; A-I-57, CNBr fragment 4. Antibody A-I-57 failed to recognized a mutant form of apoA-I, A-IMilano (Arg173----Cys) by immunoblotting and by competitive radioimmunoassay demonstrating that substitution of a single amino acid in human apoA-I may cause the loss of an antigenic determinant. 相似文献
8.
HLA class I and H ferritin gene polymorphisms in normal subjects and patients with haemochromatosis 总被引:4,自引:4,他引:0
Summary The gene for idiopathic haemochromatosis is located on the short arm of chromosome 6 within 1 cM of the HLA-A locus. In this region there are many HLA class I genes, and there may also be a gene for the H subunit of ferritin. Both HLA class I and H ferritin genes are therefore candidates for the abnormal gene in idiopathic haemochromatosis. In 15 unrelated patients the frequency of HLA-A3 was 80% compared with 24% for 600 unrelated individuals from South Wales. The most common haplotype involved is probably HLA-A3, B7. DNA was prepared from leucocytes from 12 of these patients and from 85 normal subjects. After digestion with Taq1, electrophoresis, and Southern blotting, class I sequences were detected by hybridisation to an HLA class I probe (pHLA-A). Of the 34 restriction fragments detected, 22 were polymorphic. Particular fragments correlated with the presence of HLA-A antigens A1, 2, 3, 10, 11, w19, and 28, but there was little correlation with B antigens. Restriction fragment patterns specific for haemochromatosis were not found with TaqI or during less extensive studies with other restriction enzymes. No differences in restriction fragment patterns were found between four patients and four normal subjects apparently homozygous for HLA-A3 and B7. Examination of Southern blotting patterns for genomic DNA from patients and normal subjects with a panel of 12 restriction enzymes and a probe for the H ferritin gene (pDBR-2) revealed no polymorphisms associated with either idiopathic haemochromatosis or particular HLA phenotypes. These studies provide no support for either HLA class I genes or the H ferritin gene as candidates for the haemochromatosis gene. 相似文献
9.
Polymorphisms in toll-like receptors (TLRs) have been reported to increase susceptibility for some diseases. TLR-2 gene polymorphisms
in Turkish children with recurrent respiratory tract infections and without well-known humoral immunodeficiencies were examined.
The study consisted of 52 children with recurrent infections (study group) and 91 healthy children with a maximum of two infections
in a year (control group). Recurrent infection was defined as the presence of at least six febrile bacterial infection episodes
in a year. Not only TLR-2 gene polymorphisms but also immunoglobulins (IgG, IgM, IgA), IgG subsets (G1, G2, G3), and specific
antibody levels (anti-tetanus and anti-hemophilus influenza) were determined to exclude humoral immunodeficiencies. The Arg753Gln
and Arg677Trp polymorphisms were genotyped by polymerase chain reaction restriction fragment length polymorphism. The Arg753Arg
genotype was significantly decreased in the study group compared to the control (P < 0.05). Children with recurrent infections were also found to be more frequently Arg753Gln heterozygous (P < 0.05), and their Gln allele distribution was higher than that of the control subjects (23% vs. 4.9%; P < 0.001). In contrast to these results, we did not detect any case with Arg677Trp polymorphism in both groups. These results
have indicated that there is a strong significant relationship between susceptibility to recurrent bacterial infections and
Arg753Gln polymorphism of the TLR-2 gene. 相似文献
10.
Jauhiainen M Huuskonen J Baumann M Metso J Oka T Egashira T Hattori H Olkkonen VM Ehnholm C 《Journal of lipid research》1999,40(4):654-664
Plasma phospholipid transfer protein (PLTP) is a factor that plays an important role in HDL metabolism. In this study we present data suggesting that PLTP has an inherent protease activity. After incubation of HDL3 in the presence of purified plasma PLTP, the d < 1.25 g/ml particles (fusion particles) contained intact 28.2 kDa apoA-I while the d > 1.25 g/ml fraction (apoA-I-PL complexes) contained, in addition to intact apoA-I, a cleaved 23 kDa form of apoA-I. Purified apoA-I was also cleaved by PLTP and produced a similar 23 kDa apoA-I fragment. The cleavage of apoA-I increased as a function of incubation time and the amount of PLTP added. The process displayed typically an 8-10 h lag or induction period, after which the cleavage proceeded in a time-dependent manner. This lag-phase was necessary for the development of the cleavage activity during incubation at 37 degrees C. The specific apoA-I cleavage activity of different PLTP preparations varied between 0.4-0.8 microg apoA-I degraded/h per 1000 nmol per h of PLTP activity. The 23 kDa apoA-I fragment reacted with monoclonal antibodies specific for the N-terminal part of apoA-I, indicating that the apoA-I cleavage occurred in the C-terminal portion. The apoA-I cleavage products were further characterized by mass spectrometry. The 23 kDa fragment yielded a mass of 22.924 kDa, demonstrating that the cleavage occurs in the C-terminal portion of apoA-I between amino acid residues 196 (alanine) and 197 (threonine). The intact apoA-I and the 23 kDa fragment revealed identical N-terminal amino acid sequences. The cleavage of apoA-I could be inhibited with APMSF and chymostatin, suggesting that it is due to a serine esterase-type of proteolytic activity. Recombinant PLTP produced in CHO cells or using the baculovirus-insect cell system caused an apoA-I cleavage pattern identical to that obtained with plasma PLTP. The present results raise the question of whether PLTP-mediated proteolytic cleavage of apoA-I might affect plasma HDL metabolism by generating a novel kinetic compartment of apoA-I with an increased turnover rate. 相似文献
11.
Thomàs-Moyà E Gianotti M Lladó I Proenza AM 《The Journal of nutritional biochemistry》2006,17(3):197-203
Paraoxonase 1 (PON1) associates to specific high-density lipoproteins (HDLs)--those containing apolipoprotein A-I (apoA-I) and apolipoprotein J (apoJ)--and is largely responsible for their antiatherogenic properties. Caloric restriction (CR) has been shown to reduce major atherosclerotic risk factors. The aims of this work were to study PON1 activity response to CR (40% over 14 weeks) and to elucidate whether there are adaptive differences related to gender. Serum and liver paraoxonase and arylesterase activities, serum triglyceride, total and HDL cholesterol concentrations, serum PON1, apoA-I and apoJ contents and liver PON1 mRNA levels were measured. No effects of CR or gender were observed in triglyceride, total cholesterol concentration and PON1 mRNA levels. HDL cholesterol was higher in female rats than in male rats and increased with CR only in the latter animals. Serum PON1 activities tended to be higher in female rats and dropped with CR, with females showing the biggest decrease. Serum PON1 content was higher in female rats and decreased in both genders with CR, whereas apoA-I and apoJ contents, which were higher in female rats too, decreased only in the former animals, accounting for the high PON1 activity decrease observed in these animals. In conclusion, the short-term CR-associated reduction of serum PON1 activity and PON1, apoA-I and apoJ levels points toward a reduced stability of HDL-PON1 complexes and/or HDL particle levels responsible for PON1 transport and function in the blood. Moreover, the variations in PON1 activity and apolipoprotein levels show gender-related differences that are indicative of a different adaptive strategy of male and female rats when faced with a period of food restriction. 相似文献
12.
Gary K. L. Chan Andrzej Witkowski Donald L. Gantz Tianqi O. Zhang Martin T. Zanni Shobini Jayaraman Giorgio Cavigiolio 《The Journal of biological chemistry》2015,290(17):10958-10971
High plasma levels of apolipoprotein A-I (apoA-I) correlate with cardiovascular health, whereas dysfunctional apoA-I is a cause of atherosclerosis. In the atherosclerotic plaques, amyloid deposition increases with aging. Notably, apoA-I is the main component of these amyloids. Recent studies identified high levels of oxidized lipid-free apoA-I in atherosclerotic plaques. Likely, myeloperoxidase (MPO) secreted by activated macrophages in atherosclerotic lesions is the promoter of such apoA-I oxidation. We hypothesized that apoA-I oxidation by MPO levels similar to those present in the artery walls in atherosclerosis can promote apoA-I structural changes and amyloid fibril formation. ApoA-I was exposed to exhaustive chemical (H2O2) oxidation or physiological levels of enzymatic (MPO) oxidation and incubated at 37 °C and pH 6.0 to induce fibril formation. Both chemically and enzymatically oxidized apoA-I produced fibrillar amyloids after a few hours of incubation. The amyloid fibrils were composed of full-length apoA-I with differential oxidation of the three methionines. Met to Leu apoA-I variants were used to establish the predominant role of oxidation of Met-86 and Met-148 in the fibril formation process. Importantly, a small amount of preformed apoA-I fibrils was able to seed amyloid formation in oxidized apoA-I at pH 7.0. In contrast to hereditary amyloidosis, wherein specific mutations of apoA-I cause protein destabilization and amyloid deposition, oxidative conditions similar to those promoted by local inflammation in atherosclerosis are sufficient to transform full-length wild-type apoA-I into an amyloidogenic protein. Thus, MPO-mediated oxidation may be implicated in the mechanism that leads to amyloid deposition in the atherosclerotic plaques in vivo. 相似文献
13.
DNA polymorphisms of the insulin receptor gene in Japanese subjects with non-insulin-dependent diabetes mellitus 总被引:1,自引:0,他引:1
Genotypes identified by two restriction fragment length polymorphisms (RFLPs) of the insulin receptor gene (IRG) with the restriction endonuclease Sst-1 were determined in a Japanese group comprising 51 patients with non-insulin-dependent diabetes mellitus (NIDDM) and 50 control subjects. Southern hybridization using a probe for the beta subunit of the human IRG identifies 4 alleles, termed S1(+) (5.3 kb), S1(-) (5.8 kb), S2(+) (7.0 and 2.4 kb) and S2(-) (9.4 kb). The frequencies of genotypes possessing the S1(-) allele in Japanese controls and Japanese NIDDM patients were 0.11 and 0.16, respectively. Unlike the previously reported association of the S1(-) allele with NIDDM found in Caucasians there was no significant difference in the frequency of the S1(-) allele between non-diabetic and NIDDM Japanese patients. There was a significant difference in the frequency of the S2(+) allele between Caucasian control subjects (0.14) and Japanese controls (0.0) and NIDDM patients (0.02). 相似文献
14.
Chatterjee B Bahadur M Srivastava S Sharma T 《Indian journal of experimental biology》2003,41(1):53-57
Southern blot hybridization analysis of genomic DNAs digested with restriction endonuclease EcoR I and Ava II from Mus musculus domesticus, Mus booduga and Mus terricolor with a cloned repetitive DNA fragment of Mus booduga as a probe showed difference in restriction pattern of this DNA in these three species. Further Southern analysis of the BamH I digested genomic DNAs from these species hybridized with cloned DNA fragment as a probe and sequencing of the cloned DNA revealed that this 252 bp cloned DNA fragment is a part of BamHI repeat element of genus Mus and is 87% homologous to the contiguous portion of the Mus musculus domesticus LINE-1 element. The species specific fragment pattern generated by different restriction endonucleases using this DNA as a probe revealed difference in the organization of LINE-1 repetitive element in the three species of genus Mus. 相似文献
15.
DNAs from 122 individuals representing 5 ethnic groups (Black, Chinese, Japanese, Caucasian and Melanesian) were analyzed for restriction fragment length polymorphisms (RFLPs) with a hypervariable repeated sequence located uniquely on chromosome 1 (hMF No.1; is a component of the D1Z2 locus). When human genomic DNA is digested with a variety of enzymes (TaqI, EcoRI, SinI, PstI, HaeIII) the hMF No.1 probe reveals multiple RFLPs. Ethnic group differences were found in the frequencies of specific EcoRI bands. The most striking ethnic group variation was the presence of a unique fragment amongst the Japanese. 相似文献
16.
R Frénais K Ouguerram C Maugeais J S Marchini P Benlian J M Bard T Magot M Krempf 《Journal of lipid research》1999,40(8):1506-1511
Heterozygous familial hypercholesterolemia (FH) is associated with a moderate decrease of plasma apoA-I and HDL-cholesterol levels. The aim of the study was to test the hypothesis that these abnormalities were related to an increase of HDL-apoA-I fractional catabolic rate (FCR). We performed a 14-h infusion of [5,5,5-(2)H(3)]leucine in seven control subjects and seven heterozygous FH patients (plasma total cholesterol 422 +/- 27 vs. 186 +/- 42 mg/dL, P < 0.001, respectively). Plasma apoA-I concentration was not changed in FH compared to controls (respectively 115 +/- 18 vs. 122 +/- 15 mg/dL, NS), and HDL-cholesterol level was decreased (37 +/- 7 vs. 46 +/- 19 mg/dL, NS). Kinetics of HDL metabolism were modeled as a single compartment as no differences were observed between HDL(2) and HDL(3) subclasses. Both mean apoA-I FCR and absolute production rate (APR) were increased in FH (respectively, 0.36 +/- 0.14 vs. 0.22 +/- 0.05 pool/d, P < 0.05, and 18.0 +/- 7.7 and 11.2 +/- 2.3 mg/kg/d, P < 0.05). Higher HDL-triglyceride and HDL-apoE levels were observed in patients with heterozygous FH. (Respectively 19 +/- 8 vs. 8 +/- 3 mg/dL, P < 0.05, and 5.3 +/- 0.8 vs. 3.7 +/- 0.9 mg/dL, P < 0.05). We conclude that the catabolism of HDL-apoA-I is increased in heterozygous FH patients. However, plasma apoA-I concentration was maintained because of an increased HDL-apoA-I production rate. 相似文献
17.
The G20210A mutation variant of prothrombin gene is the second most frequent mutation identified in patients withdeep venous thrombosis, after factor V Leiden. The risk for developing deep venous thrombosis is high in patients identified as heterozygous for G20210A mutation. In order to identify this polymorphism in the gene coding prothrombin, the 345bp fragment in the 3'- untranslated region of the prothrombin gene was amplified using amplification by polymerase chain reaction and enzymatic digestion by HindIII (restriction endonuclease enzyme). The products of amplification and enzymatic's digestion were analized using agarose gel electrophoresis. We investigated 20 patients with venous leg ulcers and we found 2 heterozygous (10%) for G20210A mutation. None of the patients in the control group had G20210A mutation. Our study confirms the presence of G20210A mutation in the Romanian population. Our study also shows the link between venous leg ulcers and this polymorphism in the prothrombin gene. 相似文献
18.
Three monoclonal mouse hybridoma antibodies, designated 2AI, 4AI, and 5AI, specific for human plasma apolipoprotein A-I (apoA-I) were characterized. In an enzyme-linked immunosorbent assay (ELISA) each of the antibodies reacted with purified apoA-I and with A-I in normal human serum. Immunoblotting of apoA-I subjected to isoelectric focusing revealed that the three antibodies reacted with all the charge isomorphs of apoA-I and with proapoA-I. Using a solid phase competitive displacement assay, the antigenic determinant for antibody 5AI could be localized to cyanogen bromide fragment 3 of apoA-I (residues 113-148), while the epitope for antibody 4AI resided in cyanogen bromide fragment 4. Dot blot experiments and data obtained by the competitive displacement assay revealed that antibody 2AI reacts with high affinity with CNBr fragment 2 but that it also reacts with lower affinity with fragments 1 and 4. The antibody 5AI did not bind to a genetic variant of apoA-I (Glu----136 Lys), demonstrating that the substitution of a single amino acid in human apoA-I can cause the loss of an antigenic determinant. 相似文献
19.
Tissue-type plasminogen activator restriction fragment length polymorphism in the Chinese, Indians and Malays of Singapore 总被引:1,自引:0,他引:1
N Saha 《Human heredity》1989,39(6):364-366
A total of 215 subjects comprising 95 Chinese, 66 Malays and 54 Indians were investigated for restriction fragment length polymorphisms of the tissue-type plasminogen activator (PLAT) gene at an EcoRI site using the probe ptPA-4352. The phenotypic distribution showed a good agreement with the Hardy-Weinberg equilibrium. The gene frequencies of PLAT*1 were found to be 0.47 in the Chinese, 0.52 in the Malays and 0.41 in South Indians. 相似文献
20.
Rearrangements of highly polymorphic regions near telomeres of Saccharomyces cerevisiae. 总被引:28,自引:7,他引:21
We have examined the mitotic and meiotic properties of telomeric regions in various laboratory strains of yeast. Using a sequence (Y probe) derived from a cloned yeast telomere (J. Szostak and E. Blackburn, Cell 29:245-255, 1982), we found that various strains of Saccharomyces cerevisiae show extensive polymorphisms of restriction endonuclease fragment length. Some of the variation in the lengths of telomeric fragments appears to be under the control of a small number of genes. When DNA from various strains was digested with endonuclease KpnI, nearly all of the fragments homologous to the Y probe were found to be of different size. The pattern of fragments in different strains was extremely variable, with a greater degree of polymorphism than that observed for fragments containing the mobile TY1 element. Tetrad analysis of haploid meiotic segregants from diploids heterozygous for many different Y-homologous KpnI fragments revealed that most of them exhibited Mendelian (2:0) segregation. However, only a small proportion of these fragments displayed the obligate 2:2 parental segregation expected of simple allelic variants at the same chromosome end. From the segregations of these fragments, we concluded that some yeast telomeres lack a Y-homologous sequence and that the chromosome arms containing a Y-homologous sequence are different among various yeast strains. Regions near yeast telomeres frequently undergo rearrangement. Among eight tetrads from three different diploids, we have found three novel Y-homologous restriction fragments that appear to have arisen during meiosis. In all three cases, the appearance of a new fragment was accompanied by the loss of another band. In one of these cases, the rearrangement leading to a novel fragment arose in an isogenic diploid, in which both homologous chromosomes should have been identical. Among these same tetrads we also found examples of apparent mitotic gene conversions and mitotic recombination involving telemetric regions. 相似文献