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Sample records for actn3 r577x polymorphism

  1. The ACTN3 R577X polymorphism is associated with muscle power in male Japanese athletes.

    PubMed

    Kikuchi, Naoki; Nakazato, Koichi; Min, Seok-ki; Ueda, Dai; Igawa, Shoji

    2014-07-01

    In this study, we investigated whether the ACTN3 R577X polymorphism is associated with muscular power in Japanese collegiate athletes by analyzing the mean and peak power results of a 30-second Wingate anaerobic test (WAnT) with respect to the ACTN3 R577X genotype in 253 Japanese athletes (144 men and 109 women). Each athlete performed a 30-second WAnT with a resistance equal to 7.5% of his or her body weight. Genotyping for the ACTN3 R577X (rs1815739) polymorphism was performed using the TaqMan approach. The ACTN3 R577X genotypes exhibited a Hardy-Weinberg equilibrium distribution in our population. The relative and absolute mean power results of the 30-second WAnT did not differ significantly among the genotypes. However, the relative peak power result of the WAnT was significantly higher in the R-allele-dominant model groups than in the XX group in male but not female athletes. These results suggest that the ACTN3 R allele is associated with the relative peak power during the WAnT in male Japanese collegiate athletes.

  2. Is there an ACE ID - ACTN3 R577X polymorphisms interaction that influences sprint performance?

    PubMed

    Eynon, N; Alves, A J; Yamin, C; Sagiv, M; Duarte, J A; Oliveira, J; Ayalon, M; Goldhammer, E; Sagiv, M; Meckel, Y

    2009-12-01

    Functional R577X (rs.1815739) and ID (rs.5186) polymorphisms in the alpha-actinin-3 ( ACTN3) and the angiotensin converting enzyme (ACE) genes, respectively, have been associated with sprint performance. The aim of this study was to determine their effect on sprint performance among 81 Israeli sprinters and 240 healthy controls. Results revealed that the ACE II genotype+ ACTN3 R allele (P=0.003 for sprinters vs. controls), and the ACTN3 RR genotype +ACE I allele (P=0.001 for sprinters vs. controls) might be the genotype for sprinters. In the whole cohort the probability of ACTN3 RR genotype+ ACE I allele being a sprinter (odds ratio 2.67, 95% confidence interval 1.45-4.93) and of ACE II genotype+ ACTN3 R allele being a sprinter (odds ratio 3.57, 95% confidence interval 1.78-7.15) was significantly higher than that in the controls. In conclusion, the above data suggest that ACE ID/ ACTN3 R577X genotype combination is associated with sprint ability. However, ACE ID/ ACTN3 R577X genotype combination is not related to the level of performance.

  3. The ACTN3 R577X Polymorphism across Three Groups of Elite Male European Athletes

    PubMed Central

    Eynon, Nir; Ruiz, Jonatan R.; Femia, Pedro; Pushkarev, Vladimir P.; Cieszczyk, Pawel; Maciejewska-Karlowska, Agnieszka; Sawczuk, Marek; Dyatlov, Dmitry A.; Lekontsev, Evgeny V.; Kulikov, Leonid M.; Birk, Ruth

    2012-01-01

    The ACTN3 R577X polymorphism (rs1815739) is a strong candidate to influence elite athletic performance. Yet, controversy exists in the literature owing to between-studies differences in the ethnic background and sample size of the cohorts, the latter being usually low, which makes comparisons difficult. In this case:control genetic study we determined the association between elite athletic status and the ACTN3 R577X polymorphism within three cohorts of European Caucasian men, i.e. Spanish, Polish and Russian [633 cases (278 elite endurance and 355 power athletes), and 808 non-athletic controls]. The odds ratio (OR) of a power athlete harbouring the XX versus the RR genotype compared with sedentary controls was 0.54 [95% confidence interval (CI): 0.34–0.48; P = 0.006]. We also observed that the OR of an endurance athlete having the XX versus the RR genotype compared with power athletes was 1.88 (95%CI: 1.07–3.31; P = 0.028). In endurance athletes, the OR of a “world-class” competitor having the XX genotype versus the RR+RX genotype was 3.74 (95%CI: 1.08–12.94; P = 0.038) compared with those of a lower (“national”) competition level. No association (P>0.1) was noted between the ACTN3 R577X polymorphism and competition level (world-class versus national-level) in power athletes. Our data provide comprehensive support for the influence of the ACTN3 R577X polymorphism on elite athletic performance. PMID:22916217

  4. Relationship Between ACTN3 R577X Polymorphism and Physical Abilities in Polish Athletes.

    PubMed

    Orysiak, Joanna; Busko, Krzysztof; Mazur-RóŻycka, Joanna; Michalski, Radoslaw; Gajewski, Jan; Malczewska-Lenczowska, Jadwiga; Sitkowski, Dariusz

    2015-08-01

    The purpose of this study was to examine the association between α-actinin 3 (ACTN3) R577X polymorphism and physical abilities of male athletes performing various sports (volleyball, ice hockey, canoeing, swimming). One hundred eighty-five subjects were recruited for the study. The following measurements were taken: height of jump and power output in countermovement jump and spike jump (SPJ) and muscle strength of 10 muscle groups. The R577X polymorphism of ACTN3 was typed using polymerase chain reaction restriction fragment length polymorphism. The results showed that RR genotype carriers develop greater power output in SPJ than RX and XX individuals (44.6 ± 11.1, 42.6 ± 11.0, and 38.4 ± 7.9 W·kg(-1) for RR, RX, and XX genotypes, respectively) and height of jump in SPJ (0.537 ± 0.075, 0.523 ± 0.072, and 0.498 ± 0.053 m for RR, RX, and XX genotypes, respectively). Muscle strength did not differ between genotype groups. This suggests that the ACTN3 gene has a greater impact on determining dynamic movements than influencing static muscle strength.

  5. The ACTN3 R577X Polymorphism Is Associated with Cardiometabolic Fitness in Healthy Young Adults

    PubMed Central

    Deschamps, Chelsea L.; Connors, Kimberly E.; Klein, Matthias S.; Johnsen, Virginia L.; Shearer, Jane; Vogel, Hans J.; Devaney, Joseph M.; Gordish-Dressman, Heather; Many, Gina M.; Barfield, Whitney; Hoffman, Eric P.; Kraus, William E.; Hittel, Dustin S.

    2015-01-01

    Homozygosity for a premature stop codon (X) in the ACTN3 “sprinter” gene is common in humans despite the fact that it reduces muscle size, strength and power. Because of the close relationship between skeletal muscle function and cardiometabolic health we examined the influence of ACTN3 R577X polymorphism over cardiovascular and metabolic characteristics of young adults (n = 98 males, n = 102 females; 23 ± 4.2 years) from our Assessing Inherent Markers for Metabolic syndrome in the Young (AIMMY) study. Both males and females with the RR vs XX genotype achieved higher mean VO2 peak scores (47.8 ± 1.5 vs 43.2 ±1.8 ml/O2/min, p = 0.002) and exhibited higher resting systolic (115 ± 2 vs 105 ± mmHg, p = 0.027) and diastolic (69 ± 3 vs 59 ± 3 mmHg, p = 0.005) blood pressure suggesting a role for ACTN3 in the maintenance of vascular tone. We subsequently identified the expression of alpha-actinin 3 protein in pulmonary artery smooth muscle, which may explain the genotype-specific differences in cardiovascular adaptation to acute exercise. In addition, we utilized targeted serum metabolomics to distinguish between RR and XX genotypes, suggesting an additional role for the ACTN3 R577X polymorphism in human metabolism. Taken together, these results identify significant cardiometabolic effects associated with possessing one or more functional copies of the ACTN3 gene. PMID:26107372

  6. ACTN3 R577X polymorphism does not influence explosive leg muscle power in elite volleyball players.

    PubMed

    Ruiz, J R; Fernández del Valle, M; Verde, Z; Díez-Vega, I; Santiago, C; Yvert, T; Rodríguez-Romo, G; Gómez-Gallego, F; Molina, J J; Lucia, A

    2011-12-01

    We examined the association of R577X polymorphism (rs1815739) in the α-actinin-3 (ACTN3) gene with "explosive" leg muscle power performance in a group of male and female elite volleyball players (n=66, 31 men, 35 women) and in a group of non-athletic male and female young adults (n=334, 243 men, 91 women). We assessed power performance by means of the vertical squat and counter-movement jump tests. We also determined whether the genotypic frequencies of the ACTN3 R577X genotypes differed between groups. We did not observe any effect of the ACTN3 R577X polymorphism on study phenotypes in both groups, regardless of gender (all P>0.05). Genotype frequencies were similar between volleyball and control groups (P=0.095). Moreover, we did not find an association between the ACTN3 R577X polymorphism and the likelihood of being an elite volleyball player using the dominant (RR vs RX+XX) and the recessive model (RR+RX vs XX). In summary, these findings suggest that the ACTN3 R577X polymorphism does not influence explosive leg muscle power in elite volleyball players.

  7. Effective utilization of genetic information for athletes and coaches: focus on ACTN3 R577X polymorphism

    PubMed Central

    Kikuchi, Naoki; Nakazato, Koichi

    2015-01-01

    Training variants (type, intensity, and duration of exercise) can be selected according to individual aims and fitness assessment. Recently, various methods of resistance and endurance training have been used for muscle hypertrophy and VO2max improvement. Although several genetic variants are associated with elite athletic performance and muscle phenotypes, genetic background has not been used as variant for physical training. ACTN3 R577X is a well-studied genetic polymorphism. It is the only genotype associated with elite athletic performance in multiple cohorts. This association is strongly supported by mechanistic data from an Actn3-knockout mouse model. In this review, possible guidelines are discussed for effective utilization of ACTN3 R577X polymorphism for physical training. PMID:26526670

  8. ACTN3 R577X and other polymorphisms are not associated with elite endurance athlete status in the Genathlete study.

    PubMed

    Döring, Frank E; Onur, Simone; Geisen, Ulf; Boulay, Marcel R; Pérusse, Louis; Rankinen, Tuomo; Rauramaa, Rainer; Wolfahrt, Bernd; Bouchard, C

    2010-10-01

    Homozygosity for a premature stop codon at amino acid position 577 in the alpha-actinin-3 (ACTN3) gene leads to α-actinin-3 deficiency. This genotype is observed in approximately 18% of Caucasians. The ACTN3 R577X polymorphism has been previously associated with indicators of physical performance in several, but not all, studies. We examined the prevalence of R577X (rs1815739) and two additional haplotype tagging single nucleotide polymorphisms (htSNPs) of the ACTN3 gene (rs1791690 and rs2275998) in the Genathlete study comprising 316 male elite endurance athletes (VO2max 79.0+3.5 ml · kg(-1) · min(-1); mean +/- s) from North America, Finland, and Germany and 304 sedentary controls (VO2max 40.1+7.0 ml · kg(-1) · min(-1) matched by country of origin. The distribution of genotype and allele frequencies between the two groups was tested by Pearson chi-square and/or Fischer exact test. The prevalence of the 577X homozygote genotype was similar in endurance athletes and controls (20% and 17.5%, respectively). The resulting odds ratio for endurance performance in 577X homozygotes compared with 577R-allele carriers was 1.24 (95%CI 0.82-1.87, P = 0.3). The genotype distribution of the two htSNPs and haplotype frequencies did not differ significantly between athletes and controls. In conclusion, our findings indicate that ACTN3 R577X and other SNPs in ACTN3 are not genetic determinants of endurance performance in Caucasian males.

  9. Differing Evolutionary Histories of the ACTN3*R577X Polymorphism among the Major Human Geographic Groups

    PubMed Central

    Amorim, Carlos Eduardo G.; Acuña-Alonzo, Victor; Salzano, Francisco M.; Bortolini, Maria Cátira; Hünemeier, Tábita

    2015-01-01

    It has been proposed that the functional ACTN3*R577X polymorphism might have evolved due to selection in Eurasian human populations. To test this possibility we surveyed all available population-based data for this polymorphism and performed a comprehensive evolutionary analysis of its genetic diversity, in order to assess the action of adaptive and random mechanisms on its variation across human geographical distribution. The derived 577X allele increases in frequency with distance from Africa, reaching the highest frequencies on the American continent. Positive selection, detected by an extended haplotype homozygosisty test, was consistent only with the Eurasian data, but simulations with neutral models could not fully explain the results found in the American continent. It is possible that particularities of Native American population structure could be responsible for the observed allele frequencies, which would have resulted from a complex interaction between selective and random factors. PMID:25706920

  10. Genetic ACE I/D and ACTN3 R577X polymorphisms and adolescent idiopathic scoliosis.

    PubMed

    Luciano, R P; Wajchenberg, M; Almeida, S S; Amorim, C E N; Rodrigues, L M R; Araujo, R C; Puertas, E B; Faloppa, F

    2016-11-03

    The etiology of adolescent idiopathic scoliosis remains unknown. Angiotensin-converting enzyme and α-actinin-3 polymorphisms influence the characteristics of muscle fibers. The aim of this study was to examine the association between idiopathic scoliosis and genetic polymorphism of angiotensin-converting enzyme and α-actinin-3. Ninety-seven females with scoliosis, and 137 healthy, age-matched control females were studied. The presence of polymorphisms was determined by PCR. A χ(2) test was used to analyze differences, and odds ratios were estimated. The frequencies of ACE genotypes in the scoliotic group were 46.4% DD, 45.4% ID, and 8.2% II, while in the control group they were 40.1% DD, 43.8% ID, and 16.1% II (P = 0.197). The D allele had a frequency of 69.1% in patients with idiopathic scoliosis and 62% in the control group (P = 0.116). The frequencies of ACTN3 genotypes in females with scoliosis were 31.8% RR, 49.4% RX, and 18.8% XX, while in the control group they were 35% RR, 49% RX, and 16% XX (P = 0.810). The frequency of the R allele was 56.4% in the scoliotic group and 59.6% in the control group (P = 0.518). There was no statistically significant association between angiotensin-converting enzyme or α-actinin-3 polymorphisms and the presence of adolescent idiopathic scoliosis in females.

  11. The ACTN3 R577X genotype is associated with muscle function in a Japanese population.

    PubMed

    Kikuchi, Naoki; Yoshida, Shou; Min, Seok-ki; Lee, Kihyuk; Sakamaki-Sunaga, Mikako; Okamoto, Takanobu; Nakazato, Koichi

    2015-04-01

    Homozygosity for the common nonsense polymorphism R577X in the α-actinin-3 gene (ACTN3) causes complete α-actinin-3 deficiency in fast-twitch skeletal muscle fibers. This study investigated whether the ACTN3 R577X polymorphism affects fitness status using a battery of tests in a large Japanese cohort. In the present study, 1227 subjects (age: 25-85 years) were genotyped for the ACTN3 R577X polymorphism (rs1815739) using a TaqMan SNP genotyping assay (Applied Biosystems). All subjects were divided into 2 groups based on their age (<55 years and ≥55 years). All subjects completed a questionnaire about exercise habits and were subjected to a battery of tests to assess their fitness status (including grip strength test, chair stand test, and 8-foot walking test). A significant association between the ACTN3 R577X genotype and chair stand test performance was observed in the group of men ≥55 using ANCOVA adjusted for age and exercise habits (p = 0.036). The ACTN3 R577X genotype accounted for 2.5% of the variability in the results of the chair stand test among men in the ≥55 age group. Moreover, for the ≥55 age group, performance in the chair stand test was lower among those with the XX genotype than among those with the RR genotype (p = 0.024) or RX genotype (p = 0.005), unlike results for the <55 age group. No significant difference was noted for hand grip strength or 8-foot walking time. Thus, our results suggest that the ACTN3 R577X genotype is associated with lower-extremity muscle function in the Japanese population.

  12. ACTN3 R577X genotype is associated with sprinting in elite Japanese athletes.

    PubMed

    Mikami, E; Fuku, N; Murakami, H; Tsuchie, H; Takahashi, H; Ohiwa, N; Tanaka, H; Pitsiladis, Y P; Higuchi, M; Miyachi, M; Kawahara, T; Tanaka, M

    2014-02-01

    The ACTN3 R577X genotype has been found to associate with sprint/power phenotypes in all elite athlete cohorts investigated. This association has not been extensively studied in elite Asian athletes. The present study was undertaken to investigate the association between the ACTN3 R577X genotype and elite Japanese track and field athlete status. 299 elite Japanese track and field athletes (134 sprint/power athletes; 165 endurance/middle-power athletes) and 649 Japanese controls were genotyped for the ACTN3 R577X polymorphism. All athletes were of national or international level. Sprint/power athletes showed a higher frequency of RR + RX genotype than controls (111/134 [82.8%] vs. 478/649 [73.7%], P = 0.025 under the R-dominant model), while there was no significant difference between endurance/middle-power athletes and controls (126/165 [76.4%] vs. 478/649 [73.7%], P = 0.48 under the R-dominant model). Sprinters with the RR + RX genotype had significantly faster personal best times for the 100 m than those with XX genotype (10.42 ± 0.05 s vs. 10.64 ± 0.09 s, P = 0.042); no such association was found in the 400 m sprinters (47.02 ± 0.36 s vs. 47.56 ± 0.99 s, P = 0.62). ACTN3 R577X genotype is associated with sprint/power performance in elite Japanese track and field athletes, especially short sprint performance.

  13. ACTN3 R577X Genotypes Associate with Class II and Deep Bite Malocclusions

    PubMed Central

    Zebrick, Brian; Teeramongkolgul, Teesit; Nicot, Romain; Horton, Michael J.; Raoul, Gwenael; Ferri, Joel; Vieira, Alexandre R.; Sciote, James J.

    2014-01-01

    Introduction α-actinins are myofibril anchor proteins which influence contractile properties of skeletal muscle. ACTN2 is expressed in slow type I and fast type II fibers whereas ACTN3 is expressed only in fast fibers. ACTN3 homozygosity for the 577X stop codon (i.e. changing 577RR to 577XX - the R577X polymorphism) results in the absence of α-actinin-3 in about 18% of Europeans, diminished fast contractile ability, enhanced endurance performance and reduced bone mass or bone mineral density. We have examined ACTN3 expression and genetic variation in masseter muscle of orthognathic surgery patients to determine genotype associations with malocclusion. Methods Clinical information, masseter muscle biopsies and saliva samples were obtained from 60 subjects. Genotyping for ACTN3 SNPs, RT-PCR quantitation of muscle gene message and muscle morphometric fiber type properties were compared to determine statistical differences between genotype and phenotype. Results Muscle mRNA expression level was significantly different for ACTN3 SNP genotypes (p<0.01). The frequency of ACTN3 genotypes was significantly different for sagittal and vertical classifications of malocclusion with the clearest association being elevated 577XX genotype in skeletal class II malocclusion (p = 0.003). This genotype also resulted in significantly smaller diameter of fast type II fibers in masseter muscle (p = 0.002). Conclusion ACTN3 577XX is overrepresented in skeletal class II malocclusion, suggesting a biologic influence during bone growth. ACTN3 577XX is underrepresented in deep bite malocclusion, suggesting muscle differences contribute to variations in vertical facial dimensions. PMID:25439211

  14. ACTN3 R577X Gene Variant is Associated with Muscle-related Phenotypes in elite Chinese Sprint/Power Athletes.

    PubMed

    Yang, Ruoyu; Shen, Xunzhang; Wang, Yubin; Voisin, Sarah; Cai, Guang; Fu, Yongnan; Xu, Wangyu; Eynon, Nir; Bishop, David J; Yan, Xu

    2016-07-16

    The ACTN3 R577X polymorphism (rs1815739) has been shown to influence athletic performance. The aim of the current study was to investigate the prevalence of this polymorphism in elite Chinese track and field athletes, and to explore its effects on athletes' level of competition and lower-extremity power. We compared the ACTN3 R577X genotypes and allele frequencies in 59 elite sprint/power athletes, 44 elite endurance athletes, and 50 healthy controls from Chinese Han origin. We then subcategorized the athletes into international-level and national-level, and investigated the effects of ACTN3 genotype on lower-extremity power. Genotype distribution of the sprint/power athletes was significantly different from endurance athletes (p = 0.001) and controls (p < 0.001). The frequency of the RR genotype was significantly higher in international-level than in the national-level sprint/power athletes (p = 0.004), with no international-level sprint/power athletes with XX genotype. The best standing long jump (SLJ) and standing vertical jump (SVJ) results of sprint/power athletes were better in the RR than the RX+XX genotypes (p = 0.004 and p = 0.001, respectively). In conclusion, the ACTN3 R577X polymorphism influences the level of competition and lower extremity power of elite Chinese S/P athletes. Including relevant phenotypes such as muscle performance in future studies is important to further understand the effects of gene variants on elite athletic performance.

  15. Association of ACTN3 R577X but not ACE I/D gene variants with elite rugby union player status and playing position.

    PubMed

    Heffernan, S M; Kilduff, L P; Erskine, R M; Day, S H; McPhee, J S; McMahon, G E; Stebbings, G K; Neale, J P H; Lockey, S J; Ribbans, W J; Cook, C J; Vance, B; Raleigh, S M; Roberts, C; Bennett, M A; Wang, G; Collins, M; Pitsiladis, Y P; Williams, A G

    2016-03-01

    We aimed to quantify the ACE I/D and ACTN3 R577X (rs1815739) genetic variants in elite rugby athletes (rugby union and league) and compare genotype frequencies to controls and between playing positions. The rugby athlete cohort consisted of 507 Caucasian men, including 431 rugby union athletes that for some analyses were divided into backs and forwards and into specific positional groups: front five, back row, half backs, centers, and back three. Controls were 710 Caucasian men and women. Real-time PCR of genomic DNA was used to determine genotypes using TaqMan probes and groups were compared using χ(2) and odds ratio (OR) statistics. Correction of P values for multiple comparisons was according to Benjamini-Hochberg. There was no difference in ACE I/D genotype between groups. ACTN3 XX genotype tended to be underrepresented in rugby union backs (15.7%) compared with forwards (24.8%, P = 0.06). Interestingly, the 69 back three players (wings and full backs) in rugby union included only six XX genotype individuals (8.7%), with the R allele more common in the back three (68.8%) than controls (58.0%; χ(2) = 6.672, P = 0.04; OR = 1.60) and forwards (47.5%; χ(2) = 11.768, P = 0.01; OR = 2.00). Association of ACTN3 R577X with playing position in elite rugby union athletes suggests inherited fatigue resistance is more prevalent in forwards, while inherited sprint ability is more prevalent in backs, especially wings and full backs. These results also demonstrate the advantage of focusing genetic studies on a large cohort within a single sport, especially when intrasport positional differences exist, instead of combining several sports with varied demands and athlete characteristics.

  16. Association of ACTN3 R577X but not ACE I/D gene variants with elite rugby union player status and playing position

    PubMed Central

    Kilduff, L. P.; Erskine, R. M.; Day, S. H.; McPhee, J. S.; McMahon, G. E.; Stebbings, G. K.; Neale, J. P. H.; Lockey, S. J.; Ribbans, W. J.; Cook, C. J.; Vance, B.; Raleigh, S. M.; Roberts, C.; Bennett, M. A.; Wang, G.; Collins, M.; Pitsiladis, Y. P.; Williams, A. G.

    2016-01-01

    We aimed to quantify the ACE I/D and ACTN3 R577X (rs1815739) genetic variants in elite rugby athletes (rugby union and league) and compare genotype frequencies to controls and between playing positions. The rugby athlete cohort consisted of 507 Caucasian men, including 431 rugby union athletes that for some analyses were divided into backs and forwards and into specific positional groups: front five, back row, half backs, centers, and back three. Controls were 710 Caucasian men and women. Real-time PCR of genomic DNA was used to determine genotypes using TaqMan probes and groups were compared using χ2 and odds ratio (OR) statistics. Correction of P values for multiple comparisons was according to Benjamini-Hochberg. There was no difference in ACE I/D genotype between groups. ACTN3 XX genotype tended to be underrepresented in rugby union backs (15.7%) compared with forwards (24.8%, P = 0.06). Interestingly, the 69 back three players (wings and full backs) in rugby union included only six XX genotype individuals (8.7%), with the R allele more common in the back three (68.8%) than controls (58.0%; χ2 = 6.672, P = 0.04; OR = 1.60) and forwards (47.5%; χ2 = 11.768, P = 0.01; OR = 2.00). Association of ACTN3 R577X with playing position in elite rugby union athletes suggests inherited fatigue resistance is more prevalent in forwards, while inherited sprint ability is more prevalent in backs, especially wings and full backs. These results also demonstrate the advantage of focusing genetic studies on a large cohort within a single sport, especially when intrasport positional differences exist, instead of combining several sports with varied demands and athlete characteristics. PMID:26757799

  17. Interaction Between ACE I/D and ACTN3 R557X Polymorphisms in Polish Competitive Swimmers.

    PubMed

    Grenda, Agata; Leońska-Duniec, Agata; Kaczmarczyk, Mariusz; Ficek, Krzysztof; Król, Paweł; Cięszczyk, Paweł; Zmijewski, Piotr

    2014-09-29

    We hypothesized that the ACE ID / ACTN3 R577X genotype combination was associated with sprint and endurance performance. Therefore, the purpose of the present study was to determine the interaction between both ACE ID and ACTN3 R577X polymorphisms and sprint and endurance performance in swimmers. Genomic DNA was extracted from oral epithelial cells using GenElute Mammalian Genomic DNA Miniprep Kit (Sigma, Germany). All samples were genotyped using a real-time poly- merase chain reaction. The ACE I/D and the ACTN3 R577X genotype frequencies met Hardy-Weinberg expectations in both swimmers and controls. When the two swimmer groups, long distance swimmers (LDS) and short distance swimmers (SDS), were compared with control subjects in a single test, a significant association was found only for the ACE polymorphism, but not for ACTN3. Additionally, four ACE/ACTN3 combined genotypes (ID/RX, ID/XX, II/RX and II/XX) were statistically significant for the LDS versus Control comparison, but none for the SDS versus Control comparison. The ACE I/D and the ACTN3 R577X polymorphisms did not show any association with sprint swimming, taken individually or in combination. In spite of numerous previous reports of associations with athletic status or sprint performance in other sports, the ACTN3 R577X polymorphism, in contrast to ACE I/D, was not significantly associated with elite swimming status when considered individually. However, the combined analysis of the two loci suggests that the co-occurrence of the ACE I and ACTN3 X alleles may be beneficial to swimmers who compete in long distance races.

  18. Association of the ACTN3 R557X polymorphism with glucose tolerance and gene expression of sarcomeric proteins in human skeletal muscle

    PubMed Central

    Riedl, Isabelle; Osler, Megan E; Benziane, Boubacar; Chibalin, Alexander V; Zierath, Juleen R

    2015-01-01

    A common polymorphism (R577X) in the α-actinin (ACTN) 3 gene, which leads to complete deficiency of a functional protein in skeletal muscle, could directly influence metabolism in the context of health and disease. Therefore, we tested the hypothesis that states of glucose tolerance are associated with the ACTN3 R577X genotype. We analyzed the prevalence of the ACTN3 R577X polymorphism in people with normal glucose tolerance (NGT) and type 2 diabetes (T2D) and measured muscle-specific α-actinin 2 and 3 mRNA and protein abundance in skeletal muscle biopsies. Furthermore, we investigated the protein abundance of the myosin heavy chain isoforms and the components of the mitochondrial electron transport chain in skeletal muscle from people with NGT or T2D. mRNA of selected sarcomeric z-disk proteins was also assessed. Although the prevalence of the ACTN3 577XX genotype was higher in T2D patients, genotype distribution was unrelated to metabolic control or obesity. ACTN2 and ACTN3 mRNA expression and protein abundance was unchanged between NGT and T2D participants. Protein abundance of mitochondrial complexes II and IV was related to genotype and glucose tolerance status. Gene expression of sarcomeric z-disk proteins was increased in skeletal muscle from NGT participants with the ACTN3 577XX genotype. While genetic variation in ACTN3 does not influence metabolic control, genotype does appear to influence gene expression of other sarcomeric proteins, which could contribute to the functional properties of skeletal muscle and the fatigue-resistant phenotype associated with the R577X polymorphism. PMID:25780092

  19. Association of ACTN3 polymorphisms with BMD, and physical fitness of elderly women

    PubMed Central

    Min, Seok-Ki; Lim, Seung-Taek; Kim, Chang-Sun

    2016-01-01

    [Purpose] Association of ACTN3 polymorphism with bone mineral density and the physical fitness of elderly women is still unclear. Therefore, this study investigated the association between ACTN3 genotype and bone mineral density, and the physical fitness of elderly women. [Subjects and Methods] Sixty-eight elderly women (67.38 ± 3.68 years) were recruited at a Seongbuk-Gu (Seoul, Korea) Medical Service Public Health Center. Measurements of physical fitness included muscle strength, muscle endurance, flexibility, agility, balance and VO2max. Bone mineral density (BMD), upper limb muscle mass, lower limb muscle mass, percent body fat and body fat mass for the entire body were measured by dual-energy X-ray absorptiometry and an analyzer. Genotyping for the ACTN3 R577X (rs1815739) polymorphism was performed using the TaqMan approach. [Results] ACTN3 gene distribution of subjects were in the Hardy-Weinberg equilibrium (p=0.694). The relative bone mineral density trunk, pelvis and spine differed significantly among the ACTN3 genotypes. There were no significant differences among bone mineral densities of the head, arms, legs, ribs and total, but the RR genotype tended to be higher than other genotypes. Physical fitness was not significantly different among the ACTN3 genotypes. [Conclusion] These results suggest that ACTN3 gene polymorphisms could be used as one of the genetic determinants of bone mass in elderly women, and in particular, they indicate that individuals with the RR genotype have higher BMD and bone mineral composition. PMID:27821924

  20. ACE and ACTN3 genes polymorphisms among female Hungarian athletes in the aspect of sport disciplines.

    PubMed

    Bosnyák, E; Trájer, E; Udvardy, A; Komka, Z; Protzner, A; Kováts, T; Györe, I; Tóth, M; Pucsok, J; Szmodis, M

    2015-12-01

    The aim of the study was to determine the importance of two sport-associated gene polymorphisms, alpha-actinin-3 R577X (ACTN3) and angiotensin-converting enzyme I/D (ACE), among Hungarian athletes in different sports. The examination was carried out only on women (n = 100). Sport-specific groups were formed in order to guarantee the most homogeneous clusters. Human genomic DNA was isolated from blood, and genotyping was performed by polymerase chain reaction. To measure the differences between the participating groups, Chi-squared test was performed using Statistica 9.0 for Windows® (significance level: p < 0.05). In comparing the ACE I/D allele frequencies, significant difference was detected between water polo (I = 61.11%; D = 38.89%) and combat sports (I = 35.71%, D = 64.29%) athletes (p < 0.03). There was no statistical difference when ACE I/D alleles in combat sports and kayaking/rowing (p > 0.05) were compared. A similarity was detectable in the I allele frequencies of the water polo (61.11%) and kayaking/rowing (56.67%) groups. The ACTN3 R/X polymorphism showed no differences in comparison with the sport groups. R allele frequencies were higher in every group compared to the X allele. The potential significance of the ACE I allele in sports of an aerobic nature was not clearly confirmed among Hungarian athletes.

  1. ACE I/D and ACTN3 R/X polymorphisms as potential factors in modulating exercise-related phenotypes in older women in response to a muscle power training stimuli.

    PubMed

    Pereira, Ana; Costa, Aldo M; Izquierdo, Mikel; Silva, António J; Bastos, Estela; Marques, Mário C

    2013-10-01

    Genetic variation of the human ACE I/D and ACTN3 R577X polymorphisms subsequent to 12 weeks of high-speed power training on maximal strength (1RM) of the arm and leg muscles, muscle power performance (counter-movement jump), and functional capacity (sit-to-stand test) was examined in older Caucasian women [n = 139; mean age 65.5 (8.2) years; 67.0 (10.0) kg and 1.57 (0.06) m]. Chelex 100 was used for DNA extraction, and genotype was determined by PCR-RFLP methods. Muscular strength, power, and functional testing were conducted at baseline (T1) and after 12 weeks (T2) of high-speed power training. At baseline, the ACE I/D and ACTN3 R/X polymorphisms were not associated with muscle function or muscularity phenotypes in older Caucasian women. After the 12-week high-speed training program, subjects significantly increased their muscular and functional capacity performance (p < 0.05). For both polymorphisms, significant genotype-training interaction (p < 0.05) was found in all muscular performance indices, except for 1RM leg extension in the ACE I/D (p = 0.187). Analyses of the combined effects between genotypes showed significant differences in all parameters (p < 0.05) in response to high-speed power training between the power (ACTN3 RR + RX & ACE DD) versus "non-power" muscularity-oriented genotypes (ACTN3 XX & ACE II + ID)]. Our data suggest that the ACE and ACTN3 genotypes (single or combined) exert a significant influence in the muscle phenotypes of older Caucasian women in response to high-speed power training. Thus, the ACE I/D and ACTN3 R/X polymorphisms are likely factors in modulating exercise-related phenotypes in older women, particularly in response to a resistance training stimuli.

  2. Sequence analysis of the equine ACTN3 gene in Australian horse breeds.

    PubMed

    Thomas, K C; Hamilton, N A; North, K N; Houweling, P J

    2014-03-15

    The sarcomeric α-actinins, encoded by the genes ACTN2 and ACTN3, are major structural components of the Z-line and have high sequence similarity. α-Actinin-2 is present in all skeletal muscle fibres, while α-actinin-3 has developed specialized expression in only type 2 (fast, glycolytic) fibres. A common single nucleotide polymorphism (SNP) in the human ACTN3 gene (R577X) has been found to influence muscle performance in elite athletes and the normal population. For this reason, equine ACTN3 (eACTN3) is considered to be a possible candidate that may influence horse performance. In this study, the intron/exon boundaries and entire coding region of eACTN3 have been sequenced in five Australian horse breeds (Thoroughbred, Arabian, Standardbred, Clydsdale and Shire) and compared to the eACTN3 GenBank sequence. A total of 34 SNPs were identified, of which 26 were intronic and eight exonic. All exonic SNPs were synonymous; however, five intronic SNPs showed significant differences between breeds. A total of 72 horses were genotyped for a SNP located in the promoter region of the eACTN3 gene (g. 1104 G>A) which differed significantly between breed groups. We hypothesize that this polymorphism influences eACTN3 expression and with further studies may provide a novel marker of horse performance in the future.

  3. Muscle-Related Polymorphisms (MSTN rs1805086 and ACTN3 rs1815739) Are Not Associated with Exceptional Longevity in Japanese Centenarians

    PubMed Central

    Yvert, Thomas; Zempo, Hirofumi; Naito, Hisashi; Abe, Yukiko; Arai, Yasumichi; Murakami, Haruka; Miyachi, Motohiko; Pareja-Galeano, Helios; Emanuele, Enzo; Hirose, Nobuyoshi; Lucia, Alejandro

    2016-01-01

    Myostatin (MSTN) and α-actinin-3 (ACTN3) genes are potentially associated with preservation of muscle mass and oxidative capacity, respectively. To explore the possible role of these genes in exceptional longevity (EL), the allele/genotype frequency distribution of two polymorphisms in MSTN (rs1805086, K153R) and ACTN3 (rs1815739, R577X) was studied in Japanese centenarians of both sexes (n = 742) and healthy controls (n = 814). The rs1805086 R-allele (theoretically associated with muscle mass preservation at the expense of oxidative capacity) was virtually absent in the two groups, where genotype distributions were virtually identical. Likewise, no differences in allele (p = 0.838 (women); p = 0.193 (men); p = 0.587 (both sexes)) or genotype distribution were found between groups for ACTN3 rs1815739 (p = 0.975 (women), p = 0.136 (men), p = 0.752 (both sexes)). Of note, however, the frequency of the rs1805086 R-allele observed here is the lowest been reported to date whereas that of the ‘highly oxidative/efficient’ rs1815739 XX genotype in Japanese male centenarians (33.3%) or supercentenarians of both sexes (≥110 years) are the highest (32.6%), for a non-American population. No definite conclusions can be inferred in relation to EL owing to its lack of association with both rs1815739 and rs1805086. However, it cannot be excluded that these gene variants could eventually be related to a “healthy” metabolic phenotype in the Japanese population. Further research might determine if such metabolic profile is among the factors that can potentially predispose these individuals to live longer than Caucasians and what genetic variants might be actually involved. PMID:27861536

  4. Single and combined influence of ACE and ACTN3 genotypes on muscle phenotypes in octogenarians.

    PubMed

    Garatachea, Nuria; Fiuza-Luces, Carmen; Torres-Luque, Gema; Yvert, Thomas; Santiago, Catalina; Gómez-Gallego, Félix; Ruiz, Jonatan R; Lucia, Alejandro

    2012-07-01

    We studied the single and combined influence of the ACE I/D and the ACTN3 R577X polymorphisms on muscle phenotypes (thigh muscles' cross-sectional area assessed with magnetic resonance imaging) and strength (maximal handgrip, 30-s chair stand test), functional ability during activities of daily living (Barthel index) and bone mineral density (proximal femur) in Caucasian (Spanish) community-dwelling old people [n = 81, 59 women; mean age 82.8 ± 4.8 years (range 71-93 years)]. We found no significantly differences in the aforementioned phenotypes across ACE and ACTN3 genotypes (all P > 0.05), except for handgrip in the ACE I/D recessive model (DD 19.5 ± 6.7 kg, ID 24.0 ± 9.1 kg, II 22.1 ± 7.9; P = 0.047), yet statistical significance disappeared after correction for multiple comparisons. Likewise, the analyses of the combined effects between genotypes did not yield any significant difference (all P > 0.05) between the two 'extreme' genotypes [theoretically 'power or muscularity oriented' [(ACTN3 RR + RX & ACE DD) versus 'non-power' (ACTN3 XX & ACE II + ID)]. The aforementioned analyses were adjusted by sex, age and physical activity levels as covariates. Logistic regression analysis revealed no significant association of single or combined effect of ACE and ACTN3 genotypes or genotype combination group (ACE + ACTN3) with sarcopenia (i.e. being in the lowest 25th sex-specific percentile for a combined score of the muscle and functional phenotypes we measured). Though ACE I/D and ACTN3 R577X polymorphisms are candidates to modulate exercise-related phenotypes in adults, our data suggest that they do not exert a major influence in the muscle phenotypes of old people. More studies with larger sample sizes are needed.

  5. Overrepresentation of the ACTN3 XX genotype in elite canoe and kayak paddlers.

    PubMed

    Orysiak, Joanna; Sitkowski, Dariusz; Zmijewski, Piotr; Malczewska-Lenczowska, Jadwiga; Cieszczyk, Pawel; Zembron-Lacny, Agnieszka; Pokrywka, Andrzej

    2015-04-01

    The aim of the study was to examine the association between the ACTN3 R577X polymorphism in canoe sprint athletes (canoe and kayak paddlers) and their results at 200- or 1000-m distance. Eighty-six European white male athletes divided into 2 groups-successful, who were outstanding at national championships, and nonsuccessful in these competitions-and 354 nonathletic controls were included in this study. The R577X polymorphism of ACTN3 was typed using PCR-RFLP. ACTN3 genotype distribution among all tested athletes and controls was in Hardy-Weinberg equilibrium. The odds ratio (OR) for successful 1000-m athletes harboring the XX genotype compared with sedentary controls was 2.95 (95% confidence interval [CI]: 1.37-6.35), but the OR for nonsuccessful 200-m athletes having the XX genotype compared with controls was 2.64 (95% CI: 1.30-5.36). These results suggest that factors associated with the ACTN3 XX genotype in canoe and kayak paddlers might provide some competitive advantage in performance at 1000 m, but it seems to limit at 200 m. Further studies aimed at development of training strategies based on genetic factors are needed.

  6. Analysis of the ACTN3 heterozygous genotype suggests that α-actinin-3 controls sarcomeric composition and muscle function in a dose-dependent fashion

    PubMed Central

    Hogarth, Marshall W.; Garton, Fleur C.; Houweling, Peter J.; Tukiainen, Taru; Lek, Monkol; Macarthur, Daniel G.; Seto, Jane T.; Quinlan, Kate G.R.; Yang, Nan; Head, Stewart I.; North, Kathryn N.

    2016-01-01

    A common null polymorphism (R577X) in ACTN3 causes α-actinin-3 deficiency in ∼18% of the global population. There is no associated disease phenotype, but α-actinin-3 deficiency is detrimental to sprint and power performance in both elite athletes and the general population. However, despite considerable investigation to date, the functional consequences of heterozygosity for ACTN3 are unclear. A subset of studies have shown an intermediate phenotype in 577RX individuals, suggesting dose-dependency of α-actinin-3, while others have shown no difference between 577RR and RX genotypes. Here, we investigate the effects of α-actinin-3 expression level by comparing the muscle phenotypes of Actn3+/− (HET) mice to Actn3+/+ [wild-type (WT)] and Actn3−/− [knockout (KO)] littermates. We show reduction in α-actinin-3 mRNA and protein in HET muscle compared with WT, which is associated with dose-dependent up-regulation of α-actinin-2, z-band alternatively spliced PDZ-motif and myotilin at the Z-line, and an incremental shift towards oxidative metabolism. While there is no difference in force generation, HET mice have an intermediate endurance capacity compared with WT and KO. The R577X polymorphism is associated with changes in ACTN3 expression consistent with an additive model in the human genotype-tissue expression cohort, but does not influence any other muscle transcripts, including ACTN2. Overall, ACTN3 influences sarcomeric composition in a dose-dependent fashion in mouse skeletal muscle, which translates directly to function. Variance in fibre type between biopsies likely masks this phenomenon in human skeletal muscle, but we suggest that an additive model is the most appropriate for use in testing ACTN3 genotype associations. PMID:26681802

  7. Analysis of the ACTN3 heterozygous genotype suggests that α-actinin-3 controls sarcomeric composition and muscle function in a dose-dependent fashion.

    PubMed

    Hogarth, Marshall W; Garton, Fleur C; Houweling, Peter J; Tukiainen, Taru; Lek, Monkol; Macarthur, Daniel G; Seto, Jane T; Quinlan, Kate G R; Yang, Nan; Head, Stewart I; North, Kathryn N

    2016-03-01

    A common null polymorphism (R577X) in ACTN3 causes α-actinin-3 deficiency in ∼ 18% of the global population. There is no associated disease phenotype, but α-actinin-3 deficiency is detrimental to sprint and power performance in both elite athletes and the general population. However, despite considerable investigation to date, the functional consequences of heterozygosity for ACTN3 are unclear. A subset of studies have shown an intermediate phenotype in 577RX individuals, suggesting dose-dependency of α-actinin-3, while others have shown no difference between 577RR and RX genotypes. Here, we investigate the effects of α-actinin-3 expression level by comparing the muscle phenotypes of Actn3(+/-) (HET) mice to Actn3(+/+) [wild-type (WT)] and Actn3(-/-) [knockout (KO)] littermates. We show reduction in α-actinin-3 mRNA and protein in HET muscle compared with WT, which is associated with dose-dependent up-regulation of α-actinin-2, z-band alternatively spliced PDZ-motif and myotilin at the Z-line, and an incremental shift towards oxidative metabolism. While there is no difference in force generation, HET mice have an intermediate endurance capacity compared with WT and KO. The R577X polymorphism is associated with changes in ACTN3 expression consistent with an additive model in the human genotype-tissue expression cohort, but does not influence any other muscle transcripts, including ACTN2. Overall, ACTN3 influences sarcomeric composition in a dose-dependent fashion in mouse skeletal muscle, which translates directly to function. Variance in fibre type between biopsies likely masks this phenomenon in human skeletal muscle, but we suggest that an additive model is the most appropriate for use in testing ACTN3 genotype associations.

  8. Individual and combined influence of ACE and ACTN3 genes on muscle phenotypes in Polish athletes.

    PubMed

    Orysiak, Joanna; Mazur-Różycka, Joanna; Busko, Krzysztof; Gajewski, Jan; Szczepanska, Beata; Malczewska-Lenczowska, Jadwiga

    2017-02-08

    The aim of this study was to examine the association between ACE and ACTN3 genes, independently or in combination, and muscle strength and power in male and female athletes. The study involved 398 young male (n=266) and female (n=132) athletes representing various sport disciplines (ice hockey, canoeing, swimming, volleyball). All were Caucasians. The following measurements were taken: height of jump and mechanical power in countermovement jump (CMJ) and spike jump (SPJ), and muscle strength of 10 muscle groups (flexors and extensors of the elbow, shoulder, hip, knee and trunk). The ID polymorphism of ACE and the R577X polymorphism of ACTN3 were typed using PCR (polymerase chain reaction) and PCR-RFLP (polymerase chain reaction - restriction fragment length polymorphism), respectively. The genotype distribution of the ACE and ACTN3 genes did not differ significantly between groups of athletes for either sex. There was no association between ACE and ACTN3 genotypes (alone or in combination) and sum of muscle strength, height of jump or mechanical power in both jump tests (CMJ and SPJ) for male and female athletes. These findings do not support an influential role of the ACE and ACTN3 genes in determining power/strength performance of elite athletes.

  9. Evidence for ACTN3 as a genetic modifier of Duchenne muscular dystrophy.

    PubMed

    Hogarth, Marshall W; Houweling, Peter J; Thomas, Kristen C; Gordish-Dressman, Heather; Bello, Luca; Pegoraro, Elena; Hoffman, Eric P; Head, Stewart I; North, Kathryn N

    2017-01-31

    Duchenne muscular dystrophy (DMD) is characterized by muscle degeneration and progressive weakness. There is considerable inter-patient variability in disease onset and progression, which can confound the results of clinical trials. Here we show that a common null polymorphism (R577X) in ACTN3 results in significantly reduced muscle strength and a longer 10 m walk test time in young, ambulant patients with DMD; both of which are primary outcome measures in clinical trials. We have developed a double knockout mouse model, which also shows reduced muscle strength, but is protected from stretch-induced eccentric damage with age. This suggests that α-actinin-3 deficiency reduces muscle performance at baseline, but ameliorates the progression of dystrophic pathology. Mechanistically, we show that α-actinin-3 deficiency triggers an increase in oxidative muscle metabolism through activation of calcineurin, which likely confers the protective effect. Our studies suggest that ACTN3 R577X genotype is a modifier of clinical phenotype in DMD patients.

  10. Evidence for ACTN3 as a genetic modifier of Duchenne muscular dystrophy

    PubMed Central

    Hogarth, Marshall W.; Houweling, Peter J.; Thomas, Kristen C.; Gordish-Dressman, Heather; Bello, Luca; Vishwanathan, V.; Chidambaranathan, S.; Douglas Biggar, W.; McAdam, Laura C.; Mah, Jean K.; Tulinius, Mar; Cnaan, Avital; Morgenroth, Lauren P.; Leshner, Robert; Tesi-Rocha, Carolina; Thangarajh, Mathula; Duong, Tina; Kornberg, Andrew; Ryan, Monique; Nevo, Yoram; Dubrovsky, Alberto; Clemens, Paula R.; Abdel-Hamid, Hoda; Connolly, Anne M.; Pestronk, Alan; Teasley, Jean; Bertorini, Tulio E.; Webster, Richard; Kolski, Hanna; Kuntz, Nancy; Driscoll, Sherilyn; Bodensteiner, John B.; Carlo, Jose; Gorni, Ksenija; Lotze, Timothy; Day, John W.; Karachunski, Peter; Henricson, Erik K.; Abresch, Richard T.; McDonald, Craig M.; Pegoraro, Elena; Hoffman, Eric P.; Head, Stewart I.; North, Kathryn N.

    2017-01-01

    Duchenne muscular dystrophy (DMD) is characterized by muscle degeneration and progressive weakness. There is considerable inter-patient variability in disease onset and progression, which can confound the results of clinical trials. Here we show that a common null polymorphism (R577X) in ACTN3 results in significantly reduced muscle strength and a longer 10 m walk test time in young, ambulant patients with DMD; both of which are primary outcome measures in clinical trials. We have developed a double knockout mouse model, which also shows reduced muscle strength, but is protected from stretch-induced eccentric damage with age. This suggests that α-actinin-3 deficiency reduces muscle performance at baseline, but ameliorates the progression of dystrophic pathology. Mechanistically, we show that α-actinin-3 deficiency triggers an increase in oxidative muscle metabolism through activation of calcineurin, which likely confers the protective effect. Our studies suggest that ACTN3 R577X genotype is a modifier of clinical phenotype in DMD patients. PMID:28139640

  11. Interaction of ACTN3 gene polymorphism and muscle imbalance effects on kinematic efficiency in combat sports athletes

    PubMed Central

    Lee, Namju; Park, Sok

    2016-01-01

    [Purpose] The purpose of this study was to determine the interaction of ACTN3 gene polymorphism and muscle imbalance effects on kinematic efficiency changes in combat sports athletes. [Methods] Six types of combat sports athletes (Judo, Taekwondo, boxing, kendo, wrestling, and Korean Ssi-reum) participated in the study. ATCN3 gene polymorphism and muscle imbalance in lower extremity were evaluated followed by analysis of differences of moment in hip, knee, and ankle joint during V-cut jumping and stop. To examine the moment difference due to an interaction of ATCN3 polymorphism and muscle imbalance, all participants were divided into 4 groups (R+MB, R+MIB, X+MB, and X+MIB). [Results] There was no significant difference of hip, knee, and ankle joint moment in R allele and X allele during V-cut jumping and stop based on ACTN3 gene polymorphism. Otherwise, muscle imbalance of knee moment in X-axis and ground reaction force of knee in Z-axis showed a higher significance in muscle imbalance during V-cut jumping and stop compared to muscle balance (p<0.05). In addition, joint analysis showed that muscle imbalance in X allele group had significantly higher knee moment of V-cut ground reaction force in X-axis and higher ankle moment of jumping ground reaction force in X and Z-axis compared to muscle balance with R and/or X group (p <0.05). [Conclusion] This study confirmed that muscle imbalance in lower extremity of combat athletes might induce higher risk factors of sports injury incidence than genetic factor and training might reduce the ratio of sports injury risk incidence. PMID:27508148

  12. Altered Ca2+ kinetics associated with α-actinin-3 deficiency may explain positive selection for ACTN3 null allele in human evolution.

    PubMed

    Head, Stewart I; Chan, Stephen; Houweling, Peter J; Quinlan, Kate G R; Murphy, Robyn; Wagner, Sören; Friedrich, Oliver; North, Kathryn N

    2015-01-01

    Over 1.5 billion people lack the skeletal muscle fast-twitch fibre protein α-actinin-3 due to homozygosity for a common null polymorphism (R577X) in the ACTN3 gene. α-Actinin-3 deficiency is detrimental to sprint performance in elite athletes and beneficial to endurance activities. In the human genome, it is very difficult to find single-gene loss-of-function variants that bear signatures of positive selection, yet intriguingly, the ACTN3 null variant has undergone strong positive selection during recent evolution, appearing to provide a survival advantage where food resources are scarce and climate is cold. We have previously demonstrated that α-actinin-3 deficiency in the Actn3 KO mouse results in a shift in fast-twitch fibres towards oxidative metabolism, which would be more "energy efficient" in famine, and beneficial to endurance performance. Prolonged exposure to cold can also induce changes in skeletal muscle similar to those observed with endurance training, and changes in Ca2+ handling by the sarcoplasmic reticulum (SR) are a key factor underlying these adaptations. On this basis, we explored the effects of α-actinin-3 deficiency on Ca2+ kinetics in single flexor digitorum brevis muscle fibres from Actn3 KO mice, using the Ca2+-sensitive dye fura-2. Compared to wild-type, fibres of Actn3 KO mice showed: (i) an increased rate of decay of the twitch transient; (ii) a fourfold increase in the rate of SR Ca2+ leak; (iii) a threefold increase in the rate of SR Ca2+ pumping; and (iv) enhanced maintenance of tetanic Ca2+ during fatigue. The SR Ca2+ pump, SERCA1, and the Ca2+-binding proteins, calsequestrin and sarcalumenin, showed markedly increased expression in muscles of KO mice. Together, these changes in Ca2+ handling in the absence of α-actinin-3 are consistent with cold acclimatisation and thermogenesis, and offer an additional explanation for the positive selection of the ACTN3 577X null allele in populations living in cold environments during recent

  13. Genes for elite power and sprint performance: ACTN3 leads the way.

    PubMed

    Eynon, Nir; Hanson, Erik D; Lucia, Alejandro; Houweling, Peter J; Garton, Fleur; North, Kathryn N; Bishop, David J

    2013-09-01

    The ability of skeletal muscles to produce force at a high velocity, which is crucial for success in power and sprint performance, is strongly influenced by genetics and without the appropriate genetic make-up, an individual reduces his/her chances of becoming an exceptional power or sprinter athlete. Several genetic variants (i.e. polymorphisms) have been associated with elite power and sprint performance in the last few years and the current paradigm is that elite performance is a polygenic trait, with minor contributions of each variant to the unique athletic phenotype. The purpose of this review is to summarize the specific knowledge in the field of genetics and elite power performance, and to provide some future directions for research in this field. Of the polymorphisms associated with elite power and sprint performance, the α-actinin-3 R577X polymorphism provides the most consistent results. ACTN3 is the only gene that shows a genotype and performance association across multiple cohorts of elite power athletes, and this association is strongly supported by mechanistic data from an Actn3 knockout mouse model. The angiotensin-1 converting enzyme insertion/deletion polymorphism (ACE I/D, registered single nucleotide polymorphism [rs]4646994), angiotensinogen (AGT Met235Thr rs699), skeletal adenosine monophosphate deaminase (AMPD1) Gln(Q)12Ter(X) [also termed C34T, rs17602729], interleukin-6 (IL-6 -174 G/C, rs1800795), endothelial nitric oxide synthase 3 (NOS3 -786 T/C, rs2070744; and Glu298Asp, rs1799983), peroxisome proliferator-activated receptor-α (PPARA Intron 7 G/C, rs4253778), and mitochondrial uncoupling protein 2 (UCP2 Ala55Val, rs660339) polymorphisms have also been associated with elite power performance, but the findings are less consistent. In general, research into the genetics of athletic performance is limited by a small sample size in individual studies and the heterogeneity of study samples, often including athletes from multiple

  14. G Allele of the IGF2 ApaI Polymorphism Is Associated With Judo Status.

    PubMed

    Itaka, Toshio; Agemizu, Kenichiro; Aruga, Seiji; Machida, Shuichi

    2016-07-01

    Itaka, T, Agemizu, K, Aruga, S, and Machida, S. G allele of the IGF2 ApaI polymorphism is associated with judo status. J Strength Cond Res 30(7): 2043-2048, 2016-Previous studies have reported that the insulin-like growth factor 2 (IGF2) ApaI polymorphism is associated with body mass index, fat mass, and grip strength. Competitive judo requires high levels of strength and power. The purpose of this study was to investigate the association between the IGF2 ApaI and ACTN3 R577X polymorphisms and judo status. The subjects were 156 male judo athletes from a top-level university in Japan. They were divided into 3 groups based on their competitive history: international-level athletes, national-level athletes, and others. Genomic DNA was extracted from the saliva of each athlete, and the maximal isometric strength of the trunk muscles and handgrip strength were measured. Genotyping by polymerase chain reaction-restriction fragment length polymorphism was used to detect IGF2 (rs680) and α-actinin-3 (ACTN3) (rs1815739) gene polymorphisms. The genotype frequencies of the 2 gene polymorphisms were compared among the 3 groups of judo athletes and controls. International-level judo athletes showed a higher frequency of the GG + GA genotype of the IGF2 gene than that of the national-level athletes and others. There was an inverse linear correlation between the frequency of the IGF2 AA genotype and level of judo performance (p = 0.041). Back muscle strength relative to height and weight was higher in subjects with the GG + GA genotype than in those with the AA genotype. Conversely, the ACTN3 R577X polymorphism was not associated with judo status. Additionally, no differences were found in back muscle or handgrip strength among the ACTN3 genotypes. In conclusion, the results indicate that the IGF2 gene polymorphism may be associated with judo status.

  15. Effect of angiotensin I-converting enzyme and α-actinin-3 gene polymorphisms on sport performance.

    PubMed

    Gunel, Tuba; Gumusoglu, Ece; Hosseini, Mohammad Kazem; Yilmazyildirim, Eda; Dolekcap, Ismail; Aydinli, Kilic

    2014-04-01

    Genetic polymorphism is considered to be associated with human physical performance. The angiotensin I-converting enzyme insertion/deletion (ACE I/D) and the α-actinin-3 gene (ACTN3) R577X polymorphisms have been widely investigated for such associations, and functional ACE I/D and ACTN3 R577X polymorphisms have been associated with sprinter performance. The aim of this study was to determine the effect of these polymorphisms on sport performance among 37 elite athletes and 37 healthy controls. The ACE II genotype was identified in 32.43% of the control group and 8.11% of elite athletes, the DD genotype in 37.84% of the control group and 51.35% of the elite athletes, and the ID genotype in 29.73% of the control group and 40.54% of the elite athletes. With regard to the ACTN3 gene, the XX genotype, which confers an advantage for endurance activities, was identified in 10.81% of the control group and 35.14% of the elite athletes. The XX genotype was observed more frequently than the RR genotype (advantageous for sprinting), which was identified in 2.70% of the control group and 10.81% of elite athletes. The RX genotype (observed in 86.48% of the control group and in 54.05% of the elite athletes) was the most common genotype of the individuals in the present study. The study showed that ACTN3 and ACE gene polymorphisms have an effect on muscle power; however, larger studies are required.

  16. ACTN3 Genotype, Athletic Status, and Life Course Physical Capability: Meta-Analysis of the Published Literature and Findings from Nine Studies

    PubMed Central

    Alfred, Tamuno; Ben-Shlomo, Yoav; Cooper, Rachel; Hardy, Rebecca; Cooper, Cyrus; Deary, Ian J; Gunnell, David; Harris, Sarah E; Kumari, Meena; Martin, Richard M; Moran, Colin N; Pitsiladis, Yannis P; Ring, Susan M; Sayer, Avan Aihie; Smith, George Davey; Starr, John M; Kuh, Diana; Day, Ian NM

    2011-01-01

    The ACTN3 R577X (rs1815739) genotype has been associated with athletic status and muscle phenotypes, although not consistently. Our objective was to conduct a meta-analysis of the published literature on athletic status and investigate its associations with physical capability in several new population-based studies. Relevant data were extracted from studies in the literature, comparing genotype frequencies between controls and sprint/power and endurance athletes. For life course physical capability, data were used from two studies of adolescents and seven studies in the Healthy Ageing across the Life Course (HALCyon) collaborative research program, involving individuals aged between 53 and 90+ years. We found evidence from the published literature to support the hypothesis that in Europeans the RR genotype is more common among sprint/power athletes compared with their controls. There is currently no evidence that the X allele is advantageous to endurance athleticism. We found no association between R577X and grip strength (P = 0.09, n = 7,672 in males; P = 0.90, n = 7,839 in females), standing balance, timed get up and go, or chair rises in our studies of physical capability. The ACTN3 R577X genotype is associated with sprint/power athletic status in Europeans, but does not appear to be associated with objective measures of physical capability in the general population. Hum Mutat 32:1–11, 2011. © 2011 Wiley-Liss, Inc. PMID:21542061

  17. The influence of genetic polymorphisms on performance and cardiac and hemodynamic parameters among Brazilian soccer players.

    PubMed

    Dionísio, Thiago José; Thiengo, Carlos Rogério; Brozoski, Daniel Thomas; Dionísio, Evandro José; Talamoni, Guilherme Augusto; Silva, Roberto Braga; Garlet, Gustavo Pompermaier; Santos, Carlos Ferreira; Amaral, Sandra Lia

    2017-01-24

    This study investigated whether ACTN3 R577X, AMPD1 C34T, I/D ACE, and M235T AGT polymorphisms can affect performance tests such as jumping, sprinting, and endurance in 220 young male athletes from professional minor league soccer team from São Paulo Futebol Clube, Brazil. I/D ACE and M235T AGT polymorphisms were also analyzed according to cardiac and hemodynamic parameters. Athletes were grouped or not by age. DNA from saliva and Taqman assays were used for genotyping 220 athletes and the results were associated with performance tests. Ventricle mass, ventricle end-diastolic diameter, end-diastolic volume, and ejection fraction were assessed by echocardiogram. Arterial pressure, heart rate, and oximetry were assessed by a cardioscope. The main results of this study were that athletes who carried RR/RX (ACTN3) and DD (ACE) genotypes presented better performance during jump and sprint tests. On the other hand, athletes with ID/II genotype presented better results during endurance test, while AGT genotypes did not seem to favor the athletes during the evaluated physical tests. CC genotype (AMPD1) only favored the athletes during 10-m sprint test. Although there are environmental interactions influencing performance, the present results suggest that RR/RX ACTN3 and ACE DD genotypes may benefit athletes in activities that require strength and speed, while II ACE genotype may benefit athletes in endurance activities. This information could help coaches to plan the training session to improve the athletes' performance.

  18. Effect of ACTN3 gene on strength and endurance in soccer players.

    PubMed

    Pimenta, Eduardo M; Coelho, Daniel B; Veneroso, Christiano E; Barros Coelho, Ering J; Cruz, Izinara R; Morandi, Rodrigo F; De A Pussieldi, Guilherme; Carvalho, Maria R S; Garcia, Emerson S; De Paz Fernández, José A

    2013-12-01

    Sports efficiency in activities in which strength and speed are the determining factors has been associated to the ACTN3 gene, which is responsible for the expression of α-actinin-3. Soccer is a mainly aerobic sport because of its long duration, but the acute actions that define the game demand a lot of strength and speed. The purpose of the present study was to compare the performance capacity of soccer players with different genotype groups of ACTN3 (XX, RX, and RR) in strength, speed, and endurance tests. Two hundred professional players of Brazilian soccer first division teams participated in this study. Speed, jump, and endurance test results were compared with the polymorphisms of the ACTN3 gene. It was noticed that RR individuals spent less time to run a 10-m path, compared with XX individuals (p < 0.05). The RR individuals also presented lower time rates at the 20- and 30-m path, compared with RX and XX individuals (p < 0.05). In jump tests, RR individuals presented higher rates, compared with RX and XX individuals (p < 0.05). As for aerobic tests, the XX individuals presented higher rates of V[Combining Dot Above]O2 max, compared with the RR group (p < 0.05), and did not differ from the RX group. The main conclusion of this study is that soccer players of genotype ACTN3/RR are the fastest in short distances and present higher jump potential. ACTN3/XX individuals presented the highest aerobic capacity. These findings can be used in training load adjustment and can influence the development of tactical schemes in soccer matches.

  19. The ACTN3 genotype in soccer players in response to acute eccentric training.

    PubMed

    Pimenta, Eduardo Mendonça; Coelho, Daniel Barbosa; Cruz, Izinara Rosse; Morandi, Rodrigo Figueiredo; Veneroso, Christiano Eduardo; de Azambuja Pussieldi, Guilherme; Carvalho, Maria Raquel Santos; Silami-Garcia, Emerson; De Paz Fernández, José Antonio

    2012-04-01

    Genetic factors can interfere with sporting performance. The identification of genetic predisposition of soccer players brings important information to trainers and coaches for individual training loads adjustment. Different responses to eccentric training could be observed by the genotype referred to as α-actinin-3 (ACTN3) in biomarkers of muscle damage, hormones and inflammatory responses. The aim of this study was to compare acute inflammatory responses, muscle damage and hormonal variations according to the eccentric training in soccer professional athletes with different genetic profiles of ACTN3 (XX, RX and RR). 37 soccer professional athletes (9 XX, 13 RX, 15 RR) were randomly divided into five stations associated to eccentric muscle contraction and plyometrics. Blood samples were taken from athletes pre-eccentric training, immediately after (post), 2- and 4-h post-eccentric training to determine hormone responses (cortisol and testosterone), muscle damage (CK and α-actin), and inflammatory responses (IL-6). After eccentric training, athletes XX presented higher levels for CK (4-h post), α-actin (post and 2-h post) and cortisol (post) compared to RR and RX athletes. However, RR and RX athletes presented higher levels of testosterone (post) and IL-6 (2 h post and 4 h post) compared to athletes XX. The main conclusion of this study is that professional soccer athletes homozygous to ACTN3XX gene are more susceptible to eccentric damage and present a higher catabolic state, demonstrated by metabolic, hormonal and immune responses post an eccentric training, in comparison to ACTN3RR and ACTN3RX groups.

  20. Distribution of Angiotensin-1 Converting Enzyme Insertion/Deletion and α-Actinin-3 Codon 577 Polymorphisms in Turkish Male Soccer Players.

    PubMed

    Ulucan, Korkut; Sercan, Canan; Biyikli, Türker

    2015-01-01

    Angiotensin-1 converting enzyme (ACE) gene and α-actinin-3 (ACTN3) gene polymorphisms are considered to be the most important candidate genes for genetic predisposition to human athletic performance. In the present study, we aimed to analyze the distribution of ACE and ACTN3 polymorphisms for the first time in male Turkish soccer players. In this prospective study, our cohort consisted of 25 professional players, all with Turkish ancestry. Polymerase chain reaction (PCR)-restriction length polymorphism was used for the characterization of the genotype of ACTN3 and single PCR for ACE. For ACE genotype, 16%, 44%, and 40% of the players had insertion/insertion (II), insertion/deletion (ID), and deletion/deletion (DD) genotypes, respectively, whereas 20% had XX, 36% had RX, and 44% had RR genotypes for ACTN3. When we examined the allelic percentages, for ACE, D allele was recorded as 62 and I as 38, and for ACTN3, R allele was 62 and X was 38. Our results were in agreement with the previous reports, indicating the presence of ACTN3 D and ACE X allele in soccer players. We suggest that ACE and ACTN3 genotypes are important biomarkers for genetic counseling for the individuals who are prone to be successful soccer players.

  1. α -Actinin TvACTN3 of Trichomonas vaginalis is an RNA-binding protein that could participate in its posttranscriptional iron regulatory mechanism.

    PubMed

    Calla-Choque, Jaeson Santos; Figueroa-Angulo, Elisa Elvira; Ávila-González, Leticia; Arroyo, Rossana

    2014-01-01

    Trichomonas vaginalis is a sexually transmitted flagellated protist parasite responsible for trichomoniasis. This parasite is dependent on high levels of iron, favoring its growth and multiplication. Iron also differentially regulates some trichomonad virulence properties by unknown mechanisms. However, there is evidence to support the existence of gene regulatory mechanisms at the transcriptional and posttranscriptional levels that are mediated by iron concentration in T. vaginalis. Thus, the goal of this study was to identify an RNA-binding protein in T. vaginalis that interacts with the tvcp4 RNA stem-loop structure, which may participate in a posttranscriptional iron regulatory mechanism mediated by RNA-protein interactions. We performed RNA electrophoretic mobility shift assay (REMSA) and supershift, UV cross-linking, Northwestern blot, and western blot (WB) assays using cytoplasmic protein extracts from T. vaginalis with the tvcp4 RNA hairpin structure as a probe. We identified a 135-kDa protein isolated by the UV cross-linking assays as α-actinin 3 (TvACTN3) by MALDI-TOF-MS that was confirmed by LS-MS/MS and de novo sequencing. TvACTN3 is a cytoplasmic protein that specifically binds to hairpin RNA structures from trichomonads and humans when the parasites are grown under iron-depleted conditions. Thus, TvACTN3 could participate in the regulation of gene expression by iron in T. vaginalis through a parallel posttranscriptional mechanism similar to that of the IRE/IRP system.

  2. Preliminary Findings of α -Actinin-3 Gene Distribution in Elite Turkish Wind Surfers.

    PubMed

    Ulucan, K; Göle, S; Altindas, N; Güney, Ai

    2013-06-01

    A common polymorphism in the α -actinin-3 ( ACTN3 R577X) gene represents one of the most widely examined variations in terms of performance and genetic predisposition to certain sports. The aim of the present study was to examine the ACTN3 R577X polymorphism in elite Turkish wind surfers. The genotyping procedure was carried out by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Five male and three female wind surfers, eight elite wind surfers in total, were enrolled in the study. Five of the surfers had RX, two had XX and one had RR genotypes. Previous findings indicated that the X allele was the endurance allele. Our findings were in agreement with the previous reports. Seven of our subjects had at least one copy of the X allele that was considered to have a tendency to prolong endurance. Our preliminary results must be supported with further studies in greater numbers of subjects to clarify the effect of gene polymorphism.

  3. New frontiers in sport training: genetics and artistic gymnastics.

    PubMed

    Morucci, Gabriele; Punzi, Tiziana; Innocenti, Giovanni; Gulisano, Massimo; Ceroti, Marco; Pacini, Stefania

    2014-02-01

    The increasing understanding of the genetic influences in sport has prompted an association study between the athletic performances and the polymorphisms of the angiotensin-converting enzyme (ACE), the α-actinin-3 (ACTN3), and the vitamin D receptor genes. The details of these gene polymorphisms can provide useful information to improve and plan new modern training programs for elite athletes. Eighty Italian male high level gymnasts were trained and tested for gymnastic-specific exercises and tested in all the men's artistic gymnastic apparatus (floor, pommel horse, rings, vault, parallel bars, and horizontal bar), and then genotyped. The training parameters of volume, intensity, and density of each gymnast were periodically measured during the season in each apparatus from the tests performed, and the seasonal average values were calculated. Gene polymorphisms were determined by polymerase chain reaction restriction fragment length polymorphism assay and studied in association with the performance results. The performances of ACE II gymnasts were significantly lower than that of the ACE ID/DD gymnasts in the apparatus expressing power features, confirming the predisposition of these athletes toward power-oriented sport. Gymnasts with ACTN3 RR/RX genotypes did not show a predisposition to the power-oriented apparatus, having worse performances compared with that of the ACTN3 XX gymnasts. Similarly, gymnasts with ACE II + ACTN3 RR/RX combined genotypes showed lower performances in comparison with that of the other gymnasts. Vitamin D receptor polymorphisms showed no significant association with the athletic performances. Because ACE insertion/deletion (I/D) and ACTN3 R577X polymorphisms heavily affect the physical performance of elite male gymnasts, the Italian Gymnastic Federation trainers have started to customize the current high-level training programs.

  4. Genetic characterization of physical activity behaviours in university students enrolled in kinesiology degree programs.

    PubMed

    Many, Gina M; Kendrick, Zachary; Deschamps, Chelsea L; Sprouse, Courtney; Tosi, Laura L; Devaney, Joseph M; Gordish-Dressman, Heather; Barfield, Whitney; Hoffman, Eric P; Houmard, Joseph A; Pescatello, Linda S; Vogel, Hans J; Shearer, Jane; Hittel, Dustin S

    2017-03-01

    Studies of physical activity behaviours have increasingly shown the importance of heritable factors such as genetic variation. Nonsynonymous polymorphisms of alpha-actinin 3 (ACTN3) and the β-adrenergic receptors 1 and 3 (ADRB1 and ADRB3) have been previously associated with exercise capacity and cardiometabolic health. We thus hypothesized that these polymorphisms are also related to physical activity behaviours in young adults. To test this hypothesis we examined relationships between ACTN3 (R577X), ARDB1 (Arg389Gly), ADRB3 (Trp64Arg), and physical activity behaviours in university students. We stratified for student enrollment in kinesiology degree programs compared with nonmajors as we previously found this to be a predictor of physical activity. We did not identify novel associations between physical activity and ACTN3. However, the minor alleles of ADRB1 and ADRB3 were significantly underrepresented in kinesiology students compared with nonmajors. Furthermore, carriers of the ADRB1 minor allele reported reduced participation in moderate physical activity and increased afternoon fatigue compared with ancestral allele homozygotes. Together, these findings suggest that the heritability of physical activity behaviours in young adults may be linked to nonsynonymous polymorphisms within β-adrenergic receptors.

  5. Optimum polygenic profile to resist exertional rhabdomyolysis during a marathon

    PubMed Central

    Valero, Marjorie; Salinero, Juan José; Lara, Beatriz; Gallo-Salazar, César; Areces, Francisco

    2017-01-01

    Purpose Exertional rhabdomyolysis can occur in individuals performing various types of exercise but it is unclear why some individuals develop this condition while others do not. Previous investigations have determined the role of several single nucleotide polymorphisms (SNPs) to explain inter-individual variability of serum creatine kinase (CK) concentrations after exertional muscle damage. However, there has been no research about the interrelationship among these SNPs. The purpose of this investigation was to analyze seven SNPs that are candidates for explaining individual variations of CK response after a marathon competition (ACE = 287bp Ins/Del, ACTN3 = p.R577X, CKMM = NcoI, IGF2 = C13790G, IL6 = 174G>C, MLCK = C37885A, TNFα = 308G>A). Methods Using Williams and Folland’s model, we determined the total genotype score from the accumulated combination of these seven SNPs for marathoners with a low CK response (n = 36; serum CK <400 U·L-1) vs. marathoners with a high CK response (n = 31; serum CK ≥400 U·L-1). Results At the end of the race, low CK responders had lower serum CK (290±65 vs. 733±405 U·L-1; P<0.01) and myoglobin concentrations (443±328 vs. 1009±971 ng·mL-1, P<0.01) than high CK responders. Although the groups were similar in age, anthropometric characteristics, running experience and training habits, total genotype score was higher in low CK responders than in high CK responders (5.2±1.4 vs. 4.4±1.7 point, P = 0.02). Conclusion Marathoners with a lower CK response after the race had a more favorable polygenic profile than runners with high serum CK concentrations. This might suggest a significant role of genetic polymorphisms in the levels of exertional muscle damage and rhabdomyolysis. Yet other SNPs, in addition to exercise training, might also play a role in the values of CK after damaging exercise. PMID:28257486

  6. Genetic influences in sport and physical performance.

    PubMed

    Puthucheary, Zudin; Skipworth, James R A; Rawal, Jai; Loosemore, Mike; Van Someren, Ken; Montgomery, Hugh E

    2011-10-01

    ). Almost 200 polymorphisms are known to exist in the vitamin D receptor (VDR) gene. VDR genotype is associated with differences in strength in premenopausal women. VDR expression decreases with age and VDR genotype is associated with fat-free mass and strength in elderly men and women. Muscle fibre type determination is complex. Whilst initial composition is likely to be strongly influenced by genetic factors, training has significant effects on fibre shifts. Polymorphisms of the peroxisome proliferator-activated receptor α (PPARα) gene and R577x polymorphism of the ACTN3 gene are both associated with specific fibre compositions. Alterations in cardiac size have been associated with both increased performance and excess cardiovascular mortality. PPARα is a ligand-activated transcription factor that regulates genes involved in fatty acid uptake and oxidation, lipid metabolism and inflammation. Psychology plays an important role in training, competition, tolerance of pain and motivation. However, the role of genetic variation in determining psychological state and responses remains poorly understood; only recently have specific genes been implicated in motivational behaviour and maintenance of exercise. Thyroid hormone receptors exist within the brain and influence both neurogenesis and behaviour. With the current state of knowledge, the field of genetic influences on sports performance remains in its infancy, despite over a decade of research.

  7. Polymorphism in Energetic Materials

    DTIC Science & Technology

    2008-01-01

    2008 NRL REVIEW 71 Polymorphism in Energetic Materials J.R. Deschamps,1 D.A. Parrish,1 and R.J. Butcher2 1Laboratory for Structure of Matter...can lead to substantial alterations in stability and performance. The authors recently reported on the crystal structures of five polymorphs of picryl...cally distinct forms. Since the properties of a solid sub- stance are determined by its composition and structure , polymorphs, although chemically

  8. Polymorphous computing fabric

    DOEpatents

    Wolinski, Christophe Czeslaw [Los Alamos, NM; Gokhale, Maya B [Los Alamos, NM; McCabe, Kevin Peter [Los Alamos, NM

    2011-01-18

    Fabric-based computing systems and methods are disclosed. A fabric-based computing system can include a polymorphous computing fabric that can be customized on a per application basis and a host processor in communication with said polymorphous computing fabric. The polymorphous computing fabric includes a cellular architecture that can be highly parameterized to enable a customized synthesis of fabric instances for a variety of enhanced application performances thereof. A global memory concept can also be included that provides the host processor random access to all variables and instructions associated with the polymorphous computing fabric.

  9. Polymorphism and solvatomorphism 2008.

    PubMed

    Brittain, Harry G

    2010-09-01

    Papers and patents that deal with polymorphism and solvatomorphism have been summarized in an annual review. The review is divided into sections that cover articles of general interest, computational and theoretical studies, preparative and isolation methods, structural characterization and properties of polymorphic and solvatomorphic systems, studies of phase transformations, effects associated with secondary processing, and United States patents issued during 2008.

  10. Disappearing Polymorphs Revisited

    PubMed Central

    Bučar, Dejan-Krešimir; Lancaster, Robert W; Bernstein, Joel

    2015-01-01

    Nearly twenty years ago, Dunitz and Bernstein described a selection of intriguing cases of polymorphs that disappear. The inability to obtain a crystal form that has previously been prepared is indeed a frustrating and potentially serious problem for solid-state scientists. This Review discusses recent occurrences and examples of disappearing polymorphs (as well as the emergence of elusive crystal forms) to demonstrate the enduring relevance of this troublesome, but always captivating, phenomenon in solid-state research. A number of these instances have been central issues in patent litigations. This Review, therefore, also highlights the complex relationship between crystal chemistry and the law. PMID:26031248

  11. Polymorphism of sorbitol

    NASA Astrophysics Data System (ADS)

    Nezzal, Amale; Aerts, Luc; Verspaille, Marleen; Henderickx, Geert; Redl, Andreas

    2009-07-01

    The polymorphism of sorbitol was investigated, confirming the existence of four anhydrous crystalline phases plus the hydrate. The crystallised melt (CM), the alpha form, and the gamma form were obtained via a dry route. The CM was confirmed to be a crystalline state with a spherulite morphology. The alpha form was obtained via direct conversion from the CM, in contrast to more complicated routes previously reported, and was found to have a very high crystallinity. Gamma crystals were obtained by seeding the melt at high temperature; however, crystallinity was clearly less than for alpha crystals. Despite its lower crystallinity, the gamma polymorph was found to be the most stable of the anhydrous crystalline forms; this was confirmed by its high melting point and low hygroscopicity. In contrast, the alpha polymorph has a relatively high melting point but lacks moisture stability at high relative humidity. The hydrate form has the same resistance to moisture as the gamma form, but melts at a lower temperature. The combination of both a high melting point and high stability in the presence of water makes the gamma polymorph best suited for confectionary applications.

  12. Investigation of Uranium Polymorphs

    SciTech Connect

    Sweet, Lucas E.; Henager, Charles H.; Hu, Shenyang Y.; Johnson, Timothy J.; Meier, David E.; Peper, Shane M.; Schwantes, Jon M.

    2011-08-01

    The UO3-water system is complex and has not been fully characterized, even though these species are common throughout the nuclear fuel cycle. As an example, most production schemes for UO3 result in a mixture of up to six or more different polymorphic phases, and small differences in these conditions will affect phase genesis that ultimately result in measureable changes to the end product. As a result, this feature of the UO3-water system may be useful as a means for determining process history. This research effort attempts to better characterize the UO3-water system with a variety of optical techniques for the purpose of developing some predictive capability for estimating process history in polymorphic phases of unknown origin. Three commercially relevant preparation methods for the production of UO3 were explored. Previously unreported low temperature routes to β- and γ-UO3 were discovered. Raman and fluorescence spectroscopic libraries were established for pure and mixed polymorphic forms of UO3 in addition to the common hydrolysis products of UO3. An advantage of the sensitivity of optical fluorescence microscopy over XRD has been demonstrated. Preliminary aging studies of the α and γ forms of UO3 have been conducted. In addition, development of a 3-D phase field model used to predict phase genesis of the system was initiated. Thermodynamic and structural constants that will feed the model have been gathered from the literature for most of the UO3 polymorphic phases.

  13. Enzyme polymorphisms in Canarium

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fifty-two accessions of Canarium involving seven species, C. ovatum, C. album, C. megalanthum, C. harveyi, C. indicum, C. mehenbethene, and C. odontophyllum were studied for isozyme polymorphisms. Starch gel electrophoresis with a histidine-citrate buffer system (pH 6.5) was employed to assay six en...

  14. Polymorphism of phosphoric oxide

    USGS Publications Warehouse

    Hill, W.L.; Faust, G.T.; Hendricks, S.B.

    1943-01-01

    The melting points and monotropic relationship of three crystalline forms of phosphoric oxide were determined by the method of quenching. Previous vapor pressure data are discussed and interpreted to establish a pressure-temperature diagram (70 to 600??) for the one-component system. The system involves three triple points, at which solid, liquid and vapor (P4O10) coexist in equilibrium, namely: 420?? and 360 cm., 562?? and 43.7 cm. and 580?? and 55.5 cm., corresponding to the hexagonal, orthorhombic and stable polymorphs, respectively, and at least two distinct liquids, one a stable polymer of the other, which are identified with the melting of the stable form and the hexagonal modification, respectively. Indices of refraction of the polymorphs and glasses were determined. The density and the thermal, hygroscopic and structural properties of the several phases are discussed.

  15. Stability of Polymeric Crystalline Polymorphs

    NASA Astrophysics Data System (ADS)

    Sinkovits, Daniel W.; Kumar, Sanat K.

    2014-03-01

    In the search for polymeric materials with novel properties, such as high dielectric constant and low loss, an important attribute of a material is its crystal structure. Most polymers can crystallize into multiple polymorphs whose properties vary. Therefore, the question of which polymorphs are thermodynamically preferred under what conditions is of great importance. We generate polymorphs using atomistic molecular dynamics simulations and tackle the question of stability using a combination of molecular dynamics and Monte Carlo techniques. Multidisciplinary University Research Initiative (MURI).

  16. Energetics of kaolin polymorphs

    SciTech Connect

    Ligny, D. de; Navrotsky, A.

    1999-04-01

    The enthalpy of formation of kaolin polymorphs at 298 K has been determined by drop-solution calorimetry into molten lead borate at 975 K. Corrections have been made for impurities in the samples. The standard enthalpy of formation from the elements is: kaolinite {minus}4120.2 {+-} 6.6 kJ/mol, dickite {minus}4107.6 {+-} 5.7 kJ/mol, nacrite {minus}4104.0 {+-} 7.6 kJ/mol, and halloysite {minus}4097.5 {+-} 5.6 kJ/mol. Using entropy data from the literature, the standard free energy of formation from the elements at 298 K is /{minus}3799.4 {+-} 6.4 kJ/mol for kaolinite, {minus}3785.1 {+-} 5.6 kJ/mol for dickite, and {minus}3776.8 {+-} 5.8 kJ/mol for halloysite. The effect of crystallinity (Hinckley index ranging from 1.6 to 0.4) on the enthalpy of formation of kaolinite is smaller than 5 kJ/mol, the experimental error. The relative stability of the polymorphs probably does not change significantly with pressure and temperature over their range of occurrence. Thus the geological occurrence of halloysite, nacrite, and dickite, which are metastable phases, must be interpreted in terms of kinetics or as the result of a specific synthesis path, rather than as resulting from changes in the thermodynamically stable phase assemblage.

  17. Polymorphic Evolutionary Games.

    PubMed

    Fishman, Michael A

    2016-06-07

    In this paper, I present an analytical framework for polymorphic evolutionary games suitable for explicitly modeling evolutionary processes in diploid populations with sexual reproduction. The principal aspect of the proposed approach is adding diploid genetics cum sexual recombination to a traditional evolutionary game, and switching from phenotypes to haplotypes as the new game׳s pure strategies. Here, the relevant pure strategy׳s payoffs derived by summing the payoffs of all the phenotypes capable of producing gametes containing that particular haplotype weighted by the pertinent probabilities. The resulting game is structurally identical to the familiar Evolutionary Games with non-linear pure strategy payoffs (Hofbauer and Sigmund, 1998. Cambridge University Press), and can be analyzed in terms of an established analytical framework for such games. And these results can be translated into the terms of genotypic, and whence, phenotypic evolutionary stability pertinent to the original game.

  18. SOD2 polymorphisms: unmasking the effect of polymorphism on splicing

    PubMed Central

    Shao, Jing; Chen, Lishan; Marrs, Brian; Lee, Lin; Huang, Hai; Manton, Kenneth G; Martin, George M; Oshima, Junko

    2007-01-01

    Background The SOD2 gene encodes an antioxidant enzyme, mitochondrial superoxide dismutase. SOD2 polymorphisms are of interest because of their potential roles in the modulation of free radical-mediated macromolecular damage during aging. Results We identified a new splice variant of SOD2 in human lymphoblastoid cell lines (LCLs). The alternatively spliced product was originally detected by exon trapping of a minigene in order to examine the consequences of an intronic polymorphism found upstream of exon 4 (nucleotide 8136, 10T vs 9T). Examination of the transcripts derived from the endogenous loci in five LCLs with or without the intron 3 polymorphism revealed low levels of an in-frame deletion of exon 4 that were different from those detected by the exon trap assay. This suggested that exon trapping of the minigene unmasked the effect of the 10T vs 9T polymorphism on the splicing of the adjacent exon. We also determined the frequencies of single nucleotide polymorphisms in a sample of US African-Americans and non-African-Americans ages 65 years and older who participated in the 1999 wave of the National Long Term Care Survey (NLTCS). Particularly striking differences between African-Americans and non-African-Americans were found for the frequencies of genotypes at the 10T/9T intron 3 polymorphism. Conclusion Exon trapping can unmask in vitro splicing differences caused by a 10T/9T intron 3 polymorphism. Given the recent evidence that SOD2 is in a region on chromosome 6 linked to susceptibility to hypertension, it will be of interest to investigate possible associations of this polymorphism with cardiovascular disorders. PMID:17331249

  19. Preferential Nucleation during Polymorphic Transformations

    PubMed Central

    Sharma, H.; Sietsma, J.; Offerman, S. E.

    2016-01-01

    Polymorphism is the ability of a solid material to exist in more than one phase or crystal structure. Polymorphism may occur in metals, alloys, ceramics, minerals, polymers, and pharmaceutical substances. Unresolved are the conditions for preferential nucleation during polymorphic transformations in which structural relationships or special crystallographic orientation relationships (OR’s) form between the nucleus and surrounding matrix grains. We measured in-situ and simultaneously the nucleation rates of grains that have zero, one, two, three and four special OR’s with the surrounding parent grains. These experiments show a trend in which the activation energy for nucleation becomes smaller – and therefore nucleation more probable - with increasing number of special OR’s. These insights contribute to steering the processing of polymorphic materials with tailored properties, since preferential nucleation affects which crystal structure forms, the average grain size and texture of the material, and thereby - to a large extent - the final properties of the material. PMID:27484579

  20. Preferential Nucleation during Polymorphic Transformations.

    PubMed

    Sharma, H; Sietsma, J; Offerman, S E

    2016-08-03

    Polymorphism is the ability of a solid material to exist in more than one phase or crystal structure. Polymorphism may occur in metals, alloys, ceramics, minerals, polymers, and pharmaceutical substances. Unresolved are the conditions for preferential nucleation during polymorphic transformations in which structural relationships or special crystallographic orientation relationships (OR's) form between the nucleus and surrounding matrix grains. We measured in-situ and simultaneously the nucleation rates of grains that have zero, one, two, three and four special OR's with the surrounding parent grains. These experiments show a trend in which the activation energy for nucleation becomes smaller - and therefore nucleation more probable - with increasing number of special OR's. These insights contribute to steering the processing of polymorphic materials with tailored properties, since preferential nucleation affects which crystal structure forms, the average grain size and texture of the material, and thereby - to a large extent - the final properties of the material.

  1. Polymorphous light eruption.

    PubMed

    Hölzle, E; Plewig, G; von Kries, R; Lehmann, P

    1987-03-01

    Polymorphous light eruption (PLE) is a common photodermatosis of unknown etiology. It afflicts mainly fair-skinned patients, with a preponderance of young females. There is, however, no absolute restriction as to age, sex, or race. Clinical variants include the papular, vesiculo-bullous, and hemorrhagic variety, as well as plaque, erythema multiforme-like, and insect bite (strophulus)-like types. Skin lesions appear only in certain exposed areas hours or a few days after intense sunshine, and are nearly always monomorphous in the same patient. The rash subsides spontaneously within several days without leaving scars. The histopathologic picture is characteristic and shows a perivascular lymphocytic infiltrate in the upper and middle corium with subepidermal edema, vacuolization of basal cells, and spongiosis in the lower epidermis. The most important differential diagnoses are solar urticaria, photosensitive erythema multiforme, and lupus erythematosus. The action spectrum of PLE is under debate. Reproduction of skin lesions has been reported with UVB, UVA, and, rarely, visible light, with UVA probably being the most effective part of the spectrum. More important than treatment of PLE is prophylaxis. UVA- and UVB-effective sunscreens are of some help. Phototherapy and especially photochemotherapy (psoralen + UVA; PUVA) offer effective ways to decrease light sensitivity. Systemic treatment with chloroquine or beta-carotene has been disappointing.

  2. New polymorphous computing fabric.

    SciTech Connect

    Wolinski, C.; Gokhale, M.; McCabe, K. P.

    2002-01-01

    This paper introduces a new polymorphous computing Fabric well suited to DSP and Image Processing and describes its implementation on a Configurable System on a Chip (CSOC). The architecture is highly parameterized and enables customization of the synthesized Fabric to achieve high performance for a specific class of application. For this reason it can be considered to be a generic model for hardware accelerator synthesis from a high level specification. Another important innovation is the Fabric uses a global memory concept, which gives the host processor random access to all the variables and instructions on the Fabric. The Fabric supports different computing models including MIMD, SPMD and systolic flow and permits dynamic reconfiguration. We present a specific implementation of a bank of FIR filters on a Fabric composed of 52 cells on the Altera Excalibur ARM running at 33 MHz. The theoretical performance of this Fabric is 1.8 GMACh. For the FIR application we obtain 1.6 GMAC/s real performance. Some automatic tools have been developed like the tool to provide a host access utility and assembler.

  3. Polymorphic light eruption sine eruption.

    PubMed

    Dover, J S; Hawk, J L

    1988-01-01

    We describe seven patients, four female and three male, who developed intense pruritus on sun-exposed skin without visible change. The clinical features resembled those of polymorphic light eruption (PLE) without rash. Four patients also occasionally developed typical PLE upon sun exposure, but sun-induced pruritus alone occurred most frequently. No patient was taking any drug therapy. One patient developed similar pruritus following solar simulated irradiation, and one following PUVA therapy. All other laboratory investigations were negative. Treatment with low dose UVB phototherapy or PUVA therapy was effective. The condition, which we have called polymorphic light eruption sine eruptione (PLESE), appears to be a variant of PLE not previously reported.

  4. Crystal Polymorphs of Barbital: News about a Classic Polymorphic System

    PubMed Central

    2013-01-01

    Barbital is a hypnotic agent that has been intensely studied for many decades. The aim of this work was to establish a clear and comprehensible picture of its polymorphic system. Four of the six known solid forms of barbital (denoted I0, III, IV, and V) were characterized by various analytical techniques, and the thermodynamic relationships between the polymorph phases were established. The obtained data permitted the construction of the first semischematic energy/temperature diagram for the barbital system. The modifications I0, III, and V are enantiotropically related to one another. Polymorph IV is enantiotropically related to V and monotropically related to the other two forms. The transition points for the pairs I0/III, I0/V, and III/IV lie below 20 °C, and the transition point for IV/V is above 20 °C. At room temperature, the order of thermodynamic stability is I0 > III > V > IV. The metastable modification III is present in commercial samples and has a high kinetic stability. The solid-state NMR spectra provide information on aspects of crystallography (viz., the asymmetric units and the nature of hydrogen bonding). The known correlation between specific N–H···O=C hydrogen bonding motifs of barbiturates and certain IR characteristics was used to predict the H-bonded pattern of polymorph IV. PMID:24283960

  5. Triclinic polymorph of dibenzotetra-thia-fulvalene.

    PubMed

    Mamada, Masashi; Yamashita, Yoshiro

    2009-08-08

    Crystals of the title compound (DBTTF), C(14)H(8)S(4), feature a triclinic polymorph different from two known monoclinic polymorphs. In this form, there are two independent centrosymmetric half-mol-ecules in the asymmetric unit. Although the mol-ecular orientations are relatively similar to one of monoclinic polymorphs, the packing motif is different.

  6. Preferential nucleation during polymorphic transformations

    DOE PAGES

    Sharma, H.; Sietsma, J.; Offerman, S. E.

    2016-08-03

    Polymorphism is the ability of a solid material to exist in more than one phase or crystal structure. Polymorphism may occur in metals, alloys, ceramics, minerals, polymers, and pharmaceutical substances. Unresolved are the conditions for preferential nucleation during polymorphic transformations in which structural relationships or special crystallographic orientation relationships (OR’s) form between the nucleus and surrounding matrix grains. We measured in-situ and simultaneously the nucleation rates of grains that have zero, one, two, three and four special OR’s with the surrounding parent grains. These experiments show a trend in which the activation energy for nucleation becomes smaller – and thereforemore » nucleation more probable - with increasing number of special OR’s. As a result, these insights contribute to steering the processing of polymorphic materials with tailored properties, since preferential nucleation affects which crystal structure forms, the average grain size and texture of the material, and thereby - to a large extent - the final properties of the material.« less

  7. Preferential nucleation during polymorphic transformations

    SciTech Connect

    Sharma, H.; Sietsma, J.; Offerman, S. E.

    2016-08-03

    Polymorphism is the ability of a solid material to exist in more than one phase or crystal structure. Polymorphism may occur in metals, alloys, ceramics, minerals, polymers, and pharmaceutical substances. Unresolved are the conditions for preferential nucleation during polymorphic transformations in which structural relationships or special crystallographic orientation relationships (OR’s) form between the nucleus and surrounding matrix grains. We measured in-situ and simultaneously the nucleation rates of grains that have zero, one, two, three and four special OR’s with the surrounding parent grains. These experiments show a trend in which the activation energy for nucleation becomes smaller – and therefore nucleation more probable - with increasing number of special OR’s. As a result, these insights contribute to steering the processing of polymorphic materials with tailored properties, since preferential nucleation affects which crystal structure forms, the average grain size and texture of the material, and thereby - to a large extent - the final properties of the material.

  8. Characterization of polymorphic ampicillin forms.

    PubMed

    Baraldi, C; Tinti, A; Ottani, S; Gamberini, M C

    2014-11-01

    In this work polymorphs of α-aminobenzylpenicillin (ampicillin), a β-lactamic antibiotic, were prepared and investigated by several experimental and theoretical methods. Amorphous monohydrate and three crystalline forms, the trihydrate, the crystal form I and the crystal form II, were investigated by FT-IR and micro-Raman. Also data obtained by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), X-ray powder diffraction (XRPD) and hot-stage Raman spectroscopy are reported. Finally, quantum mechanical calculations were performed by density functional theory (DFT) to assist the assignment of spectroscopic experimental bands. For the first time, the ampicillin molecule in its zwitterionic form was studied at the B3LYP/aug-cc-pVDZ level and the corresponding theoretical vibrational spectra were computed. In fact, ampicillin in the crystal is in zwitterionic form and concentrations of this same form are quite relevant in solutions at physiological pH. Experimental and theoretical results allowed identification of specific features for polymorph characterization. Bands typical of the different polymorphs are identified both in IR and Raman spectra: in particular in the NH stretching region (IR), in the amide I+δNH region (both techniques), in the 1520-1490cm(-1) region (IR), in the 1320-1300cm(-1) and 1280-1220cm(-1) (IR), in the 1200-1170cm(-1) (Raman), in the amide V region (IR), and, finally, in the 715-640cm(-1) and 220-200cm(-1) (Raman). Interconversion among different polymorphs was investigated by hot-stage Raman spectroscopy and thermal analysis, clarifying the complex pattern of transformations undergone as a function of temperature and heating rate. In particular, DSC scans show how the trihydrate crystals transform into anhydrous forms on heating. Finally, stability tests demonstrated, after a two years period, that no transformation or degradation of the polymorphs occurred.

  9. IPD: the Immuno Polymorphism Database.

    PubMed

    Robinson, James; Marsh, Steven G E

    2007-01-01

    The Immuno Polymorphism Database (IPD) (http://www.ebi.ac.uk/ipd/) is a set of specialist databases related to the study of polymorphic genes in the immune system. IPD currently consists of four databases: IPD-KIR, contains the allelic sequences of killer cell immunoglobulin-like receptors (KIRs); IPD-MHC, a database of sequences of the major histocompatibility complex (MHC) of different species; IPD-HPA, alloantigens expressed only on platelets; and IPD-ESTAB, which provides access to the European Searchable Tumour Cell Line Database, a cell bank of immunologically characterized melanoma cell lines. The IPD project works with specialist groups or nomenclature committees who provide and curate individual sections before they are submitted to IPD for online publication. The IPD project stores all the data in a set of related databases. Those sections with similar data, such as IPD-KIR and IPD-MHC, share the same database structure.

  10. Lipid Polymorphisms and Membrane Shape

    PubMed Central

    Frolov, Vadim A.; Shnyrova, Anna V.; Zimmerberg, Joshua

    2011-01-01

    Morphological plasticity of biological membrane is critical for cellular life, as cells need to quickly rearrange their membranes. Yet, these rearrangements are constrained in two ways. First, membrane transformations may not lead to undesirable mixing of, or leakage from, the participating cellular compartments. Second, membrane systems should be metastable at large length scales, ensuring the correct function of the particular organelle and its turnover during cellular division. Lipids, through their ability to exist with many shapes (polymorphism), provide an adequate construction material for cellular membranes. They can self-assemble into shells that are very flexible, albeit hardly stretchable, which allows for their far-reaching morphological and topological behaviors. In this article, we will discuss the importance of lipid polymorphisms in the shaping of membranes and its role in controlling cellular membrane morphology. PMID:21646378

  11. Superhard monoclinic polymorph of carbon.

    PubMed

    Li, Quan; Ma, Yanming; Oganov, Artem R; Wang, Hongbo; Wang, Hui; Xu, Ying; Cui, Tian; Mao, Ho-Kwang; Zou, Guangtian

    2009-05-01

    We report a novel phase of carbon possessing a monoclinic C2/m structure (8 atoms/cell) identified using an ab initio evolutionary structural search. This polymorph, which we call M-carbon, is related to the (2x1) reconstruction of the (111) surface of diamond and can also be viewed as a distorted (through sliding and buckling of the sheets) form of graphite. It is stable over cold-compressed graphite above 13.4 GPa. The simulated x-ray diffraction pattern and near K-edge spectroscopy are in satisfactory agreement with the experimental data [W. L. Mao, Science 302, 425 (2003)10.1126/science.1089713] on overcompressed graphite. The hardness and bulk modulus of this new carbon polymorph are calculated to be 83.1 and 431.2 GPa, respectively, which are comparable to those of diamond.

  12. Superhard Monoclinic Polymorph of Carbon

    SciTech Connect

    Li, Quan; Ma, Yanming; Oganov, Artem R.; Wang, Hongbo; Wang, Hui; Xu, Ying; Cui, Tian; Mao, Ho-Kwang; Zou, Guangtian; Jilin; SBU; CIW

    2009-05-08

    We report a novel phase of carbon possessing a monoclinic C2/m structure (8 atoms/cell) identified using an ab initio evolutionary structural search. This polymorph, which we call M-carbon, is related to the (2x1) reconstruction of the (111) surface of diamond and can also be viewed as a distorted (through sliding and buckling of the sheets) form of graphite. It is stable over cold-compressed graphite above 13.4 GPa. The simulated x-ray diffraction pattern and near K-edge spectroscopy are in satisfactory agreement with the experimental data [W.L. Mao et al., Science 302, 425 (2003)] on overcompressed graphite. The hardness and bulk modulus of this new carbon polymorph are calculated to be 83.1 and 431.2 GPa, respectively, which are comparable to those of diamond.

  13. The Single Nucleotide Polymorphism Consortium

    NASA Technical Reports Server (NTRS)

    Morgan, Michael

    2003-01-01

    I want to discuss both the Single Nucleotide Polymorphism (SNP) Consortium and the Human Genome Project. I am afraid most of my presentation will be thin on law and possibly too high on rhetoric. Having been engaged in a personal and direct way with these issues as a trained scientist, I find it quite difficult to be always as objective as I ought to be.

  14. Chemical substitution in silica polymorph

    NASA Technical Reports Server (NTRS)

    Smith, J. V.; Steele, I. M.

    1984-01-01

    Ion and electron probe analyses are presented for trace elements (Al, Na, K, Li, Ti) in quartz, tridymite, cristobalite and melanophlogite. Quartz and melanophlogite show low levels of trace elements relative to tridymite and cristobalite. The previously determined alpha-beta inversion temperature decreases as the Al content of quartz increases. For all silica polymorphs, Al is greater than or equal to Na + K + Li on an atom basis, with the excess Al probably balanced by H.

  15. Chromosomal polymorphism in mammals: an evolutionary perspective.

    PubMed

    Dobigny, Gauthier; Britton-Davidian, Janice; Robinson, Terence J

    2017-02-01

    Although chromosome rearrangements (CRs) are central to studies of genome evolution, our understanding of the evolutionary consequences of the early stages of karyotypic differentiation (i.e. polymorphism), especially the non-meiotic impacts, is surprisingly limited. We review the available data on chromosomal polymorphisms in mammals so as to identify taxa that hold promise for developing a more comprehensive understanding of chromosomal change. In doing so, we address several key questions: (i) to what extent are mammalian karyotypes polymorphic, and what types of rearrangements are principally involved? (ii) Are some mammalian lineages more prone to chromosomal polymorphism than others? More specifically, do (karyotypically) polymorphic mammalian species belong to lineages that are also characterized by past, extensive karyotype repatterning? (iii) How long can chromosomal polymorphisms persist in mammals? We discuss the evolutionary implications of these questions and propose several research avenues that may shed light on the role of chromosome change in the diversification of mammalian populations and species.

  16. Parasitic polymorphism of Coccidioides spp

    PubMed Central

    2014-01-01

    Background Coccidioides spp. is the ethiological agent of coccidioidomycosis, an infection that can be fatal. Its diagnosis is complicated, due to that it shares clinical and histopathological characteristics with other pulmonary mycoses. Coccidioides spp. is a dimorphic fungus and, in its saprobic phase, grows as a mycelium, forming a large amount of arthroconidia. In susceptible persons, arthroconidia induce dimorphic changes into spherules/endospores, a typical parasitic form of Coccidioides spp. In addition, the diversity of mycelial parasitic forms has been observed in clinical specimens; they are scarcely known and produce errors in diagnosis. Methods We presented a retrospective study of images from specimens of smears with 15% potassium hydroxide, cytology, and tissue biopsies of a histopathologic collection from patients with coccidioidomycosis seen at a tertiary-care hospital in Mexico City. Results The parasitic polymorphism of Coccidioides spp. observed in the clinical specimens was as follows: i) spherules/endospores in different maturation stages; ii) pleomorphic cells (septate hyphae, hyphae composed of ovoid and spherical cells, and arthroconidia), and iii) fungal ball formation (mycelia with septate hyphae and arthroconidia). Conclusions The parasitic polymorphism of Coccidioides spp. includes the following: spherules/endospores, arthroconidia, and different forms of mycelia. This knowledge is important for the accurate diagnosis of coccidioidomycosis. In earlier studies, we proposed the integration of this diversity of forms in the Coccidioides spp. parasitic cycle. The microhabitat surrounding the fungus into the host would favor the parasitic polymorphism of this fungus, and this environment may assist in the evolution toward parasitism of Coccidioides spp. PMID:24750998

  17. Calcium acamprosate: a triclinic polymorph.

    PubMed

    Maccaroni, Elisabetta; Panzeri, Walter; Malpezzi, Luciana

    2011-12-01

    The title compound, poly[bis-(μ(3)-4-acetamido-propane-sulfon-ato)-calcium], [Ca(C(5)H(10)NO(4)S)(2)](n), is a triclinic polymorph of the previously reported monoclinic structure [Toffoli et al. (1988 ▶). Acta Cryst. C44, 1493-1494]. The triclinic modification was found to have an all-trans configuration of the acetamido-propane chain, in contrast with the monoclinic polymorph which shows an angle of 74.66 (8)° between the S-C-C-C chain plane and that of the amide group. The Ca(2+) cation is situated on an inversion centre and is hexa-coordinated by six O atoms belonging to different anions in a distorted octa-hedral geometry. This arrangement leads to a layered structure parallel to (011). The layers are held together by N-H⋯O hydrogen bonds and by short C-H⋯O inter-actions, both involving the sulfonate O atoms not coordinated to the Ca(2+) cations. The structure was determined from a crystal twinned by non-merohedry [twin law ([Formula: see text]00, 0[Formula: see text]0, -0.335 -0.85 1), with a fractional contribution of the minor twin domain of 46.7 (1)%].

  18. Spinning up the polymorphs of calcium carbonate

    PubMed Central

    Boulos, Ramiz A.; Zhang, Fei; Tjandra, Edwin S.; Martin, Adam D.; Spagnoli, Dino; Raston, Colin L.

    2014-01-01

    Controlling the growth of the polymorphs of calcium carbonate is important in understanding the changing environmental conditions in the oceans. Aragonite is the main polymorph in the inner shells of marine organisms, and can be readily converted to calcite, which is the most stable polymorph of calcium carbonate. Both of these polymorphs are significantly more stable than vaterite, which is the other naturally occurring polymorph of calcium carbonate, and this is reflected in its limited distribution in nature. We have investigated the effect of high shear forces on the phase behaviour of calcium carbonate using a vortex fluidic device (VFD), with experimental parameters varied to explore calcium carbonate mineralisation. Variation of tilt angle, rotation speed and temperature allow for control over the size, shape and phase of the resulting calcium carbonate. PMID:24448077

  19. Investigation of the riddle of sulfathiazole polymorphism.

    PubMed

    Abu Bakar, Mohd R; Nagy, Zoltan K; Rielly, Chris D; Dann, Sandy E

    2011-07-29

    Since the discovery of sulfathiazole as an antimicrobial agent in 1939, numerous works in the screening for its different polymorphic forms, which is an essential part of drug development, have been conducted and published. These works consequently result in the availability of various methods for generating a particular polymorph. By following these methods, however, one cannot be guaranteed to obtain the intended pure polymorph because most of the methods do not clearly and adequately describe the crystallisation conditions, such as cooling rates and initial solute concentrations. In this paper, the available methods for generating all the known polymorphs of sulfathiazole are reviewed and selected methods for generating certain polymorphs, performed with their processes monitored using process analytical technology tools, i.e. focussed beam reflectance measurement and attenuated total reflectance ultraviolet spectroscopy, are presented. The properties of the obtained crystals, examined using various characterisation methods, are also presented and whenever possible, are compared with those of other workers.

  20. Vibrational study of tamoxifen citrate polymorphism

    NASA Astrophysics Data System (ADS)

    Gamberini, M. C.; Baraldi, C.; Tinti, A.; Palazzoli, F.; Ferioli, V.

    2007-09-01

    The trans isomer of ( Z)-2-[ p-(1,2-diphenyl-butenyl)phenoxy]- N, N-dimethyletylamine (tamoxifen) is well known for its endocrine activity as an antiestrogenic agent. Its citrate salt, a widely used pharmaceutical agent, appears in three main polymorphic forms, two of which are well known (I and II) and another form not yet well evidenced. A vibrational study has been conducted for identifying the two known polymorphic forms of tamoxifen citrate (I and II) and for characterising the other form (form III) examined in this study. Other techniques for the characterization of the different polymorphs, such as XRDP, have been used.

  1. Rivastigmine hydrogen tartrate polymorphs: Solid-state characterisation of transition and polymorphic conversion via milling

    NASA Astrophysics Data System (ADS)

    Amaro, Maria Inês; Simon, Alice; Cabral, Lúcio Mendes; de Sousa, Valéria Pereira; Healy, Anne Marie

    2015-11-01

    Rivastigmine (RHT) is an active pharmaceutical ingredient that is used for the treatment of mild to moderately severe dementia in Alzheimer's disease, and is known to present two polymorphic forms and to amorphise upon granulation. To date there is no information in the scientific or patent literature on polymorphic transition and stability. Hence, the aim of the current study was to gain a fundamental understanding of the polymorphic forms by (1) evaluating RHT thermodynamic stability (monotropy or enantiotropy) and (2) investigating the potential for polymorphic transformation upon milling. The two polymorphic and amorphous forms were characterised using X-ray powder diffractometry, thermal analyses, infra-red spectroscopy and water sorption analysis. The polymorphic transition was found to be spontaneous (ΔG0 < 0) and exothermic (ΔH0 < 0), indicative of a monotropic polymorph pair. The kinetic studies showed a fast initial polymorphic transition characterised by a heterogeneous nucleation, followed by a slow crystal growth. Ball milling can be used to promote the polymorphic transition and for the production of RHT amorphous form.

  2. Polymorphism Control of Poly(vinylidene fluoride)

    NASA Astrophysics Data System (ADS)

    Zheng, Jianfen; He, Aihua; Li, Junxing; Han, Charles C.

    2008-03-01

    Poly(vinylidene fluoride) (PVDF) is well-known for its polymorphism, and can exhibit five different polymorphs depending on its processing conditions. The α-phase is the most common and stable polymorph and the β-phase is the most important one due to its piezoelectric and pyroelectric properties. Polymorphism control of PVDF has been realized through electrospinning. PVDF fibrous membranes with fiber diameter in the range of 100 nm to several micrometers were produced by electrospinning and the crystal phase of electrospun PVDF fibers can be adjusted at the same time. Through the control of electrospinning parameters such as the solvent and electrospinning temperature, PVDF fibrous membranes containing mainly α- or β- or γ-phase could be fabricated successfully.

  3. Purification of polymorphic components of complex genomes

    DOEpatents

    Stodolsky, M.

    1988-01-21

    A method for processing related subject and reference macromolecule composed of complementary strand into their respective subject and reference populations of representative fragments and effectuating purification of unique polymorphic subject fragments. 1 fig.

  4. Gene polymorphisms and chronic obstructive pulmonary disease.

    PubMed

    Wu, Xiaodan; Yuan, Bowei; López, Elena; Bai, Chunxue; Wang, Xiangdong

    2014-01-01

    The genetic component was suggested to contribute to the development of chronic obstructive pulmonary disease (COPD), a major and growing public health burden. The present review aims to characterize the evidence that gene polymorphisms contribute to the aetiology of COPD and related traits, and explore the potential relationship between certain gene polymorphisms and COPD susceptibility, severity, lung function, phenotypes, or drug effects, even though limited results from related studies lacked consistency. Most of these studies were association studies, rather than confirmatory studies. More large-sized and strictly controlled studies are needed to prove the relationship between gene polymorphisms and the reviewed traits. More importantly, prospective confirmatory studies beyond initial association studies will be necessary to evaluate true relationships between gene polymorphisms and COPD and help individualized treatment for patients with COPD.

  5. Purification of polymorphic components of complex genomes

    DOEpatents

    Stodolsky, M.

    1991-07-16

    A method is disclosed for processing related subject and reference macromolecule populations composed of complementary strands into their respective subject and reference populations of representative fragments and effectuating purification of unique polymorphic subject fragments. 1 figure.

  6. Polymorph Discrimination using Low Wavenumber Raman Spectroscopy

    PubMed Central

    Roy, Saikat; Chamberlin, Brianna; Matzger, Adam J.

    2016-01-01

    Characterization of crystalline polymorphs and their quantitation has become an integral part of the pre-clinical drug development process. Raman spectroscopy is a powerful technique for the rapid identification of phases of pharmaceuticals. In the present work we demonstrate the use of low wavenumber Raman vibrational spectroscopy (including phonon measurement) for discrimination among polymorphs. A total of 10 polymorphic pharmaceuticals were employed to conduct a critical assessment. Raman scattering in the low frequency region (10–400 cm−1), which includes crystal lattice vibrations, has been analyzed and the results indicate lattice phonon Raman scattering can be used for rapid discrimination of polymorphic phases with additional discriminating power compared to conventional collection strategies. Moreover structural insight and conformational changes can be detected with this approach. PMID:27642248

  7. Purification of polymorphic components of complex genomes

    DOEpatents

    Stodolsky, Marvin

    1991-01-01

    A method is disclosed for processing related subject and reference macromolecule populations composed of complementary strands into their respective subject and reference populations of representative fragments and effectuating purification of unique polymorphic subject fragments.

  8. Crystal Polymorphism and Multiple Crystal Forms

    NASA Astrophysics Data System (ADS)

    Braga, Dario; Grepioni, Fabrizia; Maini, Lucia; Polito, Marco

    This chapter discusses the phenomenon of polymorphism in organic and organometallic compounds. Polymorphism is first introduced and then, to give the work some context, background information is given concerning properties and techniques for characterizing the solid phases. In particular, desolvation and interconverstion are examined, and the gas-solid reactions are presented as a successful route to obtaining new crystalline phases. Co-crystal definition is then described and the problem in distinguishing co-crystals and salts is evaluated.

  9. DNA polymorphism identity determination using flow cytometry

    DOEpatents

    Nolan, John P.; White, P. Scott; Cai, Hong

    2001-01-01

    DNA polymorphism identity determination using flow cytometry. Primers designed to be immobilized on microspheres are allowed to anneal to the DNA strand under investigation, and are extended by either DNA polymerase using fluorescent dideoxynucleotides or ligated by DNA ligase to fluorescent reporter oligonucleotides. The fluorescence of either the dideoxynucleotide or the reporter oligonucleotide attached to the immobilized primer is measured by flow cytometry, thereby identifying the nucleotide polymorphism on the DNA strand.

  10. Tetrazolium Oxidase Polymorphism in Rainbow Trout

    PubMed Central

    Cederbaum, Stephen D.; Yoshida, Akira

    1972-01-01

    Tetrazolium oxidase from the blood and liver of rainbow trout was found to be genetically polymorphic. The inheritance pattern of the liver enzyme was compatible only with a one locus-two allele hypothesis. The enzymes in the blood while having an electrophoretically identical polymorphism could differ genotypically from that of the liver in a given fish. The significance of these findings to the understanding of the evolution of the salmonid genome is discussed. PMID:4675090

  11. Polymorphic crystals selected in the nucleation stage

    NASA Astrophysics Data System (ADS)

    Zhang, Hui-Jun; Peng, Shu-Ming; Zhou, Xiao-Song; Ju, Xin

    2014-08-01

    Molecular dynamics simulations are used to explore the atomic mechanism of formation of polymorphic crystals. Cooling the Lennard-Jones systems, we observe that the system almost always evolves into a polymorphic crystal with either fivefold-symmetric stacking faults or single-direction stacking faults. The detailed analysis reveals that such an evolution depends on the configuration of fcc/hcp concomitance in the nucleation stage. A defect-induced model is then introduced to illustrate these two evolution routes. Through calculating the formation energies of the defective critical nuclei, we find that the polymorphic crystals seem to be determined by their critical nuclei, in which the relatively lower formation energy ensures the preponderance of the fivefold-symmetric cluster. Before the nucleation, we observe that thermal fluctuations prefer hcp-like particles over fcc-like ones while in the nucleation and growth stage this preference reverses. Notably, an extended step rule of Ostwald is seemingly suitable to characterise the growth process because of the temporary hcp layers appearing among fcc layers in the growth stage. Although the crystalline cluster with single-direction stacking faults has higher growth rate and structural order than its competitor, the component (fcc and hcp) proportion of the final crystals is almost always constant regardless of the polymorphic type. Our finding renews the understanding of the polymorphism of crystals, and possibly draws more attention of people intending to control the polymorphic structures through nucleation.

  12. Cytochrome P450 gene polymorphism and cancer.

    PubMed

    Agundez, Jose A G

    2004-06-01

    Human cytochrome P450 (CYP) enzymes play a key role in the metabolism of drugs and environmental chemicals. Several CYP enzymes metabolically activate procarcinogens to genotoxic intermediates. Phenotyping analyses revealed an association between CYP enzyme activity and the risk to develop several forms of cancer. Research carried out in the last decade demonstrated that several CYP enzymes are polymorphic due to single nucleotide polymorphisms, gene duplications and deletions. As genotyping procedures became available for most human CYP, an impressive number of association studies on CYP polymorphisms and cancer risk were conducted. Here we review the findings obtained in these studies regarding CYP1A1, CYP1A2, CYP1B1, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C18, CYP2C19, CYP2D6, CYP2E1, CYP3A4, CYP3A5, CYP3A7, CYP8A1 and CYP21 gene polymorphisms. Consistent evidences for association between CYP polymorphisms and lung, head and neck, and liver cancer were reported. Controversial findings suggest that colorectal and prostate cancers may be associated to CYP polymorphisms, whereas no evidences for a relevant association with breast or bladder cancers were reported. We summarize the available information related to the association of CYP polymorphisms with leukaemia, lymphomas and diverse types of cancer that were investigated only for some CYP genes, including brain, esophagus, stomach, pancreas, pituitary, cervical epithelium, melanoma, ovarian, kidney, anal and vulvar cancers. This review discusses on causes of heterogeneity in the proposed associations, controversial findings on cancer risk, and identifies topics that require further investigation. In addition, some recommendations on study design, in order to obtain more conclusive findings in further studies, are provided.

  13. MHC polymorphism under host-pathogen coevolution.

    PubMed

    Borghans, José A M; Beltman, Joost B; De Boer, Rob J

    2004-02-01

    The genes encoding major histocompatibility (MHC) molecules are among the most polymorphic genes known for vertebrates. Since MHC molecules play an important role in the induction of immune responses, the evolution of MHC polymorphism is often explained in terms of increased protection of hosts against pathogens. Two selective pressures that are thought to be involved are (1) selection favoring MHC heterozygous hosts, and (2) selection for rare MHC alleles by host-pathogen coevolution. We have developed a computer simulation of coevolving hosts and pathogens to study the relative impact of these two mechanisms on the evolution of MHC polymorphism. We found that heterozygote advantage per se is insufficient to explain the high degree of polymorphism at the MHC, even in very large host populations. Host-pathogen coevolution, on the other hand, can easily account for realistic polymorphisms of more than 50 alleles per MHC locus. Since evolving pathogens mainly evade presentation by the most common MHC alleles in the host population, they provide a selective pressure for a large variety of rare MHC alleles. Provided that the host population is sufficiently large, a large set of MHC alleles can persist over many host generations under host-pathogen coevolution, despite the fact that allele frequencies continuously change.

  14. Prdm9 polymorphism unveils mouse evolutionary tracks.

    PubMed

    Kono, Hiromitsu; Tamura, Masaru; Osada, Naoki; Suzuki, Hitoshi; Abe, Kuniya; Moriwaki, Kazuo; Ohta, Kunihiro; Shiroishi, Toshihiko

    2014-06-01

    PR/SET domain containing 9 (Prdm9) mediates histone modifications such as H3K4me3 and marks hotspots of meiotic recombination. In many mammalian species, the Prdm9 gene is highly polymorphic. Prdm9 polymorphism is assumed to play two critical roles in evolution: to diversify the spectrum of meiotic recombination hotspots and to cause male hybrid sterility, leading to reproductive isolation and speciation. Nevertheless, information about Prdm9 sequences in natural populations is very limited. In this study, we conducted a comprehensive population survey on Prdm9 polymorphism in the house mouse, Mus musculus. Overall M. musculus Prdm9 displays an extraordinarily high level of polymorphism, particularly in regions encoding zinc finger repeats, which recognize recombination hotspots. Prdm9 alleles specific to various M. musculus subspecies dominate in subspecies territories. Moreover, introgression into other subspecies territories was found for highly divergent Prdm9 alleles associated with t-haplotype. The results of our phylogeographical analysis suggest that the requirement for hotspot diversity depends on geographical range and time span in mouse evolution, and that Prdm9 polymorphism has not been maintained by a simple balanced selection in the population of each subspecies.

  15. Solvable model for polymorphic dynamics of biofilaments.

    PubMed

    Mohrbach, Hervé; Kulić, Igor M

    2012-03-01

    We investigate an analytically tractable toy model for thermally induced polymorphic dynamics of cooperatively rearranging biofilaments-like microtubules. The proposed four-block model, which can be seen as a coarse-grained approximation of the full polymorphic tube model, permits a complete analytical treatment of all thermodynamic properties including correlation functions and angular Fourier mode distributions. Due to its mathematical tractability the model straightforwardly leads to some physical insights in recently discussed phenomena like the "length dependent persistence length." We show that a polymorphic filament can disguise itself as a classical worm-like chain on small and on large scales and yet display distinct anomalous tell-tale features indicating an inner switching dynamics on intermediate length scales.

  16. Human FcR Polymorphism and Disease

    PubMed Central

    Li, Xinrui; Gibson, Andrew W.; Kimberly, Robert P.

    2014-01-01

    Fc receptors play a central role in maintaining the homeostatic balance in the immune system. Our knowledge of the structure and function of these receptors and their naturally occurring polymorphisms, including single nucleotide polymorphisms and/or copy number variations, continues to expand. Through studies of their impact on human biology and clinical phenotype, the contributions of these variants to the pathogenesis, progression, and/or treatment outcome of many diseases that involve immunoglobulin have become evident. They affect susceptibility to bacterial and viral pathogens, constitute as risk factors for IgG or IgE mediated inflammatory diseases, and impact the development of many autoimmune conditions. In this chapter, we will provide an overview of these genetic variations in classical FcγRs, FcRLs, and other Fc receptors, as well as challenges in achieving an accurate and comprehensive understanding of the FcR polymorphisms and genomic architecture. PMID:25116105

  17. Novel polymorphisms in ovine prion protein gene.

    PubMed

    Meydan, H; Ozkan, M M; Yildiz, M A; Goldmann, W

    2013-08-01

    The aim of this study was to identify the PRNP polymorphisms outside the standard codons 136, 154 and 171 in 1110 sheep with no clinical sign of scrapie from all 18 Turkish native sheep breeds and compare our results with published data on ovine PRNP polymorphism from other regions of the world. Among the 22 amino acid polymorphisms and three silent mutations, 10 were novel for ovine PRNP: p.Gly94Gly, p.Leu128Ile, p.Met132Leu, p.Ser135Arg, p.Met137Val, p.Asn146Lys, p.Arg159Arg, p.Tyr160Asn, p.Gln163His and p.Thr193Ser. These data reveal that sheep breeds close to the historic center of small ruminant domestication have remained highly diverse in the prion gene locus, with distinctive genetic similarities to both Asian and European sheep breeds.

  18. Single Nucleotide Polymorphisms and Osteoarthritis

    PubMed Central

    Wang, Ting; Liang, Yuting; Li, Hong; Li, Haibo; He, Quanze; Xue, Ying; Shen, Cong; Zhang, Chunhua; Xiang, Jingjing; Ding, Jie; Qiao, Longwei; Zheng, Qiping

    2016-01-01

    Abstract Osteoarthritis (OA) is a complex disorder characterized by degenerative articular cartilage and is largely attributed to genetic risk factors. Single nucleotide polymorphisms (SNPs) are common DNA variants that have shown promising and efficiency, compared with positional cloning, to map candidate genes of complex diseases, including OA. In this study, we aim to provide an overview of multiple SNPs from a number of genes that have recently been linked to OA susceptibility. We also performed a comprehensive meta-analysis to evaluate the association of SNP rs7639618 of double von Willebrand factor A domains (DVWA) gene with OA susceptibility. A systematic search of studies on the association of SNPs with susceptibility to OA was conducted in PubMed and Google scholar. Studies subjected to meta-analysis include human and case-control studies that met the Hardy–Weinberg equilibrium model and provide sufficient data to calculate an odds ratio (OR). A total of 9500 OA cases and 9365 controls in 7 case-control studies relating to SNP rs7639618 were included in this study and the ORs with 95% confidence intervals (CIs) were calculated. Over 50 SNPs from different genes have been shown to be associated with either hip (23), or knee (20), or both (13) OA. The ORs of these SNPs for OA and the subtypes are not consistent. As to SNP rs7639618 of DVWA, increased knee OA risk was observed in all genetic models analyzed. Specifically, people from Asian with G-allele showed significantly increased risk of knee OA (A versus G: OR = 1.28, 95% CI 1.13–1.46; AA versus GG: OR = 1.60, 95% CI 1.25–2.05; GA versus GG: OR = 1.31, 95% CI 1.18–1.44; AA versus GA+GG: OR = 1.34, 95% CI 1.12–1.61; AA+GA versus GG: OR = 1.40, 95% CI 1.19–1.64), but not in Caucasians or with hip OA. Our results suggest that multiple SNPs play different roles in the pathogenesis of OA and its subtypes; SNP rs7639618 of DVWA gene is associated with a significantly increased

  19. Clinical applications of Genome Polymorphism Scans

    PubMed Central

    Weber, James L

    2006-01-01

    Applications of Genome Polymorphism Scans range from the relatively simple such as gender determination and confirmation of biological relationships, to the relatively complex such as determination of autozygosity and propagation of genetic information throughout pedigrees. Unlike nearly all other clinical DNA tests, the Scan is a universal test – it covers all people and all genes. In balance, I argue that the Genome Polymorphism Scan is the most powerful, affordable clinical DNA test available today. Reviewers: This article was reviewed by Scott Weiss (nominated by Neil Smalheiser), Roberta Pagon (nominated by Jerzy Jurka) and Val Sheffield (nominated by Neil Smalheiser). PMID:16756678

  20. TNF-alpha polymorphisms and breast cancer.

    PubMed

    Yang, Yu; Feng, Rennan; Bi, Sheng; Xu, Yuqing

    2011-09-01

    Tumor necrosis factor-α (TNF-α) is an important pro-inflammatory cytokine in the development and progress in human cancer. TNF-α polymorphisms have been confirmed to influence the risk for several types of cancer, however, the associations between TNF-α polymorphisms and breast cancer (BC) remain controversial and ambiguous. The aim of this meta-analysis is to explore more precise estimations regarding this point. Electronic searches of several databases were conducted for all online publications on the associations between TNF-α-238, -308, -857, -863, -1031, -1210 polymorphisms and BC through March 2011. Odds ratios (OR) with 95% confidence intervals (95% CI) were calculated to assess the strength of these associations in fixed- and random-effect models with Review manager 5.0. A total of 17 studies with 44,442 BC patients and 49,926 controls involved were identified. This meta-analysis showed no significant association between TNF-α-308 polymorphism and BC (AA + GA vs. GG: OR = 0.95, 95% CI = 0.82-1.09) in overall and (OR = 1.44, 95% CI = 0.61-3.40) Asian populations, however, a negative association was shown in Caucasian subgroup (OR = 0.91, 95% CI = 0.85-0.97). As regards the TNF-α-238 polymorphism, the OR values (95% CI) were 0.99 (0.94-1.05), 0.94 (0.78-1.14), and 1.00 (0.95-1.05) for the overall, Asian, and Caucasian studies, respectively. No significant associations were found for other polymorphisms. Furthermore, there was a coincidence in the sensitivity analysis of these associations. No publication bias was detected in this study. To sum up, no significant associations were found between the TNF-α-308, -238, -857, -863, -1031, -1210 polymorphisms and the risk for BC in overall populations, whereas a negative association was found between TNF-α-308 polymorphism and BC in Caucasian populations.

  1. Polymorphs calcium carbonate on temperature reaction

    SciTech Connect

    Chong, Kai-Yin; Chia, Chin-Hua; Zakaria, Sarani

    2014-09-03

    Calcium carbonate (CaCO{sub 3}) has three different crystal polymorphs, which are calcite, aragonite and vaterite. In this study, effect of reaction temperature on polymorphs and crystallite structure of CaCO{sub 3} was investigated. X-ray powder diffraction (XRD), fourier transform infrared (FTIR), and variable pressure scanning electron microscope (VPSEM) were used to characterize the obtained CaCO{sub 3} particles. The obtained results showed that CaCO{sub 3} with different crystal and particle structures can be formed by controlling the temperature during the synthesis process.

  2. Polymorphic transformation of helical flagella of bacteria

    NASA Astrophysics Data System (ADS)

    Lim, Sookkyung; Howard Berg Collaboration; William Ko Collaboration; Yongsam Kim Collaboration; Wanho Lee Collaboration; Charles Peskin Collaboration

    2016-11-01

    Bacteria such as E. coli swim in an aqueous environment by utilizing the rotation of flagellar motors and alternate two modes of motility, runs and tumbles. Runs are steady forward swimming driven by bundles of flagellar filaments whose motors are turning CCW; tumbles involve a reorientation of the direction of swimming triggered by motor reversals. During tumbling, the helical flagellum undergoes polymorphic transformations, which is a local change in helical pitch, helical radius, and handedness. In this work, we investigate the underlying mechanism of structural conformation and how this polymorphic transition plays a role in bacterial swimming. National Science Foundation.

  3. Mitochondrial DNA polymorphism in mitochondrial myopathy.

    PubMed

    Holt, I J; Harding, A E; Morgan-Hughes, J A

    1988-05-01

    In order to test the hypothesis that mitochondrial myopathy may be caused by mutation of the mitochondrial (mt) genome, restriction fragment length polymorphism in leucocyte mt DNA has been studied in 38 patients with mitochondrial myopathy, 44 of their unaffected matrilineal relatives, and 35 normal control subjects. Previously unreported mt DNA polymorphisms were identified in both patients and controls. No differences in restriction fragment patterns were observed between affected and unaffected individuals in the same maternal line, and there was no evidence of major deletion of mt DNA in patients. This study provides no positive evidence of mitochondrial inheritance in mitochondrial myopathy, but this has not been excluded.

  4. Simultaneous detection of the exon 10 polymorphism and a novel intronic single base insertion polymorphism in the XPD gene using single strand conformation polymorphism.

    PubMed

    Kumar, Rajiv; Angelini, Sabrina; Hemminki, Kari

    2003-03-01

    We developed a new method based on the single strand conformation polymorphism (SSCP) technique for the detection of a G23591A (Asp312Asn) polymorphism in exon 10 of the XPD gene. In the process we also identified a novel polymorphism 23623C-ins (IVS10+17C-ins) in intron 10 of the same gene. With this newly developed SSCP-based method of genotyping we could detect both polymorphisms in the same assay and thus consequently determine the haplotype. In order to determine the population frequency of the novel polymorphism and the haplotype frequency, 302 healthy individuals were genotyped. The allelic frequency of the 23623C-ins intronic polymorphism was 0.16, whereas the frequency of the variant allele for the G23591A polymorphism was 0.39. Forty-three individuals (14%) were heterozygous for both polymorphisms but none carried polymorphic variants for both G23591A and 23623C-ins on the same allele. The effect of the novel intronic insertion polymorphism, which is located 16 nt downstream of the 3'-end of exon 10 of the XPD gene and involves a mononucleotide C repeat sequence, on expression remains to be determined.

  5. Idealized powder diffraction patterns for cellulose polymorphs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cellulose samples are routinely analyzed by X-ray diffraction to determine their crystal type (polymorph) and crystallinity. However, the connection is seldom made between those efforts and the crystal structures of cellulose that have been determined with synchrotron X-radiation and neutron diffrac...

  6. Treatment of asymptomatic catecholaminergic polymorphic ventricular tachycardia.

    PubMed

    Obeyesekere, Manoj N; Sy, Raymond W; Leong-Sit, Peter; Gula, Lorne J; Yee, Raymond; Skanes, Allan C; Klein, George J; Krahn, Andrew D

    2012-05-01

    Catecholaminergic polymorphic ventricular tachycardia is a rare genetic disorder caused by mutations in genes involved in the intracellular calcium homeostasis of cardiac cells. Affected patients typically present with life-threatening ventricular arrhythmias precipitated by emotional/physical stress. The diagnosis is based on the demonstration of polymorphic or bidirectional ventricular tachycardia associated with adrenergic stress. Genetic testing can be confirmatory in some patients. Treatment for catecholaminergic polymorphic ventricular tachycardia includes medical and surgical efforts to suppress the effects of epinephrine at the myocardial level and/or modulation of calcium homeostasis. Mortality is high when untreated and sudden cardiac death may be the first manifestation of the disease. First-degree relatives of a proband should be offered genetic testing if the causal mutation is known. If the family mutation is not known, relatives should be clinically evaluated with provocative testing. In the absence of rigorous trials, prophylactic treatment of the asymptomatic catecholaminergic polymorphic ventricular tachycardia patient appears to reduce morbidity and mortality.

  7. Difficulties in Learning Inheritance and Polymorphism

    ERIC Educational Resources Information Center

    Liberman, Neomi; Beeri, Catriel; Kolikant, Yifat Ben-David

    2011-01-01

    This article reports on difficulties related to the concepts of inheritance and polymorphism, expressed by a group of 22 in-service CS teachers with an experience with the procedural paradigm, as they coped with a course on OOP. Our findings are based on the analysis of tests, questionnaires that the teachers completed in the course, as well as on…

  8. ARH missense polymorphisms and plasma cholesterol levels.

    PubMed

    Hubacek, Jaroslav A; Hyatt, Tommy

    2004-01-01

    Mutations in a putative low-density lipoprotein (LDL) receptor adaptor protein called ARH have been recently described in patients with autosomal recessive hypercholesterolemia (ARH). ARH plays a tissue-specific role in determination of LDL receptor function. In the ARH gene three mismatched polymorphisms have been detected: Pro202Ser, Pro202His and Arg238Trp. These are of putative interest in plasma cholesterol level determination. To evaluate the effect of polymorphisms on plasma cholesterol levels, all polymorphisms were analyzed by PCR and restriction enzyme analysis by MnII, HpyCH4IV and SacII in 100 Caucasian males with high (>90%, 6.29 +/- 0.89 mmol/l), and 100 males with low (<10%, 3.60 +/- 0.57 mmol/l), total plasma cholesterol levels. No significant differences were observed in frequencies of ARH genotypes or alleles between these two extreme groups. These results suggest that ARH polymorphisms are unlikely to be important genetic determinants of plasma cholesterol levels.

  9. Molecular basis for amyloid-[beta] polymorphism

    SciTech Connect

    Colletier, Jacques-Philippe; Laganowsky, Arthur; Landau, Meytal; Zhao, Minglei; Soriaga, Angela B.; Goldschmidt, Lukasz; Flot, David; Cascio, Duilio; Sawaya, Michael R.; Eisenberga, David

    2011-10-19

    Amyloid-beta (A{beta}) aggregates are the main constituent of senile plaques, the histological hallmark of Alzheimer's disease. A{beta} molecules form {beta}-sheet containing structures that assemble into a variety of polymorphic oligomers, protofibers, and fibers that exhibit a range of lifetimes and cellular toxicities. This polymorphic nature of A{beta} has frustrated its biophysical characterization, its structural determination, and our understanding of its pathological mechanism. To elucidate A{beta} polymorphism in atomic detail, we determined eight new microcrystal structures of fiber-forming segments of A{beta}. These structures, all of short, self-complementing pairs of {beta}-sheets termed steric zippers, reveal a variety of modes of self-association of A{beta}. Combining these atomic structures with previous NMR studies allows us to propose several fiber models, offering molecular models for some of the repertoire of polydisperse structures accessible to A{beta}. These structures and molecular models contribute fundamental information for understanding A{beta} polymorphic nature and pathogenesis.

  10. The Effect of Polymorphism on Surface Energetics of D-Mannitol Polymorphs.

    PubMed

    Smith, Robert R; Shah, Umang V; Parambil, Jose V; Burnett, Daniel J; Thielmann, Frank; Heng, Jerry Y Y

    2017-01-01

    The aim of this work was to assess the effect of different crystalline polymorphism on surface energetics of D-mannitol using finite dilution inverse gas chromatography (FD-IGC). Pure α, β and δ polymorphs were prepared via solution crystallisation and characterised by powder X-ray diffraction (P-XRD). The dispersive surface energies were found to range from 43 to 34 mJ/m(2), 50 to 41 mJ/m(2), and 48 to 38 mJ/m(2), for α, β, and δ, respectively, for surface coverage ranging from 0.006 to 0.095. A deconvolution modelling approach was employed to establish their energy sites. The primary sites corresponded to maxima in the dispersive surface energy of 37.1 and 33.5; 43.3 and 39.5; and 38.6, 38.4 and 33.0; for α, β, and δ, respectively. This methodology was also extended to an α-β polymorph mixture to estimate the amount of the constituent α and β components present in the sample. The dispersive surface energies of the α-β mixture were found to be in the range of 48 to 37 mJ/m(2) with 40.0, 42.4, 38.4 and 33.1 mJ/m(2) sites. The deconvolution modelling method extracted the energy contribution of each of the polymorphs from data for the polymorphic mixture. The mixture was found to have a β-polymorph surface content of ∼19%. This work shows the influence of polymorphism on surface energetics and demonstrates that FD-IGC coupled with a simple modelling approach to be a powerful tool for assessing the specific nature of this energetic distribution including the quantification of polymorphic content on the surface.

  11. Vibrational spectroscopic study of polymorphism and polymorphic transformation of the anti-viral drug lamivudine.

    PubMed

    Du, Yong; Zhang, Huili; Xue, Jiadan; Tang, Wenjian; Fang, Hongxia; Zhang, Qi; Li, Yafang; Hong, Zhi

    2015-02-25

    Vibrational spectra of hydrated and anhydrous lamivudines, and also the dynamic process of polymorphic transformation have been characterized by Fourier transform infrared (FT-IR) and Raman spectroscopic techniques. The vibrational modes of both polymorphic lamivudines are assigned. FT-IR and Raman spectral results show that the interaction between crystalline water and lamivudine molecular has an important effect on the molecular vibration motions of polymorphic lamivudines. The two characteristic Raman peaks at 783 and 798 cm(-1) represent hydrated and anhydrous lamivudine respectively. The relationship between changes of two characteristic peak normalized areas and heating time could be fitted with single exponential functions, and the dynamic information of polymorphic transformation of lamivudine drug is obtained. The decay rate of characteristic peak for hydrated lamivudine and the growth rate of that for anhydrous lamivudine are consistent during dehydration transformation process. The reported results provide us important benchmark for qualitatively monitoring different polymorphic drugs and also establishing the corresponding model for the polymorphic transformation of drugs in related pharmaceutical research fields.

  12. Vibrational spectroscopic study of polymorphism and polymorphic transformation of the anti-viral drug lamivudine

    NASA Astrophysics Data System (ADS)

    Du, Yong; Zhang, Huili; Xue, Jiadan; Tang, Wenjian; Fang, Hongxia; Zhang, Qi; Li, Yafang; Hong, Zhi

    2015-02-01

    Vibrational spectra of hydrated and anhydrous lamivudines, and also the dynamic process of polymorphic transformation have been characterized by Fourier transform infrared (FT-IR) and Raman spectroscopic techniques. The vibrational modes of both polymorphic lamivudines are assigned. FT-IR and Raman spectral results show that the interaction between crystalline water and lamivudine molecular has an important effect on the molecular vibration motions of polymorphic lamivudines. The two characteristic Raman peaks at 783 and 798 cm-1 represent hydrated and anhydrous lamivudine respectively. The relationship between changes of two characteristic peak normalized areas and heating time could be fitted with single exponential functions, and the dynamic information of polymorphic transformation of lamivudine drug is obtained. The decay rate of characteristic peak for hydrated lamivudine and the growth rate of that for anhydrous lamivudine are consistent during dehydration transformation process. The reported results provide us important benchmark for qualitatively monitoring different polymorphic drugs and also establishing the corresponding model for the polymorphic transformation of drugs in related pharmaceutical research fields.

  13. Wnt antagonist gene polymorphisms and renal cancer

    PubMed Central

    Hirata, Hiroshi; Hinoda, Yuji; Nakajima, Koichi; Kikuno, Nobuyuki; Yamamura, Soichiro; Kawakami, Kazumori; Suehiro, Yutaka; Tabatabai, Z. Laura; Ishii, Nobuhisa; Dahiya, Rajvir

    2014-01-01

    Purpose Epigenetic silencing of several Wnt pathway related genes has been reported in renal cancer. Except for the TCF4 gene, there are no reports regarding Wnt pathway gene polymorphisms in renal cancer. Therefore, we hypothesized that the polymorphisms in Wnt signaling genes may be risk factors for renal cancer. Experimental Design A total of 210 patients (145 male and 65 female) with pathologically confirmed renal cell carcinoma (RCC), and 200 age- and sex-matched control individuals were enrolled in this study. We genotyped 14 SNPs in six genes including DKK2 (rs17037102, rs419558, rs447372), DKK3 (rs3206824, rs11022095, rs1472189, rs7396187, rs2291599), DKK4 (rs2073664), sFRP4 (rs1802073, rs1802074), SMAD7 (rs12953717), DAAM2 (rs6937133, rs2504106) using PCR-RFLP and direct sequencing in RCC and age-matched healthy subjects. We also tested the relationship between these polymorphisms and clinicopathologic data including gender, grade, tumor stage, lymph-node involvement, distant metastasis, and overall survival. Results A significant decrease in the frequency of the G/A+A/A genotypes in the DKK3 codon335 rs3206824 was observed in RCC patients compared with controls. The frequency of the rs3206824 (G/A) A- rs7396187 (G/C) C haplotype was significantly lower in RCC compared with other haplotypes. We also found that DKK3 rs1472189 C/T is associated with distant metastasis and furthermore, DKK2 rs17037102 G homozygous patients had a decreased risk for death by multivariate Cox regression analysis. Conclusions This is the first report documenting that DKK3 polymorphisms are associated with RCC and that the DKK2 rs17037102 polymorphism may be a predictor for survival in RCC patients after radical nephrectomy. PMID:19562778

  14. IPD--the Immuno Polymorphism Database.

    PubMed

    Robinson, James; Mistry, Kavita; McWilliam, Hamish; Lopez, Rodrigo; Marsh, Steven G E

    2010-01-01

    The Immuno Polymorphism Database (IPD) (http://www.ebi.ac.uk/ipd/) is a set of specialist databases related to the study of polymorphic genes in the immune system. The IPD project works with specialist groups or nomenclature committees who provide and curate individual sections before they are submitted to IPD for online publication. The IPD project stores all the data in a set of related databases. IPD currently consists of four databases: IPD-KIR, contains the allelic sequences of Killer-cell Immunoglobulin-like Receptors, IPD-MHC, is a database of sequences of the Major Histocompatibility Complex of different species; IPD-human platelet antigens, alloantigens expressed only on platelets and IPD-ESTDAB, which provides access to the European Searchable Tumour cell-line database, a cell bank of immunologically characterised melanoma cell lines. The data is currently available online from the website and ftp directory.

  15. IPD--the Immuno Polymorphism Database.

    PubMed

    Robinson, James; Halliwell, Jason A; McWilliam, Hamish; Lopez, Rodrigo; Marsh, Steven G E

    2013-01-01

    The Immuno Polymorphism Database (IPD), http://www.ebi.ac.uk/ipd/ is a set of specialist databases related to the study of polymorphic genes in the immune system. The IPD project works with specialist groups or nomenclature committees who provide and curate individual sections before they are submitted to IPD for online publication. The IPD project stores all the data in a set of related databases. IPD currently consists of four databases: IPD-KIR, contains the allelic sequences of killer-cell immunoglobulin-like receptors, IPD-MHC, a database of sequences of the major histocompatibility complex of different species; IPD-HPA, alloantigens expressed only on platelets; and IPD-ESTDAB, which provides access to the European Searchable Tumour Cell-Line Database, a cell bank of immunologically characterized melanoma cell lines. The data is currently available online from the website and FTP directory. This article describes the latest updates and additional tools added to the IPD project.

  16. Carbon nitride frameworks and dense crystalline polymorphs

    NASA Astrophysics Data System (ADS)

    Pickard, Chris J.; Salamat, Ashkan; Bojdys, Michael J.; Needs, Richard J.; McMillan, Paul F.

    2016-09-01

    We used ab initio random structure searching (AIRSS) to investigate polymorphism in C3N4 carbon nitride as a function of pressure. Our calculations reveal new framework structures, including a particularly stable chiral polymorph of space group P 43212 containing mixed s p2 and s p3 bonding, that we have produced experimentally and recovered to ambient conditions. As pressure is increased a sequence of structures with fully s p3 -bonded C atoms and three-fold-coordinated N atoms is predicted, culminating in a dense P n m a phase above 250 GPa. Beyond 650 GPa we find that C3N4 becomes unstable to decomposition into diamond and pyrite-structured CN2.

  17. Gene polymorphisms, apoptotic capacity and cancer risk.

    PubMed

    Imyanitov, Evgeny N

    2009-04-01

    Programmed cell death has been implicated in various aspects of cancer development. Apoptotic capacity is a subject of significant interindividual variations, which are largely attributed to hereditary traits. Single nucleotide polymorphisms (SNPs) located within cell death genes may influence cancer risk in various ways. Low activity of apoptosis may favor cancer development because of the failure to eliminate cellular clones carrying DNA damage and propensity to inflammation, but may also protect against malignancy due to preservation of antitumor immune cells. Phenotyping studies assessing cell death rate in cancer patients versus healthy controls are limited in number and produced controversial results. TP53 R72P polymorphism is the only SNP whose functional impact on apoptotic response has been replicated in independent investigations. Intriguingly, meta-analysis of TP53 genotyping studies has provided evidence for the association between apoptosis-deficient TP53 genotype and tumor susceptibility. Systematic analysis of cancer-predisposing relevance of other apoptotic gene SNPs remains to be done.

  18. IPD—the Immuno Polymorphism Database

    PubMed Central

    Robinson, James; Mistry, Kavita; McWilliam, Hamish; Lopez, Rodrigo; Marsh, Steven G. E.

    2010-01-01

    The Immuno Polymorphism Database (IPD) (http://www.ebi.ac.uk/ipd/) is a set of specialist databases related to the study of polymorphic genes in the immune system. The IPD project works with specialist groups or nomenclature committees who provide and curate individual sections before they are submitted to IPD for online publication. The IPD project stores all the data in a set of related databases. IPD currently consists of four databases: IPD-KIR, contains the allelic sequences of Killer-cell Immunoglobulin-like Receptors, IPD-MHC, is a database of sequences of the Major Histocompatibility Complex of different species; IPD-human platelet antigens, alloantigens expressed only on platelets and IPD-ESTDAB, which provides access to the European Searchable Tumour cell-line database, a cell bank of immunologically characterised melanoma cell lines. The data is currently available online from the website and ftp directory. PMID:19875415

  19. Kinetics versus Thermodynamics in Virus Capsid Polymorphism.

    PubMed

    Moerman, Pepijn; van der Schoot, Paul; Kegel, Willem

    2016-07-07

    Virus coat proteins spontaneously self-assemble into empty shells in aqueous solution under the appropriate physicochemical conditions, driven by an interaction free energy per bond on the order of 2-5 times the thermal energy kBT. For this seemingly modest interaction strength, each protein building block nonetheless gains a very large binding free energy, between 10 and 20 kBT. Because of this, there is debate about whether the assembly process is reversible or irreversible. Here we discuss capsid polymorphism observed in in vitro experiments from the perspective of nucleation theory and of the thermodynamics of mass action. We specifically consider the potential contribution of a curvature free energy term to the effective interaction potential between the proteins. From these models, we propose experiments that may conclusively reveal whether virus capsid assembly into a mixture of polymorphs is a reversible or an irreversible process.

  20. APOE gene polymorphisms and diabetic peripheral neuropathy.

    PubMed

    Monastiriotis, Christodoulos; Papanas, Nikolaos; Veletza, Stavroula; Maltezos, Efstratios

    2012-09-08

    Genetic factors may influence the natural course of diabetic peripheral neuropathy and explain some of its variability. The aim of this review was to examine the association between apolipoprotein E (apoE) gene polymorphisms and diabetic peripheral neuropathy. Four relevant studies were identified. The two earlier works provided evidence that the ɛ4 allele is a risk factor for this complication, while the two more recent studies were negative. Important differences in the methodology used and in the populations included are obvious, rendering difficult the comparison between studies. In conclusion, the association between APOE gene polymorphisms and diabetic peripheral neuropathy is still unclear. Available evidence is rather limited and results have so far been contradictory. Future studies should employ more robust methodology, adjusting for potential confounders and for the prevalence of neuropathy in the general population with diabetes.

  1. New polymorphic variants of human blood clotting factor IX

    SciTech Connect

    Surin, V.L.; Luk`yanenko, A.V.; Tagiev, A.F.; Smirnova, O.V.; Plutalov, O.V.; Berlin, Yu.A.

    1995-04-01

    The polymorphism of Alu-repeats, which are located in the introns of the human factor IX gene (copies 1-3), was studied. To identify polymorphic variants, direct sequencing of PCR products that contained appropriate repeats was used. In each case, 20 unrelated X chromosomes were studied. A polymorphic Dra I site was found near the 3{prime}-end of Alu copy 3 within the region of the polyA tract. A PCR-based testing system with internal control of restriction hydrolysis was suggested. Testing 81 unrelated X chromosomes revealed that the frequency of the polymorphic Dra I site is 0.23. Taq I polymorphism, which was revealed in Alu copy 4 of factor IX gene in our previous work, was found to be closely linked to Dra I polymorphism. Studies in linkage between different types of polymorphisms of the factor IX gene revealed the presence of a rare polymorphism in intron a that was located within the same minisatellite region as the known polymorphic insertion 50 bp/Dde I. However, the size of the insertion in our case was 26 bp. Only one polymorphic variant was found among over 150 unrelated X chromosomes derived from humans from Moscow and its vicinity. 10 refs., 4 figs., 1 tab.

  2. Calorimetric determinations and theoretical calculations of polymorphs of thalidomide

    NASA Astrophysics Data System (ADS)

    Lara-Ochoa, F.; Pérez, G. Espinosa; Mijangos-Santiago, F.

    2007-09-01

    The analysis of the thermograms of thalidomide obtained for the two reported polymorphs α and β by differential scanning calorimetry (DSC) shows some inconsistencies that are discussed in the present work. The conception of a new polymorph form, named β ∗, allowed us to explain the observed thermal behavior more satisfactorily. This new polymorph shows enantiotropy with both α and β polymorphs, reflected in the unique endotherm obtained in the DSC-thermograms, when a heating rate of 10 °C/min is applied. Several additional experiments, such as re-melting of both polymorph forms, showed that there is indeed a new polymorph with an endotherm located between the endotherms of α and β. IR, Raman, and powder X-ray permit us to characterize the isolated compound, resulting from the re-melting of both polymorph forms. Mechanical calculations were performed to elucidate the conformations of each polymorph, and ab initio quantum chemical calculations were performed to determine the energy of the more stable conformers and the spatial cell energy for both polymorphs α and β. These results suggested a possible conformation for the newly discovered polymorph β ∗.

  3. Single nucleotide polymorphisms and suicidal behaviour.

    PubMed

    Pregelj, Peter

    2012-09-01

    The World Health Organization estimates that almost one million deaths each year are attributable to suicide, and suicide attempt is close to 10 times more common than suicide completion. Suicidal behaviour has multiple causes that are broadly divided into proximal stressors or triggers and predisposition such as genetic. It is also known that single nucleotide polymorphisms (SNPs) occur throughout a human DNA influencing the structure, quantity and the function of proteins and other molecules. Abnormalities of the serotonergic system were observed in suicide victims. Beside 5-HT1A and other serotonin receptors most studied are the serotonin transporter 5' functional promoter variant, and monoamine oxidase A and the tryptophan-hydroxylase 1 and 2 (TPH) polymorphisms. It seems that especially genes regulating serotoninergic system and neuronal systems involved in stress response are associated with suicidal behaviour. Most genetic studies on suicidal behaviour have considered a small set of functional polymorphisms relevant mostly to monoaminergic neurotransmission. However, genes involved in regulation of other factors such as brain-derived neurotropic factor seems to be even more relevant for further research.

  4. Introgressive hybridization in a trophically polymorphic cichlid

    PubMed Central

    Hulsey, C Darrin; García-de-León, Francisco J

    2013-01-01

    Trophically polymorphic species could represent lineages that are rapidly diverging along an ecological axis or could phenotypically mark the collapse of species through introgressive hybridization. We investigated patterns of introgression between the trophically polymorphic cichlid fish Herichthys minckleyi and its relative H. cyanoguttatus using a combination of population genetics and species tree analyses. We first examined the distribution of mitochondrial haplotypes within the alternative H. minckleyi pharyngeal jaw morphotypes that are endemic to the small desert valley of Cuatro Ciénegas. We recovered two clusters of mitochondrial haplotypes. The first contained a number of slightly differentiated cytochrome b (cytb) haplotypes that showed some phylogeographic signal and were present in both jaw morphotypes. The other haplotype was monomorphic, highly differentiated from the other cluster, present in equal frequencies in the morphotypes, and identical to H. cyanoguttatus haplotypes found outside Cuatro Ciénegas. Then, we investigated whether H. minckleyi individuals with the H. cyanoguttatus cytb were more evolutionarily similar to H. cyanoguttatus or other H. minckleyi using a species tree analysis of 84 nuclear loci. Both H. minckleyi pharyngeal morphotypes, regardless of their cytb haplotype, were quite distinct from H. cyanoguttatus. However, hybridization could be blurring subdivision within H. minckleyi as the alternative jaw morphotypes were not genetically distinct from one another. Accounting for introgression from H. cyanoguttatus will be essential to understand the evolution of the trophically polymorphic cichlid H. minckleyi. PMID:24340193

  5. Polymorphisms within inflammatory genes and colorectal cancer

    PubMed Central

    Landi, Stefano; Gemignani, Federica; Bottari, Fabio; Gioia-Patricola, Lydie; Guino, Elisabet; Cambray, María; Biondo, Sebastiano; Capella, Gabriel; Boldrini, Laura; Canzian, Federico; Moreno, Victor

    2006-01-01

    Background Chronic inflammation is a risk factor for colorectal cancer and polymorphisms in the inflammatory genes could modulate the levels of inflammation. We have investigated ten single nucleotide polymorphisms (SNPs) in the following inflammation-related genes: TLR4 (Asp299Gly), CD14 (-260 T>C), MCP1 (-2518 A>G), IL12A (+7506 A>T, +8707 A>G, +9177 T>A, +9508 G>A), NOS2A (+524T>C), TNF (-857C>T), and PTGS1 (V444I) in 377 colorectal (CRC) cancer cases and 326 controls from Barcelona (Spain). Results There was no statistically significant association between the SNPs investigated and colorectal cancer risk. Conclusion The lack of association may show that the inflammatory genes selected for this study are not involved in the carcinogenic process of colorectum. Alternatively, the negative results may derive from no particular biological effect of the analysed polymorphisms in relation to CRC. Otherwise, the eventual biological effect is so little to go undetected, unless analysing a much larger sample size. PMID:17062130

  6. An orthorhombic polymorph of mulinic acid.

    PubMed

    Brito, Iván; Bórquez, Jorge; Loyola, Luis Alberto; López-Rodríguez, Matías; Cárdenas, Alejandro

    2010-01-09

    THE TITLE COMPOUND [SYSTEMATIC NAME: (3S,3aS,10bR)-3-isopropyl-5a,8-dimethyl-2,3,4,5,5a,6,7,10,10a,10b-deca-hydro-endo-epidioxy-cyclo-hepta-[e]indene-3a(1H)-carboxylic acid], C(20)H(30)O(4), is a polymorphic form of a previously reported structure [Loyola et al. (1990 ▶). Tetra-hedron, 46, 5413-5420]. The newly found ortho-rhom-bic polymorph crystallizes in P2(1)2(1)2(1) with two mol-ecules in the asymmetric unit. The mol-ecules are linked into discrete D(2) chains by simple O-H⋯O inter-actions. There are only slight variations in the mol-ecular geometry and supra-molecular organization in the crystal structures of the two polymorphs. The densities are 1.145 (monoclinic, P2(1)) and 1.155 Mg m(-3) (ortho-rhom-bic, P2(1)2(1)2(1)).

  7. Polymorphic growth rates in myrmecophilous insects.

    PubMed

    Schönrogge, K; Wardlaw, J C; Thomas, J A; Elmes, G W

    2000-04-22

    A polymorphism in growth rates was recently described affecting the larval development of the myrmecophilous butterfly Maculinea rebeli, spanning different years in a single insect population. The close integration of M. rebeli into the host ant colonies, facilitated by adaptations in behaviour and chemical mimicry, make extended larval development a successful strategy. Here we present additional data for M. rebeli and new data for Maculinea alcon (another cuckoo-feeding lycaenid) and the two myrmecophilous predators Maculinea arion and Microdon mutabilis (Diptera: Syrphidae). As predicted, M. alcon shows the same growth pattern as M. rebeli with a proportion of caterpillars developing in one year and the remainder over two years. This pattern holds in both northern and southern European populations, where M. alcon exploits different species of host. Against expectation, the same bimodal distribution of pre-pupation body weights, indicating one and two year developers, was found for the larvae of M. arion and M. mutabilis. As predators, both species are less closely integrated in their host ant colonies, suggesting that the polymorphism in growth rates is a more general adaptation to a myrmecophilous life style, arrived at by convergent evolution between the Maculinea and Microdon species. For predatory species we suggest that biennialism is an adaptation to the migratory behaviour of the host made possible by the predators' ability to fast over extended periods. We also hypothesize that M. arion represents an ancestral strategy in Maculinea butterflies and that the growth polymorphism might have become genetically fixed in the cuckoo-feeding species.

  8. Genetic polymorphisms linked to susceptibility to malaria.

    PubMed

    Driss, Adel; Hibbert, Jacqueline M; Wilson, Nana O; Iqbal, Shareen A; Adamkiewicz, Thomas V; Stiles, Jonathan K

    2011-09-19

    The influence of host genetics on susceptibility to Plasmodium falciparum malaria has been extensively studied over the past twenty years. It is now clear that malaria parasites have imposed strong selective forces on the human genome in endemic regions. Different genes have been identified that are associated with different malaria related phenotypes. Factors that promote severity of malaria include parasitaemia, parasite induced inflammation, anaemia and sequestration of parasitized erythrocytes in brain microvasculature.Recent advances in human genome research technologies such as genome-wide association studies (GWAS) and fine genotyping tools have enabled the discovery of several genetic polymorphisms and biomarkers that warrant further study in host-parasite interactions. This review describes and discusses human gene polymorphisms identified thus far that have been shown to be associated with susceptibility or resistance to P. falciparum malaria. Although some polymorphisms play significant roles in susceptibility to malaria, several findings are inconclusive and contradictory and must be considered with caution. The discovery of genetic markers associated with different malaria phenotypes will help elucidate the pathophysiology of malaria and enable development of interventions or cures. Diversity in human populations as well as environmental effects can influence the clinical heterogeneity of malaria, thus warranting further investigations with a goal of developing new interventions, therapies and better management against malaria.

  9. Colour Polymorphism Protects Prey Individuals and Populations Against Predation.

    PubMed

    Karpestam, Einat; Merilaita, Sami; Forsman, Anders

    2016-02-23

    Colour pattern polymorphism in animals can influence and be influenced by interactions between predators and prey. However, few studies have examined whether polymorphism is adaptive, and there is no evidence that the co-occurrence of two or more natural prey colour variants can increase survival of populations. Here we show that visual predators that exploit polymorphic prey suffer from reduced performance, and further provide rare evidence in support of the hypothesis that prey colour polymorphism may afford protection against predators for both individuals and populations. This protective effect provides a probable explanation for the longstanding, evolutionary puzzle of the existence of colour polymorphisms. We also propose that this protective effect can provide an adaptive explanation for search image formation in predators rather than search image formation explaining polymorphism.

  10. N-Acetyltransferase 1 Polymorphism and Breast Cancer Risk

    DTIC Science & Technology

    2011-10-01

    analysis of the N-acetyltransferase 1 gene (NAT1*) using polymerase chain reaction-restriction fragment- single strand conformation polymorphism assay...risk of smoking-induced lung cancer (Bouchardy et al., 1998). NAT1*14B is characterized by a single nucleotide polymorphism (SNP) G560A (rs4986782...Structure-function analyses of single nucleotide polymorphisms in human N-acetyltransferase 1. Drug Metab Rev 40, 169-184. Zheng, W., Deitz, A.C., Campbell

  11. Genetic Polymorphisms, Hormone Levels, and Hot Flashes in Midlife Women

    PubMed Central

    Schilling, Chrissy; Gallicchio, Lisa; Miller, Susan R.; Langenberg, Patricia; Zacur, Howard; Flaws, Jodi A.

    2007-01-01

    Objective Hot flashes disrupt the lives of millions of women each year. Although hot flashes are a public health concern, little is known about risk factors that predispose women to hot flashes. Thus, the objective of this study was to examine whether sex steroid hormone levels and genetic polymorphisms in hormone biosynthesis and degradation enzymes are associated with the risk of hot flashes. Methods In a cross-sectional study design, midlife women aged 45 to 54 years (n=639) were recruited from Baltimore and its surrounding counties. Participants completed a questionnaire and donated a blood sample for steroid hormone analysis and genotyping. The associations between genetic polymorphisms and hormone levels, as well as the associations between genetic polymorphisms, hormone levels, and hot flashes were examined using statistical models. Results A polymorphism in CYP1B1 was associated with lower dehydroepiandrosterone-sulfate (DHEA-S) and progesterone levels, while a polymorphism in CYP19 (aromatase) was associated with higher testosterone and DHEA-S levels. Lower progesterone and sex hormone binding globulin levels, lower free estradiol index, and a higher ratio of total androgens to total estrogens were associated with the experiencing of hot flashes. A polymorphism in CYP1B1 and a polymorphism in 3βHSD were both associated with hot flashes. Conclusion Some genetic polymorphisms may be associated with altered levels of hormones in midlife women. Further, selected genetic polymorphisms and altered hormone levels may be associated with the risk of hot flashes in midlife women. PMID:17187946

  12. Single-nucleotide polymorphism discovery by targeted DNA photocleavage.

    PubMed

    Hart, Jonathan R; Johnson, Martin D; Barton, Jacqueline K

    2004-09-28

    Single-nucleotide polymorphisms are the largest source of genetic variation in humans. We report a method for the discovery of single-nucleotide polymorphisms within genomic DNA. Pooled genomic samples are amplified, denatured, and annealed to generate mismatches at polymorphic DNA sites. Upon photoactivation, these DNA mismatches are then cleaved site-specifically by using a small molecular probe, a bulky metallointercalator, Rhchrysi or Rhphzi. Fluorescent labeling of the cleaved products and separation by capillary electrophoresis permits rapid identification with single-base resolution of the single-nucleotide polymorphism site. This method is remarkably sensitive and minor allele frequencies as low as 5% can be readily detected.

  13. Persistence of neutral polymorphisms in Lake Victoria cichlid fish

    PubMed Central

    Nagl, Sandra; Tichy, Herbert; Mayer, Werner E.; Takahata, Naoyuki; Klein, Jan

    1998-01-01

    Phylogenetic trees for groups of closely related species often have different topologies, depending on the genes used. One explanation for the discordant topologies is the persistence of polymorphisms through the speciation phase, followed by differential fixation of alleles in the resulting species. The existence of transspecies polymorphisms has been documented for alleles maintained by balancing selection but not for neutral alleles. In the present study, transspecific persistence of neutral polymorphisms was tested in the endemic haplochromine species flock of Lake Victoria cichlid fish. Putative noncoding region polymorphisms were identified at four randomly selected nuclear loci and tested on a collection of 12 Lake Victoria species and their putative riverine ancestors. At all loci, the same polymorphism was found to be present in nearly all the tested species, both lacustrine and riverine. Different polymorphisms at these loci were found in cichlids of other East African lakes (Malawi and Tanganyika). The Lake Victoria polymorphisms must have therefore arisen after the flocks now inhabiting the three great lakes diverged from one another, but before the riverine ancestors of the Lake Victoria flock colonized the Lake. Calculations based on the mtDNA clock suggest that the polymorphisms have persisted for about 1.4 million years. To maintain neutral polymorphisms for such a long time, the population size must have remained large throughout the entire period. PMID:9826684

  14. Persistence of neutral polymorphisms in Lake Victoria cichlid fish.

    PubMed

    Nagl, S; Tichy, H; Mayer, W E; Takahata, N; Klein, J

    1998-11-24

    Phylogenetic trees for groups of closely related species often have different topologies, depending on the genes used. One explanation for the discordant topologies is the persistence of polymorphisms through the speciation phase, followed by differential fixation of alleles in the resulting species. The existence of transspecies polymorphisms has been documented for alleles maintained by balancing selection but not for neutral alleles. In the present study, transspecific persistence of neutral polymorphisms was tested in the endemic haplochromine species flock of Lake Victoria cichlid fish. Putative noncoding region polymorphisms were identified at four randomly selected nuclear loci and tested on a collection of 12 Lake Victoria species and their putative riverine ancestors. At all loci, the same polymorphism was found to be present in nearly all the tested species, both lacustrine and riverine. Different polymorphisms at these loci were found in cichlids of other East African lakes (Malawi and Tanganyika). The Lake Victoria polymorphisms must have therefore arisen after the flocks now inhabiting the three great lakes diverged from one another, but before the riverine ancestors of the Lake Victoria flock colonized the Lake. Calculations based on the mtDNA clock suggest that the polymorphisms have persisted for about 1.4 million years. To maintain neutral polymorphisms for such a long time, the population size must have remained large throughout the entire period.

  15. 2-Quinolinecarboxaldehyde: Polymorphic behavior of a small rigid molecule

    NASA Astrophysics Data System (ADS)

    Maria, Teresa M. R.; Ermelinda S. Eusébio, M.; Almeida e Silva, J.; Sobral, Abílio J. F. N.; Cardoso, C.; Paixão, J. A.; Ramos Silva, M.

    2012-12-01

    This work reports an investigation on the polymorphism of 2-quinolinecarboxaldehyde, a quinoline derivative, frequently used as a ligand in the synthesis of metal complexes. 2-Quinolinecarboxaldehyde lacks both molecular flexibility and the ability to form strong hydrogen bonds, two characteristics often seen as driving forces for the occurrence of polymorphism. Nevertheless, a rich polymorphic behavior was found for this substance. Polymorphic forms were generated by crystallization from solutions, and by melt cooling. Four polymorphic forms could be clearly identified by thermal analysis investigation and the crystalline structures of forms I and III were solved by single-crystal X-ray diffraction, at room temperature. In polymorph I, molecules are joined by π-π and weak C-H⋯O interactions while in polymorph III helicoidal chiral chains are formed and very weak C-H⋯O intermolecular interactions can be identified. Neither of these intermolecular interactions involves the formyl hydrogen atom. Concomitant polymorph crystallization from the melt was often observed. XRPD diffractograms which showed similarities to that of polymorph I but presented striking differences were obtained in some experiments. In certain cases the discrepancies may be ascribed to effects of preferential orientation. However, the existence of multiple but slightly different structures with small differences seems to be a better explanation for these experimental observations.

  16. Adrenergic Polymorphism and the Human Stress Response

    PubMed Central

    Rao, Fangwen; Zhang, Lian; Wessel, Jennifer; Zhang, Kuixing; Wen, Gen; Kennedy, Brian P.; Rana, Brinda K.; Das, Madhusudan; Rodriguez-Flores, Juan L.; Smith, Douglas W.; Cadman, Peter E.; Salem, Rany M.; Mahata, Sushil K.; Schork, Nicholas J.; Taupenot, Laurent; Ziegler, Michael G.; O’Connor, Daniel T.

    2009-01-01

    Tyrosine hydroxylase (TH) is the rate-limiting enzyme in catecholamine biosynthesis. Does common genetic variation at human TH alter autonomic activity and predispose to cardiovascular disease? We undertook systematic polymorphism discovery at the TH locus, and then tested variants for contributions to sympathetic function and blood pressure. We resequenced 80 ethnically diverse individuals across the TH locus. One hundred seventy-two twin pairs were evaluated for sympathetic traits, including catecholamine production and environmental (cold) stress responses. To evaluate hypertension, we genotyped subjects selected from the most extreme diastolic blood pressure percentiles in the population. Human TH promoter haplotype/reporter plasmids were transfected into chromaffin cells. Forty-nine single nucleotide polymorphisms (SNPs) and one tetranucleotide repeat were discovered, but coding region polymorphism did not account for common phenotypic variation. A block of linkage disequilibrium spanned four common variants in the proximal promoter. Catecholamine secretory traits were significantly heritable, as were stress-induced blood pressure changes. In the TH promoter, significant associations were found for urinary catecholamine excretion, as well as blood pressure response to stress. TH promoter haplotype #2 (TGGG) showed pleiotropy, increasing both norepinephrine excretion and blood pressure during stress. In hypertension, a case–control study (1266 subjects, 53% women) established the effect of C-824T in determination of blood pressure. We conclude that human catecholamine secretory traits are heritable, displaying joint genetic determination (pleiotropy) with autonomic activity and finally with blood pressure in the population. Catecholamine secretion is influenced by genetic variation in the adrenergic pathway encoding catecholamine synthesis, especially at the classically rate-limiting step, TH. The results suggest novel pathophysiological links between a key

  17. Polymorphism in silicate-postperovskite reviewed (Invited)

    NASA Astrophysics Data System (ADS)

    Tschauner, O. D.

    2010-12-01

    Early on in the examination of postperovskite(ppv)-type magnesium metasilicate it had been debated if this potential deep mantle mineral can be subject to further structural transformation as function of composition, pressure, and temperature within the range of conditions in the lower mantle. MgSiO3-perovskite accommodates minor elements through local lattice distortions by tilt of the corner-sharing octahedral framework. The CaIrO3-type ppv structure does not seem to possess a similar mechanism of local relaxation of lattice strain. Instead minor elements may rather be accommodated by periodic kinks in this layered structure (1). This kinking-mechanism allows for generating a plethora of polymorphs similar in structure and free energy (1,2). However, the elastic properties of ppv may be strongly affected by this type of structural modification. While structural analogues of silicate-ppv exhibit this type of polymorphism (3,4) previous attempts to examine polymorphism in silicate-ppv remained suggestive (2,5). This is mostly owed to the severe constraints imposed on powder diffraction studies conducted under the extreme conditions of stability of MgSiO3-ppv. Here I present new results on silicate-ppv based on different experimental strategies which shed more light on this complex yet important issue of structural modifications in minor-element bearing silicate-ppv. (1) Oganov et al. Nature 438, 1142 (2005);(2) Tschauner et al. Am. Min. 93, 533 (2008); (3) Shirako et al. Phys. Chem. Min. 36, 455 (2009); Yakovlev et al. J. Sol. Stat. Chem. 182, 1545 (2009) Work supported through NNSA Cooperative Agreement DOE-FC88-01NV14049

  18. What Determines the Ice Polymorph in Clouds?

    PubMed

    Hudait, Arpa; Molinero, Valeria

    2016-07-20

    Ice crystals in the atmosphere nucleate from supercooled liquid water and grow by vapor uptake. The structure of the ice polymorph grown has strong impact on the morphology and light scattering of the ice crystals, modulates the amount of water vapor in ice clouds, and can impact the molecular uptake and reactivity of atmospheric aerosols. Experiments and molecular simulations indicate that ice nucleated and grown from deeply supercooled liquid water is metastable stacking disordered ice. The ice polymorph grown from vapor has not yet been determined. Here we use large-scale molecular simulations to determine the structure of ice that grows as a result of uptake of water vapor in the temperature range relevant to cirrus and mixed-phase clouds, elucidate the molecular mechanism of the formation of ice at the vapor interface, and compute the free energy difference between cubic and hexagonal ice interfaces with vapor. We find that vapor deposition results in growth of stacking disordered ice only under conditions of extreme supersaturation, for which a nonequilibrium liquid layer completely wets the surface of ice. Such extreme conditions have been used to produce stacking disordered frost ice in experiments and may be plausible in the summer polar mesosphere. Growth of ice from vapor at moderate supersaturations in the temperature range relevant to cirrus and mixed-phase clouds, from 200 to 260 K, produces exclusively the stable hexagonal ice polymorph. Cubic ice is disfavored with respect to hexagonal ice not only by a small penalty in the bulk free energy (3.6 ± 1.5 J mol(-1) at 260 K) but also by a large free energy penalty at the ice-vapor interface (89.7 ± 12.8 J mol(-1) at 260 K). The latter originates in higher vibrational entropy of the hexagonal-terminated ice-vapor interface. We predict that the free energy penalty against the cubic ice interface should decrease strongly with temperature, resulting in some degree of stacking disorder in ice grown from

  19. Placental glucose dehydrogenase polymorphism in Koreans.

    PubMed

    Kim, Y J; Paik, S G; Park, H Y

    1994-12-01

    The genetic polymorphism of placental glucose dehydrogenase (GDH) was investigated in 300 Korean placentae using horizontal starch gel electrophoresis. The allele frequencies for GDH1, GDH2 and GDH3 were 0.537, 0.440 and 0.005, respectively, which were similar to those in Japanese. We also observed an anodal allele which was similar to the GDH4 originally reported in Chinese populations at a low frequency of 0.015. An additional new cathodal allele (named GDH6) was observed in the present study with a very low frequency of 0.003.

  20. Genetic salivary protein polymorphism in Mexican population.

    PubMed

    Banderas Tarabay, J A; González Begné, M

    1996-01-01

    Genetic polymorphism is the major contributor that affects human salivary composition. In order to determine the molecular phenotypes in saliva, it is important to know the distribution of proteins with specific functions which allows the clinical diagnosis of specific diseases. Unstimulated human whole saliva samples from 120 subjects were subjected to sodium dodecyl sulfate polyacrylamide slab gel electrophoresis (SDS-PAGE). The phenotype distribution of several molecules including MG1, MG2, alpha-Amylase, PRP-I and cystatins were similar. Qualitative and quantitative characteristics were specific in each subject.

  1. Polymorphisms in Autophagy Genes and Susceptibility to Tuberculosis

    PubMed Central

    Alisjahbana, Bachti; Sahiratmadja, Edhyana; Parwati, Ida; Oosting, Marije; Plantinga, Theo S.; Joosten, Leo A. B.; Netea, Mihai G.; Ottenhoff, Tom H. M.; van de Vosse, Esther; van Crevel, Reinout

    2012-01-01

    Recent data suggest that autophagy is important for intracellular killing of Mycobacterium tuberculosis, and polymorphisms in the autophagy gene IRGM have been linked with susceptibility to tuberculosis (TB) among African-Americans, and with TB caused by particular M. tuberculosis genotypes in Ghana. We compared 22 polymorphisms of 14 autophagy genes between 1022 Indonesian TB patients and 952 matched controls, and between patients infected with different M. tuberculosis genotypes, as determined by spoligotyping. The same autophagy polymorphisms were studied in correlation with ex-vivo production of TNF, IL-1β, IL-6, IL-8, IFN-γ and IL-17 in healthy volunteers. No association was found between TB and polymorphisms in the genes ATG10, ATG16L2, ATG2B, ATG5, ATG9B, IRGM, LAMP1, LAMP3, P2RX7, WIPI1, MTOR and ATG4C. Associations were found between polymorphisms in LAMP1 (p = 0.02) and MTOR (p = 0.02) and infection with the successful M. tuberculosis Beijing genotype. The polymorphisms examined were not associated with M. tuberculosis induced cytokines, except for a polymorphism in ATG10, which was linked with IL-8 production (p = 0.04). All associations found lost statistical significance after correction for multiple testing. This first examination of a broad set of polymorphisms in autophagy genes fails to show a clear association with TB, with M. tuberculosis Beijing genotype infection or with ex-vivo pro-inflammatory cytokine production. PMID:22879892

  2. Human lymphocyte polymorphisms detected by quantitative two-dimensional electrophoresis

    SciTech Connect

    Goldman, D.; Merril, C.R.

    1983-09-01

    A survey of 186 soluble lymphocyte proteins for genetic polymorphism was carried out utilizing two-dimensional electrophoresis of /sup 14/C-labeled phytohemagglutinin (PHA)-stimulated human lymphocyte proteins. Nineteen of these proteins exhibited positional variation consistent with independent genetic polymorphism in a primary sample of 28 individuals. Each of these polymorphisms was characterized by quantitative gene-dosage dependence insofar as the heterozygous phenotype expressed approximately 50% of each allelic gene product as was seen in homozygotes. Patterns observed were also identical in monozygotic twins, replicate samples, and replicate gels. The three expected phenotypes (two homozygotes and a heterozygote) were observed in each of 10 of these polymorphisms while the remaining nine had one of the homozygous classes absent. The presence of the three phenotypes, the demonstration of gene-dosage dependence, and our own and previous pedigree analysis of certain of these polymorphisms supports the genetic basis of these variants. Based on this data, the frequency of polymorphic loci for man is: P . 19/186 . .102, and the average heterozygosity is .024. This estimate is approximately 1/3 to 1/2 the rate of polymorphism previously estimated for man in other studies using one-dimensional electrophoresis of isozyme loci. The newly described polymorphisms and others which should be detectable in larger protein surveys with two-dimensional electrophoresis hold promise as genetic markers of the human genome for use in gene mapping and pedigree analyses.

  3. Impact of host genetic polymorphisms on vaccine induced antibody response

    PubMed Central

    Linnik, Janina E.; Egli, Adrian

    2016-01-01

    ABSTRACT Many host- and vaccine-specific factors modulate an antibody response. Host genetic polymorphisms, in particular, modulate the immune response in multiple ways on different scales. This review article describes how information on host genetic polymorphisms and corresponding immune cascades may be used to generate personalized vaccine strategies to optimize the antibody response. PMID:26809773

  4. Association between Tryptophan Hydroxylase 2 Gene Polymorphism and Completed Suicide

    ERIC Educational Resources Information Center

    Fudalej, Sylwia; Ilgen, Mark; Fudalej, Marcin; Kostrzewa, Grazyna; Barry, Kristen; Wojnar, Marcin; Krajewski, Pawel; Blow, Frederic; Ploski, Rafal

    2010-01-01

    The association between suicide and a single nucleotide polymorphism (rs1386483) was examined in the recently identified tryptophan hydroxylase 2 (TPH2) gene. Blood samples of 143 suicide victims and 162 age- and sex-matched controls were examined. The frequency of the TT genotype in the TPH2 polymorphism was higher in suicide victims than in…

  5. Effects of functional polymorphisms on beef carcass merit

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To develop a resource to identify polymorphisms present in common beef cattle breeds, and relate those polymorphisms to phenotypic differences, low-coverage genomic sequence was obtained on 186 purebred bulls from 15 predominant breeds in the United States, and 84 crossbred sons of these bulls. The...

  6. Effects of human SAMHD1 polymorphisms on HIV-1 susceptibility

    SciTech Connect

    White, Tommy E.; Brandariz-Nuñez, Alberto; Valle-Casuso, Jose Carlos; Knowlton, Caitlin; Kim, Baek; Sawyer, Sara L.; Diaz-Griffero, Felipe

    2014-07-15

    SAMHD1 is a human restriction factor that prevents efficient infection of macrophages, dendritic cells and resting CD4+ T cells by HIV-1. Here we explored the antiviral activity and biochemical properties of human SAMHD1 polymorphisms. Our studies focused on human SAMHD1 polymorphisms that were previously identified as evolving under positive selection for rapid amino acid replacement during primate speciation. The different human SAMHD1 polymorphisms were tested for their ability to block HIV-1, HIV-2 and equine infectious anemia virus (EIAV). All studied SAMHD1 variants block HIV-1, HIV-2 and EIAV infection when compared to wild type. We found that these variants did not lose their ability to oligomerize or to bind RNA. Furthermore, all tested variants were susceptible to degradation by Vpx, and localized to the nuclear compartment. We tested the ability of human SAMHD1 polymorphisms to decrease the dNTP cellular levels. In agreement, none of the different SAMHD1 variants lost their ability to reduce cellular levels of dNTPs. Finally, we found that none of the tested human SAMHD1 polymorphisms affected the ability of the protein to block LINE-1 retrotransposition. - Highlights: • Human SAMHD1 single-nucleotide polymorphisms block HIV-1 and HIV-2 infection. • SAMHD1 polymorphisms do not affect its ability to block LINE-1 retrotransposition. • SAMHD1 polymorphisms decrease the cellular levels of dNTPs.

  7. Bitter Taste Receptor Polymorphisms and Human Aging

    PubMed Central

    Carrai, Maura; Crocco, Paolina; Montesanto, Alberto; Canzian, Federico; Rose, Giuseppina; Rizzato, Cosmeri

    2012-01-01

    Several studies have shown that genetic factors account for 25% of the variation in human life span. On the basis of published molecular, genetic and epidemiological data, we hypothesized that genetic polymorphisms of taste receptors, which modulate food preferences but are also expressed in a number of organs and regulate food absorption processing and metabolism, could modulate the aging process. Using a tagging approach, we investigated the possible associations between longevity and the common genetic variation at the three bitter taste receptor gene clusters on chromosomes 5, 7 and 12 in a population of 941 individuals ranging in age from 20 to 106 years from the South of Italy. We found that one polymorphism, rs978739, situated 212 bp upstream of the TAS2R16 gene, shows a statistically significant association (p = 0.001) with longevity. In particular, the frequency of A/A homozygotes increases gradually from 35% in subjects aged 20 to 70 up to 55% in centenarians. These data provide suggestive evidence on the possible correlation between human longevity and taste genetics. PMID:23133589

  8. Polymorphic collaboration in the global grid

    NASA Astrophysics Data System (ADS)

    McQuay, William K.

    2006-05-01

    Next generation collaborative systems must be able to represent the same information in different forms on a broad spectrum of devices and resources from low end personal digital assistants (PDA) to high performance computers (HPC). Users might be on a desktop then switch to a laptop and then to a PDA while accessing the global grid. The user preference profile for a collaboration session should be capable of moving with them as well as be automatically adjusted for the device type. Collaborative systems must be capable of representing the same information in many forms for different domains and on many devices and thus be polymorphic. Polymorphic collaboration will provide an ability for multiple heterogeneous resources (human to human, human to machine and machine to machine) to share information and activities, as well as the ability to regulate collaborative sessions based on client characteristics and needs; reuse user profiles, tool category choices, and settings in future collaboration session by same or different users; use intelligent agents to assist collaborative systems in learning user/resource preferences and behaviors, and autonomously derive optimal information to provide to users and decision makers. This paper discusses ongoing research in next generation collaborative environments with the goal of making electronic collaboration as easy to use as the telephone - collaboration at the touch of the screen.

  9. Salivary proteome and its genetic polymorphisms.

    PubMed

    Oppenheim, Frank G; Salih, Erdjan; Siqueira, Walter L; Zhang, Weimin; Helmerhorst, Eva J

    2007-03-01

    Salivary diagnostics for oral as well as systemic diseases is dependent on the identification of biomolecules reflecting a characteristic change in presence, absence, composition, or structure of saliva components found under healthy conditions. Most of the biomarkers suitable for diagnostics comprise proteins and peptides. The usefulness of salivary proteins for diagnostics requires the recognition of typical features, which make saliva as a body fluid unique. Salivary secretions reflect a degree of redundancy displayed by extensive polymorphisms forming families for each of the major salivary proteins. The structural differences among these polymorphic isoforms range from distinct to subtle, which may in some cases not even affect the mass of different family members. To facilitate the use of modern state-of-the-art proteomics and the development of nanotechnology-based analytical approaches in the field of diagnostics, the salient features of the major salivary protein families are reviewed at the molecular level. Knowledge of the structure and function of salivary gland-derived proteins/peptides has a critical impact on the rapid and correct identification of biomarkers, whether they originate from exocrine or non-exocrine sources.

  10. Functional relevance of human adh polymorphism.

    PubMed

    Eriksson, C J; Fukunaga, T; Sarkola, T; Chen, W J; Chen, C C; Ju, J M; Cheng, A T; Yamamoto, H; Kohlenberg-Müller, K; Kimura, M; Murayama, M; Matsushita, S; Kashima, H; Higuchi, S; Carr, L; Viljoen, D; Brooke, L; Stewart, T; Foroud, T; Su, J; Li, T K; Whitfield, J B

    2001-05-01

    This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were C. J. Peter Eriksson and Tatsushige Fukunaga. The presentations were (1) 4-Methylpyrazole as a tool in the investigation of the role of ADH in the actions of alcohol in humans, by Taisto Sarkola and C. J. Peter Eriksson; (2) ADH2 polymorphism and flushing in Asian populations, by Wei J. Chen, C. C. Chen, J. M. Ju, and Andrew T. A. Cheng; (3) Role of ADH3 genotypes in the acute effects of alcohol in a Finnish population, by Hidetaka Yamamoto, Kathrin Kohlenberg-Müller, and C. J. Peter Eriksson; (4) Clinical characteristics and disease course of alcoholics with different ADH2 genotypes, by Mitsuru Kimura, Masanobu Murayama, Sachio Matsushita, Haruo Kashima, and Susumu Higuchi; (5) ADH2 polymorphism, alcohol drinking, and birth defects, by Lucinda Carr, D. Viljoen, L. Brooke, T. Stewart, T. Foroud, J. Su, and Ting-Kai Li; and (6) ADH genotypes and alcohol use in Europeans, by John B. Whitfield.

  11. TNFA promoter polymorphism and susceptibility to brucellosis.

    PubMed

    Caballero, A; Bravo, M J; Nieto, A; Colmenero, J D; Alonso, A; Martín, J

    2000-09-01

    The aim of this study was to investigate the possible influence of the tumor necrosis factor alpha (TNFA) gene promoter polymorphisms and HLA class II genes on the susceptibility to or development of human brucellosis. TNFA genotypes (at positions -308 and -238) were determined in 59 patients with brucellosis and 160 healthy controls by polymerase chain reaction-restriction fragment length polymorphism. There were no significant differences between the patients and the controls for the TNFA-238 genotypes. However, when the overall TNFA-308 genotype distribution of the brucella patients was compared with that of the control subjects, a significant skewing was observed (P = 0.02). The TNFA-308.1/2 genotype was present at significantly higher frequency in the total patient as a whole compared with control subjects (30% versus 15%; P = 0.01, odds ratio (OR) 2.49, 95% confidence interval (CI) 1.16-5.33). No statistically significant differences in the distribution of HLA-DRB1 or DQB1 alleles were observed between brucella patients and control subjects. Stratification to correct for interdependence of TNFA-308.2 and HLA-DR3 alleles confirmed that, in spite of their strong linkage disequilibrium, the association of TNFA-308.2 with brucellosis was independent of HLA-DR3.

  12. IPD--the Immuno Polymorphism Database.

    PubMed

    Robinson, James; Waller, Matthew J; Stoehr, Peter; Marsh, Steven G E

    2005-01-01

    The Immuno Polymorphism Database (IPD) (http://www.ebi.ac.uk/ipd/) is a set of specialist databases related to the study of polymorphic genes in the immune system. IPD currently consists of four databases: IPD-KIR, contains the allelic sequences of Killer-cell Immunoglobulin-like Receptors; IPD-MHC, a database of sequences of the Major Histocompatibility Complex of different species; IPD-HPA, alloantigens expressed only on platelets; and IPD-ESTAB, which provides access to the European Searchable Tumour Cell-Line Database, a cell bank of immunologically characterized melanoma cell lines. The IPD project works with specialist groups or nomenclature committees who provide and curate individual sections before they are submitted to IPD for online publication. The IPD project stores all the data in a set of related databases. Those sections with similar data, such as IPD-KIR and IPD-MHC share the same database structure. The sharing of a common database structure makes it easier to implement common tools for data submission and retrieval. The data are currently available online from the website and ftp directory; files will also be made available in different formats to download from the website and ftp server. The data will also be included in SRS, BLAST and FASTA search engines at the European Bioinformatics Institute.

  13. IPD—the Immuno Polymorphism Database

    PubMed Central

    Robinson, James; Halliwell, Jason A.; McWilliam, Hamish; Lopez, Rodrigo; Marsh, Steven G. E.

    2013-01-01

    The Immuno Polymorphism Database (IPD), http://www.ebi.ac.uk/ipd/ is a set of specialist databases related to the study of polymorphic genes in the immune system. The IPD project works with specialist groups or nomenclature committees who provide and curate individual sections before they are submitted to IPD for online publication. The IPD project stores all the data in a set of related databases. IPD currently consists of four databases: IPD-KIR, contains the allelic sequences of killer-cell immunoglobulin-like receptors, IPD-MHC, a database of sequences of the major histocompatibility complex of different species; IPD-HPA, alloantigens expressed only on platelets; and IPD-ESTDAB, which provides access to the European Searchable Tumour Cell-Line Database, a cell bank of immunologically characterized melanoma cell lines. The data is currently available online from the website and FTP directory. This article describes the latest updates and additional tools added to the IPD project. PMID:23180793

  14. Plumage polymorphism and fitness in Swainson's hawks.

    PubMed

    Briggs, C W; Collopy, M W; Woodbridge, B

    2011-10-01

    We examine the maintenance of a plumage polymorphism, variation in plumages among the same age and sex class within a population, in a population of Swainson's Hawks. We take advantage of 32 years of data to examine two prevalent hypotheses used to explain the persistence of morphs: apostatic selection and heterozygous advantage. We investigate differences in fitness among three morph classes of a melanistic trait in Swainson's Hawks: light (7% of the local breeding population), intermediate (57%) and dark (36%). Specifically, we examined morph differences in adult apparent survival, breeding success, annual number of fledglings produced, probability of offspring recruitment into the breeding population and lifetime reproductive success (LRS). If apostatic selection were a factor in maintaining morphs, we would expect that individuals with the least frequent morph would perform best in one or more of these fitness categories. Alternatively, if heterozygous advantage played a role in the maintenance of this polymorphism, we would expect heterozygotes (i.e. intermediate morphs) to have one or more increased rates in these categories. We found no difference in adult apparent survival between morph classes. Similarly, there were no differences in breeding success, nest productivity, LRS or probability of recruitment of offspring between parental morph. We conclude that neither apostatic selection nor heterozygous advantage appear to play a role in maintaining morphs in this population.

  15. Counterintuitive compaction behavior of clopidogrel bisulfate polymorphs.

    PubMed

    Khomane, Kailas S; More, Parth K; Bansal, Arvind K

    2012-07-01

    Being a density violator, clopidogrel bisulfate (CLP) polymorphic system (forms I and II) allows us to study individually the impact of molecular packing (true density) and thermodynamic properties such as heat of fusion on the compaction behavior. These two polymorphs of CLP were investigated for in-die and out-of-die compaction behavior using CTC profile, Heckel, and Walker equations. Compaction studies were performed on a fully instrumented rotary tabletting machine. Detailed examinations of the molecular packing of each form revealed that arrangement of the sulfate anion differs significantly in both crystal forms, thus conferring different compaction behavior to two forms. Close cluster packing of molecules in form I offers a rigid structure, which has poor compressibility and hence resists deformation under compaction pressure. This results into lower densification, higher yield strength, and mean yield pressure, as compared with form II at a given pressure. However, by virtue of higher bonding strength, form I showed superior tabletability, despite its poor compressibility and deformation behavior. Form I, having higher true density and lower heat of fusion showed higher bonding strength. Hence, true density and not heat of fusion can be considered predictor of bonding strength of the pharmaceutical powders.

  16. Dynamically Alterable Arrays of Polymorphic Data Types

    NASA Technical Reports Server (NTRS)

    James, Mark

    2006-01-01

    An application library package was developed that represents data packets for Deep Space Network (DSN) message packets as dynamically alterable arrays composed of arbitrary polymorphic data types. The software was to address a limitation of the present state of the practice for having an array directly composed of a single monomorphic data type. This is a severe limitation when one is dealing with science data in that the types of objects one is dealing with are typically not known in advance and, therefore, are dynamic in nature. The unique feature of this approach is that it enables one to define at run-time the dynamic shape of the matrix with the ability to store polymorphic data types in each of its indices. Existing languages such as C and C++ have the restriction that the shape of the array must be known in advance and each of its elements be a monomorphic data type that is strictly defined at compile-time. This program can be executed on a variety of platforms. It can be distributed in either source code or binary code form. It must be run in conjunction with any one of a number of Lisp compilers that are available commercially or as shareware.

  17. Polymorphism of the IGF-I System and Sports Performance.

    PubMed

    Ben-Zaken, Sigal; Meckel, Yoav; Nemet, Dan; Dror, Nitzan; Eliakim, Alon

    2016-06-01

    The potential use genetic polymorphism, and in particularly polymorphism of hormone genes, as tool to predict athletic performance is currently very challenging. Recent studies suggest that single nucleotide polymorphisms in IGF-I and myostatin may be beneficial for endurance and short distance running, and may even be associated with elite performance. Polymorphism in IGF-I receptor may differentiate between the two edges of the endurance-power athletic performance running spectrum suggesting beneficial effects for endurance and prevent from success in power events. In contrast, and despite similar metabolic demands, the myostatin-IGF-I-IGF-IR system seems not to play an important role in swimming excellence. This suggests that combining different sport disciplines for sports genetic research purposes should be done with extreme caution. Finally, since any phenotype reflects a complex relationship between genes, environment, epigenetic factors, and the interactions between them, consulting the young athlete regarding future success cannot be based solely on genetic polymorphism.

  18. The relative stability of xylazine hydrochloride polymorphous forms.

    PubMed

    Bērziņs, Agris; Krūkle, Kristīne; Actiņs, Andris; Kreismanis, Juris P

    2010-01-01

    All four known xylazine hydrochloride polymorphous forms were obtained and their relative stabilities were compared directly at three different temperatures. At higher temperatures, it is possible to determine the relative stability of all forms directly by measuring the changes in the composition of the mixtures of two polymorphous forms using powder x-ray diffraction methods. At lower temperatures, a solvent was added to the mixture and the changes in composition were determined. Polymorph transition temperatures were determined directly. To predict the transition temperature which was not found using the direct method, the polymorph melting data and determined transition temperatures were used. A phase stability diagram was constructed from the acquired data. The stability of all anhydrous polymorphous forms was compared in the presence of water vapor pressure that was higher than the equilibrium pressure.

  19. Assortative mating counteracts the evolution of dispersal polymorphisms.

    PubMed

    Fronhofer, Emanuel A; Kubisch, Alexander; Hovestadt, Thomas; Poethke, Hans-Joachim

    2011-09-01

    Polymorphic dispersal strategies are found in many plant and animal species. An important question is how the genetic variation underlying such polymorphisms is maintained. Numerous mechanisms have been discussed, including kin competition or frequency-dependent selection. In the context of sympatric speciation events, genetic and phenotypic variation is often assumed to be preserved by assortative mating. Thus, recently, this has been advocated as a possible mechanism leading to the evolution of dispersal polymorphisms. Here, we examine the role of assortative mating for the evolution of trade-off-driven dispersal polymorphisms by modeling univoltine insect species in a metapopulation. We show that assortative mating does not favor the evolution of polymorphisms. On the contrary, assortative mating favors the evolution of an intermediate dispersal type and a uni-modal distribution of traits within populations. As an alternative, mechanism dominance may explain the occurrence of two discrete morphs.

  20. Special considerations in prognostic research in cancer involving genetic polymorphisms

    PubMed Central

    2013-01-01

    Analysis of genetic polymorphisms may help identify putative prognostic markers and determine the biological basis of variable prognosis in patients. However, in contrast to other variables commonly used in the prognostic studies, there are special considerations when studying genetic polymorphisms. For example, variable inheritance patterns (recessive, dominant, codominant, and additive genetic models) need to be explored to identify the specific genotypes associated with the outcome. In addition, several characteristics of genetic polymorphisms, such as their minor allele frequency and linkage disequilibrium among multiple polymorphisms, and the population substructure of the cohort investigated need to be accounted for in the analyses. In addition, in cancer research due to the genomic differences between the tumor and non-tumor DNA, differences in the genetic information obtained using these tissues need to be carefully assessed in prognostic studies. In this article, we review these and other considerations specific to genetic polymorphism by focusing on genetic prognostic studies in cancer. PMID:23773794

  1. A gene feature enumeration approach for describing HLA allele polymorphism.

    PubMed

    Mack, Steven J

    2015-12-01

    HLA genotyping via next generation sequencing (NGS) poses challenges for the use of HLA allele names to analyze and discuss sequence polymorphism. NGS will identify many new synonymous and non-coding HLA sequence variants. Allele names identify the types of nucleotide polymorphism that define an allele (non-synonymous, synonymous and non-coding changes), but do not describe how polymorphism is distributed among the individual features (the flanking untranslated regions, exons and introns) of a gene. Further, HLA alleles cannot be named in the absence of antigen-recognition domain (ARD) encoding exons. Here, a system for describing HLA polymorphism in terms of HLA gene features (GFs) is proposed. This system enumerates the unique nucleotide sequences for each GF in an HLA gene, and records these in a GF enumeration notation that allows both more granular dissection of allele-level HLA polymorphism and the discussion and analysis of GFs in the absence of ARD-encoding exon sequences.

  2. An integrated restriction fragment length polymorphism--amplified fragment length polymorphism linkage map for cultivated sunflower.

    PubMed

    Gedil, M A; Wye, C; Berry, S; Segers, B; Peleman, J; Jones, R; Leon, A; Slabaugh, M B; Knapp, S J

    2001-04-01

    Restriction fragment length polymorphism (RFLP) maps have been constructed for cultivated sunflower (Helianthus annuus L.) using three independent sets of RFLP probes. The aim of this research was to integrate RFLP markers from two sets with RFLP markers for resistance gene candidate (RGC) and amplified fragment length polymorphism (AFLP) markers. Genomic DNA samples of HA370 and HA372, the parents of the F2 population used to build the map, were screened for AFLPs using 42 primer combinations and RFLPs using 136 cDNA probes (RFLP analyses were performed on DNA digested with EcoRI, HindIII, EcoRV, or DraI). The AFLP primers produced 446 polymorphic and 1101 monomorphic bands between HA370 and HA372. The integrated map was built by genotyping 296 AFLP and 104 RFLP markers on 180 HA370 x HA372 F2 progeny (the AFLP marker assays were performed using 18 primer combinations). The HA370 x HA372 map comprised 17 linkage groups, presumably corresponding to the 17 haploid chromosomes of sunflower, had a mean density of 3.3 cM, and was 1326 cM long. Six RGC RFLP loci were polymorphic and mapped to three linkage groups (LG8, LG13, and LG15). AFLP markers were densely clustered on several linkage groups, and presumably reside in centromeric regions where recombination is reduced and the ratio of genetic to physical distance is low. Strategies for targeting markers to euchromatic DNA need to be tested in sunflower. The HA370 x HA372 map integrated 14 of 17 linkage groups from two independent RFLP maps. Three linkage groups were devoid of RFLP markers from one of the two maps.

  3. Gene Polymorphisms and Pharmacogenetics in Rheumatoid Arthritis

    PubMed Central

    Rego-Pérez, Ignacio; Fernández-Moreno, Mercedes; Blanco, Francisco J

    2008-01-01

    Rheumatoid arthritis (RA) is a systemic, chronic and inflammatory disease of unknown etiology with genetic predisposition. The advent of new biological agents, as well as the more traditional disease-modifying antirheumatic drugs, has resulted in highly efficient therapies for reducing the symptoms and signs of RA; however, not all patients show the same level of response in disease progression to these therapies. These variations suggest that RA patients may have different genetic regulatory mechanisms. The extensive polymorphisms revealed in non-coding gene-regulatory regions in the immune system, as well as genetic variations in drug-metabolizing enzymes, suggest that this type of variation is of functional and evolutionary importance and may provide clues for developing new therapeutic strategies. Pharmacogenetics is a rapidly advancing area of research that holds the promise that therapies will soon be tailored to an individual patient’s genetic profile. PMID:19506728

  4. Polymorphic Alu insertions among Mayan populations.

    PubMed

    Herrera, R J; Rojas, D P; Terreros, M C

    2007-01-01

    The Mayan homeland within Mesoamerica spans five countries: Belize, El Salvador, Guatemala, Honduras and Mexico. There are indications that the people we call the Maya migrated from the north to the highlands of Guatemala as early as 4000 B.C. Their existence was village-based and agricultural. The culture of these Preclassic Mayans owes much to the earlier Olmec civilization, which flourished in the southern portion of North America. In this study, four different Mayan groups were examined to assess their genetic variability. Ten polymorphic Alu insertion (PAI) loci were employed to ascertain the genetic affinities among these Mayan groups. North American, African, European and Asian populations were also examined as reference populations. Our results suggest that the Mayan groups examined in this study are not genetically homogeneous.

  5. Androgen receptor gene mutation, rearrangement, polymorphism

    PubMed Central

    Eisermann, Kurtis; Wang, Dan; Jing, Yifeng; Pascal, Laura E.

    2013-01-01

    Genetic aberrations of the androgen receptor (AR) caused by mutations, rearrangements, and polymorphisms result in a mutant receptor that has varied functions compared to wild type AR. To date, over 1,000 mutations have been reported in the AR with most of these being associated with androgen insensitivity syndrome (AIS). While mutations of AR associated with prostate cancer occur less often in early stage localized disease, mutations in castration-resistant prostate cancer (CRPC) patients treated with anti-androgens occur more frequently with 10-30% of these patients having some form of mutation in the AR. Resistance to anti-androgen therapy usually results from gain-of-function mutations in the LBD such as is seen with bicalutamide and more recently with enzalutamide (MDV3100). Thus, it is crucial to investigate these new AR mutations arising from drug resistance to anti-androgens and other small molecule pharmacological agents. PMID:25045626

  6. Tubulin bistability and polymorphic dynamics of microtubules.

    PubMed

    Mohrbach, Hervé; Johner, Albert; Kulić, Igor M

    2010-12-31

    Based on the hypothesis that the GDP-tubulin dimer is a conformationally bistable molecule-rapidly fluctuating between a discrete curved and a straight state-we develop a model for polymorphic dynamics of the microtubule lattice. We show that GDP-tubulin bistability consistently explains unusual dynamic fluctuations, the apparent length-stiffness relation of grafted taxol-stabilized microtubules, and the curved-helical appearance of microtubules in general. When clamped by one end the microtubules undergo an unusual zero energy motion-in its effect reminiscent of a limited rotational hinge. We conclude that microtubules exist in highly cooperative energy-degenerate helical states and discuss possible implications in vivo.

  7. Single nucleotide polymorphism for animal fibre identification.

    PubMed

    Subramanian, Selvi; Karthik, T; Vijayaraaghavan, N N

    2005-03-16

    Animal fibres are highly valuable industrial products often adulterated during marketing. Currently, there is no precise method available to identify and differentiate the fibres. In this study, a PCR-RFLP technique was exploited to differentiate cashmere and wool fibres derived from goat and sheep, respectively. The presence of DNA in animal hair shafts has enabled the isolation of DNA from scoured cashmere and wool fibres. The mitochondrial cytochrome b sequences of both species were amplified by PCR using primers designed from conserved regions. The polymorphism observed between the two species was detected by restricting the amplified product by endonucleases viz., BamH1 and Ssp1. The RFLP profile clearly distinguishes the cashmere and wool fibres and this technique can also be exploited to test adulteration in animal fibres qualitatively.

  8. Identification of polymorphism in ethylone hydrochloride: synthesis and characterization

    PubMed Central

    Alarcon, Idralyn Q.; Copeland, Catherine R.; Cameron, T. Stanley; Linden, Anthony; Grossert, J. Stuart

    2015-01-01

    Ethylone, a synthetic cathinone with psychoactive properties, is a designer drug which has appeared on the recreational drug market in recent years. Since 2012, illicit shipments of ethylone hydrochloride have been intercepted with increasing frequency at the Canadian border. Analysis has revealed that ethylone hydrochloride exists as two distinct polymorphs. In addition, several minor impurities were detected in some seized exhibits. In this study, the two conformational polymorphs of ethylone hydrochloride have been synthesized and fully characterized by FTIR, FT‐Raman, powder XRD, GC‐MS, ESI‐MS/MS and NMR (13C CPMAS, 1H, 13C). The two polymorphs can be distinguished by vibrational spectroscopy, solid‐state nuclear magnetic resonance spectroscopy and X‐ray diffraction. The FTIR data are applied to the identification of both polymorphs of ethylone hydrochloride (mixed with methylone hydrochloride) in a laboratory submission labelled as 'Ocean Snow Ultra’. The data presented in this study will assist forensic scientists in the differentiation of the two ethylone hydrochloride polymorphs. This report, alongside our recent article on the single crystal X‐ray structure of a second polymorph of this synthetic cathinone, is the first to confirm polymorphism in ethylone hydrochloride. © 2015 Canada Border Services Agency. Drug Testing and Analysis published by John Wiley & Sons, Ltd. © 2015 Canada Border Services Agency. Drug Testing and Analysis published by John Wiley & Sons, Ltd. PMID:26344849

  9. Zoledronic acid: monoclinic and triclinic polymorphs from powder diffraction data.

    PubMed

    Chernyshev, Vladimir V; Shkavrov, Sergey V; Paseshnichenko, Ksenia A; Puryaeva, Tamara P; Velikodny, Yurii A

    2013-03-01

    The crystal structures of the monoclinic and triclinic polymorphs of zoledronic acid, C5H10N2O7P2, have been established from laboratory powder X-ray diffraction data. The molecules in both polymorphs are described as zwitterions, namely 1-(2-hydroxy-2-phosphonato-2-phosphonoethyl)-1H-imidazol-3-ium. Strong intermolecular hydrogen bonds (with donor-acceptor distances of 2.60 Å or less) link the molecules into layers, parallel to the (100) plane in the monoclinic polymorph and to the (1-10) plane in the triclinic polymorph. The phosphonic acid groups form the inner side of each layer, while the imidazolium groups lie to the outside of the layer, protruding in opposite directions. In both polymorphs, layers related by translation along [100] interact through weak hydrogen bonds (with donor-acceptor distances greater than 2.70 Å), forming three-dimensional layered structures. In the monoclinic polymorph, there are hydrogen-bonded centrosymmetric dimers linked by four strong O-H...O hydrogen bonds, which are not present in the triclinic polymorph.

  10. Identification of polymorphism in ethylone hydrochloride: synthesis and characterization.

    PubMed

    Maheux, Chad R; Alarcon, Idralyn Q; Copeland, Catherine R; Cameron, T Stanley; Linden, Anthony; Grossert, J Stuart

    2016-08-01

    Ethylone, a synthetic cathinone with psychoactive properties, is a designer drug which has appeared on the recreational drug market in recent years. Since 2012, illicit shipments of ethylone hydrochloride have been intercepted with increasing frequency at the Canadian border. Analysis has revealed that ethylone hydrochloride exists as two distinct polymorphs. In addition, several minor impurities were detected in some seized exhibits. In this study, the two conformational polymorphs of ethylone hydrochloride have been synthesized and fully characterized by FTIR, FT-Raman, powder XRD, GC-MS, ESI-MS/MS and NMR ((13) C CPMAS, (1) H, (13) C). The two polymorphs can be distinguished by vibrational spectroscopy, solid-state nuclear magnetic resonance spectroscopy and X-ray diffraction. The FTIR data are applied to the identification of both polymorphs of ethylone hydrochloride (mixed with methylone hydrochloride) in a laboratory submission labelled as 'Ocean Snow Ultra'. The data presented in this study will assist forensic scientists in the differentiation of the two ethylone hydrochloride polymorphs. This report, alongside our recent article on the single crystal X-ray structure of a second polymorph of this synthetic cathinone, is the first to confirm polymorphism in ethylone hydrochloride. © 2015 Canada Border Services Agency. Drug Testing and Analysis published by John Wiley & Sons, Ltd. © 2015 Canada Border Services Agency. Drug Testing and Analysis published by John Wiley & Sons, Ltd.

  11. KCNN2 polymorphisms and cardiac tachyarrhythmias

    PubMed Central

    Yu, Chih-Chieh; Chia-Ti, Tsai; Chen, Pei-Lung; Wu, Cho-Kai; Chiu, Fu-Chun; Chiang, Fu-Tien; Chen, Peng-Sheng; Chen, Chi-Ling; Lin, Lian-Yu; Juang, Jyh-Ming; Ho, Li-Ting; Lai, Ling-Ping; Yang, Wei-Shiung; Lin, Jiunn-Lee

    2016-01-01

    Abstract Potassium calcium-activated channel subfamily N member 2 (KCNN2) encodes an integral membrane protein that forms small-conductance calcium-activated potassium (SK) channels. Recent studies in animal models show that SK channels are important in atrial and ventricular repolarization and arrhythmogenesis. However, the importance of SK channels in human arrhythmia remains unclear. The purpose of the present study was to test the association between genetic polymorphism of the SK2 channel and the occurrence of cardiac tachyarrhythmias in humans. We enrolled 327 Han Chinese, including 72 with clinically significant ventricular tachyarrhythmias (VTa) who had a history of aborted sudden cardiac death (SCD) or unexplained syncope, 98 with a history of atrial fibrillation (AF), and 144 normal controls. We genotyped 12 representative tag single nucleotide polymorphisms (SNPs) across a 141-kb genetic region containing the KCNN2 gene; these captured the full haplotype information. The rs13184658 and rs10076582 variants of KCNN2 were associated with VTa in both the additive and dominant models (odds ratio [OR] 2.89, 95% confidence interval [CI] = 1.505–5.545, P = 0.001; and OR 2.55, 95% CI = 1.428–4.566, P = 0.002, respectively). After adjustment for potential risk factors, the association remained significant. The population attributable risks of these 2 variants of VTa were 17.3% and 10.6%, respectively. One variant (rs13184658) showed weak but significant association with AF in a dominant model (OR 1.91, CI = 1.025–3.570], P = 0.042). There was a significant association between the KCNN2 variants and clinically significant VTa. These findings suggest an association between KCNN2 and VTa; it also appears that KCNN2 variants may be adjunctive markers for risk stratification in patients susceptible to SCD. PMID:27442679

  12. HLA polymorphism in Sudanese renal donors.

    PubMed

    Dafalla, Ameer M; McCloskey, D J; Alemam, Almutaz A; Ibrahim, Amel A; Babikir, Adil M; Gasmelseed, Nagla; El Imam, Mohamed; Mohamedani, Ahmed A; Magzoub, Mubarak M

    2011-07-01

    The main objective of this study is to provide a database for renal transplantation in Sudan and to determine the HLA antigens and haplotype frequencies (HFs) in the study subjects. HLA typing was performed using the complement-dependant lymphocytotoxicity test in 250 unrelated healthy individuals selected as donors in the Sudanese Renal Transplantation Program. Considerable polymorphism was observed at each locus; A2 (0.28), A30 (0.12), A3 (0.09), A24 (0.09), A1 (0.09), and A68 (0.06) were the most frequent antigens in the A locus, while B51 (0.092), B41 (0.081), B39 (0.078), B57 (0.060), B35 (0.068), B 50 (0.053) and B 52 (0.051) were the most common B locus antigens. DR13 (0.444) and DR15 (0.160) showed the highest antigen frequencies (AFs) in the DR locus. In the DQ locus, DQ1 showed the highest gene frequency (0.498), while DQ2 and DQ3 AFs were (0.185) and (0.238), respectively. The most common HLA-A and -B haplotypes in positive linkage disequilibrium were A24, B38; A1, B7; and A3, B52. The common HLA-A and -B HFs in positive linkage disequilibrium in the main three tribe-stocks of the study subjects (Gaalia, Nile Nubian and Johyna) were A24, B38 for Gaalia; A24, B38 and A2, B7 for Johyna; and A2, B64 and A3, B53 for Nile Nubian. These results suggest that both class I and class II polymorphisms of the study subjects depict considerable heterogeneity, which reflects recent admixture of this group with neighboring Arabs and African populations.

  13. Polymorphism of starch pathway genes in cassava.

    PubMed

    Vasconcelos, L M; Brito, A C; Carmo, C D; Oliveira, E J

    2016-12-02

    The distribution and frequency of single nucleotide polymorphisms (SNPs) can help to understand changes associated with characteristics of interest. We aimed to evaluate nucleotide diversity in six genes involved in starch biosynthesis in cassava using a panel of 96 unrelated accessions. The genes were sequenced, aligned, and used to obtain values for nucleotide diversity (π), segregating sites (θ), Tajima's D test, and neighbor-joining (NJ) clustering. On average, one SNP per 147 and 171 bp was identified in exon and intron regions, respectively. Thirteen heterozygous loci were found. Three of seven SNPs in the exon region resulted in non-synonymous replacement or four synonymous substitutions. However, no associations were noted between SNPs and root dry-matter content. The parameter π ranged from 0.0001 (granule bound starch synthase I) to 0.0033 (α-amylase), averaging 0.0011, while θ ranged from 0.00014 (starch branching enzyme) to 0.00584 (starch synthase I), averaging 0.002353. The θ diversity value was typically double that of the π. Results of the D test did not suggest any evidence of deviance of neutrality in these genes. Among the evaluated accession, 82/96 were clustered using the NJ method but without a clear separation of the root dry-matter content, root pulp coloration, and classification of the cyanogenic compound content. High variation in genes of the starch biosynthetic pathway can be used to identify associations with the functional properties of starch for the use of polymorphisms for selection purposes.

  14. Prenatal diagnosis of polymorphic ventricular tachycardia using 64-channel magnetocardiography.

    PubMed

    Fukushima, Akimune; Nakai, Kenji; Matsumoto, Atsushi; Strasburger, Janette; Sugiyama, Toru

    2010-05-01

    We describe polymorphic ventricular tachycardia (VT) diagnosed using fetal magnetocardiography (FMCG). The fetus of a 33-year-old Japanese female at 24 weeks of pregnancy was diagnosed as bradycardia (60 beats/min) by fetal cardiotocography (CTG). Ultrasound findings indicated a diagnosis of an atrioventricular (AV) block involving extrasystole, but FMCG revealed a polymorphic VT followed by ventricular asystole. Standard ECG immediately after cesarean section at 37 weeks of pregnancy confirmed long QT syndrome followed by nonsustained polymorphic VT and an advanced AV block with wide QRS. Echocardiography demonstrated moderate left ventricular dysfunction in the neonate requiring implantation with a permanent pacemaker.

  15. CD24 Ala/Val polymorphism and multiple sclerosis.

    PubMed

    Goris, An; Maranian, Melanie; Walton, Amie; Yeo, Tai Wai; Ban, Maria; Gray, Julia; Dubois, Bénédicte; Compston, Alastair; Sawcer, Stephen

    2006-06-01

    CD24 is expressed on a broad range of cells in the immune and central nervous systems and appears to be required for development of experimental autoimmune encephalomyelitis in mice. Association of a CD24 Ala/Val coding polymorphism with susceptibility to and progression of multiple sclerosis was recently reported. We typed this coding polymorphism in a combined cohort of 1,180 cases and 1,168 unrelated and family-based controls from Belgium and the UK, but were unable to confirm either association. Since the CD24 gene is part of a segmental duplication, special care is required for the identification and genotyping of single nucleotide polymorphisms.

  16. Endometriosis and RAS system gene polymorphisms: the association of ACE A2350G polymorphism with endometriosis in Polish individuals.

    PubMed

    Kowalczyńska, Liliana J; Ferenc, Tomasz; Wojciechowski, Michał; Mordalska, Anna; Pogoda, Krzysztof; Malinowski, Andrzej

    2014-05-01

    To analyze the polymorphisms of angiotensin I converting enzyme (ACE) gene (insertion/deletion [I/D], A2350G) and angiotensin II type 1 receptor gene (A1166C) in women with endometriosis and to determine the correlation of the identified genotypes with the severity of the disease. Additionally, to estimate the prognostic value of the polymorphisms in patients with endometriosis treated due to infertility. The study group included 241 women, the control group (without endometriosis)-127. The molecular analysis was performed by polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism technique. For I/D ACE and A1166C AT1 polymorphisms no significant differences were observed between the study and control groups and between the severity grades of the disease (p>0.05). For A2350G ACE polymorphism the frequency of genotypes for the study and control groups respectively was the following: AA-31.54%, AG-54.36%, GG-14.11% and AA-55.12%, AG-36.22%, GG-8.66% (x(2)=19.36, p<0.0001). Statistically significant differences were found between the frequency of A and G alleles between both groups (x(2)=15.16, p=0.0001), but not when individual grades of the disease severity were compared. There was no association between the investigated polymorphisms and the effect of infertility treatment. A2350G polymorphism (allele G, AG genotype) of ACE gene seems to be associated with the development of endometriosis.

  17. [Advances in the Association between Apolipoprotein (a) Gene Polymorphisms and Coronary Heart Disease].

    PubMed

    Zhu, Li; L, Zhan; Song, Yong-yan

    2015-08-01

    Human apolipoprotein (a) (LPA) gene is highly polymorphic, and the polymorphic loci on this gene include the Kringle 4 subtype 2(KIV-2) repeat polymorphism, the pentanucleotide repeat (TTTTA)n polymorphism, and a number of single nucleotide polymorphisms. KIV-2 repeat polymorphism was found to be significantly associated with coronary heart disease(CHD), and the reducing number of KIV-2 repeats is a risk factor for CHD. Both the increase and decrease of the pentanucleotide repeat(TTTTA)n polymorphism repeats are possibly associated with CHD risk. In single nucleotide polymorphisms loci, the rs10455872 and rs3798220 loci were widely reported to be associated with CHD, while other loci were less reported. The association between LPA polymorphisms and CHD may be mediated by either the elevation of plasma LPA level or the change of LPA subtypes. This article reviews the association between the LPA polymorphisms and CHD and the underlying mechanisms.

  18. Chromosome Polymorphism in Microtus (Alexandromys) mujanensis (Arvicolinae, Rodentia).

    PubMed

    Lemskaya, Natalya A; Kartavtseva, Irina V; Rubtsova, Nadezhda V; Golenishchev, Fedor N; Sheremetyeva, Irina N; Graphodatsky, Alexander S

    2015-01-01

    The Muya Valley vole (Microtus mujanensis) has a constant diploid chromosome number of 2n = 38, but an unstable karyotype with polymorphic chromosome pairs. Here, we describe 4 karyotypic variants involving 2 polymorphic chromosome pairs, MMUJ8 and MMUJ14, in 6 animals from Buryatia using a combination of GTG-banding and chromosome painting with M. agrestis probes. We suggest that the polymorphic pairs MMUJ8 and MMUJ14 were formed through pericentric inversions that played a major role during karyotype evolution of the species. We also propose that the stable diploid number with some ongoing polymorphism in the number of chromosome arms indicates that this evolutionarily young endemic species of Russian Far East is on the way to karyotype and likely species stabilization.

  19. Polymorphic microsatellite loci for the razor clam, Sinonovacula constricta.

    PubMed

    Ma, H-T; Jiang, H-B; Liu, X-Q; Wu, X-P; Wei, X-M

    2015-01-15

    The razor clam, Sinonovacula constricta, is an important commercial bivalve and a popular mollusca food in China. Twelve polymorphic microsatellite markers were isolated from the razor clam using a partial genomic library enriched for tandem repeat sequences of (CA)16, (GA)16. Polymorphisms of these loci were evaluated in a wild population of 30 individuals. The allele number of these polymorphic markers ranged from 5-15 per locus with an average of 9.333. Observed and expected heterozygosity values ranged from 0.192-1.000 and 0.219-0.906. Polymorphism information content ranged from 0.209-0.892 with an average of 0.704. Three loci significantly deviated from Hardy-Weinberg equilibrium after Bonferroni correction. No significant linkage disequilibrium was detected between these loci. This set of microsatellite loci are useful for genetic studies in S. constricta.

  20. Lowest enthalpy polymorph of cold-compressed graphite phase.

    PubMed

    Li, Da; Bao, Kuo; Tian, Fubo; Zeng, Zhenwu; He, Zhi; Liu, Bingbing; Cui, Tian

    2012-04-07

    Based on an ab initio evolutionary algorithm, a novel carbon polymorph with an orthorhombic Cmcm symmetry is predicted, named as C carbon, which has the lowest enthalpy among the previously proposed cold-compressed graphite phases.

  1. Diabat Interpolation for Polymorph Free-Energy Differences.

    PubMed

    Kamat, Kartik; Peters, Baron

    2017-02-02

    Existing methods to compute free-energy differences between polymorphs use harmonic approximations, advanced non-Boltzmann bias sampling techniques, and/or multistage free-energy perturbations. This work demonstrates how Bennett's diabat interpolation method ( J. Comput. Phys. 1976, 22, 245 ) can be combined with energy gaps from lattice-switch Monte Carlo techniques ( Phys. Rev. E 2000, 61, 906 ) to swiftly estimate polymorph free-energy differences. The new method requires only two unbiased molecular dynamics simulations, one for each polymorph. To illustrate the new method, we compute the free-energy difference between face-centered cubic and body-centered cubic polymorphs for a Gaussian core solid. We discuss the justification for parabolic models of the free-energy diabats and similarities to methods that have been used in studies of electron transfer.

  2. No association between apolipoprotein E polymorphisms and recurrent pregnancy loss.

    PubMed

    Bianca, Sebastiano; Barrano, Barbara; Cutuli, Nunzio; Indaco, Lara; Cataliotti, Antonella; Milana, Gabriella; Barone, Chiara; Ettore, Giuseppe

    2010-01-01

    Our study does not support the reported association between APOE and recurrent pregnancy loss (RPL) than the clinical management of these patients should not be influenced by the presence or not of APO E polymorphisms.

  3. Mineralogy of Silica Polymorphs in Basaltic Clasts in Eucrites

    NASA Astrophysics Data System (ADS)

    Ono, H.; Takenouchi, A.; Mikouchi, T.

    2016-08-01

    We analyzed silica polymorphs in basaltic clasts in Y-75011, Pasamonte and Stannern eucrites. Cristobalite and quartz have been found, which suggests wide occurrence of hydrothermal activity throughout the crust of Vesta.

  4. [Study of Chloroplast DNA Polymorphism in the Sunflower (Helianthus L.)].

    PubMed

    Markina, N V; Usatov, A V; Logacheva, M D; Azarin, K V; Gorbachenko, C F; Kornienko, I V; Gavrilova, V A; Tihobaeva, V E

    2015-08-01

    The polymorphism of microsatellite loci of chloroplast genome in six Helianthus species and 46 lines of cultivated sunflower H. annuus (17 CMS lines and 29 Rf-lines) were studied. The differences between species are confined to four SSR loci. Within cultivated forms of the sunflower H. annuus, the polymorphism is absent. A comparative analysis was performed on sequences of the cpDNA inbred line 3629, line 398941 of the wild sunflower, and the American line HA383 H. annuus. As a result, 52 polymorphic loci represented by 27 SSR and 25 SNP were found; they can be used for genotyping of H. annuus samples, including cultural varieties: twelve polymorphic positions, of which eight are SSR and four are SNP.

  5. Posterior polymorphous dystrophy and keratoglobus in a child.

    PubMed

    Patel, Sangita P; Sajnani, Manoj M; Pineda, Roberto

    2011-01-01

    A 13-year-old boy presented with gradually progressive deterioration of vision in both eyes, bilateral photophobia, and regular headaches. Clinical examination, anterior segment findings, and specular microscopy findings were consistent with the diagnosis of posterior polymorphous dystrophy and keratoglobus. To the authors' knowledge, this is the first pediatric case and the second case overall of the simultaneous occurrence of posterior polymorphous dystrophy and keratoglobus.

  6. Hydrogen chemisorption on gallium oxide polymorphs.

    PubMed

    Collins, Sebastián E; Baltanás, Miguel A; Bonivardi, Adrian L

    2005-02-01

    The chemisorption of H(2) over a set of gallia polymorphs (alpha-, beta-, and gamma-Ga(2)O(3)) has been studied by temperature-programmed adsorption equilibrium and desorption (TPA and TPD, respectively) experiments, using in situ transmission infrared spectroscopy. Upon heating the gallium oxides above 500 K in 101.3 kPa of H(2), two overlapped infrared signals developed. The 2003- and 1980-cm(-1) bands were assigned to the stretching frequencies of H bonded to coordinatively unsaturated (cus) gallium cations in tetrahedral and octahedral positions [nu(Ga(t)-H) and nu(Ga(o)-H), respectively]. Irrespective to the gallium cation geometrical environment, (i) a linear relationship between the integrated intensity of the whole nu(Ga-H) infrared band versus the Brunauer-Emmett-Teller surface area of the gallia was found and (ii) TPA and TPD results revealed that molecular hydrogen is dissociatively chemisorbed on any bulk gallium oxide polymorph following two reaction pathways. An endothermal, homolytic dissociation occurs over surface cus-gallium sites at T > 450 K, giving rise to Ga-H(I) bonds. The heat and entropy of this type I hydrogen adsorption were determined by the Langmuir's adsorption model as Deltah(I) = 155 +/- 25 kJ mol(-1) and Deltas(I) = 0.27 +/- 0.11 kJ mol(-1) K(-1). In addition, another exothermic, heterolytic adsorption sets in already in the low-temperature region. This type of hydrogen chemisorption involves surface Ga-O-Ga species, originating GaO-H and Ga-H(II) bonds which can only be removed from the gallia surface after heating under evacuation at T > 650 K. The measured desorption energy of this last, second-order process was equal to 77 +/- 10 kJ mol(-1). The potential of the H(2) chemisorption as a tool to measure or estimate the specific surface area of gallia and to discern the nature and proportion of gallium cation coordination sites on the surface of bulk gallium oxides is also analyzed.

  7. MTHFR Gene C677T Polymorphism in Autism Spectrum Disorders

    PubMed Central

    Oztop, Didem Behice; Ozkul, Yusuf

    2014-01-01

    Aim. Autism is a subgroup of autism spectrum disorders, classified as a heterogeneous neurodevelopmental disorder and symptoms occur in the first three years of life. The etiology of autism is largely unknown, but it has been accepted that genetic and environmental factors may both be responsible for the disease. Recent studies have revealed that the genes involved in the folate/homocysteine pathway may be risk factors for autistic children. In particular, C677T polymorphism in the MTHFR gene as a possible risk factor for autism is still controversial. We aimed to investigate the possible effect of C677T polymorphism in a Turkish cohort. Methods. Autism patients were diagnosed by child psychiatrists according to DSM-IV and DSM-V criteria. A total of 98 children diagnosed as autistic and 70 age and sex-matched children who are nonautistic were tested for C677T polymorphism. This polymorphism was studied by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. Results. MTHFR 677T-allele frequency was found to be higher in autistic children compared with nonautistic children (29% versus 24%), but it was not found statistically significant. Conclusions. We conclude that other MTHFR polymorphisms such as A1298C or other folate/homocysteine pathway genes may be studied to show their possible role in autism. PMID:25431675

  8. Epitaxial stabilization and phase instability of VO2 polymorphs

    PubMed Central

    Lee, Shinbuhm; Ivanov, Ilia N.; Keum, Jong K.; Lee, Ho Nyung

    2016-01-01

    The VO2 polymorphs, i.e., VO2(A), VO2(B), VO2(M1) and VO2(R), have a wide spectrum of functionalities useful for many potential applications in information and energy technologies. However, synthesis of phase pure materials, especially in thin film forms, has been a challenging task due to the fact that the VO2 polymorphs are closely related to each other in a thermodynamic framework. Here, we report epitaxial stabilization of the VO2 polymorphs to synthesize high quality single crystalline thin films and study the phase stability of these metastable materials. We selectively deposit all the phases on various perovskite substrates with different crystallographic orientations. By investigating the phase instability, phonon modes and transport behaviours, not only do we find distinctively contrasting physical properties of the VO2 polymorphs, but that the polymorphs can be on the verge of phase transitions when heated as low as ~400 °C. Our successful epitaxy of both VO2(A) and VO2(B) phases, which are rarely studied due to the lack of phase pure materials, will open the door to the fundamental studies of VO2 polymorphs for potential applications in advanced electronic and energy devices. PMID:26787259

  9. Effect of Cytokine Signaling 3 Gene Polymorphisms in Childhood Obesity

    PubMed Central

    Boyraz, Mehmet; Yeşilkaya, Ediz; Ezgü, Fatih; Bideci, Aysun; Doğan, Haldun; Ulucan, Korkut; Cinaz, Peyami

    2016-01-01

    Objective: Although polymorphisms in suppressor of cytokine signaling 3 (SOCS3) was reported to be related to obesity, Metabolic syndrome (MS), and type 2 diabetes mellitus in various adult studies, there is a lack of data in children. In this study, we examined eight reported polymorphisms of SOCS3 in obese Turkish children and adolescent with and without MS and compared the results with that of controls. Methods: One hundred and forty eight obese and 63 age- and sex-matched control subjects were enrolled in the study. Obesity classification was carried out according to body mass index. World Health Organization and National Cholesterol Education Program criteria were used for the diagnosis of MS. Genotyping procedure was carried out by polymerase chain reaction and Sanger sequencing protocol. Results: The frequency of rs2280148 polymorphism was significantly higher in obese subjects with MS than in the control group, whereas the frequency of rs8064821 polymorphism was significantly higher in obese subjects with MS than in obese children without MS. Conclusion: The significant associations of certain SOCS3 polymorphisms with obesity parameters in both MS and MS -related insulin resistance, hypertension, and fatty liver suggest that polymorphisms in this gene may play a role in the pathogenesis of MS and also that they can be potentially used as a marker for attenuated or aggressive disease. PMID:27611604

  10. Polymorphism of CAG repeats in androgen receptor of carnivores.

    PubMed

    Wang, Qin; Zhang, Xiuyue; Wang, Xiaofang; Zeng, Bo; Jia, Xiaodong; Hou, Rong; Yue, Bisong

    2012-03-01

    Androgen effect is mediated by the androgen receptor (AR). The polymorphism of CAG triplet repeat (polyCAG), in the N-terminal transactivation domain of the AR protein, has been involved either in endocrine or neurological disorders in human. We obtained partial sequence of AR exon 1 in 10 carnivore species. In most carnivore species, polyglutamine length polymorphism presented in all three CAG repeat regions of AR, in contrast, only CAG-I site polymorphism presented in primate species, and CAG-I and CAG-III sites polymorphism presented in Canidae. Therefore, studies focusing on disease-associated polymorphism of poly(CAG) in carnivore species AR should investigate all three CAG repeats sites, and should not only consider CAG-I sites as the human disease studies. The trinucleotide repeat length in carnivore AR exon 1 had undergone from expansions to contractions during carnivores evolution, unlike a linear increase in primate species. Furthermore, the polymorphisms of the triplet-repeats in the same tissue (somatic mosaicism) were demonstrated in Moutain weasel, Eurasian lynx, Clouded leopard, Chinese tiger, Black leopard and Leopard AR. And, the abnormal stop codon was found in the exon 1 of three carnivore species AR (Moutain weasel, Eurasian lynx and Black leopard). It seemed to have a high frequency presence of tissue-specific somatic in carnivores AR genes. Thus the in vivo mechanism leading to such highly variable phenotypes of the described mutations, and their impact on these animals, are worthwhile to be further elucidated.

  11. Computational Approach for Epitaxial Polymorph Stabilization through Substrate Selection

    SciTech Connect

    Ding, Hong; Dwaraknath, Shyam S.; Garten, Lauren; Ndione, Paul; Ginley, David; Persson, Kristin A.

    2016-05-25

    With the ultimate goal of finding new polymorphs through targeted synthesis conditions and techniques, we outline a computational framework to select optimal substrates for epitaxial growth using first principle calculations of formation energies, elastic strain energy, and topological information. To demonstrate the approach, we study the stabilization of metastable VO2 compounds which provides a rich chemical and structural polymorph space. We find that common polymorph statistics, lattice matching, and energy above hull considerations recommends homostructural growth on TiO2 substrates, where the VO2 brookite phase would be preferentially grown on the a-c TiO2 brookite plane while the columbite and anatase structures favor the a-b plane on the respective TiO2 phases. Overall, we find that a model which incorporates a geometric unit cell area matching between the substrate and the target film as well as the resulting strain energy density of the film provide qualitative agreement with experimental observations for the heterostructural growth of known VO2 polymorphs: rutile, A and B phases. The minimal interfacial geometry matching and estimated strain energy criteria provide several suggestions for substrates and substrate-film orientations for the heterostructural growth of the hitherto hypothetical anatase, brookite, and columbite polymorphs. These criteria serve as a preliminary guidance for the experimental efforts stabilizing new materials and/or polymorphs through epitaxy. The current screening algorithm is being integrated within the Materials Project online framework and data and hence publicly available.

  12. Epitaxial stabilization and phase instability of VO2 polymorphs

    DOE PAGES

    Lee, Shinbuhm; Ivanov, Ilia N.; Keum, Jong K.; ...

    2016-01-20

    The VO2 polymorphs, i.e., VO2(A), VO2(B), VO2(M1) and VO2(R), have a wide spectrum of functionalities useful for many potential applications in information and energy technologies. However, synthesis of phase pure materials, especially in thin film forms, has been a challenging task due to the fact that the VO2 polymorphs are closely related to each other in a thermodynamic framework. Here, we report epitaxial stabilization of the VO2 polymorphs to synthesize high quality single crystalline thin films and study the phase stability of these metastable materials. We selectively deposit all the phases on various perovskite substrates with different crystallographic orientations. Bymore » investigating the phase instability, phonon modes and transport behaviours, not only do we find distinctively contrasting physical properties of the VO2 polymorphs, but that the polymorphs can be on the verge of phase transitions when heated as low as ~400 °C. In conclusion, our successful epitaxy of both VO2(A) and VO2(B) phases, which are rarely studied due to the lack of phase pure materials, will open the door to the fundamental studies of VO2 polymorphs for potential applications in advanced electronic and energy devices.« less

  13. Major histocompatibility complex class I polymorphism in Asiatic lions.

    PubMed

    Sachdev, M; Sankaranarayanan, R; Reddanna, P; Thangaraj, K; Singh, L

    2005-07-01

    Asiatic lions (Panthera leo persica), whose only natural habitat in the world is the Gir forest sanctuary of Gujarat State in India, are highly endangered and are considered to be highly inbred with narrow genetic diversity. An objective assessment of genetic diversity in their immune loci will help in assessing their survivability and may provide vital clues in designing strategies for their scientific management and conservation. We analyzed the comparative sequence polymorphism at exon 2 and exon 3 of major histocompatibility complex (MHC) class I in three groups of lions, i.e. wild Asiatic (from Gir forest), captive-bred Asiatic (from zoological parks in India), and Afro-Asiatic hybrid groups (from zoological parks in India) through polymorphism chain reaction-assisted sequence-based typing. The two exons were amplified, cloned, sequenced, and analyzed for polymorphism at nucleotide and putative translated product level. The analysis revealed extensive sequence polymorphism not only between clones derived from different lions but also the clones derived from a single lion. Furthermore, the wild Asiatic lions of Gir forest exhibited abundant sequence polymorphism at MHC class I comparable with that of Afro-Asiatic hybrid lions and significantly higher than that of captive-bred Asiatic lions. We hypothesize that Asiatic lions of Gir forest are not highly inbred as thought earlier and they possess abundant sequence polymorphism at MHC class I loci. During this study, 52 new sequences of the multigene MHC class I family were also identified among Asiatic lions.

  14. Identification of conserved and polymorphic STRs for personal genomes

    PubMed Central

    2014-01-01

    Background Short tandem repeats (STRs) are abundant in human genomes. Numerous STRs have been shown to be associated with genetic diseases and gene regulatory functions, and have been selected as genetic markers for evolutionary and forensic analyses. High-throughput next generation sequencers have fostered new cutting-edge computing techniques for genome-scale analyses, and cross-genome comparisons have facilitated the efficient identification of polymorphic STR markers for various applications. Results An automated and efficient system for detecting human polymorphic STRs at the genome scale is proposed in this study. Assembled contigs from next generation sequencing data were aligned and calibrated according to selected reference sequences. To verify identified polymorphic STRs, human genomes from the 1000 Genomes Project were employed for comprehensive analyses, and STR markers from the Combined DNA Index System (CODIS) and disease-related STR motifs were also applied as cases for evaluation. In addition, we analyzed STR variations for highly conserved homologous genes and human-unique genes. In total 477 polymorphic STRs were identified from 492 human-unique genes, among which 26 STRs were retrieved and clustered into three different groups for efficient comparison. Conclusions We have developed an online system that efficiently identifies polymorphic STRs and provides novel distinguishable STR biomarkers for different levels of specificity. Candidate polymorphic STRs within a personal genome could be easily retrieved and compared to the constructed STR profile through query keywords, gene names, or assembled contigs. PMID:25560225

  15. Color polymorphism in an aphid is maintained by attending ants

    PubMed Central

    Watanabe, Saori; Murakami, Taiga; Yoshimura, Jin; Hasegawa, Eisuke

    2016-01-01

    The study of polymorphisms is particularly informative for enhancing our understanding of phenotypic and genetic diversity. The persistence of polymorphism in a population is generally explained by balancing selection. Color polymorphisms that are often found in many insects and arthropods are prime examples of the maintenance of polymorphisms via balancing selection. In some aphids, color morphs are maintained through frequency-dependent predation by two predatory insects. However, the presence of color polymorphism in ant-attended aphids cannot be explained by traditional balancing selection because these aphids are free from predation. We examined the selective advantages of the existence of two color (red and green) morphs in the ant-attended aphid, Macrosiphoniella yomogicola, in fields. We measured the degree of ant attendance on aphid colonies with different proportions of color morphs. The results show that the ants strongly favor aphid colonies with intermediate proportions of the two color morphs. The relationship between the degree of ant attendance and the proportion of color morphs in the field is convex when aphid colony size and ant colony size are controlled. This function has a peak of approximately 65% of green morphs in a colony. This system represents the first case of a balancing polymorphism that is not maintained by opposing factors but by a symbiotic relationship. PMID:27617289

  16. A second triclinic polymorph of azimsulfuron.

    PubMed

    Kwon, Eunjin; Kim, Jineun; Park, Hyunjin; Kim, Tae Ho

    2016-10-01

    The title compound, C13H16N10O5S (systematic name: 1-(4,6-di-meth-oxypyrimidin-2-yl)-3-{[1-methyl-4-(2-methyl-2H-tetra-zol-5-yl)pyrazol-5-yl]sulfonyl}urea), is a second triclinic polymorph of this crystal [for the other, see: Jeon et al., (2015 ▸). Acta Cryst. E71, o470-o471]. There are two mol-ecules, A and B, in the asymmetric unit; the dihedral angles between the pyrazole ring and the tetra-zole and di-meth-oxy-pyrimidine ring planes are 72.84 (10) and 37.24 (14)°, respectively (mol-ecule A) and 84.38 (9) and 26.09 (15)°, respectively (mol-ecule B). Each mol-ecule features an intra-molecular N-H⋯N hydrogen bond. In the crystal, aromatic π-π stacking inter-actions [centroid-centroid separations = 3.9871 (16), 3.4487 (14) and 3.5455 (16) Å] link the mol-ecules into [001] chains. In addition, N-H⋯N, N-H⋯O, C-H⋯O and C-H⋯N hydrogen bonds occur, forming a three-dimensional architecture. We propose that the dimorphism results from differences in conformations and packing owing to different inter-molecular inter-actions, especially aromatic π-π stacking.

  17. A stable genetic polymorphism underpinning microbial syntrophy

    PubMed Central

    Großkopf, Tobias; Zenobi, Simone; Alston, Mark; Folkes, Leighton; Swarbreck, David; Soyer, Orkun S

    2016-01-01

    Syntrophies are metabolic cooperations, whereby two organisms co-metabolize a substrate in an interdependent manner. Many of the observed natural syntrophic interactions are mandatory in the absence of strong electron acceptors, such that one species in the syntrophy has to assume the role of electron sink for the other. While this presents an ecological setting for syntrophy to be beneficial, the potential genetic drivers of syntrophy remain unknown to date. Here, we show that the syntrophic sulfate-reducing species Desulfovibrio vulgaris displays a stable genetic polymorphism, where only a specific genotype is able to engage in syntrophy with the hydrogenotrophic methanogen Methanococcus maripaludis. This 'syntrophic' genotype is characterized by two genetic alterations, one of which is an in-frame deletion in the gene encoding for the ion-translocating subunit cooK of the membrane-bound COO hydrogenase. We show that this genotype presents a specific physiology, in which reshaping of energy conservation in the lactate oxidation pathway enables it to produce sufficient intermediate hydrogen for sustained M. maripaludis growth and thus, syntrophy. To our knowledge, these findings provide for the first time a genetic basis for syntrophy in nature and bring us closer to the rational engineering of syntrophy in synthetic microbial communities. PMID:27258948

  18. Gene Polymorphism Studies in a Teaching Laboratory

    NASA Astrophysics Data System (ADS)

    Shultz, Jeffry

    2009-02-01

    I present a laboratory procedure for illustrating transcription, post-transcriptional modification, gene conservation, and comparative genetics for use in undergraduate biology education. Students are individually assigned genes in a targeted biochemical pathway, for which they design and test polymerase chain reaction (PCR) primers. In this example, students used genes annotated for the steroid biosynthesis pathway in soybean. The authoritative Kyoto encyclopedia of genes and genomes (KEGG) interactive database and other online resources were used to design primers based first on soybean expressed sequence tags (ESTs), then on ESTs from an alternate organism if soybean sequence was unavailable. Students designed a total of 50 gene-based primer pairs (37 soybean, 13 alternative) and tested these for polymorphism state and similarity between two soybean and two pea lines. Student assessment was based on acquisition of laboratory skills and successful project completion. This simple procedure illustrates conservation of genes and is not limited to soybean or pea. Cost per student estimates are included, along with a detailed protocol and flow diagram of the procedure.

  19. Cell line fingerprinting using retroelement insertion polymorphism.

    PubMed

    Ustyugova, Svetlana V; Amosova, Anna L; Lebedev, Yuri B; Sverdlov, Eugene D

    2005-04-01

    Human cell lines are an indispensable tool for functional studies of living entities in their numerous manifestations starting with integral complex systems such as signal pathways and networks, regulation of gene ensembles, epigenetic factors, and finishing with pathological changes and impact of artificially introduced elements, such as various transgenes, on the behavior of the cell. Therefore, it is highly desirable to have reliable cell line identification techniques to make sure that the cell lines to be used in experiments are exactly what is expected. To this end, we developed a set of informative markers based on insertion polymorphism of human retroelements (REs). The set includes 47 pairs of PCR primers corresponding to introns of the human genes with dimorphic LINE1 (L1) and Alu insertions. Using locus-specific PCR assays, we have genotyped 10 human cell lines of various origins. For each of these cell lines, characteristic fingerprints were obtained. An estimated probability that two different cell lines possess the same marker genotype is about 10-18. Therefore, the proposed set of markers provides a reliable tool for cell line identification.

  20. Epitaxial Retrieval of a Disappearing Polymorph

    PubMed Central

    2014-01-01

    Recrystallization of [PdCl2([9]aneS2O)] ([9]aneS2O = 1-oxa-4,7-dithiacyclononane), 1, and [PtCl2([9]aneS2O)], 2, by diffusion of Et2O vapor into solutions of the complexes in MeNO2 yielded three phases of 1 and two phases of 2. The known phase of 1, herein designated α-1, was obtained under ambient conditions. A second phase, designated β-1, was initially also obtained by this method; however, following the advent of a third phase, γ-1, all subsequent efforts over a period of a year to crystallize β-1 yielded either γ-1, obtained by carrying out the recrystallization at elevated temperature, or α-1, commonly found throughout the study. This persistent absence of a phase which could initially be crystallized with ease led us to the conclusion that β-1 was an example of a “disappearing polymorph”. The first phase obtained of 2, designated α-2, was obtained by recrystallization under ambient conditions and is isomorphous and isostructural with α-1. The second phase β-2 was obtained by slight elevation of the recrystallization temperature and was found to be isomorphous and isostructural with β-1. Subsequently, β-2 was used to seed the growth of the disappearing polymorph β-1. No third phase of 2 (γ-2) has been isolated thus far. PMID:25598741

  1. Polymorphism of the ovine calpastatin gene.

    PubMed

    Zhou, H; Hickford, J G H; Gong, H

    2007-06-01

    Calpastatin is a specific inhibitor of calpains and has been implicated in the regulation of beef tenderization. Variation in the ovine calpastatin gene (CAST) was investigated by amplification of a fragment containing the entire exon 6 using polymerase chain reaction (PCR), followed by single-strand conformational polymorphism (PCR-SSCP) analysis and DNA sequencing. Five novel SSCP patterns, representing five different sequences, were identified. Either one or two different sequences were detected in individual sheep and all the sequences identified shared high homology to the published ovine and bovine CAST sequences, suggesting that these sequences represent allelic variants of the ovine CAST gene. Sequence analysis revealed a non-synonymous amino acid variation in exon 6, which would result in a Gln/Leu substitution in Domain L of the mature protein. Considerable variation was detected in an intron region close to the acceptor splice site, with both sequence variation and length variation being observed in this region. Variation detected here might have an impact on both the function and expression of ovine calpastatin.

  2. Apolipoprotein E Polymorphism in Tuberculosis Patients

    NASA Astrophysics Data System (ADS)

    Naserpour Farivar, Taghi; Sharifi Moud, Batool; Sargazi, Mansur; Moeenrezakhanlou, Alireza

    In this study, we aimed to determine the significance of association between Tuberculosis and apolipoprotein E polymorphism. The apolipoprotein E genotypes were assayed in 250 tuberculosis patients by polymerase chain reaction followed by enzymatic digestion with Hha I. The results were compared with the results of the same experiments on 250 sex and age matched control peoples. Present results showed that in studied populations, prevalence of E4 genotype was lower in controls than in patients (8 v. 13.2%; OR = 1.75, p<0.05) and prevalence of E3 genotype was high in controls than in patients (86 v.51%; OR = 0.17, p<0.05). Statistically significant difference was found between patients and controls with respect to ɛ2 allele frequencies, while ɛ2 allele frequency was found to be much less prevalent in controls (6%) than in patients (35.8%; OR = 8.72, p<0.05). Also, our study revealed that there is an association between apolipoprotein E genotypes and amplitude to tuberculosis in studied populations. However, large population-based studies are needed to understand the exact role played by the locus in causing the condition.

  3. Dispersal Polymorphisms in Invasive Fire Ants

    PubMed Central

    Helms, Jackson A.; Godfrey, Aaron

    2016-01-01

    In the Found or Fly (FoF) hypothesis ant queens experience reproduction-dispersal tradeoffs such that queens with heavier abdomens are better at founding colonies but are worse flyers. We tested predictions of FoF in two globally invasive fire ants, Solenopsis geminata (Fabricius, 1804) and S. invicta (Buren, 1972). Colonies of these species may produce two different monogyne queen types—claustral queens with heavy abdomens that found colonies independently, and parasitic queens with small abdomens that enter conspecific nests. Claustral and parasitic queens were similarly sized, but the abdomens of claustral queens weighed twice as much as those of their parasitic counterparts. Their heavier abdomens adversely impacted morphological predictors of flight ability, resulting in 32–38% lower flight muscle ratios, 55–63% higher wing loading, and 32–33% higher abdomen drag. In lab experiments maximum flight durations in claustral S. invicta queens decreased by about 18 minutes for every milligram of abdomen mass. Combining our results into a simple fitness tradeoff model, we calculated that an average parasitic S. invicta queen could produce only 1/3 as many worker offspring as a claustral queen, but could fly 4 times as long and have a 17- to 36-fold larger potential colonization area. Investigations of dispersal polymorphisms and their associated tradeoffs promises to shed light on range expansions in invasive species, the evolution of alternative reproductive strategies, and the selective forces driving the recurrent evolution of parasitism in ants. PMID:27082115

  4. Intrahaplotype polymorphism at the Brassica S locus.

    PubMed Central

    Miege, C; Ruffio-Châble, V; Schierup, M H; Cabrillac, D; Dumas, C; Gaude, T; Cock, J M

    2001-01-01

    The S locus receptor kinase and the S locus glycoproteins are encoded by genes located at the S locus, which controls the self-incompatibility response in Brassica. In class II self-incompatibility haplotypes, S locus glycoproteins can be encoded by two different genes, SLGA and SLGB. In this study, we analyzed the sequences of these genes in several independently isolated plants, all of which carry the same S haplotype (S(2)). Two groups of S(2) haplotypes could be distinguished depending on whether SRK was associated with SLGA or SLGB. Surprisingly, SRK alleles from the two groups could be distinguished at the sequence level, suggesting that recombination rarely occurs between haplotypes of the two groups. An analysis of the distribution of polymorphisms along the S domain of SRK showed that hypervariable domains I and II tend to be conserved within haplotypes but to be highly variable between haplotypes. This is consistent with these domains playing a role in the determination of haplotype specificity. PMID:11606555

  5. Polymorphic Admixture Typing in Human Ethnic Populations

    PubMed Central

    Dean, Michael; Stephens, J. Claiborne; Winkler, Cheryl; Lomb, Deborah A.; Ramsburg, Mark; Boaze, Raleigh; Stewart, Claudia; Charbonneau, Lauren; Goldman, David; Albaugh, Bernard J.; Goedert, James J.; Beasley, R. Palmer; Hwang, Lu-Yu; Buchbinder, Susan; Weedon, Michael; Johnson, Patricia A.; Eichelberger, Mary; O'Brien, Stephen J.

    1994-01-01

    A panel of 257 RFLP loci was selected on the basis of high heterozygosity in Caucasian DNA surveys and equivalent spacing throughout the human genome. Probes from each locus were used in a Southern blot survey of allele frequency distribution for four human ethnic groups: Caucasian, African American, Asian (Chinese), and American Indian (Cheyenne). Nearly all RFLP loci were polymorphic in each group, albeit with a broad range of differing allele frequencies (δ). The distribution of frequency differences (δ values) was used for three purposes: (1) to provide estimates for genetic distance (differentiation) among these ethnic groups, (2) to revisit with a large data set the proportion of human genetic variation attributable to differentiation within ethnic groups, and (3) to identify loci with high δ values between recently admixed populations of use in mapping by admixture linkage disequilibrium (MALD). Although most markers display significant allele frequency differences between ethnic groups, the overall genetic distances between ethnic groups were small (.066–.098), and <10% of the measured overall molecular genetic diversity in these human samples can be attributed to “racial” differentiation. The median δ values for pairwise comparisons between groups fell between .15 and .20, permitting identification of highly informative RFLP loci for MALD disease association studies. PMID:7942857

  6. Dispersal Polymorphisms in Invasive Fire Ants.

    PubMed

    Helms, Jackson A; Godfrey, Aaron

    2016-01-01

    In the Found or Fly (FoF) hypothesis ant queens experience reproduction-dispersal tradeoffs such that queens with heavier abdomens are better at founding colonies but are worse flyers. We tested predictions of FoF in two globally invasive fire ants, Solenopsis geminata (Fabricius, 1804) and S. invicta (Buren, 1972). Colonies of these species may produce two different monogyne queen types-claustral queens with heavy abdomens that found colonies independently, and parasitic queens with small abdomens that enter conspecific nests. Claustral and parasitic queens were similarly sized, but the abdomens of claustral queens weighed twice as much as those of their parasitic counterparts. Their heavier abdomens adversely impacted morphological predictors of flight ability, resulting in 32-38% lower flight muscle ratios, 55-63% higher wing loading, and 32-33% higher abdomen drag. In lab experiments maximum flight durations in claustral S. invicta queens decreased by about 18 minutes for every milligram of abdomen mass. Combining our results into a simple fitness tradeoff model, we calculated that an average parasitic S. invicta queen could produce only 1/3 as many worker offspring as a claustral queen, but could fly 4 times as long and have a 17- to 36-fold larger potential colonization area. Investigations of dispersal polymorphisms and their associated tradeoffs promises to shed light on range expansions in invasive species, the evolution of alternative reproductive strategies, and the selective forces driving the recurrent evolution of parasitism in ants.

  7. Surveying expression level polymorphism and single-feature polymorphism in near-isogenic wheat lines differing for the Yr5 stripe rust resistance locus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    DNA polymorphisms are valuable for several applications including genotyping, molecular mapping and marker-assisted selection. The Affymetrix Wheat GeneChip was used to survey expression level polymorphisms (ELPs) and single-feature polymorphisms (SFPs) between two near-isogenic wheat genotypes (BC7...

  8. Surveying expression level polymorphism and single-feature polymorphism in near-isogenic wheat lines differing for the Yr5 stripe rust resistance locus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    DNA polymorphisms are valuable for several applications including genotyping, molecular mapping and marker-assisted selection. The Affymetrix Wheat GeneChip was used to survey expression level polymorphisms (ELPs) and single-feature polymorphisms (SFPs) between two near-isogenic wheat genotypes (BC...

  9. Complexity Reduction of Polymorphic Sequences (CRoPS™): A Novel Approach for Large-Scale Polymorphism Discovery in Complex Genomes

    PubMed Central

    van Orsouw, Nathalie J.; Hogers, René C. J.; Janssen, Antoine; Yalcin, Feyruz; Snoeijers, Sandor; Verstege, Esther; Schneiders, Harrie; van der Poel, Hein; van Oeveren, Jan; Verstegen, Harold; van Eijk, Michiel J. T.

    2007-01-01

    Application of single nucleotide polymorphisms (SNPs) is revolutionizing human bio-medical research. However, discovery of polymorphisms in low polymorphic species is still a challenging and costly endeavor, despite widespread availability of Sanger sequencing technology. We present CRoPS™ as a novel approach for polymorphism discovery by combining the power of reproducible genome complexity reduction of AFLP® with Genome Sequencer (GS) 20/GS FLX next-generation sequencing technology. With CRoPS, hundreds-of-thousands of sequence reads derived from complexity-reduced genome sequences of two or more samples are processed and mined for SNPs using a fully-automated bioinformatics pipeline. We show that over 75% of putative maize SNPs discovered using CRoPS are successfully converted to SNPWave® assays, confirming them to be true SNPs derived from unique (single-copy) genome sequences. By using CRoPS, polymorphism discovery will become affordable in organisms with high levels of repetitive DNA in the genome and/or low levels of polymorphism in the (breeding) germplasm without the need for prior sequence information. PMID:18000544

  10. Genetic diversity among elite Sorghum lines revealed by restriction fragment length polymorphisms and random amplified polymorphic DNAs.

    PubMed

    Vierling, R A; Xiang, Z; Joshi, C P; Gilbert, M L; Nguyen, H T

    1994-02-01

    The genetic diversity of sorghum, as compared to corn, is less well characterized at the genetic and molecular levels despite its worldwide economic importance. The objectives of this study were to: (1) investigate genetic diversity for restriction fragment length polymorphism (RFLPs) and random amplified polymorphic DNAs (RAPDs) in elite sorghum lines, (2) compare similarities based on molecular markers with pedigree relationships, and (3) examine the potential of RFLPs and RAPDs for assigning sorghum lines to the A/B (sterile) and R (restorer) groups. Using four restriction enzymes, polymorphism was detected with 61% of the RFLP probes used, compared to 77% of the random primers. One hundred and sixteen (64%) probe-enzyme combinations yielded multiple-band profiles compared to 98% of the random primers. RFLP profiles generated 290 polymorphic bands compared to 177 polymorphic RAPDs. Pair-wise comparisons of polymorphic RFLPs and RAPDs were used to calculate Nei and Jaccard coefficients. These were employed to generate phenograms using UPGMA and neighborjoining clustering methods. Analysis of RFLP data with Jaccard's coefficient and neighbor-joining clustering produced the phenogram with the closest topology to the known pedigree.

  11. New pressure-induced polymorphic transitions of anhydrous magnesium sulfate.

    PubMed

    Benmakhlouf, A; Errandonea, D; Bouchenafa, M; Maabed, S; Bouhemadou, A; Bentabet, A

    2017-03-31

    The effects of pressure on the crystal structure of the three known polymorphs of magnesium sulfate (α-MgSO4, β-MgSO4, and γ-MgSO4) have been theoretically studied by means of density-functional theory calculations up to 45 GPa. We determined that under ambient conditions γ-MgSO4 is an unstable polymorph, which decomposes into MgO + SO3, and that the response of the other two polymorphs to hydrostatic pressure is non-isotropic. Additionally, we found that at all pressures β-MgSO4 has a larger enthalpy than α-MgSO4. This indicates that β-MgSO4 is thermodynamically unstable versus α-MgSO4 and predicts the occurrence of a β-α phase transition under moderate compression. Our calculations also predict the existence under pressure of additional phase transitions to two new polymorphs of MgSO4, which we named δ-MgSO4 and ε-MgSO4. The α-δ transition is predicted to occur at 17.5 GPa, and the δ-ε transition at 35 GPa, pressures that nowadays can be experimentally easily achieved. All the predicted structural transformations are characterized as first-order transitions. This suggests that they can be non-reversible, and therefore the new polymorphs could be recovered as metastable polymorphs under ambient conditions. The crystal structure of the two new polymorphs is reported. In them, the coordination number of sulfur is four as in the previously known polymorphs, but the coordination number of magnesium is eight instead of six. In this article we will report the axial and bond compressibility for the four polymorphs of MgSO4. The pressure-volume equation of state of each phase is also given, which is described by a third-order Birch-Murnaghan equation. The values obtained for the bulk modulus are 62 GPa, 57 GPa, 102 GPa, and 119 GPa for α-MgSO4, β-MgSO4, δ-MgSO4, and ε-MgSO4, respectively. Finally, the electronic band structure of these four polymorphs of MgSO4 has been calculated for the first time. The obtained results will be presented and discussed.

  12. COMT Val158Met Polymorphism Modulates Huntington's Disease Progression

    PubMed Central

    Rebeix, Isabelle; Dupoux, Emmanuel; Durr, Alexandra; Brice, Alexis; Charles, Perrine; Cleret de Langavant, Laurent; Youssov, Katia; Verny, Christophe; Damotte, Vincent; Azulay, Jean-Philippe; Goizet, Cyril; Simonin, Clémence; Tranchant, Christine; Maison, Patrick; Rialland, Amandine; Schmitz, David; Jacquemot, Charlotte; Fontaine, Bertrand; Bachoud-Lévi, Anne-Catherine

    2016-01-01

    Little is known about the genetic factors modulating the progression of Huntington’s disease (HD). Dopamine levels are affected in HD and modulate executive functions, the main cognitive disorder of HD. We investigated whether the Val158Met polymorphism of the catechol-O-methyltransferase (COMT) gene, which influences dopamine (DA) degradation, affects clinical progression in HD. We carried out a prospective longitudinal multicenter study from 1994 to 2011, on 438 HD gene carriers at different stages of the disease (34 pre-manifest; 172 stage 1; 130 stage 2; 80 stage 3; 17 stage 4; and 5 stage 5), according to Total Functional Capacity (TFC) score. We used the Unified Huntington’s Disease Rating Scale to evaluate motor, cognitive, behavioral and functional decline. We genotyped participants for COMT polymorphism (107 Met-homozygous, 114 Val-homozygous and 217 heterozygous). 367 controls of similar ancestry were also genotyped. We compared clinical progression, on each domain, between groups of COMT polymorphisms, using latent-class mixed models accounting for disease duration and number of CAG (cytosine adenine guanine) repeats. We show that HD gene carriers with fewer CAG repeats and with the Val allele in COMT polymorphism displayed slower cognitive decline. The rate of cognitive decline was greater for Met/Met homozygotes, which displayed a better maintenance of cognitive capacity in earlier stages of the disease, but had a worse performance than Val allele carriers later on. COMT polymorphism did not significantly impact functional and behavioral performance. Since COMT polymorphism influences progression in HD, it could be used for stratification in future clinical trials. Moreover, DA treatments based on the specific COMT polymorphism and adapted according to disease duration could potentially slow HD progression. PMID:27657697

  13. CLPTM1L polymorphism and lung cancer risk.

    PubMed

    Tang, Min; Bian, Xiaonian; Zhao, Qiuliang

    2015-01-01

    The association of Cleft Lip and Palate Transmembrane Protein 1 (CLPTM1L) rs31489 polymorphism with risk of lung cancer has been evaluated in many studies; however, the results from these studies are controversial. Thus, further analysis on association between CLPTM1L rs31489 polymorphism and risk of lung cancer is needed among a larger study population. A literature search in PubMed, Embase, Web of Science, Science Direct, SpringerLink, EBSCO, Wanfang, and Chinese National Knowledge Infrastructure (CNKI) databases was carried out to identify studies investigating the association between lung cancer risk and CLPTM1L rs31489 polymorphism. The strength of the association between CLPTM1L rs31489 polymorphism and lung cancer risk was estimated by calculating odds ratios (ORs) and corresponding 95% confidence intervals (CIs). In the overall analysis, there was significant association between CLPTM1L rs31489 polymorphism and lung cancer risk under an allele model (OR = 1.12; 95% CI, 1.06-1.18; P < 0.00001; I(2) = 57%). Subgroup analysis by ethnicity was performed. Stratified analysis by ethnicity showed that a statistically increased cancer risk was found in the Caucasian population (OR = 1.15; 95% CI, 1.10-1.21; P < 0.00001; I(2) = 22%), but there was no significant association between lung cancer risk and CLPTM1L rs31489 polymorphism in the Asian population (OR = 1.03; 95% CI, 0.97-1.08; P = 0.37; I(2) = 15%). In conclusion, this meta-analysis demonstrates that CLPTM1L rs31489 polymorphism significantly modified the risk of lung cancer.

  14. CLPTM1L polymorphism and lung cancer risk

    PubMed Central

    Tang, Min; Bian, Xiaonian; Zhao, Qiuliang

    2015-01-01

    The association of Cleft Lip and Palate Transmembrane Protein 1 (CLPTM1L) rs31489 polymorphism with risk of lung cancer has been evaluated in many studies; however, the results from these studies are controversial. Thus, further analysis on association between CLPTM1L rs31489 polymorphism and risk of lung cancer is needed among a larger study population. A literature search in PubMed, Embase, Web of Science, Science Direct, SpringerLink, EBSCO, Wanfang, and Chinese National Knowledge Infrastructure (CNKI) databases was carried out to identify studies investigating the association between lung cancer risk and CLPTM1L rs31489 polymorphism. The strength of the association between CLPTM1L rs31489 polymorphism and lung cancer risk was estimated by calculating odds ratios (ORs) and corresponding 95% confidence intervals (CIs). In the overall analysis, there was significant association between CLPTM1L rs31489 polymorphism and lung cancer risk under an allele model (OR = 1.12; 95% CI, 1.06-1.18; P < 0.00001; I2 = 57%). Subgroup analysis by ethnicity was performed. Stratified analysis by ethnicity showed that a statistically increased cancer risk was found in the Caucasian population (OR = 1.15; 95% CI, 1.10-1.21; P < 0.00001; I2 = 22%), but there was no significant association between lung cancer risk and CLPTM1L rs31489 polymorphism in the Asian population (OR = 1.03; 95% CI, 0.97-1.08; P = 0.37; I2 = 15%). In conclusion, this meta-analysis demonstrates that CLPTM1L rs31489 polymorphism significantly modified the risk of lung cancer. PMID:26064290

  15. Polymorphisms in DNA repair genes and associations with cancer risk.

    PubMed

    Goode, Ellen L; Ulrich, Cornelia M; Potter, John D

    2002-12-01

    Common polymorphisms in DNA repair genes may alter protein function and an individual's capacity to repair damaged DNA; deficits in repair capacity may lead to genetic instability and carcinogenesis. To establish our overall understanding of possible in vivo relationships between DNA repair polymorphisms and the development of cancer, we performed a literature review of epidemiological studies that assessed associations between such polymorphisms and risk of cancer. Thirty studies of polymorphisms in OGG1, XRCC1, ERCC1, XPC, XPD, XPF, BRCA2, and XRCC3 were identified in the April 30, 2002 MEDLINE database (National Center for Biotechnology Information. PubMed Database: http://www.ncbi.nlm.nih.gov/entrez). These studies focused on adult glioma, bladder cancer, breast cancer, esophageal cancer, lung cancer, prostate cancer, skin cancer (melanoma and nonmelanoma), squamous cell carcinoma of the head and neck, and stomach cancer. We found that a small proportion of the published studies were large and population-based. Nonetheless, published data were consistent with associations between: (a) the OGG1 S326C variant and increased risk of various types of cancer; (b) the XRCC1 R194W variant and reduced risk of various types of cancer; and (c) the BRCA2 N372H variant and increased risk of breast cancer. Suggestive results were seen for polymorphisms in other genes; however, small sample sizes may have contributed to false-positive or false-negative findings. We conclude that large, well-designed studies of common polymorphisms in DNA repair genes are needed. Such studies may benefit from analysis of multiple genes or polymorphisms and from the consideration of relevant exposures that may influence the likelihood of cancer in the presence of reduced DNA repair capacity.

  16. COMT Val158Met Polymorphism Modulates Huntington's Disease Progression.

    PubMed

    de Diego-Balaguer, Ruth; Schramm, Catherine; Rebeix, Isabelle; Dupoux, Emmanuel; Durr, Alexandra; Brice, Alexis; Charles, Perrine; Cleret de Langavant, Laurent; Youssov, Katia; Verny, Christophe; Damotte, Vincent; Azulay, Jean-Philippe; Goizet, Cyril; Simonin, Clémence; Tranchant, Christine; Maison, Patrick; Rialland, Amandine; Schmitz, David; Jacquemot, Charlotte; Fontaine, Bertrand; Bachoud-Lévi, Anne-Catherine

    Little is known about the genetic factors modulating the progression of Huntington's disease (HD). Dopamine levels are affected in HD and modulate executive functions, the main cognitive disorder of HD. We investigated whether the Val158Met polymorphism of the catechol-O-methyltransferase (COMT) gene, which influences dopamine (DA) degradation, affects clinical progression in HD. We carried out a prospective longitudinal multicenter study from 1994 to 2011, on 438 HD gene carriers at different stages of the disease (34 pre-manifest; 172 stage 1; 130 stage 2; 80 stage 3; 17 stage 4; and 5 stage 5), according to Total Functional Capacity (TFC) score. We used the Unified Huntington's Disease Rating Scale to evaluate motor, cognitive, behavioral and functional decline. We genotyped participants for COMT polymorphism (107 Met-homozygous, 114 Val-homozygous and 217 heterozygous). 367 controls of similar ancestry were also genotyped. We compared clinical progression, on each domain, between groups of COMT polymorphisms, using latent-class mixed models accounting for disease duration and number of CAG (cytosine adenine guanine) repeats. We show that HD gene carriers with fewer CAG repeats and with the Val allele in COMT polymorphism displayed slower cognitive decline. The rate of cognitive decline was greater for Met/Met homozygotes, which displayed a better maintenance of cognitive capacity in earlier stages of the disease, but had a worse performance than Val allele carriers later on. COMT polymorphism did not significantly impact functional and behavioral performance. Since COMT polymorphism influences progression in HD, it could be used for stratification in future clinical trials. Moreover, DA treatments based on the specific COMT polymorphism and adapted according to disease duration could potentially slow HD progression.

  17. Predicting drug response and toxicity based on gene polymorphisms.

    PubMed

    Robert, Jacques; Morvan, Valérie Le; Smith, Denis; Pourquier, Philippe; Bonnet, Jacques

    2005-06-01

    The sequencing of the human genome has allowed the identification of thousands of gene polymorphisms, most often single nucleotide polymorphims (SNP), which may play an important role in the expression level and activity of the corresponding proteins. When these polymorphisms occur at the level of drug metabolising enzymes or transporters, the disposition of the drug may be altered and, consequently, its efficacy may be compromised or its toxicity enhanced. Polymorphisms can also occur at the level of proteins directly involved in drug action, either when the protein is the target of the drug or when the protein is involved in the repair of drug-induced lesions. There again, these polymorphisms may lead to alterations in drug efficacy and/or toxicity. The identification of functional polymorphisms in patients undergoing chemotherapy may help the clinician prescribe the optimal drug combination or schedule and predict with more accuracy the response to these prescriptions. We have recorded in this review the polymorphisms that have been identified up till now in genes involved in anticancer drug activity. Some of them appear especially important in predicting drug toxicity and should be determined in routine before drug administration; this is the case of the most common variations of thiopurine methyltransferase for 6-mercaptopurine and of dihydropyrimidine dehydrogenase for fluorouracil. Other appear determinant for drug response, such as the common SNPs found in glutathione S-transferase P1 or xereoderma pigmentosum group D enzyme for the activity of oxaliplatin. However, confusion factors may exist between the role of gene polymorphisms in cancer risk or overall prognosis and their role in drug response.

  18. Raman detected differential scanning calorimetry of polymorphic transformations in acetaminophen.

    PubMed

    Kauffman, John F; Batykefer, Linda M; Tuschel, David D

    2008-12-15

    Acetaminophen is known to crystallize in three polymorphic forms. Thermally induced transformations between the crystalline forms and the super-cooled liquid have been observed by differential scanning calorimetry (DSC), but the assignment of calorimetric transitions to specific polymorphic transformations remains challenging, because the transition temperatures for several transformations are close to one another, and the characteristics of the observed transitions depend on experimental variables that are often poorly controlled. This paper demonstrates the simultaneous application of DSC and Raman microscopy for the observation of thermally driven transitions between polymorphs of pharmaceutical materials. Raman detected differential scanning calorimetry (RD-DSC) has been used to monitor the DSC thermograms of super-cooled liquid acetaminophen and confirms the assignment of two exothermic transitions to specific polymorphic transformations. Principal component analysis of the Raman spectra have been used to determine the number of independent components that participate in the phase transformations, and multivariate regression has been used to determine transition temperatures from the spectral data. The influence of the laser excitation source on measured DSC thermograms has also been investigated, and it has been demonstrated that a baseline shift occurs in RD-DSC when a polymorphic transformation occurs between crystalline and amorphous forms. RD-DSC has been used to examine the influence of sample aging and sample pan configuration on the observed polymorphic transformations, and both of these variables were found to influence the thermal behavior of the sample. The results demonstrate the advantage of simultaneous Raman spectroscopy and differential scanning calorimetry for the unambiguous assignment of thermally driven polymorphic transformations.

  19. Structural origin of polymorphism of Alzheimer's amyloid β-fibrils.

    PubMed

    Agopian, Audrey; Guo, Zhefeng

    2012-10-01

    Formation of senile plaques containing amyloid fibrils of Aβ (amyloid β-peptide) is a pathological hallmark of Alzheimer's disease. Unlike globular proteins, which fold into unique structures, the fibrils of Aβ and other amyloid proteins often contain multiple polymorphs. Polymorphism of amyloid fibrils leads to different toxicity in amyloid diseases and may be the basis for prion strains, but the structural origin for fibril polymorphism is still elusive. In the present study we investigate the structural origin of two major fibril polymorphs of Aβ40: an untwisted polymorph formed under agitated conditions and a twisted polymorph formed under quiescent conditions. Using electron paramagnetic resonance spectroscopy, we studied the inter-strand side-chain interactions at 14 spin-labelled positions in the Aβ40 sequence. The results of the present study show that the agitated fibrils have stronger inter-strand spin-spin interactions at most of the residue positions investigated. The two hydrophobic regions at residues 17-20 and 31-36 have the strongest interactions in agitated fibrils. Distance estimates on the basis of the spin exchange frequencies suggest that inter-strand distances at residues 17, 20, 32, 34 and 36 in agitated fibrils are approximately 0.2 Å (1 Å=0.1 nm) closer than in quiescent fibrils. We propose that the strength of inter-strand side-chain interactions determines the degree of β-sheet twist, which then leads to the different association patterns between different cross β-units and thus distinct fibril morphologies. Therefore the inter-strand side-chain interaction may be a structural origin for fibril polymorphism in Aβ and other amyloid proteins.

  20. Human enamel thickness and ENAM polymorphism

    PubMed Central

    Daubert, Diane M; Kelley, Joanna L; Udod, Yuriy G; Habor, Carolina; Kleist, Chris G; Furman, Ilona K; Tikonov, Igor N; Swanson, Willie J; Roberts, Frank A

    2016-01-01

    The tooth enamel development gene, enamelin (ENAM), showed evidence of positive selection during a genome-wide scan of human and primate DNA for signs of adaptive evolution. The current study examined the hypothesis that a single-nucleotide polymorphism (SNP) C14625T (rs7671281) in the ENAM gene identified in the genome-wide scan is associated with a change in enamel phenotype. African Americans were selected as the target population, as they have been reported to have a target SNP frequency of approximately 50%, whereas non-Africans are predicted to have a 96% SNP frequency. Digital radiographs and DNA samples from 244 teeth in 133 subjects were analysed, and enamel thickness was assessed in relation to SNP status, controlling for age, sex, tooth number and crown length. Crown length was found to increase with molar number, and females were found to have thicker enamel. Teeth with larger crowns also had thicker enamel, and older subjects had thinner enamel. Linear regression and generalized estimating equations were used to investigate the relationship between enamel thickness of the mandibular molars and ENAM SNP status; enamel in subjects with the derived allele was significantly thinner (P=0.040) when the results were controlled for sex, age, tooth number and crown length. The derived allele demonstrated a recessive effect on the phenotype. The data indicate that thinner dental enamel is associated with the derived ENAM genotype. This is the first direct evidence of a dental gene implicated in human adaptive evolution as having a phenotypic effect on an oral structure. PMID:27357321

  1. The polymorphisms of the chromatin fiber

    NASA Astrophysics Data System (ADS)

    Boulé, Jean-Baptiste; Mozziconacci, Julien; Lavelle, Christophe

    2015-01-01

    In eukaryotes, the genome is packed into chromosomes, each consisting of large polymeric fibers made of DNA bound with proteins (mainly histones) and RNA molecules. The nature and precise 3D organization of this fiber has been a matter of intense speculations and debates. In the emerging picture, the local chromatin state plays a critical role in all fundamental DNA transactions, such as transcriptional control, DNA replication or repair. However, the molecular and structural mechanisms involved remain elusive. The purpose of this review is to give an overview of the tremendous efforts that have been made for almost 40 years to build physiologically relevant models of chromatin structure. The motivation behind building such models was to shift our representation and understanding of DNA transactions from a too simplistic ‘naked DNA’ view to a more realistic ‘coated DNA’ view, as a step towards a better framework in which to interpret mechanistically the control of genetic expression and other DNA metabolic processes. The field has evolved from a speculative point of view towards in vitro biochemistry and in silico modeling, but is still longing for experimental in vivo validations of the proposed structures or even proof of concept experiments demonstrating a clear role of a given structure in a metabolic transaction. The mere existence of a chromatin fiber as a relevant biological entity in vivo has been put into serious questioning. Current research is suggesting a possible reconciliation between theoretical studies and experiments, pointing towards a view where the polymorphic and dynamic nature of the chromatin fiber is essential to support its function in genome metabolism.

  2. A second triclinic polymorph of azimsulfuron

    PubMed Central

    Kwon, Eunjin; Kim, Jineun; Park, Hyunjin; Kim, Tae Ho

    2016-01-01

    The title compound, C13H16N10O5S (systematic name: 1-(4,6-di­meth­oxypyrimidin-2-yl)-3-{[1-methyl-4-(2-methyl-2H-tetra­zol-5-yl)pyrazol-5-yl]sulfonyl}urea), is a second triclinic polymorph of this crystal [for the other, see: Jeon et al., (2015 ▸). Acta Cryst. E71, o470–o471]. There are two mol­ecules, A and B, in the asymmetric unit; the dihedral angles between the pyrazole ring and the tetra­zole and di­meth­oxy­pyrimidine ring planes are 72.84 (10) and 37.24 (14)°, respectively (mol­ecule A) and 84.38 (9) and 26.09 (15)°, respectively (mol­ecule B). Each mol­ecule features an intra­molecular N—H⋯N hydrogen bond. In the crystal, aromatic π–π stacking inter­actions [centroid–centroid separations = 3.9871 (16), 3.4487 (14) and 3.5455 (16) Å] link the mol­ecules into [001] chains. In addition, N—H⋯N, N—H⋯O, C—H⋯O and C—H⋯N hydrogen bonds occur, forming a three-dimensional architecture. We propose that the dimorphism results from differences in conformations and packing owing to different inter­molecular inter­actions, especially aromatic π–π stacking. PMID:27746943

  3. Vitamin D Receptor (VDR) Polymorphisms in Pediatric Patients Presenting With Hodgkin's Lymphoma.

    PubMed

    Tekgündüz, Sibel A; Yeşil, Şule; Ören, Ayşe C; Tanyildiz, Hikmet G; Çandir, Mehmet O; Bozkurt, Ceyhun; Şahin, Gürses

    2017-03-01

    Vitamin D receptor (VDR) polymorphisms are found more commonly in some tumor types than in healthy individuals, suggesting that some polymorphisms (Cdx2, Fok1, Bsm1, Apa1, Taq1) contribute to tumor development. There is no previous report on VDR polymorphism in Hodgkin's lymphoma (HL) patients. VDR polymorphism patterns in 95 pediatric HL cases with 100 healthy controls were compared. No statistically significant difference was found between the patient group and control group in terms of Cdx2, Fok1, Bsm1, Apa1, and Taq1 polymorphisms (P>0.5). Our findings suggest that VDR polymorphisms may not play a role in HL development.

  4. Efficient development of highly polymorphic microsatellite markers based on polymorphic repeats in transcriptome sequences of multiple individuals.

    PubMed

    Vukosavljev, M; Esselink, G D; van 't Westende, W P C; Cox, P; Visser, R G F; Arens, P; Smulders, M J M

    2015-01-01

    The first hurdle in developing microsatellite markers, cloning, has been overcome by next-generation sequencing. The second hurdle is testing to differentiate polymorphic from nonpolymorphic loci. The third hurdle, somewhat hidden, is that only polymorphic markers with a large effective number of alleles are sufficiently informative to be deployed in multiple studies. Both steps are laborious and still performed manually. We have developed a strategy in which we first screen reads from multiple genotypes for repeats that show the most length variants, and only these are subsequently developed into markers. We validated our strategy in tetraploid garden rose using Illumina paired-end transcriptome sequences of 11 roses. Of 48 tested two markers failed to amplify, but all others were polymorphic. Ten loci amplified more than one locus, indicating duplicated genes or gene families. Completely avoiding duplicated loci will be difficult because the range of numbers of predicted alleles of highly polymorphic single- and multilocus markers largely overlapped. Of the remainder, half were replicate markers (i.e. multiple primer pairs for one locus), indicating the difficulty of correctly filtering short reads containing repeat sequences. We subsequently refined the approach to eliminate multiple primer sets to the same loci. The remaining 18 markers were all highly polymorphic, amplifying on average 11.7 alleles per marker (range = 6-20) in 11 tetraploid roses, exceeding the 8.2 alleles per marker of the 24 most polymorphic markers genotyped previously. This strategy therefore represents a major step forward in the development of highly polymorphic microsatellite markers.

  5. Development of novel polymorphic microsatellite markers in Siganus fuscescens.

    PubMed

    Mao, X Q; Li, Z B; Ning, Y F; Shangguan, J B; Yuan, Y; Huang, Y S; Li, B B

    2016-07-29

    Rabbitfish, Siganus fuscescens, is widely distributed in the Indo-Pacific regions and eastern Mediterranean. Its dwelling place includes reef flats, coral reef regions, and seagrass meadows in tropical area and reef areas or shallow waters in locations at high latitudes. In the present study, 10 new polymorphic microsatellite markers were screened from 30 wild S. fuscescens individuals, using a method of fast isolation protocol and amplified fragment length polymorphism of sequences containing repeats. The number of polymorphic alleles per locus was 3 to 5 with a mean of 4.3, while the value of polymorphic information content ranged from 0.283 to 0.680. The values of the observed and expected heterozygosities were in the range 0.3333-0.8462 and 0.3011-0.7424, respectively. Deviation from Hardy-Weinberg equilibrium was not observed in this study. These polymorphic loci are expected to be effective in evaluating the genetic diversity, population structure, and gene flow and in determining the paternity in S. fuscescens, as well as for conservation management.

  6. PPARγ2Pro12Ala Polymorphism and Human Health

    PubMed Central

    He, Weimin

    2009-01-01

    The nuclear hormone receptor peroxisome proliferator activated receptor gamma (PPARγ) is an important transcription factor regulating adipocyte differentiation, lipid and glucose homeostasis, and insulin sensitivity. Numerous genetic mutations of PPARγ have been identified and these mutations positively or negatively regulate insulin sensitivity. Among these, a relatively common polymorphism of PPARγ, Pro12Ala of PPARγ2, the isoform expressed only in adipose tissue has been shown to be associated with lower body mass index, enhanced insulin sensitivity, and resistance to the risk of type 2 diabetes in human subjects carrying this mutation. Subsequent studies in different ethnic populations, however, have revealed conflicting results, suggesting a complex interaction between the PPARγ2 Pro12Ala polymorphism and environmental factors such as the ratio of dietary unsaturated fatty acids to saturated fatty acids and/or between the PPARγ2 Pro12Ala polymorphism and genetic factors such as polymorphic mutations in other genes. In addition, this polymorphic mutation in PPARγ2 is associated with other aspects of human diseases, including cancers, polycystic ovary syndrome, Alzheimer disease and aging. This review will highlight findings from recent studies. PMID:19390629

  7. Association of TNF, MBL, and VDR Polymorphisms with Leprosy Phenotypes

    PubMed Central

    Sapkota, Bishwa R.; Macdonald, Murdo; Berrington, William R.; Misch, E. Ann; Ranjit, Chaman; Siddiqui, M. Ruby; Kaplan, Gilla; Hawn, Thomas R.

    2010-01-01

    Background Although genetic variants in tumor necrosis factor (TNF), mannose binding lectin (MBL), and the vitamin D receptor (VDR) have been associated with leprosy clinical outcomes these findings have not been extensively validated. Methods We used a case-control study design with 933 patients in Nepal, which included 240 patients with type I reversal reaction (RR), and 124 patients with erythema nodosum leprosum (ENL) reactions. We compared genotype frequencies in 933 cases and 101 controls of 7 polymorphisms, including a promoter region variant in TNF (G−308A), three polymorphisms in MBL (C154T, G161A and G170A), and three variants in VDR (FokI, BsmI, and TaqI). Results We observed an association between TNF −308A and protection from leprosy with an odds ratio (OR) of 0.52 (95% confidence interval (CI) of 0.29 to 0.95, P = 0.016). MBL polymorphism G161A was associated with protection from lepromatous leprosy (OR (95% CI) = 0.33 (0.12–0.85), P = 0.010). VDR polymorphisms were not associated with leprosy phenotypes. Conclusion These results confirm previous findings of an association of TNF −308A with protection from leprosy and MBL polymorphisms with protection from lepromatous leprosy. The statistical significance was modest and will require further study for conclusive validation. PMID:20650301

  8. Germline TP53 mutations and single nucleotide polymorphisms in children.

    PubMed

    Valva, Pamela; Becker, Pablo; Streitemberger, Patricia; Lombardi, García Mercedes; Rey, Guadalupe; Guzman, Carlos A; Preciado, María Victoria

    2009-01-01

    Mutations in the gene TP53, which codifies the tumor suppressor protein p53, are found in about 50% of tumors. These mutations can occur not only at somatic level, but also in germline. Pediatric cancer patients, mostly with additional family history of malignancy, should be considered as potential TP53 germline mutation carriers. Germline TP53 mutations and polymorphisms have been widely studied to determine their relation with different tumors' pathogenesis. Our aim was to analyze the occurrence frequency of germline TP53 mutations and polymorphisms and to relate these to tumor development in a pediatric series. Peripheral blood mononuclear cell samples from 26 children with solid tumors [PST] and 21 pediatric healthy donors [HD] were analyzed for germline mutations and polymorphisms in TP53 gene spanning from exon 5 to 8 including introns 5 and 7. These PCR amplified fragments were sequenced to determine variations. A heterozygous mutation at codon 245 was found in 1/26 PST and 0/21 HD. Comparative polymorphisms distribution, at position 14181 and 14201(intron 7), between HD and PST revealed a trend of association (p= 0.07) with cancer risk. HD group disclosed a similar polymorphism distribution as published data for Caucasian and Central/South American populations. This is the first study about TP53 variant frequency and distribution in healthy individuals and cancer patients in Argentina.

  9. STAT4 gene polymorphism in patients after renal allograft transplantation

    PubMed Central

    Dąbrowska-Żamojcin, Ewa; Dziedziejko, Violetta; Safranow, Krzysztof; Domański, Leszek; Słuczanowska-Głabowska, Sylwia

    2016-01-01

    Introduction STAT4 (signal transducer and activator of transcription 4) is involved in the regulation of innate and adaptive immune responses. Some studies have suggested that STAT4 may be involved in the immune response after graft transplantation. Several polymorphisms in the STAT4 gene have been identified. The most commonly studied polymorphism in the STAT4 gene is rs7574865. In our study, we examined whether this polymorphism is associated with the early and late functions of renal allografts. Material and methods A total of 270 recipients of first renal transplants were included in the study. Single nucleotide polymorphisms (SNPs) within the STAT4 gene were genotyped using TaqMan genotyping assays. Results There were no statistically significant associations between the STAT4 gene rs7574865 polymorphism and delayed graft function, acute rejection, chronic allograft dysfunction, post-transplant diabetes mellitus, or creatinine serum concentrations after transplantation. Conclusions Our results suggest a lack of association between the STAT4 rs7574865 SNP and kidney allograft function in the Polish population. PMID:27833442

  10. A low-temperature polymorph of m-quinquephenyl.

    PubMed

    Gomes, Ligia R; Howie, R Alan; Low, John Nicolson; Rodrigues, Ana S M C; Santos, Luís M N B F

    2012-12-01

    A low-temperature polymorph of 1,1':3',1'':3'',1''':3''',1''''-quinquephenyl (m-quinquephenyl), C(30)H(22), crystallizes in the space group P2(1)/c with two molecules in the asymmetric unit. The crystal is a three-component nonmerohedral twin. A previously reported room-temperature polymorph [Rabideau, Sygula, Dhar & Fronczek (1993). Chem. Commun. pp. 1795-1797] also crystallizes with two molecules in the asymmetric unit in the space group P-1. The unit-cell volume for the low-temperature polymorph is 4120.5 (4) Å(3), almost twice that of the room-temperature polymorph which is 2102.3 (6) Å(3). The molecules in both structures adopt a U-shaped conformation with similar geometric parameters. The structural packing is similar in both compounds, with the molecules lying in layers which stack perpendicular to the longest unit-cell axis. The molecules pack alternately in the layers and in the stacked columns. In both polymorphs, the only interactions between the molecules which can stabilize the packing are very weak C-H...π interactions.

  11. Relationship between TBX20 gene polymorphism and congenital heart disease.

    PubMed

    Yang, X F; Zhang, Y F; Zhao, C F; Liu, M M; Si, J P; Fang, Y F; Xing, W W; Wang, F L

    2016-06-02

    Congenital heart disease in children is a type of birth defect. Previous studies have suggested that the transcription factor, TBX20, is involved in the occurrence and development of congenital heart disease in children; however, the specific regulatory mechanisms are yet to be evaluated. Hence, this study aimed to evaluate the relationship between the TBX20 polymorphism and the occurrence and development of congenital heart disease. The TBX20 gene sequence was obtained from the NCBI database and the polymorphic locus candidate was predicted. Thereafter, the specific gene primers were designed for the restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) of DNA extracted from the blood of 80 patients with congenital heart disease and 80 controls. The results of the PCR were subjected to correlation analysis to identify the differences between the amplicons and to determine the relationship between the TBX20 gene polymorphism and congenital heart disease. One of the single nucleotide polymorphic locus was found to be rs3999950: c.774T>C (Ala265Ala). The TC genotype frequency in the patients was higher than that in the controls, similar to that for the C locus. The odds ratio of the TC genotypes was above 1, indicating that the presence of the TC genotype increases the incidence of congenital heart diseases. Thus, rs3999950 may be associated with congenital heart disease, and TBX20 may predispose children to the defect.

  12. CYP2C19 polymorphism influences Helicobacter pylori eradication

    PubMed Central

    Kuo, Chao-Hung; Lu, Chien-Yu; Shih, Hsiang-Yao; Liu, Chung-Jung; Wu, Meng-Chieh; Hu, Huang-Ming; Hsu, Wen-Hung; Yu, Fang-Jung; Wu, Deng-Chyang; Kuo, Fu-Chen

    2014-01-01

    The known factors that have contributed to the decline of Helicobacter pylori (H. pylori) eradication rate include antibiotic resistance, poor compliance, high gastric acidity, high bacterial load, and cytochrome P450 2C19 (CYP2C19) polymorphism. Proton pump inhibitor (PPI) is important in the eradication regimen. The principal enzyme implicated in the metabolism of PPIs is CYP2C19. The effects of PPI depend on metabolic enzyme, cytochrome P450 enzymes, and CYP2C19 with genetic differences in the activity of this enzyme (the homozygous EM, heterozygous EM (HetEM), and poor metabolizer). The frequency of the CYP2C19 polymorphism is highly varied among different ethnic populations. The CYP2C19 genotype is a cardinal factor of H. pylori eradication in patients taking omeprazole- based or lansoprazole-based triple therapies. In contrast, the CYP2C19 polymorphism has no significant effect on the rabeprazole-based or esomeprazole-based triple therapies. The efficacy of levofloxacin-based rescue triple therapy might be also affected by the CYP2C19 polymorphism, but CYP2C19 genotypes did not show obvious impact on other levofloxacin-based rescue therapies. Choice of different PPIs and/or increasing doses of PPIs should be individualized based on the pharmacogenetics background of each patient and pharmacological profile of each drug. Other possible factors influencing gastric acid secretion (e.g., IL-1β- 511 polymorphism) would be also under consideration. PMID:25473155

  13. BDNF and TNF-α polymorphisms in memory.

    PubMed

    Yogeetha, B S; Haupt, L M; McKenzie, K; Sutherland, H G; Okolicsyani, R K; Lea, R A; Maher, B H; Chan, R C K; Shum, D H K; Griffiths, L R

    2013-09-01

    Here, we investigate the genetic basis of human memory in healthy individuals and the potential role of two polymorphisms, previously implicated in memory function. We have explored aspects of retrospective and prospective memory including semantic, short term, working and long-term memory in conjunction with brain derived neurotrophic factor (BDNF) and tumor necrosis factor-alpha (TNF-α). The memory scores for healthy individuals in the population were obtained for each memory type and the population was genotyped via restriction fragment length polymorphism for the BDNF rs6265 (Val66Met) SNP and via pyrosequencing for the TNF-α rs113325588 SNP. Using univariate ANOVA, a significant association of the BDNF polymorphism with visual and spatial memory retention and a significant association of the TNF-α polymorphism was observed with spatial memory retention. In addition, a significant interactive effect between BDNF and TNF-α polymorphisms was observed in spatial memory retention. In practice visual memory involves spatial information and the two memory systems work together, however our data demonstrate that individuals with the Val/Val BDNF genotype have poorer visual memory but higher spatial memory retention, indicating a level of interaction between TNF-α and BDNF in spatial memory retention. This is the first study to use genetic analysis to determine the interaction between BDNF and TNF-α in relation to memory in normal adults and provides important information regarding the effect of genetic determinants and gene interactions on human memory.

  14. Identifying potential BO2 oxide polymorphs for epitaxial growth candidates.

    PubMed

    Mehta, Prateek; Salvador, Paul A; Kitchin, John R

    2014-03-12

    Transition metal dioxides (BO2) exhibit a number of polymorphic structures with distinct properties, but the isolation of different polymorphs for a given composition is carried out using trial and error experimentation. We present computational studies of the relative stabilities and equations of state for six polymorphs (anatase, brookite, rutile, columbite, pyrite, and fluorite) of five different BO2 dioxides (B = Ti, V, Ru, Ir, and Sn). These properties were computed in a consistent fashion using several exchange correlation functionals within the density functional theory formalism, and the effects of the different functionals are discussed relative to their impact on predictive synthesis. We compare the computational results to prior observations of high-pressure synthesis and epitaxial film growth and then use this discussion to predict new accessible polymorphs in the context of epitaxial stabilization using isostructural substrates. For example, the relative stabilities of the columbite polymorph for VO2 and RuO2 are similar to those of TiO2 and SnO2, the latter two of which have been previously stabilized as epitaxial films.

  15. Turner syndrome and genetic polymorphism: a systematic review

    PubMed Central

    de Marqui, Alessandra Bernadete Trovó

    2015-01-01

    Objective: To present the main results of the literature on genetic polymorphisms in Turner syndrome and their association with the clinical signs and the etiology of this chromosomal disorder. Data sources: The review was conducted in the PubMed database without any time limit, using the terms Turner syndrome and genetic polymorphism. A total of 116 articles were found, and based on the established inclusion and exclusion criteria 17 were selected for the review. Data synthesis: The polymorphisms investigated in patients with Turner syndrome were associated with growth deficit, causing short stature, low bone mineral density, autoimmunity and cardiac abnormalities, which are frequently found in patients with Turner syndrome. The role of single nucleotide polymorphisms in the etiology of Turner syndrome, i.e., in chromosomal nondisjunction, was also confirmed. Conclusions: Genetic polymorphisms appear to be associated with Turner syndrome. However, in view of the small number of published studies and their contradictory findings, further studies in different populations are needed in order to clarify the role of genetic variants in the clinical signs and etiology of the Turner syndrome. PMID:25765448

  16. Estrogen Receptor Polymorphisms and the Vascular Effects of Hormone Therapy

    PubMed Central

    Rossouw, Jacques; Bray, Paul; Liu, Jingmin; Kooperberg, Charles; Hsia, Judith; Lewis, Cora; Cushman, Mary; Bonds, Denise; Hendrix, Susan; Papanicolaou, George; Howard, Tim; Herrington, David

    2010-01-01

    Objective To test whether estrogen receptor polymorphisms modify the effects of postmenopausal hormone therapy on biomarkers and on risk of coronary heart disease events, stroke, or venous thrombo-embolism. Methods and Results The design was a nested case-control study in the Women’s Health Initiative trials of postmenopausal hormone therapy. The study included all cases in the first 4 years: coronary heart disease, 359; stroke, 248; venous thrombo-embolism, 217). Six estrogen receptor-αand one estrogen receptor-β polymorphisms were genotyped; 8 biomarkers known to be affected by hormone therapy were measured at baseline and one year after randomization. The polymorphisms were not associated with risk of vascular events, and did not modify the increased risks of coronary heart disease, stroke, or venous thrombo-embolism due to hormone therapy. However, a reduced response of plasmin-antiplasmin (PAP) to hormone therapy was noted for ESR1 IVS1-354 (interaction P<0.0001, corrected for multiple comparisons P=0.014) and ESR1 IVS1-1415 (interaction P<0.0001, corrected P= 0.014). Conclusions Estrogen receptor polymorphisms reduce the effect of postmenopausal hormone therapy on PAP, a marker of coagulation and fibrinolysis. However screening for ER polymorphisms to identify women at less risk of adverse cardiovascular outcomes is not likely to be useful for making HT treatment decisions. PMID:21106950

  17. The associations between MDM4 gene polymorphisms and cancer risk

    PubMed Central

    Xu, Xiao-Liang; Yao, Guo-Liang; Liu, Rui-Ping; Zhao, Hui

    2016-01-01

    Considerable studies have investigated the associations between MDM4 gene polymorphisms and cancer risk recently, but with contradictory results. The aim of this meta-analysis was to evaluate the associations between MDM4 gene polymorphisms and cancer risk. Relevant studies were identified by a systematic search of PubMed, Embase, and CNKI databases. Crude odds ratios (ORs) and 95% confidence intervals (CIs) were used to describe the strength of the associations. Fifty-six studies published in 11 publications involving 18,910 cases and 51,609 controls were included in this meta-analysis. Five MDM4 gene polymorphisms were evaluated: rs4245739, rs1563828, rs11801299, rs10900598, and rs1380576. Our analyses suggested that the rs4245739 polymorphism was significantly associated with overall cancer risk. Furthermore, stratification analyses of ethnicity indicated that rs4245739 decreased the risk of cancer among the Asian population, and stratification analyses of smoking status indicated that rs4245739 decreased the risk of cancer among nonsmokers. However, stratification analyses of cancer type and sex suggested that rs4245739 was not related to cancer risk. There were no associations of rs1563828, rs11801299, rs10900598, or rs1380576 with overall cancer risk. In conclusion, our analyses indicated that rs4245739 polymorphism in the MDM4 gene may play an important role in the etiology of cancer. PMID:27742919

  18. Immune sensitization against epidermal antigens in polymorphous light eruption

    SciTech Connect

    Gonzalez-Amaro, R.; Baranda, L.; Salazar-Gonzalez, J.F.; Abud-Mendoza, C.; Moncada, B. )

    1991-01-01

    To get further insight into the pathogenesis of polymorphous light eruption, we studied nine patients with polymorphous light eruption and six healthy persons. Two skin biopsy specimens were obtained from each person, one from previously ultraviolet light-irradiated skin and another one from unirradiated skin. An epidermal cell suspension, skin homogenate, or both were prepared from each specimen. Autologous cultures were made with peripheral blood mononuclear cells combined with irradiated or unirradiated skin homogenate and peripheral blood mononuclear cells combined with irradiated or unirradiated epidermal cell suspension. Cell proliferation was assessed by 3H-thymidine incorporation assay. The response of peripheral blood mononuclear cells to unirradiated epidermal cells or unirradiated skin homogenate was similar in both patients and controls. However, peripheral blood mononuclear cells from patients with polymorphous light eruption showed a significantly increased proliferative response to both irradiated epidermal cells and irradiated skin homogenate. Our results indicate that ultraviolet light increases the stimulatory capability of polymorphous light eruption epidermal cells in a unidirectional mixed culture with autologous peripheral blood mononuclear cells. This suggests that an immune sensitization against autologous ultraviolet light-modified skin antigens occurs in polymorphous light eruption.

  19. Micro-evolution in grasshoppers mediated by polymorphic Robertsonian translocations.

    PubMed

    Colombo, Pablo C

    2013-01-01

    This review focuses on grasshoppers that are polymorphic for Robertsonian translocations because in these organisms the clarity of meiotic figures allows the study of both chiasma distribution and the orientation of trivalents and multivalents in metaphase I. Only five species of such grasshoppers were found in the literature, and all of them were from the New World: Oedaleonotus enigma (Scudder) (Orthoptera: Acrididae), Leptysma argentina Bruner, Dichroplus pratensis Bruner, Sinipta dalmani Stål, and Cornops aquaticum Bruner. A general feature of these species (except O. enigma) is that fusion carriers suffer a marked reduction of proximal and interstitial (with respect to the centromere) chiasma frequency; this fact, along with the reduction in the number of linkage groups with the consequent loss of independent segregation, produces a marked decrease of recombination in fusion carriers. This reduction in recombination has led to the conclusion that Robertsonian polymorphic grasshopper species share some properties with inversion polymorphic species of Drosophila, such as the central-marginal pattern (marginal populations are monomorphic, central populations are highly polymorphic). This pattern might be present in D. pratensis, which is certainly the most complex Robertsonian polymorphism system in the present study. However, L. argentina and C. aquaticum do not display this pattern. This issue is open to further research. Since C. aquaticum is soon to be released in South Africa as a biological control, the latitudinal pattern found in South America may repeat there. This experiment's outcome is open and deserves to be followed.

  20. Micro-Evolution in Grasshoppers Mediated by Polymorphic Robertsonian Translocations

    PubMed Central

    Colombo, Pablo C.

    2013-01-01

    This review focuses on grasshoppers that are polymorphic for Robertsonian translocations because in these organisms the clarity of meiotic figures allows the study of both chiasma distribution and the orientation of trivalents and multivalents in metaphase I. Only five species of such grasshoppers were found in the literature, and all of them were from the New World: Oedaleonotus enigma (Scudder) (Orthoptera: Acrididae), Leptysma argentina Bruner, Dichroplus pratensis Bruner, Sinipta dalmani Stål, and Cornops aquaticum Bruner. A general feature of these species (except O. enigma) is that fusion carriers suffer a marked reduction of proximal and interstitial (with respect to the centromere) chiasma frequency; this fact, along with the reduction in the number of linkage groups with the consequent loss of independent segregation, produces a marked decrease of recombination in fusion carriers. This reduction in recombination has led to the conclusion that Robertsonian polymorphic grasshopper species share some properties with inversion polymorphic species of Drosophila, such as the central-marginal pattern (marginal populations are monomorphic, central populations are highly polymorphic). This pattern might be present in D. pratensis, which is certainly the most complex Robertsonian polymorphism system in the present study. However, L. argentina and C. aquaticum do not display this pattern. This issue is open to further research. Since C. aquaticum is soon to be released in South Africa as a biological control, the latitudinal pattern found in South America may repeat there. This experiment's outcome is open and deserves to be followed. PMID:23909914

  1. Geographic variation in animal colour polymorphisms and its role in speciation.

    PubMed

    McLean, Claire A; Stuart-Fox, Devi

    2014-11-01

    Polymorphic species, in which multiple variants coexist within a population, are often used as model systems in evolutionary biology. Recent research has been dominated by the hypothesis that polymorphism can be a precursor to speciation. To date, the majority of research regarding polymorphism and speciation has focused on whether polymorphism is maintained within a population or whether morphs within populations may diverge to form separate species (sympatric speciation); however, the geographical context of speciation in polymorphic systems is likely to be both diverse and complex. In this review, we draw attention to the geographic variation in morph composition and frequencies that characterises many, if not most polymorphic species. Recent theoretical and empirical developments suggest that such variation in the number, type and frequency of morphs present among populations can increase the probability of speciation. Thus, the geographical context of a polymorphism requires a greater research focus. Here, we review the prevalence, causes and evolutionary consequences of geographic variation in polymorphism in colour-polymorphic animal species. The prevalence and nature of geographic variation in polymorphism suggests that polymorphism may be a precursor to and facilitate speciation more commonly than appreciated previously. We argue that a better understanding of the processes generating geographic variation in polymorphism is vital to understanding how polymorphism can promote speciation.

  2. The Y Alu polymorphism in southern African populations and its relationship to other Y-specific polymorphisms

    SciTech Connect

    Spurdle, A.B.; Jenkins, T. ); Hammer, M.F. )

    1994-02-01

    Y-linked polymorphisms were studied in a number of African populations. The frequency of the alleles of a Y-specific Alu insertion polymorphism, termed the [open quotes]Y Alu polymorphism,[close quotes] was determined in 889 individuals from 23 different African population groups. A trend in frequency was observed, with the insert largely absent in Caucasoid populations, at intermediate frequency in the Khoisan, and at high frequency in Negroids. The insert predates diversification of Homo sapiens, since it occurs in all groups. The Alu insertion is believed to result from a unique mutation event, and comparisons between this and several other Y-linked polymorphisms were carried out in an attempt to validate their usefulness in population and evolutionary studies. The p21A1/Taql and pDP31/EcoRI polymorphisms and 49a/TaqI alleles were all shown to have arisen on more than one occasion, and evidence exists for a preraciation crossover event between the Y-linked pseudoautosomal XY275 locus and the Y chromosome pseudoautosomal boundary. 33 refs., 4 figs., 5 tabs.

  3. High-pressure polymorphism of acetylsalicylic acid (aspirin): Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Crowell, Ethan L.; Dreger, Zbigniew A.; Gupta, Yogendra M.

    2015-02-01

    Micro-Raman spectroscopy was used to elucidate the high-pressure polymorphic behavior of acetylsalicylic acid (ASA), an important pharmaceutical compound known as aspirin. Using a diamond anvil cell (DAC), single crystals of the two polymorphic phases of aspirin existing at ambient conditions (ASA-I and ASA-II) were compressed to 10 GPa. We found that ASA-I does not transform to ASA-II, but instead transforms to a new phase (ASA-III) above ∼2 GPa. It is demonstrated that this transformation primarily introduces structural changes in the bonding and arrangement of the acetyl groups and is reversible upon the release of pressure. In contrast, a less dense ASA-II shows no transition in the pressure range studied, though it appears to exhibit a disordered structure above 7 GPa. Our results suggest that ASA-III is the most stable polymorph of aspirin at high pressures.

  4. Compositions and methods for detecting single nucleotide polymorphisms

    SciTech Connect

    Yeh, Hsin-Chih; Werner, James; Martinez, Jennifer S.

    2016-11-22

    Described herein are nucleic acid based probes and methods for discriminating and detecting single nucleotide variants in nucleic acid molecules (e.g., DNA). The methods include use of a pair of probes can be used to detect and identify polymorphisms, for example single nucleotide polymorphism in DNA. The pair of probes emit a different fluorescent wavelength of light depending on the association and alignment of the probes when hybridized to a target nucleic acid molecule. Each pair of probes is capable of discriminating at least two different nucleic acid molecules that differ by at least a single nucleotide difference. The methods can probes can be used, for example, for detection of DNA polymorphisms that are indicative of a particular disease or condition.

  5. Hepatitis-related hepatocellular carcinoma: Insights into cytokine gene polymorphisms

    PubMed Central

    Dondeti, Mahmoud Fathy; El-Maadawy, Eman Anwar; Talaat, Roba Mohamed

    2016-01-01

    Hepatocellular carcinoma (HCC) is a primary liver cancer, which is one of the most prevalent cancers among humans. Many factors are involved in the liver carcinogenesis as lifestyle and environmental factors. Hepatitis virus infections are now recognized as the chief etiology of HCC; however, the precise mechanism is still enigmatic till now. The inflammation triggered by the cytokine-mediated immune response, was reported to be the closest factor of HCC development. Cytokines are immunoregulatory proteins produced by immune cells, functioning as orchestrators of the immune response. Genes of cytokines and their receptors are known to be polymorphic, which give rise to variations in their genes. These variations have a great impact on the expression levels of the secreted cytokines. Therefore, cytokine gene polymorphisms are involved in the molecular mechanisms of several diseases. This piece of work aims to shed much light on the role of cytokine gene polymorphisms as genetic host factor in hepatitis related HCC. PMID:27570418

  6. The epidemiology of Plasmodium vivax circumsporozoite protein polymorphs in Thailand.

    PubMed

    Suwanabun, N; Sattabongkot, J; Wirtz, R A; Rosenberg, R

    1994-04-01

    Enzyme-linked immunosorbent assays (ELISAs) highly specific for the characteristic repeat units of the circumsporozoite proteins of the VK 247 and VK 210 polymorphs of Plasmodium vivax were used to test sporozoites produced by feeding mosquitoes on 1,711 human volunteers presenting at four locations in Thailand over five years. There was no evidence for the existence of any polymorph other than the two already described. Based on the ELISAs, the overall prevalence of the VK 247 type was 29.5%, including those found mixed with VK 210. Relative proportions of VK 210 and VK 247 differed between collection sites. At all places, the ratio of VK 210 to VK 247 was significantly higher at the end of the nontransmission season than it was later during the annual monsoon, suggesting that there may be intrinsic biological differences between the polymorphs that affect their survival.

  7. Catecholaminergic polymorphic ventricular tachycardia: a rare cause of recurrent syncope

    PubMed Central

    Azevedo, Ana Isabel; Dias, Adelaide; Teixeira, Madalena; Gama Ribeiro, Vasco

    2015-01-01

    Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia characterized by adrenergically induced polymorphic or bidirectional ventricular tachycardia (VT). Although a rare disease, its recognition is important because of its high mortality rate when left untreated. We report an index case of a 32-year-old woman who presented with recurrent syncope. The diagnosis was confirmed by exercise-induced polymorphic ventricular premature beats and episodes of non-sustained VT, in the absence of structural heart abnormalities. She remained event free with beta-blocker therapy. CPVT is a potentially life-threatening disease and should be considered in the case of recurrent syncope, in young individuals. Diagnosis is based on clinical history and exercise testing, which is the gold standard. Therapy is mandatory in all diagnosed individuals. Exercise testing in first-degree relatives is recommended, even in the case of a mutation-negative index patient. PMID:26512332

  8. DNA polymorphism analysis of hereditary multiple exostoses in horses.

    PubMed

    Li, J K; Moloney, B K; Shupe, J L; Gardner, E J; Leone, N C; Elsner, Y

    1989-06-01

    Genomic DNA polymorphisms obtained by restriction fragment-length polymorphism from healthy horses and horses with hereditary multiple exostoses were analyzed. These DNA were digested by 12 restriction enzymes and were hybridized against 6 isotopically labeled oncogene probes. Hybridization was not detected with the viral oncogene, v-ras, which indicated this oncogene was absent in the equine genome. Oncogenes (c-raf-1, c-fes, c-myb, c-myc, and c-sis) were present and had similar hybridization patterns and signal intensities in DNA from healthy horses and horses with hereditary multiple exostoses. Unique and distinct restriction fragment-length polymorphisms were detected with the c-raf-1 probe only in BamHI- and PstI-digested equine DNA.

  9. [Pathogenic mutation or polymorphism? (How to find criteria)].

    PubMed

    Kochański, Andrzej

    2006-01-01

    The classification of amino-acid substitutions into pathogenic mutations and harmless polymorphisms should be revised. In the recent years it was shown that some amino-acid substitutions considered as pathogenic mutations were polymorphisms. Similarly, some 'harmless' polymorphisms have been shown to be pathogenic mutations. Functional analysis considered as a good method to estimate the pathogenic nature of mutations is also limited. The selection of DNA samples for the control group is also difficult. Due to the molecular mechanism mediated by recently discovered exonic splicing enhancers and silencers (ESE and ESS) it is hard to predict a pathogenic effect of some mutations. In addition, the phenotype variability observed between unrelated patients harboring the same mutation may reflect the effects of modifying genes as well as the lack of association between mutation and "its" phenotype. The aim of this study is to describe the problem of the pathogenic effect of mutations.

  10. Collagen polymorphism in idiopathic chronic pulmonary fibrosis.

    PubMed Central

    Seyer, J M; Hutcheson, E T; Kang, A H

    1976-01-01

    diminished, ranging from 12 to 24% in different patients. These results indicate that an alteration in tissue collagen polymorphism as well as subtle variations in the collagen structure accompany the fibrotic process in the diseased state, and suggest that these alterations may have possible pathogenetic implications. PMID:777026

  11. Emergence of polymorphic mating strategies in robot colonies.

    PubMed

    Elfwing, Stefan; Doya, Kenji

    2014-01-01

    Polymorphism has fascinated evolutionary biologists since the time of Darwin. Biologists have observed discrete alternative mating strategies in many different species. In this study, we demonstrate that polymorphic mating strategies can emerge in a colony of hermaphrodite robots. We used a survival and reproduction task where the robots maintained their energy levels by capturing energy sources and physically exchanged genotypes for the reproduction of offspring. The reproductive success was dependent on the individuals' energy levels, which created a natural trade-off between the time invested in maintaining a high energy level and the time invested in attracting mating partners. We performed experiments in environments with different density of energy sources and observed a variety in the mating behavior when a robot could see both an energy source and a potential mating partner. The individuals could be classified into two phenotypes: 1) forager, who always chooses to capture energy sources, and 2) tracker, who keeps track of potential mating partners if its energy level is above a threshold. In four out of the seven highest fitness populations in different environments, we found subpopulations with distinct differences in genotype and in behavioral phenotype. We analyzed the fitnesses of the foragers and the trackers by sampling them from each subpopulation and mixing with different ratios in a population. The fitness curves for the two subpopulations crossed at about 25% of foragers in the population, showing the evolutionary stability of the polymorphism. In one of those polymorphic populations, the trackers were further split into two subpopulations: (strong trackers) and (weak trackers). Our analyses show that the population consisting of three phenotypes also constituted several stable polymorphic evolutionarily stable states. To our knowledge, our study is the first to demonstrate the emergence of polymorphic evolutionarily stable strategies within a

  12. Emergence of Polymorphic Mating Strategies in Robot Colonies

    PubMed Central

    Elfwing, Stefan; Doya, Kenji

    2014-01-01

    Polymorphism has fascinated evolutionary biologists since the time of Darwin. Biologists have observed discrete alternative mating strategies in many different species. In this study, we demonstrate that polymorphic mating strategies can emerge in a colony of hermaphrodite robots. We used a survival and reproduction task where the robots maintained their energy levels by capturing energy sources and physically exchanged genotypes for the reproduction of offspring. The reproductive success was dependent on the individuals' energy levels, which created a natural trade-off between the time invested in maintaining a high energy level and the time invested in attracting mating partners. We performed experiments in environments with different density of energy sources and observed a variety in the mating behavior when a robot could see both an energy source and a potential mating partner. The individuals could be classified into two phenotypes: 1) forager, who always chooses to capture energy sources, and 2) tracker, who keeps track of potential mating partners if its energy level is above a threshold. In four out of the seven highest fitness populations in different environments, we found subpopulations with distinct differences in genotype and in behavioral phenotype. We analyzed the fitnesses of the foragers and the trackers by sampling them from each subpopulation and mixing with different ratios in a population. The fitness curves for the two subpopulations crossed at about 25% of foragers in the population, showing the evolutionary stability of the polymorphism. In one of those polymorphic populations, the trackers were further split into two subpopulations: (strong trackers) and (weak trackers). Our analyses show that the population consisting of three phenotypes also constituted several stable polymorphic evolutionarily stable states. To our knowledge, our study is the first to demonstrate the emergence of polymorphic evolutionarily stable strategies within a

  13. Polymorphism of the DNA Base Excision Repair Genes in Keratoconus

    PubMed Central

    Wojcik, Katarzyna A.; Synowiec, Ewelina; Sobierajczyk, Katarzyna; Izdebska, Justyna; Blasiak, Janusz; Szaflik, Jerzy; Szaflik, Jacek P.

    2014-01-01

    Keratoconus (KC) is a degenerative corneal disorder for which the exact pathogenesis is not yet known. Oxidative stress is reported to be associated with this disease. The stress may damage corneal biomolecules, including DNA, and such damage is primarily removed by base excision repair (BER). Variation in genes encoding BER components may influence the effectiveness of corneal cells to cope with oxidative stress. In the present work we genotyped 5 polymorphisms of 4 BER genes in 284 patients and 353 controls. The A/A genotype of the c.–1370T>A polymorphism of the DNA polymerase γ (POLG) gene was associated with increased occurrence of KC, while the A/T genotype was associated with decreased occurrence of KC. The A/G genotype and the A allele of the c.1196A>G polymorphism of the X-ray repair cross-complementing group 1 (XRCC1) were associated with increased, and the G/G genotype and the G allele, with decreased KC occurrence. Also, the C/T and T as well as C/C genotypes and alleles of the c.580C>T polymorphism of the same gene displayed relationship with KC occurrence. Neither the g.46438521G>C polymorphism of the Nei endonuclease VIII-like 1 (NEIL1) nor the c.2285T>C polymorphism of the poly(ADP-ribose) polymerase-1 (PARP-1) was associated with KC. In conclusion, the variability of the XRCC1 and POLG genes may play a role in KC pathogenesis and determine the risk of this disease. PMID:25356504

  14. A new polymorph of triphenylmethylamine: the effect of hydrogen bonding.

    PubMed

    Khrustalev, Victor N; Borisova, Irina V; Zemlyansky, Nikolai N; Antipin, M Yu

    2009-02-01

    Crystallization of the hexane reaction mixture after treatment of LiGe(OCH(2)CH(2)NMe(2))(3) with Ph(3)CN(3) gives rise to a new triclinic (space group P\\overline{1}) polymorph of triphenylmethylamine, C(19)H(17)N, (I), containing dimers formed by N-H...N hydrogen bonds, whereas the structure of the known orthorhombic (space group P2(1)2(1)2(1)) polymorph of this compound, (II), consists of isolated molecules. While the dimers in (I) lie across crystallographic inversion centres, the molecules are not truly related by them. The centrosymmetric structure is due to the statistical disordering of the amino H atoms participating in the N-H...N hydrogen-bonding interactions, and thus the inversion centre is superpositional. The conformations and geometric parameters of the molecules in (I) and (II) are very similar. It was found that the polarity of the solvent does not affect the capability of triphenylmethylamine to crystallize in the different polymorphic modifications. The orthorhombic polymorph, (II), is more thermodynamically stable under normal conditions than the triclinic polymorph, (I). The experimental data indicate the absence of a phase transition in the temperature interval 120-293 K. The densities of (I) (1.235 Mg m(-3)) and (II) (1.231 Mg m(-3)) at 120 K are practically equal. It would seem that either the kinetic factors or the effects of the other products of the reaction facilitating the hydrogen-bonded dimerization of triphenylmethylamine molecules are the determining factor for the isolation of the triclinic polymorph (I) of triphenylmethylamine.

  15. Cytokine production in patients with cirrhosis and TLR4 polymorphisms

    PubMed Central

    Nieto, Juan Camilo; Sánchez, Elisabet; Román, Eva; Vidal, Silvia; Oliva, Laia; Guarner-Argente, Carlos; Poca, Maria; Torras, Xavier; Juárez, Cándido; Guarner, Carlos; Soriano, German

    2014-01-01

    AIM: To analyze the cytokine production by peripheral blood cells from cirrhotic patients with and without TLR4 D299G and/or T399I polymorphisms. METHODS: The study included nine patients with cirrhosis and TLR4 D299G and/or T399I polymorphisms, and 10 wild-type patients matched for age, sex and degree of liver failure. TLR4 polymorphisms were determined by sequence-based genotyping. Cytokine production by peripheral blood cells was assessed spontaneously and also after lipopolysaccharide (LPS) and lipoteichoic acid (LTA) stimulation. RESULTS: Patients with TLR4 polymorphisms had a higher incidence of previous hepatic encephalopathy than wild-type patients (78% vs 20%, P = 0.02). Spontaneous production of interleukin (IL)-6 and IL-10 was lower in patients with TLR4 polymorphisms than in wild-type patients [IL-6: 888.7 (172.0-2119.3) pg/mL vs 5540.4 (1159.2-26053.9) pg/mL, P < 0.001; IL-10: 28.7 (6.5-177.1) pg/mL vs 117.8 (6.5-318.1) pg/mL, P = 0.02]. However, the production of tumor necrosis factor-α, IL-6 and IL-10 after LPS and LTA stimulation was similar in the two groups. CONCLUSION: TLR4 polymorphisms were associated with a distinctive pattern of cytokine production in cirrhotic patients, suggesting that they play a role in the development of cirrhosis complications. PMID:25516666

  16. The association between IGF-1 polymorphisms and high myopia

    PubMed Central

    Zhang, Xiaoyu; Zhou, Xingtao; Qu, Xinhua

    2015-01-01

    Background: The potential association between IGF-1 polymorphisms and high myopia has been investigated in previous studies, but the actual relationship remains controversial. Accordingly, we conducted a meta-analysisincludingcase-control and cohort studies to assess the existing relationship between high myopia and IGF-1 polymorphisms. We searched MEDLINE, EMBASE, and OVID. Odds ratios (OR) with 95% confidence intervals (CI) were derived for single-nucleotide polymorphisms (SNPs) involved in the studies obtained from the retrospective database search. Analyses of heterogeneity, sensitivity, and publication bias were also conducted. The findings from this meta-analysis were based on approximately 2,187 high myopia cases and 1,183 controls, and were used to assess the association between three IGF-1 genetic polymorphisms (rs6214, rs12423791, and rs5742632) and high myopia risks. We investigated the association of the IGF-1 gene SNP rs6214, but no statistical association was observed in the resulting odds ratios (OR) in the allelic (OR = 1.06, 95% CI = 0.89-1.25), dominant (OR = 1.07, 95% CI = 0.90-1.27), or recessive models (OR = 1.06, 95% CI = 0.89-1.26), or in the homozygote (OR = 1.12, 95% CI = 0.91-1.38) and heterozygote comparisons (OR = 1.06, 95% CI = 0.88-1.27). Simultaneously, two other selected SNPs, rs12423791 and rs5742632, were also studied, but similarly, no statistical association existed between these polymorphisms and the risk of high myopia. In conclusions, no statistical association between IGF-1 polymorphisms (rs6214, rs12423791, and rs5742632) and the risk of high myopia was observed following the reported meta-analysis. PMID:26309715

  17. Endothelin-1 Pathway Polymorphisms and Outcomes in Pulmonary Arterial Hypertension

    PubMed Central

    Gomberg-Maitland, Mardi; Demarco, Teresa; Frost, Adaani E.; Torbicki, Adam; Langleben, David; Pulido, Tomas; Correa-Jaque, Priscilla; Passineau, Michael J.; Wiener, Howard W.; Tamari, Mayumi; Hirota, Tomomitsu; Kubo, Michiaki; Tiwari, Hemant K.

    2015-01-01

    Rationale: Pulmonary arterial hypertension (PAH) is a progressive fatal disease. Variable response and tolerability to PAH therapeutics suggests that genetic differences may influence outcomes. The endothelin pathway is central to pulmonary vascular function, and several polymorphisms and/or mutations in the genes coding for endothelin (ET)-1 and its receptors correlate with the clinical manifestations of other diseases. Objectives: To examine the interaction of ET-1 pathway polymorphisms and treatment responses of patients with PAH treated with ET receptor antagonists (ERAs). Methods: A total of 1,198 patients with PAH were prospectively enrolled from 45 U.S. and Canadian pulmonary hypertension centers or retrospectively from global sites participating in the STRIDE (Sitaxsentan To Relieve Impaired Exercise) trials. Comprehensive objective measures including a 6-minute-walk test, Borg dyspnea score, functional class, and laboratory studies were completed at baseline, before the initiation of ERAs, and repeated serially. Single-nucleotide polymorphisms from ET-1 pathway candidate genes were selected from a completed genome-wide association study performed on the study cohort. Measurements and Main Results: Patient efficacy outcomes were analyzed for a relationship between ET-1 pathway polymorphisms and clinical efficacy using predefined, composite positive and negative outcome measures in 715 European descent samples. A single-nucleotide polymorphism (rs11157866) in the G-protein alpha and gamma subunits gene was significantly associated, accounting for multiple testing, with a combined improvement in functional class and 6-minute-walk distance at 12 and 18 months and marginally significant at 24 months. Conclusions: ET-1 pathway associated polymorphisms may influence the clinical efficacy of ERA therapy for PAH. Further prospective studies are needed. PMID:26252367

  18. Aspirin-induced peptic ulcer and genetic polymorphisms.

    PubMed

    Shiotani, Akiko; Sakakibara, Takashi; Nomura, Maki; Yamanaka, Yoshiyuki; Nishi, Ryuji; Imamura, Hiroshi; Tarumi, Ken-ichi; Kamada, Tomoari; Hata, Jiro; Haruma, Ken

    2010-05-01

    There are a few studies of the association between genetic polymorphisms and the risks of acetylsalicylic acid (aspirin)-induced ulcer or its complications. Two single nucleotide polymorphisms (SNP) of cyclooxygenase-1 (COX-1), A-842G and C50T, exhibited increased sensitivity to aspirin and had lower prostaglandin synthesis capacity, lacking statistical significance in the association with bleeding peptic ulcer. A recent Japanese study indicated that the number of COX-1-1676T alleles was a significant risk factor for peptic ulcer in users of non-steroidal anti-inflammatory drugs (NSAIDs). There are some genetic polymorphisms for aspirin resistance, such as platelet membrane glycoproteins, thromboxane A2 (TXA2) receptor, platelet activating factor acetylhydrolase and coagulation factor XIII; however, data on the frequency of gastrointestinal (GI) events in these variants are lacking. Carrying the CYP2C9 variants is reported a significantly increased risk of non-aspirin NSAID-related GI bleeding. The polymorphisms of interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) have been associated with development of peptic ulcer or gastric cancer. In a recent investigation, carriage of the IL-1beta-511 T allele was significantly associated with peptic ulcer among low-dose aspirin users. Hypoacidity in corpus gastritis related to polymorphisms of pro-inflammatory cytokines seems to reduce NSAIDs or aspirin-related injury. Data on which polymorphisms are significant risk factors for GI events in aspirin users are still lacking and further large-scale clinical studies are required.

  19. Polymorphic phases of sp3-hybridized carbon under cold compression.

    PubMed

    Zhou, Rulong; Zeng, Xiao Cheng

    2012-05-02

    It is well established that graphite can be transformed into superhard carbons under cold compression (Mao et al. Science 2003, 302, 425). However, structure of the superhard carbon is yet to be determined experimentally. We have performed an extensive structural search for the high-pressure crystalline phases of carbon using the evolutionary algorithm. Nine low-energy polymorphic structures of sp(3)-hybridized carbon result from the unbiased search. These new polymorphic carbon structures together with previously reported low-energy sp(3)-hybridized carbon structures (e.g., M-carbon, W-carbon, and Cco-C(8) or Z-carbon) can be classified into three groups on the basis of different ways of stacking two (or more) out of five (A-E) types of buckled graphene layers. Such a classification scheme points out a simple way to construct a variety of sp(3)-hybridized carbon allotropes via stacking buckled graphene layers in different combinations of the A-E types by design. Density-functional theory calculations indicate that, among the nine low-energy crystalline structures, seven are energetically more favorable than the previously reported most stable crystalline structure (i.e., Cco-C(8) or Z-carbon) in the pressure range 0-25 GPa. Moreover, several newly predicted polymorphic sp(3)-hybridized carbon structures possess elastic moduli and hardness close to those of the cubic diamond. In particular, Z-carbon-4 possesses the highest hardness (93.4) among all the low-energy sp(3)-hybridized carbon structures predicted today. The calculated electronic structures suggest that most polymorphic carbon structures are optically transparent. The simulated X-ray diffraction (XRD) spectra of a few polymorphic structures are in good agreement with the experimental spectrum, suggesting that samples from the cold-compressed graphite experiments may consist of multiple polymorphic phases of sp(3)-hybridized carbon.

  20. Catalog of microRNA seed polymorphisms in vertebrates.

    PubMed

    Zorc, Minja; Skok, Dasa Jevsinek; Godnic, Irena; Calin, George Adrian; Horvat, Simon; Jiang, Zhihua; Dovc, Peter; Kunej, Tanja

    2012-01-01

    MicroRNAs (miRNAs) are a class of non-coding RNA that plays an important role in posttranscriptional regulation of mRNA. Evidence has shown that miRNA gene variability might interfere with its function resulting in phenotypic variation and disease susceptibility. A major role in miRNA target recognition is ascribed to complementarity with the miRNA seed region that can be affected by polymorphisms. In the present study, we developed an online tool for the detection of miRNA polymorphisms (miRNA SNiPer) in vertebrates (http://www.integratomics-time.com/miRNA-SNiPer) and generated a catalog of miRNA seed region polymorphisms (miR-seed-SNPs) consisting of 149 SNPs in six species. Although a majority of detected polymorphisms were due to point mutations, two consecutive nucleotide substitutions (double nucleotide polymorphisms, DNPs) were also identified in nine miRNAs. We determined that miR-SNPs are frequently located within the quantitative trait loci (QTL), chromosome fragile sites, and cancer susceptibility loci, indicating their potential role in the genetic control of various complex traits. To test this further, we performed an association analysis between the mmu-miR-717 seed SNP rs30372501, which is polymorphic in a large number of standard inbred strains, and all phenotypic traits in these strains deposited in the Mouse Phenome Database. Analysis showed a significant association between the mmu-miR-717 seed SNP and a diverse array of traits including behavior, blood-clinical chemistry, body weight size and growth, and immune system suggesting that seed SNPs can indeed have major pleiotropic effects. The bioinformatics analyses, data and tools developed in the present study can serve researchers as a starting point in testing more targeted hypotheses and designing experiments using optimal species or strains for further mechanistic studies.

  1. Combined crystal structure prediction and high-pressure crystallization in rational pharmaceutical polymorph screening

    NASA Astrophysics Data System (ADS)

    Neumann, M. A.; van de Streek, J.; Fabbiani, F. P. A.; Hidber, P.; Grassmann, O.

    2015-07-01

    Organic molecules, such as pharmaceuticals, agro-chemicals and pigments, frequently form several crystal polymorphs with different physicochemical properties. Finding polymorphs has long been a purely experimental game of trial-and-error. Here we utilize in silico polymorph screening in combination with rationally planned crystallization experiments to study the polymorphism of the pharmaceutical compound Dalcetrapib, with 10 torsional degrees of freedom one of the most flexible molecules ever studied computationally. The experimental crystal polymorphs are found at the bottom of the calculated lattice energy landscape, and two predicted structures are identified as candidates for a missing, thermodynamically more stable polymorph. Pressure-dependent stability calculations suggested high pressure as a means to bring these polymorphs into existence. Subsequently, one of them could indeed be crystallized in the 0.02 to 0.50 GPa pressure range and was found to be metastable at ambient pressure, effectively derisking the appearance of a more stable polymorph during late-stage development of Dalcetrapib.

  2. Asymmetric Dispersal Can Maintain Larval Polymorphism: A Model Motivated by Streblospio benedicti

    PubMed Central

    Zakas, Christina; Hall, David W.

    2012-01-01

    Polymorphism in traits affecting dispersal occurs in a diverse variety of taxa. Typically, the maintenance of a dispersal polymorphism is attributed to environmental heterogeneity where parental bet-hedging can be favored. There are, however, examples of dispersal polymorphisms that occur across similar environments. For example, the estuarine polychaete Streblospio benedicti has a highly heritable offspring dimorphism that affects larval dispersal potential. We use analytical models of dispersal to determine the conditions necessary for a stable dispersal polymorphism to exist. We show that in asexual haploids, sexual haploids, and in sexual diploids in the absence of overdominance, asymmetric dispersal is required in order to maintain a dispersal polymorphism when patches do not vary in intrinsic quality. Our study adds an additional factor, dispersal asymmetry, to the short list of mechanisms that can maintain polymorphism in nature. The region of the parameter space in which polymorphism is possible is limited, suggesting why dispersal polymorphisms within species are rare. PMID:22576818

  3. Genomic and genotyping characterization of haplotype-based polymorphic microsatellites in Prunus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Efficient utilization of microsatellites in genetic studies remains impeded largely due to the unknown status of their primer reliability, chromosomal location, and allele polymorphism. Discovery and characterization of microsatellite polymorphisms in a taxon will disclose the unknowns and gain new ...

  4. 4,4'-Dimethoxy-benzophenone: a triclinic polymorph.

    PubMed

    Fun, Hoong-Kun; Franklin, S; Jebas, Samuel Robinson; Balasubramanian, T

    2008-06-13

    The title compound, C(15)H(14)O(3), has been found to crystallize as a new triclinic polymorph. The asymmetric unit of the present structure, as in the previously reported monoclinic structure [Norment & Karle (1962 ▶). Acta Cryst. 15, 873-878], contains two independent mol-ecules, which differ slightly in the orientations of the two benzene rings. The crystal packing of the triclinic polymorph is stabilized by inter-molecular C-H⋯O hydrogen bonds and C-H⋯π inter-actions.

  5. Time-resolved FRET for single-nucleotide polymorphism genotyping

    NASA Astrophysics Data System (ADS)

    Andreoni, Alessandra; Nardo, Luca; Bondani, Maria

    2009-05-01

    By tens-of-picosecond resolved fluorescence detection (TCSPC, time-correlated single-photon counting) we study Förster resonance energy transfer between a donor and a black-hole-quencher acceptor bound at the 5'- and 3'-positions of a synthetic DNA oligonucleotide. This dual labelled oligonucleotide is annealed with either the complementary sequence or with sequences that mimic single-nucleotide polymorphic gene sequences: they differ in one nucleotide at positions near either the ends or the center of the oligonucleotide. We find donor fluorescence decay times whose values are definitely distinct and discuss the feasibility of single nucleotide polymorphism genotyping by this method.

  6. Kappa-casein polymorphisms among cattle breeds and bison herds

    USGS Publications Warehouse

    Cronin, M.A.; Cockett, N.

    1993-01-01

    We identified the HindIII restriction site polymorphism Of kappa-casein in cattle reported by Pinder et al. (Animal Genetics 22, 11, 1991) and found an additonal polymorphism (RsaI) in cattle and bison. The Hin dIII and Rsa I restriction sites were mapped and three haplotypes (alleles) were identified. Preliminary screening of 39 cattle and 71 bison revealed one allele restricted to cattle, one restricted to bison, and one shared by the species. No fixed allelic differences were observed among cattle breeds or among bison herds or subspecies.

  7. New epsilon-Bi2O3 metastable polymorph.

    PubMed

    Cornei, Nicoleta; Tancret, Nathalie; Abraham, Francis; Mentré, Olivier

    2006-06-26

    The new metastable epsilon-Bi2O3 polymorph has been prepared by hydrothermal treatment and structurally characterized. It shows strong relationships with the room temperature alpha form and the metastable beta form through rearrangements of [Bi2O3] columns formed by edge-sharing OBi4 tetrahedra. Its fully ordered crystal structure yields an ionic insulating character. It irreversibly transforms at 400 degrees C to the alpha form. The chemical analysis indicates its undoped bismuth oxide nature, then leading to the fifth characterized Bi2O3 polymorph to date.

  8. Novel polymorphs of the anti-Trypanosoma cruzi drug benznidazole.

    PubMed

    Honorato, Sara Braga; Mendonça, Jorge Souza; Boechat, Nubia; Oliveira, Alcemira Conceição; Mendes Filho, Josué; Ellena, Javier; Ayala, Alejandro Pedro

    2014-01-24

    Benznidazole (N-benzyl-2-(2-nitro-1H-imidazol-1-yl)acetamide), is a nitro-heterocyclic drug used in the treatment of Chagas disease. Despite the fact that this drug was released more than 30 years ago, little information about its solid state properties is available in the literature. In this study, it was verified that this drug exhibits three polymorphs, which were characterized in situ by X-ray powder diffraction, thermal analysis, hot stage microscopy and infrared spectroscopy. The thermodynamic relationships among these polymorphs were also discussed.

  9. Molecular Docking Study of Conformational Polymorph: Building Block of Crystal Chemistry

    PubMed Central

    Dubey, Rashmi; Tewari, Ashish Kumar; Singh, Ved Prakash; Singh, Praveen; Dangi, Jawahar Singh; Puerta, Carmen; Valerga, Pedro; Kant, Rajni

    2013-01-01

    Two conformational polymorphs of novel 2-[2-(3-cyano-4,6-dimethyl-2-oxo-2H-pyridin-1-yl)-ethoxy]-4,6-dimethyl nicotinonitrile have been developed. The crystal structure of both polymorphs (1a and 1b) seems to be stabilized by weak interactions. A difference was observed in the packing of both polymorphs. Polymorph 1b has a better binding affinity with the cyclooxygenase (COX-2) receptor than the standard (Nimesulide). PMID:24250264

  10. Large number of replacement polymorphisms in rapidly evolving genes of Drosophila. Implications for genome-wide surveys of DNA polymorphism.

    PubMed Central

    Schmid, K J; Nigro, L; Aquadro, C F; Tautz, D

    1999-01-01

    We present a survey of nucleotide polymorphism of three novel, rapidly evolving genes in populations of Drosophila melanogaster and D. simulans. Levels of silent polymorphism are comparable to other loci, but the number of replacement polymorphisms is higher than that in most other genes surveyed in D. melanogaster and D. simulans. Tests of neutrality fail to reject neutral evolution with one exception. This concerns a gene located in a region of high recombination rate in D. simulans and in a region of low recombination rate in D. melanogaster, due to an inversion. In the latter case it shows a very low number of polymorphisms, presumably due to selective sweeps in the region. Patterns of nucleotide polymorphism suggest that most substitutions are neutral or nearly neutral and that weak (positive and purifying) selection plays a significant role in the evolution of these genes. At all three loci, purifying selection of slightly deleterious replacement mutations appears to be more efficient in D. simulans than in D. melanogaster, presumably due to different effective population sizes. Our analysis suggests that current knowledge about genome-wide patterns of nucleotide polymorphism is far from complete with respect to the types and range of nucleotide substitutions and that further analysis of differences between local populations will be required to understand the forces more completely. We note that rapidly diverging and nearly neutrally evolving genes cannot be expected only in the genome of Drosophila, but are likely to occur in large numbers also in other organisms and that their function and evolution are little understood so far. PMID:10581279

  11. [MOLECULAR-GENETIC POLYMORPHISM OF chs_H1 GENE IN UKRAINIAN HOP VARIETIES].

    PubMed

    Venzer, A M; Volkova, N E; Sivolap, Yu M

    2015-01-01

    Polymorphism of chs_H1 gene encoding the "true" chalcone synthase was determined by alignment of sequences. The polymorphism associates with single nucleotide changes, insertions or deletions (indels) in the promoter, exons, intron, 3'-untranslated region. The molecular-genetic polymorphism in gene chs_H1 different regions of hop varieties of Polessye Agriculture Institute' breeding NAAS was analyzed.

  12. A twinned triclinic polymorph of dibromidotetrakis(tetrahydrofuran-kappaO)magnesium(II).

    PubMed

    Lorbach, Andreas; Lerner, Hans Wolfram; Bolte, Michael

    2007-04-01

    The title compound, [MgBr(2)(C(4)H(8)O)(4)], forms crystals which appear to be monoclinic but are actually twinned triclinic. The current form is a new triclinic polymorph, with Z'= 2, in addition to the already known tetragonal polymorph. Although the geometric parameters of the two polymorphs agree well, their packing patterns are completely different.

  13. Analysis of gene-derived SNP marker polymorphism in wheat (Triticum aestivum L.)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In this study, we analyzed 359 single nucleotide polymorphisms (SNPs) previously discovered in intron sequences of wheat genes to evaluate SNP marker polymorphism in common wheat (Triticum aestivum L.). These SNPs showed an average polymorphism information content (PIC) of 0.181 among 20 US wheat c...

  14. Spectral Sensitivities and Color Signals in a Polymorphic Damselfly

    PubMed Central

    Huang, Shao-chang; Chiou, Tsyr-huei; Marshall, Justin; Reinhard, Judith

    2014-01-01

    Animal communication relies on conspicuous signals and compatible signal perception abilities. Good signal perception abilities are particularly important for polymorphic animals where mate choice can be a challenge. Behavioral studies suggest that polymorphic damselflies use their varying body colorations and/or color patterns as communication signal for mate choice and to control mating frequencies. However, solid evidence for this hypothesis combining physiological with spectral and behavioral data is scarce. We investigated this question in the Australian common blue tail damselfly, Ischnura heterosticta, which has pronounced female-limited polymorphism: andromorphs have a male-like blue coloration and gynomorphs display green/grey colors. We measured body color reflectance and investigated the visual capacities of each morph, showing that I. heterosticta have at least three types of photoreceptors sensitive to UV, blue, and green wavelength, and that this visual perception ability enables them to detect the spectral properties of the color signals emitted from the various color morphs in both males and females. We further demonstrate that different color morphs can be discriminated against each other and the vegetation based on color contrast. Finally, these findings were supported by field observations of natural mating pairs showing that mating partners are indeed chosen based on their body coloration. Our study provides the first comprehensive evidence for the function of body coloration on mate choice in polymorphic damselflies. PMID:24498233

  15. Gelatinization temperature of rice explained by polymorphisms in starch synthase.

    PubMed

    Waters, Daniel L E; Henry, Robert J; Reinke, Russell F; Fitzgerald, Melissa A

    2006-01-01

    The cooking quality of rice is associated with the starch gelatinization temperature (GT). Rice genotypes with low GT have probably been selected for their cooking quality by humans during domestication. We now report polymorphisms in starch synthase IIa (SSIIa) that explain the variation in rice starch GT. Sequence analysis of the eight exons of SSIIa identified significant polymorphism in only exon 8. These single nucleotide polymorphisms (SNPs) were determined in 70 diverse genotypes of rice. Two SNPs could classify all 70 genotypes into either high GT or low GT types which differed in GT by 8 degrees C. 'A' rather than 'G' at base 2412 determined whether a methionine or valine was present at the corresponding amino acid residue in SSIIa, whilst two adjacent SNPs at bases 2543 and 2544 coded for either leucine (GC) or phenylalanine (TT). Rice varieties with high GT starch had a combination of valine and leucine at these residues. In contrast, rice varieties with low GT starch had a combination of either methionine and leucine or valine and phenylalanine at these same residues. At least two distinct polymorphisms have apparently been selected for their desirable cooking qualities in the domestication of rice.

  16. Theoretical compressibilities of high-pressure ZnTe polymorphs

    NASA Astrophysics Data System (ADS)

    Franco, R.; Mori-Sánchez, P.; Recio, J. M.; Pandey, R.

    2003-11-01

    We report the results of a theoretical study of structural, electronic, and pressure-induced phase transition properties in ZnTe. Total energies of several high-pressure polymorphs are calculated using the density functional theory (DFT) formalism under the nonlocal approximation. Thermal effects are included by means of a nonempirical Debye-like model. In agreement with optical absorption data, the lowest direct gap of the zinc blende polymorph is found to follow a nonlinear pressure dependence that turns into linear behavior when expressed in terms of the decrease in the lattice parameter. The pressure stability ranges of cubic (zinc blende and rocksalt), trigonal (cinnabar), and orthorhombic (Cmcm) polymorphs are computed at static and room temperature conditions. Our calculations agree with the experimental and theoretical reported zinc blende →cinnabar→Cmcm pressure-induced phase sequence. Linear and bulk compressibilities are evaluated for the four polymorphs and reveal an anisotropic behavior of the cinnabar structure, which contrasts with the cubiclike compression of its shortest Zn-Te bonds. The qualitative trend shows a crystal that becomes relatively less compressible in the high-pressure phases.

  17. Maintenance of polymorphic females: do parasites play a role?

    PubMed

    Sánchez-Guillén, R A; Martínez-Zamilpa, S M J; Jiménez-Cortés, J G; Forbes, M R L; Córdoba-Aguilar, A

    2013-01-01

    The role of parasites in explaining maintenance of polymorphism is an unexplored research avenue. In odonates, female-limited color polymorphism (one female morph mimicking the conspecific male and one or more gynochromatic morphs) is widespread. Here we investigated whether parasitism contributes to color polymorphism maintenance by studying six species of female dimorphic damselflies using large databases of field-collected animals. We predicted that androchrome females (male mimics) would be more intensively parasitized than gynochrome females which is, according to previous studies, counterbalanced by the advantages of the former when evading male harassment compared to gynochrome females. Here we show that in Ischnura denticollis and Enallagma novahispaniae, androchrome females suffer from a higher degree of parasitism than gynochromatic females, and contrary to prediction, than males. Thus, our study has detected a correlation between color polymorphism and parasitic burden in odonates. This leads us to hypothesize that natural selection, via parasite pressure, can explain in part how androchrome and gynochrome female color morphs can be maintained. Both morphs may cope with parasites in a different way: given that androchrome females are more heavily parasitized, they may pay a higher fecundity costs, in comparison to gynochrome females.

  18. Comparative genomics analysis in Prunoideae to identify biologically relevant polymorphisms.

    PubMed

    Koepke, Tyson; Schaeffer, Scott; Harper, Artemus; Dicenta, Federico; Edwards, Mark; Henry, Robert J; Møller, Birger L; Meisel, Lee; Oraguzie, Nnadozie; Silva, Herman; Sánchez-Pérez, Raquel; Dhingra, Amit

    2013-09-01

    Prunus is an economically important genus with a wide range of physiological and biological variability. Using the peach genome as a reference, sequencing reads from four almond accessions and one sweet cherry cultivar were used for comparative analysis of these three Prunus species. Reference mapping enabled the identification of many biological relevant polymorphisms within the individuals. Examining the depth of the polymorphisms and the overall scaffold coverage, we identified many potentially interesting regions including hundreds of small scaffolds with no coverage from any individual. Non-sense mutations account for about 70 000 of the 13 million identified single nucleotide polymorphisms (SNPs). Blast2GO analyses on these non-sense SNPs revealed several interesting results. First, non-sense SNPs were not evenly distributed across all gene ontology terms. Specifically, in comparison with peach, sweet cherry is found to have non-sense SNPs in two 1-aminocyclopropane-1-carboxylate synthase (ACS) genes and two 1-aminocyclopropane-1-carboxylate oxidase (ACO) genes. These polymorphisms may be at the root of the nonclimacteric ripening of sweet cherry. A set of candidate genes associated with bitterness in almond were identified by comparing sweet and bitter almond sequences. To the best of our knowledge, this is the first report in plants of non-sense SNP abundance in a genus being linked to specific GO terms.

  19. Systematic Identification of Balanced Transposition Polymorphisms in Saccharomyces cerevisiae

    PubMed Central

    Faddah, Dina A.; Ganko, Eric W.; McCoach, Caroline; Pickrell, Joseph K.; Hanlon, Sean E.; Mann, Frederick G.; Mieczkowska, Joanna O.; Jones, Corbin D.; Lieb, Jason D.; Vision, Todd J.

    2009-01-01

    High-throughput techniques for detecting DNA polymorphisms generally do not identify changes in which the genomic position of a sequence, but not its copy number, varies among individuals. To explore such balanced structural polymorphisms, we used array-based Comparative Genomic Hybridization (aCGH) to conduct a genome-wide screen for single-copy genomic segments that occupy different genomic positions in the standard laboratory strain of Saccharomyces cerevisiae (S90) and a polymorphic wild isolate (Y101) through analysis of six tetrads from a cross of these two strains. Paired-end high-throughput sequencing of Y101 validated four of the predicted rearrangements. The transposed segments contained one to four annotated genes each, yet crosses between S90 and Y101 yielded mostly viable tetrads. The longest segment comprised 13.5 kb near the telomere of chromosome XV in the S288C reference strain and Southern blotting confirmed its predicted location on chromosome IX in Y101. Interestingly, inter-locus crossover events between copies of this segment occurred at a detectable rate. The presence of low-copy repetitive sequences at the junctions of this segment suggests that it may have arisen through ectopic recombination. Our methodology and findings provide a starting point for exploring the origins, phenotypic consequences, and evolutionary fate of this largely unexplored form of genomic polymorphism. PMID:19503594

  20. A Simplified Technique for Evaluating Human "CCR5" Genetic Polymorphism

    ERIC Educational Resources Information Center

    Falteisek, Lukáš; Cerný, Jan; Janštová, Vanda

    2013-01-01

    To involve students in thinking about the problem of AIDS (which is important in the view of nondecreasing infection rates), we established a practical lab using a simplified adaptation of Thomas's (2004) method to determine the polymorphism of HIV co-receptor CCR5 from students' own epithelial cells. CCR5 is a receptor involved in inflammatory…

  1. Polymorphous low-grade adenocarcinoma of the nasal fossa.

    PubMed

    González-Lagunas, Javier; Alasà-Caparrós, Cristian; Vendrell-Escofet, Gerard; Huguet-Redecilla, Pere; Raspall-Martin, Guillermo

    2005-01-01

    An unusual case of a T4N2CMx polymorphous low grade adenocarcinoma located in the nasal fossae and extending to the pterygoid area is presented. The primary tumor was excised through a Lefort I maxillotomy and the neck was managed with a supraomohyoid neck dissection. Adjuntive postoperative radiotherapy was also administered to the patient.

  2. Serotonin transporter gene polymorphisms and hyperserotonemia in autistic disorder

    PubMed Central

    Betancur, Catalina; Corbex, Marylis; Spielewoy, Cécile; Philippe, Anne; Laplanche, Jean-Louis; Launay, Jean-Marie; Gillberg, Christopher; Mouren-Simeoni, Marie-Christine; Hamon, Michel; Giros, Bruno; Nosten-Bertrand, Marika; Leboyer, Marion

    2002-01-01

    Previous studies have provided conflicting evidence regarding the association of the serotonin transporter (5-HTT) gene with autism. Two polymorphisms have been identified in the human 5-HTT gene, a VNTR in intron 21 and a functional deletion/insertion in the promoter region (5-HTTLPR) with short and long variants.2 Positive associations of the 5-HTTLPR polymorphism with autism have been reported by two family-based studies, but one found preferential transmission of the short allele3 and the other of the long allele.4 Two subsequent studies failed to find evidence of transmission disequilibrium at the 5-HTTLPR locus.5,6 These conflicting results could be due to heterogeneity of clinical samples with regard to serotonin (5-HT) blood levels, which have been found to be elevated in some autistic subjects.7–9 Thus, we examined the association of the 5-HTTLPR and VNTR polymorphisms of the 5-HTT gene with autism, and we investigated the relationship between 5-HTT variants and whole-blood 5-HT. The transmission/disequilibrium test (TDT) revealed no linkage disequilibrium at either loci in a sample of 96 families comprising 43 trios and 53 sib pairs. Furthermore, no significant relationship between 5-HT blood levels and 5-HTT gene polymorphisms was found. Our results suggest that the 5-HTT gene is unlikely to play a major role as a susceptibility factor in autism. PMID:11803447

  3. High polymorphism at microsatellite loci in the Chinese donkey.

    PubMed

    Zhang, R F; Xie, W M; Zhang, T; Lei, C Z

    2016-06-24

    To reveal the genetic diversity and phylogenetic relationships between Chinese donkey breeds, 415 individuals representing ten breeds were investigated using ten microsatellite markers. The observed number of alleles, mean effective number of alleles (NE), mean expected heterozygosity (HE), and polymorphic information content (PIC) of each breed and polymorphic locus were analyzed. The results showed that seven (HTG7, HTG10, AHT4, HTG6, HMS6, HMS3, and HMS7) of ten microsatellite loci were polymorphic. The mean PIC, HE, and NE of seven polymorphic loci for the ten donkey breeds were 0.7679, 0.8072, and 6.0275, respectively. These results suggest that domestic Chinese donkey breeds possess higher levels of genetic diversity and heterozygosity than foreign donkeys. A neighbor-joining tree based on Nei's standard genetic distance showed that there was close genetic distance among Xinjiang, Qingyang, Xiji, and Guanzhong donkey breeds. In addition, Mongolia and Dezhou donkey breeds were placed in the same category. The phylogenetic tree revealed that the genetic relationships between Chinese donkey breeds are consistent with their geographic distribution and breeding history.

  4. Polymorphism in Multilocus Host–Parasite Coevolutionary Interactions

    PubMed Central

    Tellier, Aurélien; Brown, James K. M.

    2007-01-01

    Numerous loci in host organisms are involved in parasite recognition, such as major histocompatibility complex (MHC) genes in vertebrates or genes involved in gene-for-gene (GFG) relationships in plants. Diversity is commonly observed at such loci and at corresponding loci encoding antigenic molecules in parasites. Multilocus theoretical models of host–parasite coevolution predict that polymorphism is more likely than in single-locus interactions because recurrent coevolutionary cycles are sustained by indirect frequency-dependent selection as rare genotypes have a selective advantage. These cycles are stabilized by direct frequency-dependent selection, resulting from repeated reinfection of the same host by a parasite, a feature of most diseases. Here, it is shown that for realistically small costs of resistance and virulence, polycyclic disease and high autoinfection rates, stable polymorphism of all possible genotypes is obtained in parasite populations. Two types of epistatic interactions between loci tend to increase the parameter space in which stable polymorphism can occur with all possible host and parasite genotypes. In the parasite, the marginal cost of each additional virulence allele should increase, while in the host, the marginal cost of each additional resistance allele should decrease. It is therefore predicted that GFG polymorphism will be stable (and hence detectable) when there is partial complementation of avirulence genes in the parasite and of resistance genes in the host. PMID:17947440

  5. Nestling polymorphism in a cuckoo-host system.

    PubMed

    Sato, Nozomu J; Tanaka, Keita D; Okahisa, Yuji; Yamamichi, Masato; Kuehn, Ralph; Gula, Roman; Ueda, Keisuke; Theuerkauf, Jörn

    2015-12-21

    Virulence of avian brood parasites can trigger a coevolutionary arms race, which favours rejection of parasitic eggs or chicks by host parents, and in turn leads to mimicry in parasite eggs or chicks [1-7]. The appearance of host offspring is critical to enable host parents to detect parasites. Thus, increasing accuracy of parasites' mimicry can favour a newly emerged host morph to escape parasites' mimicry. If parasites catch up with the hosts with a newly acquired mimetic morph, host polymorphism should be maintained through apostatic (negative frequency-dependent) selection, which favours hosts rarer morphs [1-3,7]. Among population-wide polymorphism, uniformity of respective host morphs in single host nests stochastically prevents parasites from targeting any specific morph of hosts and thus helps parents detect parasitism. Polymorphism in such a state is well-known in egg appearances of hosts of brood parasitic birds [2,3,7], which might also occur in chick appearances when arms races escalate. Here, we present evidence of polymorphism in chick skin coloration in a cuckoo-host system: the fan-tailed gerygone Gerygone flavolateralis and its specialist brood parasite, the shining bronze-cuckoo Chalcites lucidus in New Caledonia (Figure 1A-C).

  6. Relationship between horn fly infestation and polymorphisms in cytochrome

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Individual animal variation occurs regarding external parasite infestation in beef cattle. Our objective was to determine if horn flies infestations present on beef cattle are associated with the single nucleotide polymorphism (SNP; T-318C) in the cytochrome P450 gene (CYP3A28) and the prolactin (PR...

  7. Thermal analysis of paracetamol polymorphs by FT-IR spectroscopies.

    PubMed

    Zimmermann, Boris; Baranović, Goran

    2011-01-25

    A simple IR spectroscopy based methodology in routine screening studies of polymorphism is proposed. Reflectance and transmittance temperature-dependent IR measurements (coupled with the 2D-IR data presentation and the baseline analysis) offer a positive identification of each polymorphic phase, therefore allowing simple and rapid monitoring of the measured system. Applicability and flexibility of the methodology was demonstrated on the measurement of the model polymorphic compound paracetamol under various conditions (including geometric constraints and elevated pressure). The thermal behavior of paracetamol strongly depends on slight variations in experimental conditions that can result in formation of various phases (three polymorphs and the amorphous form). The amorphous phase can crystallize during heating into either Form II or Form III within almost identical temperature range. Likewise, the crystal transformations II→I and III→II also can proceed within almost identical temperature range. Furthermore, the thermal behavior is even more diverse than that, and includes the crystallizations of Forms I, II and III from the melt, and the high temperature II→I transition. The variety of the temperatures of the transformations is a major obstacle for unambiguous identification of a particular phase by DSC and a major reason for the implementation of these IR methods.

  8. Comparative Genomics Analysis in Prunoideae to Identify Biologically Relevant Polymorphisms

    PubMed Central

    Koepke, Tyson; Schaeffer, Scott; Harper, Artemus; Dicenta, Federico; Edwards, Mark; Henry, Robert J.; Møller, Birger Lindberg; Meisel, Lee; Oraguzie, Nnadozie; Silva, Herman; Sánchez-Pérez, Raquel; Dhingra, Amit

    2013-01-01

    Prunus is an economically important genus with a wide range of physiological and biological variability. Using the peach genome as a reference, sequencing reads from four almond accessions and one sweet cherry cultivar were used for comparative analysis of these three Prunus species. Reference mapping enabled the identification of many biological relevant polymorphisms within the individuals. Examining the depth of the polymorphisms and the overall scaffold coverage, we identified many potentially interesting regions including hundreds of small scaffolds with no coverage from any individual. Nonsense mutations account for about 70,000 of the 13 million identified single nucleotide polymorphisms (SNPs). Blast2GO analyses on these nonsense SNPs revealed several interesting results. First, nonsense SNPs were not evenly distributed across all gene ontology terms. Specifically, in comparison to peach, sweet cherry is found to have nonsense SNPs in two 1-aminocyclopropane-1-carboxylate synthase (ACS) genes and two 1-aminocyclopropane-1-carboxylate oxidase (ACO) genes. These polymorphisms may be at the root of the non-climacteric ripening of sweet cherry. A set of candidate genes associated with bitterness in almond were identified by comparing sweet and bitter almond sequences. To the best of our knowledge, this is the first report in plants of nonsense SNP abundance in a genus being linked to specific GO terms. PMID:23763653

  9. The role of glucocorticoid receptor (GR) polymorphisms in human erythropoiesis.

    PubMed

    Varricchio, Lilian; Migliaccio, Anna Rita

    2014-01-01

    Glucocorticoids are endogenous steroid hormones that regulate several biological functions including proliferation, differentiation and apoptosis in numerous cell types in response to stress. Synthetic glucocorticoids, such as dexamethasone (Dex) are used to treat a variety of diseases ranging from allergy to depression. Glucocorticoids exert their effects by passively entering into cells and binding to a specific Glucocorticoid Receptor (GR) present in the cytoplasm. Once activated by its ligand, GR may elicit cytoplasmic (mainly suppression of p53), and nuclear (regulation of transcription of GR responsive genes), responses. Human GR is highly polymorphic and may encode > 260 different isoforms. This polymorphism is emerging as the leading cause for the variability of phenotype and response to glucocorticoid therapy observed in human populations. Studies in mice and clinical observations indicate that GR controls also the response to erythroid stress. This knowledge has been exploited in-vivo by using synthetic GR agonists for treatment of the erythropoietin-refractory congenic Diamond Blackfan Anemia and in-vitro to develop culture conditions that may theoretically generate red cells in numbers sufficient for transfusion. However, the effect exerted by GR polymorphism on the variability of the phenotype of genetic and acquired erythroid disorders observed in the human population is still poorly appreciated. This review will summarize current knowledge on the biological activity of GR and of its polymorphism in non-hematopoietic diseases and discuss the implications of these observations for erythropoiesis.

  10. Genome-wide DNA polymorphism analyses using VariScan

    PubMed Central

    Hutter, Stephan; Vilella, Albert J; Rozas, Julio

    2006-01-01

    Background DNA sequence polymorphisms analysis can provide valuable information on the evolutionary forces shaping nucleotide variation, and provides an insight into the functional significance of genomic regions. The recent ongoing genome projects will radically improve our capabilities to detect specific genomic regions shaped by natural selection. Current available methods and software, however, are unsatisfactory for such genome-wide analysis. Results We have developed methods for the analysis of DNA sequence polymorphisms at the genome-wide scale. These methods, which have been tested on a coalescent-simulated and actual data files from mouse and human, have been implemented in the VariScan software package version 2.0. Additionally, we have also incorporated a graphical-user interface. The main features of this software are: i) exhaustive population-genetic analyses including those based on the coalescent theory; ii) analysis adapted to the shallow data generated by the high-throughput genome projects; iii) use of genome annotations to conduct a comprehensive analyses separately for different functional regions; iv) identification of relevant genomic regions by the sliding-window and wavelet-multiresolution approaches; v) visualization of the results integrated with current genome annotations in commonly available genome browsers. Conclusion VariScan is a powerful and flexible suite of software for the analysis of DNA polymorphisms. The current version implements new algorithms, methods, and capabilities, providing an important tool for an exhaustive exploratory analysis of genome-wide DNA polymorphism data. PMID:16968531

  11. Discovery, Validation and Characterization of 1039 Cattle Single Nucleotide Polymorphisms

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We identified approximately 13000 putative single nucleotide polymorphisms (SNPs) by comparison of repeat-masked BAC-end sequences from the cattle RPCI-42 BAC library with whole-genome shotgun contigs of cattle genome assembly Btau 1.0. Genotyping of a subset of these SNPs was performed on a panel ...

  12. A Polymorphism in Mitochondrial DNA Associated with IQ?

    ERIC Educational Resources Information Center

    Skuder, Patricia; And Others

    1995-01-01

    Of 100 DNA markers examined in an allelic association study, only 1 showed a replicated association with IQ in samples totaling 107 children. How the gene marked by the particular restriction fragment length polymorphism was tracked and its mitochondrial origin identified is described. (SLD)

  13. The role of glucocorticoid receptor (GR) polymorphisms in human erythropoiesis

    PubMed Central

    Varricchio, Lilian; Migliaccio, Anna Rita

    2014-01-01

    Glucocorticoids are endogenous steroid hormones that regulate several biological functions including proliferation, differentiation and apoptosis in numerous cell types in response to stress. Synthetic glucocorticoids, such as dexamethasone (Dex) are used to treat a variety of diseases ranging from allergy to depression. Glucocorticoids exert their effects by passively entering into cells and binding to a specific Glucocorticoid Receptor (GR) present in the cytoplasm. Once activated by its ligand, GR may elicit cytoplasmic (mainly suppression of p53), and nuclear (regulation of transcription of GR responsive genes), responses. Human GR is highly polymorphic and may encode > 260 different isoforms. This polymorphism is emerging as the leading cause for the variability of phenotype and response to glucocorticoid therapy observed in human populations. Studies in mice and clinical observations indicate that GR controls also the response to erythroid stress. This knowledge has been exploited in-vivo by using synthetic GR agonists for treatment of the erythropoietin-refractory congenic Diamond Blackfan Anemia and in-vitro to develop culture conditions that may theoretically generate red cells in numbers sufficient for transfusion. However, the effect exerted by GR polymorphism on the variability of the phenotype of genetic and acquired erythroid disorders observed in the human population is still poorly appreciated. This review will summarize current knowledge on the biological activity of GR and of its polymorphism in non-hematopoietic diseases and discuss the implications of these observations for erythropoiesis. PMID:25755906

  14. Serotonin Transporter Polymorphisms in Patients With Portopulmonary Hypertension

    PubMed Central

    Roberts, Kari E.; Fallon, Michael B.; Krowka, Michael J.; Benza, Raymond L.; Knowles, James A.; Badesch, David B.; Brown, Robert S.; Taichman, Darren B.; Trotter, James; Zacks, Steven; Horn, Evelyn M.; Kawut, Steven M.

    2009-01-01

    Background: The long allele of a functional promoter polymorphism in the serotonin transporter (SERT) is associated with an increased risk of some forms of pulmonary arterial hypertension. We hypothesized that the long allele or other polymorphisms in SERT would be associated with an increased risk of portopulmonary hypertension (PPHTN) in patients with advanced liver disease. Methods: We performed a multicenter case-control study. Subjects undergoing liver transplant evaluation at seven centers were prospectively screened for the presence of PPHTN using transthoracic echocardiography. PPHTN was confirmed by right heart catheterization using standard criteria. Results: The study sample included 30 case patients with PPHTN and 109 control subjects with advanced liver disease. There was no significant association between the long allele and case status in an adjusted additive model (odds ratio, 0.63; 95% confidence interval, 0.33 to 1.21; p = 0.17). If anything, LL genotype tended to be associated with a lower risk of PPHTN. There were no associations between other SERT polymorphisms and PPHTN. Conclusions: SERT polymorphisms are not associated with the risk of PPHTN in patients with advanced liver disease. Other clinical or genetic risk factors may play a role in this complication of portal hypertension. PMID:19141529

  15. [DRD4 polymorphism and the association with mental disorders].

    PubMed

    Aguirre-Samudio, Ana Julia; Nicolini, Humberto

    2005-01-01

    The dopamine D4 receptor (DRD4) is the most important gene in psychiatric genetics since its involvement in the physiology of behavior, pharmacology response and psychopathology. DRD4's sequence gene present some polymorphism such as in the exon 3 constituted from 2 to 10 copies of repetitive sequences of 48 base pair (bp), from class variable number tandem repeats (VNTR). An additional genetic variant in the exon 1 presents polymorphisms to 12 bp VNTR, and the variation -521 C by T of the promoter region. The -521 T allele can reduce the efficiency of the gene expression in comparison with the C allele. The DRD4 gene codes a protein transmembranal of 7 domains, distributed in front cortex, striatum, hypothalamus and hippocampus. This review discusses the biological significance of DRD4 gene and its perspective with emphasis on the impact of association studies in some illness mental and behavioral traits. The DRD4 polymorphism has been studied in association with illnesses like schizophrenia, attention deficit hyperactivity disorder (ADHD), obsessive-compulsive with tics, bipolar manic-depressive disorder, in addition behavioral traits such as novelty seeking. The DRD4 gene is a genetic marker that could play a role in etiology of different mental illness, and behavioral traits, and its polymorphism can be used in association studies, epigenetic and pharmacogenomic analysis for help to understand the genetics basis of both mental disorders and traits.

  16. Sleep and COMT Polymorphism in ADHD Children: Preliminary Actigraphic Data

    ERIC Educational Resources Information Center

    Gruber, Reut; Grizenko, Natalie; Schwartz, George; Amor, Leila Ben; Gauthier, Julie; de Guzman, Rosherrie; Joober, Ridha

    2006-01-01

    Objective: To examine whether COMT (catechol-O-methyltransferase) polymorphism modulates aspects of sleep in children diagnosed with attention-deficit/hyperactivity disorder (ADHD). Method: Nightly sleep actigraphic recordings during a double-blind, placebo-controlled, crossover clinical study (1 week of 0.5 mg/kg MPH; 1 week of placebo) were…

  17. A Laboratory Exercise for Genotyping Two Human Single Nucleotide Polymorphisms

    ERIC Educational Resources Information Center

    Fernando, James; Carlson, Bradley; LeBard, Timothy; McCarthy, Michael; Umali, Finianne; Ashton, Bryce; Rose, Ferrill F., Jr.

    2016-01-01

    The dramatic decrease in the cost of sequencing a human genome is leading to an era in which a wide range of students will benefit from having an understanding of human genetic variation. Since over 90% of sequence variation between humans is in the form of single nucleotide polymorphisms (SNPs), a laboratory exercise has been devised in order to…

  18. Genetic polymorphisms for vascular endothelial growth factor in perinatal complications.

    PubMed

    Bányász, Ilona; Bokodi, Géza; Vásárhelyi, Barna; Treszl, András; Derzbach, László; Szabó, András; Tulassay, Tivadar; Vannay, Adám

    2006-12-01

    Low birth weight (LBW) infants have increased susceptibility to perinatal complications. An immature and impaired vascular system may possibly participate in these complications. There is evidence that supports the notion that vascular endothelial growth factor (VEGF), which is an essential regulator of embryonic angiogenesis, plays a central role in the pathogenesis of perinatal complications. We aimed to test whether functional genetic polymorphisms of VEGF are associated with the risk of preterm birth or perinatal morbidity. We enrolled 128 LBW infants (< or = 1500 grams). VEGF T-460C, VEGF C-2578A and VEGF G+405C polymorphisms were determined by real-time PCR or PCR-RFLP, respectively. Their genotypes were compared with VEGF genotypes of 200 healthy, term neonates. The prevalence of the VEGF+405 C allele was higher in LBW infants than in healthy, term neonates (OR [95% CI]: 1.29 [1.01-1.65]). Carrier state for the VEGF -2578A allele was an independent risk factor for enterocolitis necrotisans (NEC) (adjusted OR [95% CI]: 2.77 [1.00-7.65]). The carrier state for the VEGF -2578AA genotype was associated with a decreased risk of acute renal failure (ARF) (adjusted OR [95% CI]: 0.2 [0.05-0.78]). These results suggest that VEGF G+405C polymorphism might be associated with a higher risk of preterm birth and that VEGF C-2578A polymorphism may participate in the development of perinatal complications such as NEC and ARF.

  19. Polymorphism among EST-based markers in tomato

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cultivated tomato (Lycopersicon esculentum Mill.) has a narrow genetic base. This is in part due to population genetic processes such as founder events, genetic bottlenecks, and natural and artificial selection during domestication. We characterize the nucleotide polymorphism in 26 EST-based markers...

  20. Single Nucleotide Polymorphisms Predict Symptom Severity of Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Jiao, Yun; Chen, Rong; Ke, Xiaoyan; Cheng, Lu; Chu, Kangkang; Lu, Zuhong; Herskovits, Edward H.

    2012-01-01

    Autism is widely believed to be a heterogeneous disorder; diagnosis is currently based solely on clinical criteria, although genetic, as well as environmental, influences are thought to be prominent factors in the etiology of most forms of autism. Our goal is to determine whether a predictive model based on single-nucleotide polymorphisms (SNPs)…

  1. Do polymorphisms in chemosensory genes matter for human ingestive behavior?

    PubMed

    Hayes, John E; Feeney, Emma L; Allen, Alissa L

    2013-12-01

    In the last decade, basic research in chemoreceptor genetics and neurobiology have revolutionized our understanding of individual differences in chemosensation. From an evolutionary perspective, chemosensory variations appear to have arisen in response to different living environments, generally in the avoidance of toxins and to better detect vital food sources. Today, it is often assumed that these differences may drive variable food preferences and choices, with downstream effects on health and wellness. A growing body of evidence indicates chemosensory variation is far more complex than previously believed. However, just because a genetic polymorphism results in altered receptor function in cultured cells or even behavioral phenotypes in the laboratory, this variation may not be sufficient to influence food choice in free living humans. Still, there is ample evidence to indicate allelic variation in TAS2R38 predicts variation in bitterness of synthetic pharmaceuticals (e.g., propylthiouracil) and natural plant compounds (e.g., goitrin), and this variation associates with differential intake of alcohol and vegetables. Further, this is only one of 25 unique bitter taste genes (TAS2Rs) in humans, and emerging evidence suggests other TAS2Rs may also contain polymorphisms that a functional with respect to ingestive behavior. For example, TAS2R16 polymorphisms are linked to the bitterness of naturally occurring plant compounds and alcoholic beverage intake, a TAS2R19 polymorphism predicts differences in quinine bitterness and grapefruit bitterness and liking, and TAS2R31 polymorphisms associate with differential bitterness of plant compounds like aristolochic acid and the sulfonyl amide sweeteners saccharin and acesulfame-K. More critically with respect to food choices, these polymorphisms may vary independently from each other within and across individuals, meaning a monolithic one-size-fits-all approach to bitterness needs to be abandoned. Nor are genetic

  2. Do polymorphisms in chemosensory genes matter for human ingestive behavior?

    PubMed Central

    Hayes, John E.; Feeney, Emma L.; Allen, Alissa L.

    2013-01-01

    In the last decade, basic research in chemoreceptor genetics and neurobiology have revolutionized our understanding of individual differences in chemosensation. From an evolutionary perspective, chemosensory variations appear to have arisen in response to different living environments, generally in the avoidance of toxins and to better detect vital food sources. Today, it is often assumed that these differences may drive variable food preferences and choices, with downstream effects on health and wellness. A growing body of evidence indicates chemosensory variation is far more complex than previously believed. However, just because a genetic polymorphism results in altered receptor function in cultured cells or even behavioral phenotypes in the laboratory, this variation may not be sufficient to influence food choice in free living humans. Still, there is ample evidence to indicate allelic variation in TAS2R38 predicts variation in bitterness of synthetic pharmaceuticals (e.g., propylthiouracil) and natural plant compounds (e.g., goitrin), and this variation associates with differential intake of alcohol and vegetables. Further, this is only one of 25 unique bitter taste genes (TAS2Rs) in humans, and emerging evidence suggests other TAS2Rs may also contain polymorphisms that a functional with respect to ingestive behavior. For example, TAS2R16 polymorphisms are linked to the bitterness of naturally occurring plant compounds and alcoholic beverage intake, a TAS2R19 polymorphism predicts differences in quinine bitterness and grapefruit bitterness and liking, and TAS2R31 polymorphisms associate with differential bitterness of plant compounds like aristolochic acid and the sulfonyl amide sweeteners saccharin and acesulfame-K. More critically with respect to food choices, these polymorphisms may vary independently from each other within and across individuals, meaning a monolithic one-size-fits-all approach to bitterness needs to be abandoned. Nor are genetic

  3. Mutations and a polymorphism in the tuberin gene

    SciTech Connect

    Northup, H.; Rodriguez, J.A.; Au, K.S.; Rodriguez, E.

    1994-09-01

    Two deletions and a polymorphism have been identified in the recently described tuberin gene. The tuberin gene (designated TSC2) when mutated causes tuberous sclerosis complex (TSC). Fifty-three affected individuals (30 from families with multiple affected and 23 isolated cases) were screened with the tuberin cDNA for gross deletions or rearrangements. Both deletions were found in families with multiple affected members (family designations: HOU-5 and HOU-22). The approximate size of the deletion in HOU-5 is ten kilobases and eliminates a BamHI restriction site. The deletion includes a portion of the 5{prime} half of the tuberin cDNA. The deletion in HOU-22 occurs in the 3{prime} half of the gene. The deletions are being further characterized. A HindIII restriction site polymorphism was detected by a 0.5 kilobase probe from the 5{prime} coding region of the tuberin gene in an individual from a family linked to chromosome 9 (posterior probability of linkage 93%). The polymorphism did not segregate with TSC in the family. The family had previously been shown to give negative results with multiple markers on chromosome 16. The polymorphism was also seen in one individual among a panel of 20 randomly selected unaffected individuals. Thirty-five additional affected probands (five from families and 30 isolated cases) are being tested with the tuberin cDNA. Testing for subtle mutations is our panel of 80 affected probands is underway utilizing SSCP. Additional mutations or polymorphisms detected will be reported. The tuberin cDNA was a kind gift of The European Chromosome 16 Tuberous Sclerosis Consortium.

  4. EFFECT OF CYTOKINE AND PHARMACOGENOMIC GENETIC POLYMORPHISMS IN TRANSPLANTATION

    PubMed Central

    Girnita, Diana M; Burckart, Gilbert; Zeevi, Adriana

    2008-01-01

    Purpose of review Recent investigations related to the polymorphism of genes that affect drug therapy and the polymorphisms of cytokines and growth factors that control immune responses have been associated with outcomes following solid organ transplantation (SOT) and hematopoietic stem cell transplantation (HSCT). This review will provide a current update on the most recent findings and discuss the challenges for developing individualized therapeutic strategies based on clinical and genetic profiles. Recent Findings Single nucleotide polymorphisms (SNPs) of cytokine genes have been shown to have an impact in vitro or in vivo protein secretion, dividing the individuals into High, Low or Intermediate producers for a given molecule. Many studies have been performed to determine the contribution of single cytokine gene SNPs on SOT or HSCT outcomes and the reported results are still controversial. However, analysis of a combination of several cytokines and/or cytokine receptor polymorphisms adjusted for known clinical risk factors and ethnicity have resulted in significant clinical correlations. Furthermore, associations with gene polymorphisms that affect immunosuppressive drug therapy in solid organ transplantation have also been extensively studied. There is a continuous flow of new information regarding functional SNPs that may affect the immune response to the allograft or to drug therapy and their impact on clinical outcomes have yet to be validated in large cohorts SOT or HSCT Summary Consolidating the information that we have on pharmacogenetics and on cytokine genetics to produce patient-oriented individualized drug regimens is an important challenge in transplantation medicine. Using a multi-variant approach based on genetic profile and other relevant clinical factors a score system may be developed to predict the severity of rejection, infection or other complications associated with transplantation. The ultimate goal of these studies is to improve patient

  5. A Novel Approach for Mining Polymorphic Microsatellite Markers In Silico

    PubMed Central

    Hoffman, Joseph I.; Nichols, Hazel J.

    2011-01-01

    An important emerging application of high-throughput 454 sequencing is the isolation of molecular markers such as microsatellites from genomic DNA. However, few studies have developed microsatellites from cDNA despite the added potential for targeting candidate genes. Moreover, to develop microsatellites usually requires the evaluation of numerous primer pairs for polymorphism in the focal species. This can be time-consuming and wasteful, particularly for taxa with low genetic diversity where the majority of primers often yield monomorphic polymerase chain reaction (PCR) products. Transcriptome assemblies provide a convenient solution, functional annotation of transcripts allowing markers to be targeted towards candidate genes, while high sequence coverage in principle permits the assessment of variability in silico. Consequently, we evaluated fifty primer pairs designed to amplify microsatellites, primarily residing within transcripts related to immunity and growth, identified from an Antarctic fur seal (Arctocephalus gazella) transcriptome assembly. In silico visualization was used to classify each microsatellite as being either polymorphic or monomorphic and to quantify the number of distinct length variants, each taken to represent a different allele. The majority of loci (n = 36, 76.0%) yielded interpretable PCR products, 23 of which were polymorphic in a sample of 24 fur seal individuals. Loci that appeared variable in silico were significantly more likely to yield polymorphic PCR products, even after controlling for microsatellite length measured in silico. We also found a significant positive relationship between inferred and observed allele number. This study not only demonstrates the feasibility of generating modest panels of microsatellites targeted towards specific classes of gene, but also suggests that in silico microsatellite variability may provide a useful proxy for PCR product polymorphism. PMID:21853104

  6. Development of Y chromosome intraspecific polymorphic markers in the Felidae.

    PubMed

    Luo, Shu-Jin; Johnson, Warren E; David, Victor A; Menotti-Raymond, Marilyn; Stanyon, Roscoe; Cai, Qing Xiu; Beck, Thomas; Yuhki, Naoya; Pecon-Slattery, Jill; Smith, James L D; O'Brien, Stephen J

    2007-01-01

    Y chromosome haplotyping based on microsatellites and single nucleotide polymorphisms (SNPs) has proved to be a powerful tool for population genetic studies of humans. However, the promise of the approach is hampered in the majority of nonhuman mammals by the lack of Y-specific polymorphic markers. We were able to identify new male-specific polymorphisms in the domestic cat Felis catus and 6 additional Felidae species with a combination of molecular genetic and cytogenetic approaches including 1) identifying domestic cat male-specific microsatellites from markers generated from a male cat microsatellite-enriched genomic library, a flow-sorted Y cosmid library, or a Y-specific cat bacteria artificial chromosome (BAC) clone, (2) constructing microsatellite-enriched libraries from flow-sorted Y chromosomes isolated directly from focal wildcat species, and (3) screening Y chromosome conserved anchored tagged sequences primers in Felidae species. Forty-one male-specific microsatellites were identified, but only 6 were single-copy loci, consistent with the repetitive nature of the Y chromosome. Nucleotide diversity (pi) of Y-linked intron sequences (2.1 kbp) was in the range of 0 (tiger) to 9.95 x 10(-4) (marbled cat), and the number of SNPs ranged from none in the tiger to 7 in the Asian leopard cat. The Y haplotyping system described here, consisting of 4 introns (SMCY3, SMCY7, UTY11, and DBY7) and 1 polymorphic microsatellite (SMCY-STR), represents the first available markers for tracking intraspecific male lineage polymorphisms in Felidae species and promises to provide significant insights to evolutionary and population genetic studies of the species.

  7. [APOE gene polymorphisms associated with Down syndrome in Colombian populations].

    PubMed

    Rengifo, Lucero; Gaviria, Duverney; Serrano, Herman

    2012-06-01

    Introduction.Gene APOEε4 allele polymorphisms have been examined in Down syndrome because of the relationship between (a) the E4 isoform and (b) the type of Alzheimer's dementia that appears in individuals with Down syndrome. This isoform is considered a risk factor for Alzheimer's disease development and has been associated with early death in Down syndrome. Objectives. The polymorphisms in the APOE gene were characterized for Down syndrome individuals and their parents, in order to detect associations between the APOE polymorphisms and Down syndrome. Materials and methods. APOE gene polymorphisms were detected by RFLP-PCR and analyzed in 134 young individuals with Down syndrome, 87 mothers and 54 fathers, residents of the departments of Quindío and Risaralda, Colombia. The controls were 525 healthy individuals. Results. The APOEε3 allele and ε3/ε3 genotype were most frequent in all the populations (83-90% and 70-78%). The allelic frequency of APOEε2 was very low and ε2/ε2 (3-7%) was absent in Down syndrome and their parents. The allele APOEε4 was more frequent (11% vs. 9%) in Down syndrome individuals than in the controls. Comparing the allelic and genotypic frequencies between the populations with Down syndrome and their parents with the controls using Pearson c2 test and Fisher's exact test odds ratio, no statistically significant differences were found. Conclusions. No statistically significant association was found between the polymorphisms of the APOE gene and Down syndrome. Sample size or ethnic influences may have affected these results. More studies are necessary with other Colombian populations to determine possible associations in other genes related to Alzheimer's disease.

  8. Crystallisation Pathways of Polymorphic Triacylglycerols Induced by Mechanical Energy

    NASA Astrophysics Data System (ADS)

    Lee, Y. L.; Ristic, R. I.; DeMatos, L. L.; Martin, C. M.

    2010-10-01

    The aim of these studies is to establish sound scientific principles to guide nucleation rate and the selection of a desired polymorph via the application of mechanical energy - ultrasound (US) irradiation. When delivered to a metastable liquid, before the offset of nucleation and under constant temperature and supercooling conditions, the wave nature of this simple form of energy should be critical for defining different crystallisation pathways of polymorphic materials including polymorph selection. To test this hypothesis, we crystallized a melt-grown trilaurin (LLL), a typical polymorphic triacylglycerols (TGA's), with and without US by using in-situ simultaneous synchrotron radiation time-resolved small-angle X-ray scattering (SAXS) and wide angle X-ray scattering (WAXS), SAXS/WAXS. Without US application, both polymorphic forms β' and β crystallized. With US treatment of the super cooled melt, the following effects were observed: (a) a marked decrease of induction times (b) an increased nucleation rate, and (c) selective crystallization of only β-form when crystallised at 25 and 30°C with input powers of 20 and 100 W and a sonication time of 2 s. Combining the existing knowledge on the dynamic nucleation of collapsing cavities and a qualitatively developed (P-T) phase diagram for the TGA's, it was possible to describe, for the first time, the behaviour of the most important parameters and the events that characterize the crystallization of these systems. It was shown that the interplay of sonication and the temperature of supercooled melts are critical to the selection of a stable β form.

  9. BRCA1 polymorphism in breast cancer patients from Argentina.

    PubMed

    Jaure, Omar; Alonso, Eliana N; Braico, Diego Aguilera; Nieto, Alvaro; Orozco, Manuela; Morelli, Cecilia; Ferro, Alejandro M; Barutta, Elena; Vincent, Esteban; Martínez, Domingo; Martínez, Ignacio; Maegli, Maria Ines; Frizza, Alejandro; Kowalyzyn, Ruben; Salvadori, Marisa; Ginestet, Paul; Gonzalez Donna, Maria L; Balogh, Gabriela A

    2015-02-01

    Breast cancer is the most common type of cancer in females in Argentina, with an incidence rate similar to that in the USA. However, the contribution of the BRCA1 or BRCA2 mutation in breast cancer incidence has not yet been investigated in Argentina. In order to evaluate which BRCA1 polymorphisms or mutations characterize female breast cancer in Argentina, the current study enrolled 206 females with breast cancer from several hospitals from the southeast of Argentina. A buccal smear sample was obtained in duplicate from each patient and the DNA samples were processed for polymorphism analysis using the single-strand conformational polymorphism technique. The polymorphisms in BRCA1 were investigated using a combination of 15 primers to analyze exons 2, 3, 5, 20 and 11 (including the 11.1 to 11.12 regions). The BRCA1 mutations were confirmed by direct sequencing. Samples were successfully examined from 154 females and, among these, 16 mutations were identified in the BRCA1 gene representing 13.9% of the samples analyzed. One patient was identified with a polymorphism in exon 2 (0.86%), four in exon 20 (3.48%), four in exon 11.3 (3.48%), one in exon 11.7 (0.86%), two in exon 11.8 (1.74%), one in exon 11.10 (0.86%) and one in exon 11.11 (0.86%). The most prevalent alteration in BRCA1 was located in exon 11 (11 out of 16 patients; 68.75%). The objective of our next study is to evaluate the prevalence of mutations in the BRCA2 gene and analyze the BRCA1 gene in the healthy relatives of BRCA1 mutation carriers.

  10. BRCA1 polymorphism in breast cancer patients from Argentina

    PubMed Central

    JAURE, OMAR; ALONSO, ELIANA N.; BRAICO, DIEGO AGUILERA; NIETO, ALVARO; OROZCO, MANUELA; MORELLI, CECILIA; FERRO, ALEJANDRO M.; BARUTTA, ELENA; VINCENT, ESTEBAN; MARTÍNEZ, DOMINGO; MARTÍNEZ, IGNACIO; MAEGLI, MARIA INES; FRIZZA, ALEJANDRO; KOWALYZYN, RUBEN; SALVADORI, MARISA; GINESTET, PAUL; GONZALEZ DONNA, MARIA L.; BALOGH, GABRIELA A.

    2015-01-01

    Breast cancer is the most common type of cancer in females in Argentina, with an incidence rate similar to that in the USA. However, the contribution of the BRCA1 or BRCA2 mutation in breast cancer incidence has not yet been investigated in Argentina. In order to evaluate which BRCA1 polymorphisms or mutations characterize female breast cancer in Argentina, the current study enrolled 206 females with breast cancer from several hospitals from the southeast of Argentina. A buccal smear sample was obtained in duplicate from each patient and the DNA samples were processed for polymorphism analysis using the single-strand conformational polymorphism technique. The polymorphisms in BRCA1 were investigated using a combination of 15 primers to analyze exons 2, 3, 5, 20 and 11 (including the 11.1 to 11.12 regions). The BRCA1 mutations were confirmed by direct sequencing. Samples were successfully examined from 154 females and, among these, 16 mutations were identified in the BRCA1 gene representing 13.9% of the samples analyzed. One patient was identified with a polymorphism in exon 2 (0.86%), four in exon 20 (3.48%), four in exon 11.3 (3.48%), one in exon 11.7 (0.86%), two in exon 11.8 (1.74%), one in exon 11.10 (0.86%) and one in exon 11.11 (0.86%). The most prevalent alteration in BRCA1 was located in exon 11 (11 out of 16 patients; 68.75%). The objective of our next study is to evaluate the prevalence of mutations in the BRCA2 gene and analyze the BRCA1 gene in the healthy relatives of BRCA1 mutation carriers. PMID:25624909

  11. The effect of pH on polymorph formation of the pharmaceutically active compound tianeptine.

    PubMed

    Orola, Liana; Veidis, Mikelis V; Sarcevica, Inese; Actins, Andris; Belyakov, Sergey; Platonenko, Aleksandrs

    2012-08-01

    The anti-depressant pharmaceutical tianeptine has been investigated to determine the dynamics of polymorph formation under various pH conditions. By varying the pH two crystalline polymorphs were isolated. The molecular and crystal structures have been determined to identify the two polymorphs. One polymorph is an amino carboxylic acid and the other polymorph is a zwitterion. In the solid state the tianeptine moieties are bonded through hydrogen bonds. The zwitterion was found to be less stable and transformed to the acid form. During this investigation an amorphous form was identified.

  12. Single nucleotide polymorphisms in the ovine casein genes detected by polymerase chain reaction-single strand conformation polymorphism.

    PubMed

    Ceriotti, G; Chessa, S; Bolla, P; Budelli, E; Bianchi, L; Duranti, E; Caroli, A

    2004-08-01

    Casein genetic polymorphisms are important and well known due to their effects on quantitative traits and technological properties of milk. At the DNA level, polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) allows for the simultaneous typing of several alleles at casein loci, as well as the detection of unknown polymorphisms. Here we describe the usefulness of the PCR-SSCP technique for casein typing in sheep. In particular, three single-nucleotide polymorphisms (SNP) are described at CSN1S1, CSN2, and CSN3, all resulting in amino acid exchanges. At CSN1S1, a transition T-->C was found, resulting in the deduced amino acid exchange Ile186-->Thr186. A transition A-->G resulting in the deduced amino acid exchange Met183-->Val183 was identified at CSN2. The 2 SNP showed a rather high frequency (ranging from 0.12 to 0.26) in 3 Italian breeds (Sarda, Comisana, Sopravissana). Another transition C-->T (Ser104-->Leu104) was found at CSN3 in one heterozygous animal.

  13. FluoMEP: a new genotyping method combining the advantages of randomly amplified polymorphic DNA and amplified fragment length polymorphism.

    PubMed

    Chang, Alex; Liew, Woei Chang; Chuah, Aaron; Lim, Zijie; Lin, Qifeng; Orban, Laszlo

    2007-02-01

    PCR-based identification of differences between two unknown genomes often requires complex manipulation of the templates prior to amplification and/or gel electrophoretic separation of a large number of samples with manual methods. Here, we describe a new genotyping method, called fluorescent motif enhanced polymorphism (fluoMEP). The fluoMEP method is based on random amplified polymorphic DNA (RAPD) assay, but combines the advantages of the large collection of unlabelled 10mer primers (ca. 5000) from commercial sources and the power of the automated CE devices used for the detection of amplified fragment length polymorphism (AFLP) patterns. The link between these two components is provided by a fluorescently labeled "common primer" that is used in a two-primer PCR together with an unlabeled RAPD primer. By using the same "common primer" and a series of RAPD primers, DNA templates can be screened quickly and effectively for polymorphisms. Our manuscript describes the optimization of the method and its characterization on different templates. We demonstrate by using several different approaches that the addition of the "common primer" to the PCR changes the profile of amplified fragments, allowing for screening various parts of the genome with the same set of unlabeled primers. We also present an in silico analysis of the genomic localization of fragments amplified by a RAPD primer with two different "common primers" and alone.

  14. Association between the CYP1B1 polymorphisms and risk of cancer: a meta-analysis.

    PubMed

    Liu, Jie-Ying; Yang, Yu; Liu, Zhi-Zhong; Xie, Jian-Jun; Du, Ya-Ping; Wang, Wei

    2015-04-01

    The previous, published data on the association between CYP1B1 polymorphisms and cancer risk remained controversial. To derive a more precise estimation of the association between the CYP1B1 polymorphisms and cancer risk, we performed a meta-analysis to investigate the association between cancer susceptibility and CYP1B1 Leu432Val, Asn453Ser, Arg48Gly, and Ala119Ser polymorphisms. For Asn453Ser and Arg48Gly polymorphisms, significantly decreased endometrial cancer was observed among Caucasians. For Ala119Ser polymorphism, we found that individuals with the minor variant genotypes had a high risk of prostate cancer. For Leu432Val polymorphism, we found that individuals with the minor variant genotypes had a higher risk of endometrial cancer and lung cancer and had a lower risk of ovarian cancer. In summary, this meta-analysis suggests that Leu432Val polymorphism is associated with ovarian cancer, lung cancer, and endometrial cancer risk; Asn453Ser and Arg48Gly polymorphisms are associated with endometrial cancer risk among Caucasians, Ala119Ser polymorphism is associated with prostate cancer risk, and Ala119Ser polymorphism is associated with breast cancer risk in Caucasians. In addition, our work also points out the importance of new studies for Ala119Ser polymorphism in endometrial cancer, because high heterogeneity was observed (I (2) > 75 %).

  15. Diffusion Monte Carlo Study of Para-Diiodobenzene Polymorphism Revisited.

    PubMed

    Hongo, Kenta; Watson, Mark A; Iitaka, Toshiaki; Aspuru-Guzik, Alán; Maezono, Ryo

    2015-03-10

    We revisit our investigation of the diffusion Monte Carlo (DMC) simulation of para-diiodobenzene (p-DIB) molecular crystal polymorphism. [See J. Phys. Chem. Lett. 2010, 1, 1789-1794.] We perform, for the first time, a rigorous study of finite-size effects and choice of nodal surface on the prediction of polymorph stability in molecular crystals using fixed-node DMC. Our calculations are the largest that are currently feasible using the resources of the K-computer and provide insights into the formidable challenge of predicting such properties from first principles. In particular, we show that finite-size effects can influence the trial nodal surface of a small (1 × 1 × 1) simulation cell considerably. Therefore, we repeated our DMC simulations with a 1 × 3 × 3 simulation cell, which is the largest such calculation to date. We used a density functional theory (DFT) nodal surface generated with the PBE functional, and we accumulated statistical samples with ∼6.4 × 10(5) core hours for each polymorph. Our final results predict a polymorph stability that is consistent with experiment, but they also indicate that the results in our previous paper were somewhat fortuitous. We analyze the finite-size errors using model periodic Coulomb (MPC) interactions and kinetic energy corrections, according to the CCMH scheme of Chiesa, Ceperley, Martin, and Holzmann. We investigate the dependence of the finite-size errors on different aspect ratios of the simulation cell (k-mesh convergence) in order to understand how to choose an appropriate ratio for the DMC calculations. Even in the most expensive simulations currently possible, we show that the finite size errors in the DMC total energies are much larger than the energy difference between the two polymorphs, although error cancellation means that the polymorph prediction is accurate. Finally, we found that the T-move scheme is essential for these massive DMC simulations in order to circumvent population explosions and

  16. Polymorphism in molecular solids: an extraordinary system of red, orange, and yellow crystals.

    PubMed

    Yu, Lian

    2010-09-21

    Diamond and graphite are polymorphs of each other: they have the same composition but different structures and properties. Many other substances exhibit polymorphism: inorganic and organic, natural and manmade. Polymorphs are encountered in studies of crystallization, phase transition, materials synthesis, and biomineralization and in the manufacture of specialty chemicals. Polymorphs can provide valuable insights into crystal packing and structure-property relationships. 5-Methyl-2-[(2-nitrophenyl)amino]-3-thiophenecarbonitrile, known as ROY for its red, orange, and yellow crystals, has seven polymorphs with solved structures, the largest number in the Cambridge Structural Database. First synthesized by medicinal chemists, ROY has attracted attention from solid-state chemists because it demonstrates the remarkable diversity possible in organic solids. Many structures of ROY polymorphs and their thermodynamic properties are known, making ROY an important model system for testing computational models. Though not the most polymorphic substance on record, ROY is extraordinary in that many of its polymorphs can crystallize simultaneously from the same liquid and are kinetically stable under the same conditions. Studies of ROY polymorphs have revealed a new crystallization mechanism that invalidates the common view that nucleation defines the polymorph of crystallization. A slow-nucleating polymorph can still dominate the product if it grows rapidly and nucleates on another polymorph. Studies of ROY have also helped understand a new, surprisingly fast mode of crystal growth in organic liquids cooled to the glass transition temperature. This growth mode exists only for those polymorphs that have more isotropic, and perhaps more liquid-like, packing. The rich polymorphism of ROY results from a combination of favorable thermodynamics and kinetics. Not only must there be many polymorphs of comparable energies or free energies, many polymorphs must be kinetically stable and

  17. Rotation-Induced Polymorphic Transitions in Bacterial Flagella

    NASA Astrophysics Data System (ADS)

    Vogel, Reinhard; Stark, Holger

    2013-04-01

    Bacteria propel themselves with the help of rotating helical flagella. They change their swimming direction during tumbling events in order to increase, for example, their supply of nutrients (chemotaxis). During tumbling a bacterial flagellum assumes different polymorphic states. Based on a continuum model for the motor-flagellum system, we demonstrate that a changing motor torque can initiate these polymorphic transformations. In particular, we investigate the run-and-stop tumble strategy of Rhodobacter sphaeroides which uses a coiled-to-normal transition in its single flagellum. We also show that torque reversal in single-flagellated Escherichia coli generates a normal-to-curly I transition as observed for tumbling E. coli that swim with a bundle of several flagella.

  18. Polymorphism Behaviors of Electrospun Poly(vinylidene fluoride) Nanofibers

    NASA Astrophysics Data System (ADS)

    Zhong, Zhenxin; Reneker, Darrell

    2009-03-01

    Poly(vinylidene fluoride) (PVDF) and its copolymers have drawn great attention in recent years due to their attractive electrical properties such as ferro-, piezo- and pyro-electricity. Depending on its processing, PVDF can exhibit five different polymorphs. Among them, the beta phase has the highest piezo-, pyro- and ferroelectric activities. Electrospinning was used to produce thin polymer fibers. The polymorphic behavior of electrospun PVDF fibers was observed. Long cylindrical PVDF specimens with cross-sections in the range of 10 nm to 1 micron was obtained by varying the electrospinning conditions. Almost pure beta phase was obtained in electrospun PVDF nanofibers. The morphology and internal structure of single PVDF electrospun nanofibers were studied by transmission electron microscopy.

  19. Glutathione S-transferase class {pi} polymorphism in baboons

    SciTech Connect

    Aivaliotis, M.J.; Cantu, T.; Gilligan, R.

    1995-02-01

    Glutathione S-transferase (GST) comprises a family of isozymes with broad substrate specificities. One or more GST isozymes are present in most animal tissues and function in several detoxification pathways through the conjugation of reduced glutathione with various electrophiles, thereby reducing their potential toxicity. Four soluble GST isozymes encoded by genes on different chromosomes have been identified in humans. The acidic class pi GST, GSTP (previously designated GST-3), is widely distributed in adult tissues and appears to be the only GST isozyme present in leukocytes and placenta. Previously reported electrophoretic analyses of erythrocyte and leukocyte extracts revealed single bands of activity, which differed slightly in mobility between the two cell types, or under other conditions, a two-banded pattern. To our knowledge, no genetically determined polymorphisms have previously been reported in GSTP from any species. We now report a polymorphism of GSTP in baboon leukocytes, and present family data that verifies autosomal codominant inheritance. 14 refs., 2 figs., 1 tab.

  20. Flow cytometry-based DNA hybridization and polymorphism analysis

    SciTech Connect

    Cai, H.; Kommander, K.; White, P.S.; Nolan, J.P.

    1998-07-01

    Functional analysis of the humane genome, including the quantification of differential gene expression and the identification of polymorphic sites and disease genes, is an important element of the Human Genome Project. Current methods of analysis are mainly gel-based assays that are not well-suited to rapid genome-scale analyses. To analyze DNA sequence on a large scale, robust and high throughput assays are needed. The authors are developing a suite of microsphere-based approaches employing fluorescence detection to screen and analyze genomic sequence. The approaches include competitive DNA hybridization to measure DNA or RNA targets in unknown samples, and oligo ligation or extension assays to analyze single-nucleotide polymorphisms. Apart from the advances of sensitivity, simplicity, and low sample consumption, these flow cytometric approaches have the potential for high throughput multiplexed analysis using multicolored microspheres and automated sample handling.

  1. BoLA DYA polymorphism in Czech cattle.

    PubMed

    Horín, P; Matiasovic, J; Trtková, K; Pavlík, I

    1998-01-01

    Polymorphism at the BoLA DYA locus was determined in two groups of Czech Black Pied cattle by PCR-RFLP detecting substitutions at nucleotide positions 112 and 219. Animals for this study were nonrandomly selected according to their health status in two BoLA-associated infections: bovine leukosis (n = 59) and Johne's disease (n = 36). A group of noninfected Czech Red Pied cows (n = 37) was used for comparison. The frequencies of DYA alleles and haplotypes were virtually identical in the two selected groups as well as in the infection-free animals. In contrast, distribution of BoLA DRB3.2 alleles differed considerably between the infected groups as expected based on the previously detected associations with BoLA. The results suggest that the polymorphism of the DYA unexpressed gene was not influenced by selecting animals for this study according to their health status.

  2. Alu polymorphic insertions reveal genetic structure of north Indian populations.

    PubMed

    Tripathi, Manorama; Tripathi, Piyush; Chauhan, Ugam Kumari; Herrera, Rene J; Agrawal, Suraksha

    2008-10-01

    The Indian subcontinent is characterized by the ancestral and cultural diversity of its people. Genetic input from several unique source populations and from the unique social architecture provided by the caste system has shaped the current genetic landscape of India. In the present study 200 individuals each from three upper-caste and four middle-caste Hindu groups and from two Muslim populations in North India were examined for 10 polymorphic Alu insertions (PAIs). The investigated PAIs exhibit high levels of polymorphism and average heterozygosity. Limited interpopulation variance and genetic flow in the present study suggest admixture. The results of this study demonstrate that, contrary to common belief, the caste system has not provided an impermeable barrier to genetic exchange among Indian groups.

  3. Polymorphism in magic-sized Au144(SR)60 clusters

    PubMed Central

    Jensen, Kirsten M.Ø.; Juhas, Pavol; Tofanelli, Marcus A.; Heinecke, Christine L.; Vaughan, Gavin; Ackerson, Christopher J.; Billinge, Simon J. L.

    2016-01-01

    Ultra-small, magic-sized metal nanoclusters represent an important new class of materials with properties between molecules and particles. However, their small size challenges the conventional methods for structure characterization. Here we present the structure of ultra-stable Au144(SR)60 magic-sized nanoclusters obtained from atomic pair distribution function analysis of X-ray powder diffraction data. The study reveals structural polymorphism in these archetypal nanoclusters. In addition to confirming the theoretically predicted icosahedral-cored cluster, we also find samples with a truncated decahedral core structure, with some samples exhibiting a coexistence of both cluster structures. Although the clusters are monodisperse in size, structural diversity is apparent. The discovery of polymorphism may open up a new dimension in nanoscale engineering. PMID:27297400

  4. Polymorphic microsatellites for forensic identification of agarwood (Aquilaria crassna).

    PubMed

    Eurlings, Marcel C M; van Beek, Henry Heuveling; Gravendeel, Barbara

    2010-04-15

    Tropical agarwood (Aquilaria) is in danger of extinction in the wild due to illegal logging. Its resin (Gaharu) is used for the production of highly valued incense throughout Asia. We have isolated and characterized microsatellite loci of Aquilaria crassna to detect the geographic origin of agarwood for forensic applications using a modified enrichment procedure based on the capture of repetitive sequences from restricted genomic DNA. We assessed the polymorphisms of five microsatellites amplified from fresh leaves of 22 trees from seven plantations in Vietnam and Thailand and dried leaves of a herbarium specimen of one wild tree. Cross specificity of these markers was confirmed on two related Aquilaria species occurring in China and Vietnam and one microsatellite locus was successfully amplified from wood and incense samples. Four of the loci were polymorphic and the number of alleles ranged from 3 to 15. The loci characterized here can provide a starting point for forensic identification of traded material and certification of sustainably produced agarwood.

  5. Flow-cytometry-based DNA hybidization and polymorphism analysis

    NASA Astrophysics Data System (ADS)

    Cai, Hong; Kommander, Kristina; White, P. S.; Nolan, John P.

    1998-05-01

    Functional analysis of the human genome, including the quantification of differential gene expression and the identification of polymorphic sites and disease genes, is an important element of the Human Genome Project. Current methods of analysis are mainly gel-based assays that are not well- suited to rapid genome-scale analyses. To analyze DNA sequence on a large scale, robust and high throughput assays are needed. We are developing a suite of microsphere-based approaches employing fluorescence detection to screen and analyze genomic sequence. Our approaches include competitive DNA hybridization to measure DNA or RNA targets in unknown samples, and oligo ligation or extension assays to analyze single-nucleotide polymorphisms. Apart from the advantages of sensitivity, simplicity, and low sample consumption, these flow cytometric approaches have the potential for high throughput multiplexed analysis using multicolored microspheres and automated sample handling.

  6. Complexity, polymorphism, and connectivity of mouse Vk gene families.

    PubMed

    Kofler, R; Duchosal, M A; Dixon, F J

    1989-01-01

    To define the polymorphism and extent of the mouse immunoglobulin kappa (Igk) gene complex, we have analyzed restriction-enzyme digested genomic DNA from 33 inbred strains of mice with labeled DNA probes corresponding to 16 Vk protein groups (1 of them previously undescribed) and the Jk/Ck region (V, variable; J, joining; C, constant). These probes detected between 1 and 25 distinct restriction enzyme fragments (REF) that appeared in up to eight polymorphic patterns, thus defining eight mouse Igk haplotypes. The investigated portion of the Vk repertoire was estimated to encompass between 60 and 120 discernable Vk gene-containing REFs. In contrast to mouse VH gene families, several Vk gene families defined by these probes appeared to overlap. This observation has implications for Vk gene analyses by nucleic acid hybridization and raises the possibility that the Vk gene complex is a continuum of related sequences.

  7. Polymorphism in magic-sized Au144(SR)60 clusters

    NASA Astrophysics Data System (ADS)

    Jensen, Kirsten M. Ø.; Juhas, Pavol; Tofanelli, Marcus A.; Heinecke, Christine L.; Vaughan, Gavin; Ackerson, Christopher J.; Billinge, Simon J. L.

    2016-06-01

    Ultra-small, magic-sized metal nanoclusters represent an important new class of materials with properties between molecules and particles. However, their small size challenges the conventional methods for structure characterization. Here we present the structure of ultra-stable Au144(SR)60 magic-sized nanoclusters obtained from atomic pair distribution function analysis of X-ray powder diffraction data. The study reveals structural polymorphism in these archetypal nanoclusters. In addition to confirming the theoretically predicted icosahedral-cored cluster, we also find samples with a truncated decahedral core structure, with some samples exhibiting a coexistence of both cluster structures. Although the clusters are monodisperse in size, structural diversity is apparent. The discovery of polymorphism may open up a new dimension in nanoscale engineering.

  8. Cervical Carcinogenesis and Immune Response Gene Polymorphisms: A Review

    PubMed Central

    Mooij, Merel

    2017-01-01

    The local immune response is considered a key determinant in cervical carcinogenesis after persistent infection with oncogenic, high-risk human papillomavirus (HPV) infections. Genetic variation in various immune response genes has been shown to influence risk of developing cervical cancer, as well as progression and survival among cervical cancer patients. We reviewed the literature on associations of immunogenetic single nucleotide polymorphism, allele, genotype, and haplotype distributions with risk and progression of cervical cancer. Studies on HLA and KIR gene polymorphisms were excluded due to the abundance on literature on that subject. We show that multiple genes and loci are associated with variation in risk of cervical cancer. Rather than one single gene being responsible for cervical carcinogenesis, we postulate that variations in the different immune response genes lead to subtle differences in the effectiveness of the antiviral and antitumour immune responses, ultimately leading to differences in risk of developing cervical cancer and progressive disease after HPV infection. PMID:28280748

  9. Polymorphous low grade adenocarcinoma presenting an uncommon radiographic aspect.

    PubMed

    de Magalhães, M H C G; de Magalhães, R P; de Araújo, V C; de Sousa, S O M

    2006-05-01

    The aim of this study was to present clinical, histological and immunohistochemical aspects of a polymorphous low grade adenocarcinoma occurring in the mandible. A radiolucent tumour, located in the right mandible, was removed from a 40-year-old woman. Radiographic and CT exams revealed that the lesion expanded bucco-lingual cortical plates and presented an irregular scalloping of the bone. The surrounding lining mucosa was intact. The patient underwent total surgical removal of the lesion with an intraoperative biopsy. Histological diagnosis was polymorphous low-grade adenocarcinoma confirmed by immunohistochemical study. One-year follow up was uneventful. The accurate diagnosis of lesions presenting unusual clinical aspects, as the one presented here, is critical for correctly handling treatment.

  10. Polymorphism in magic-sized Au144(SR)60 clusters

    SciTech Connect

    Jensen, Kirsten M. O.; Juhas, Pavol; Tofanelli, Marcus A.; Heinecke, Christine L.; Vaughan, Gavin; Ackerson, Christopher J.; Billinge, Simon J. L.

    2016-06-14

    Ultra-small, magic-sized metal nanoclusters represent an important new class of materials with properties between molecules and particles. However, their small size challenges the conventional methods for structure characterization. We present the structure of ultra-stable Au144(SR)60 magic-sized nanoclusters obtained from atomic pair distribution function analysis of X-ray powder diffraction data. Our study reveals structural polymorphism in these archetypal nanoclusters. Additionally, in order to confirm the theoretically predicted icosahedral-cored cluster, we also find samples with a truncated decahedral core structure, with some samples exhibiting a coexistence of both cluster structures. Although the clusters are monodisperse in size, structural diversity is apparent. Finally, the discovery of polymorphism may open up a new dimension in nanoscale engineering.

  11. Polymorphism in magic-sized Au144(SR)60 clusters

    DOE PAGES

    Jensen, Kirsten M. O.; Juhas, Pavol; Tofanelli, Marcus A.; ...

    2016-06-14

    Ultra-small, magic-sized metal nanoclusters represent an important new class of materials with properties between molecules and particles. However, their small size challenges the conventional methods for structure characterization. We present the structure of ultra-stable Au144(SR)60 magic-sized nanoclusters obtained from atomic pair distribution function analysis of X-ray powder diffraction data. Our study reveals structural polymorphism in these archetypal nanoclusters. Additionally, in order to confirm the theoretically predicted icosahedral-cored cluster, we also find samples with a truncated decahedral core structure, with some samples exhibiting a coexistence of both cluster structures. Although the clusters are monodisperse in size, structural diversity is apparent. Finally,more » the discovery of polymorphism may open up a new dimension in nanoscale engineering.« less

  12. '1-Antitrypsin polymorphism and systematics of eastern North American wolves

    USGS Publications Warehouse

    Mech, L.D.; Federoff, N.E.

    2002-01-01

    We used data on the polymorphic status of '1-antitrypsin ('1AT) to study the relationship of Minnesota wolves to the gray wolf (Canis lupus), which was thought to have evolved in Eurasia, and to red wolves (Canis rufus) and coyotes (Canis latrans), which putatively evolved in North America. Recent evidence had indicated that Minnesota wolves might be more closely related to red wolves and coyotes. Samples from wild-caught Minnesota wolves and from captive wolves, at least some of which originated in Alaska and western Canada, were similarly polymorphic for '1AT, whereas coyote and red wolf samples were all monomorphic. Our findings, in conjunction with earlier results, are consistent with the Minnesota wolf being a gray wolf of Eurasian origin or possibly a hybrid between the gray wolf of Eurasian origin and the proposed North American wolf.

  13. Rabbit MSTN gene polymorphisms and genetic effect analysis.

    PubMed

    Qiao, X B; Xu, K Y; Li, B; Luan, X; Xia, T; Fan, X Z

    2014-04-08

    We analyzed meat samples of nine pure lines of rabbit and its 37 hybrid combinations by sequencing and single-strand conformation polymorphism techniques to explore genetic polymorphisms of all the three exon regions and part of the 5'-regulatory region of the myostatin (MSTN) gene. Thus, we detected a single nucleotide mutation (T→C) on the 476 locus of the 5'-regulatory region, but no mutation sites were detected in the exon areas. The correlation analysis showed that the mutation had some favorable genetic effects, and it resulted in increased liver weight, carcass weight, forelegs weight, back and waist weight, ham weight, and tare weight, whereas it decreased muscle drip loss and cooking loss (P < 0.05). These results suggest that the mutations in the upstream regulatory region of the MSTN gene are beneficial to the rabbit soma development, and the mutations can be used as molecular markers for the selection of the meat quality of rabbits.

  14. Characterization of Coccidioides immitis isolates by restriction fragment length polymorphisms.

    PubMed Central

    Zimmermann, C R; Snedker, C J; Pappagianis, D

    1994-01-01

    The marked increase in the number of cases of coccidioidomycosis in California in 1992 led to a study of isolates from various patients and environmental sources by restriction fragment length polymorphism (RFLP) analysis. Of 15 different isolates, most of the isolates (13 of 15) from California and 1 from Venezuela yielded one main RFLP pattern with evidence of two subgroups. The other two isolates (both from patients in the San Joaquin Valley of California) yielded a different RFLP pattern. Images PMID:7883896

  15. Detection of an exon 53 polymorphism in the dystrophin gene.

    PubMed

    Prior, T W; Papp, A C; Snyder, P J; Sedra, M S

    1993-10-01

    We utilized a heteroduplex method to screen for small mutations in Duchenne muscular dystrophy patients who did not have deletions or duplications. A dystrophin exon 53 heteroduplex band was identified in 14.4% of the affected patients. Direct sequencing of the amplified product from DNA producing the heteroduplex revealed the presence of a polymorphism in the coding region. The codon for asparagine was converted from AAT to AAC.

  16. Chromatin fiber polymorphism triggered by variations of DNA linker lengths.

    PubMed

    Collepardo-Guevara, Rosana; Schlick, Tamar

    2014-06-03

    Deciphering the factors that control chromatin fiber structure is key to understanding fundamental chromosomal processes. Although details remain unknown, it is becoming clear that chromatin is polymorphic depending on internal and external factors. In particular, different lengths of the linker DNAs joining successive nucleosomes (measured in nucleosome-repeat lengths or NRLs) that characterize different cell types and cell cycle stages produce different structures. NRL is also nonuniform within single fibers, but how this diversity affects chromatin fiber structure is not clear. Here we perform Monte Carlo simulations of a coarse-grained oligonucleosome model to help interpret fiber structure subject to intrafiber NRL variations, as relevant to proliferating cells of interphase chromatin, fibers subject to remodeling factors, and regulatory DNA sequences. We find that intrafiber NRL variations have a profound impact on chromatin structure, with a wide range of different architectures emerging (highly bent narrow forms, canonical and irregular zigzag fibers, and polymorphic conformations), depending on the NRLs mixed. This stabilization of a wide range of fiber forms might allow NRL variations to regulate both fiber compaction and selective DNA exposure. The polymorphic forms spanning canonical to sharply bent structures, like hairpins and loops, arise from large NRL variations and are surprisingly more compact than uniform NRL structures. They are distinguished by tail-mediated far-nucleosome interactions, in addition to the near-nucleosome interactions of canonical 30-nm fibers. Polymorphism is consistent with chromatin's diverse biological functions and heterogeneous constituents. Intrafiber NRL variations, in particular, may contribute to fiber bending and looping and thus to distant communication in associated regulatory processes.

  17. A Broad Analysis of IL1 Polymorphism and Rheumatoid Arthritis

    PubMed Central

    Johnsen, Alyssa K.; Plenge, Robert M.; Butty, Vincent; Campbell, Christopher; Dieguez-Gonzalez, Rebeca; Gomez-Reino, Juan J.; Shadick, Nancy; Weinblatt, Michael; Gonzalez, Antonio; Gregersen, Peter K.; Benoist, Christophe; Mathis, Diane

    2008-01-01

    Objective It has been suggested that polymorphisms in IL1 are correlated with severe and/or erosive rheumatoid arthritis (RA), but the implicated alleles have differed among studies. The aim of this study was to perform a broad and well-powered search for association between allelic polymorphism in IL1A and IL1B and the susceptibility to or severity of RA. Methods Key coding and regulatory regions in IL1A and IL1B were sequenced in 24 patients with RA, revealing 4 novel single-nucleotide polymorphisms (SNPs) in IL1B. These and a comprehensive set of 24 SNPs tagging most of the underlying genetic diversity were genotyped in 3 independent RA case-control sample sets and 1 longitudinal RA cohort, totaling 3,561 patients and 3,062 control subjects. Results No fully significant associations were observed. Analysis of the discovery case-control sample sets indicated a potential association of IL1B promoter region SNPs with susceptibility to RA (for RA3/A, odds ratio [OR] 1.27, P = 0.0021) or with the incidence of radiographic erosions (for RA4/C, OR 1.56, P = 0.036), but these findings were not replicated in independent case-control samples. No association with rheumatoid factor, anti-cyclic citrullinated peptide, or the Disease Activity Score in 28 joints was found. None of the associations previously observed in other studies were replicated here. Conclusion In spite of a broad and highly powered study, we observed no robust, reproducible association between IL1A/B variants and the susceptibility to or severity of RA in white individuals of European descent. Our results provide evidence that, in the majority of cases, polymorphism in IL1A and IL1B is not a major contributor to genetic susceptibility to RA. PMID:18576312

  18. Cisplatin pharmacogenetics, DNA repair polymorphisms, and esophageal cancer outcomes

    PubMed Central

    Bradbury, Penelope A.; Kulke, Matthew H.; Heist, Rebecca S.; Zhou, Wei; Ma, Clement; Xu, Wei; Marshall, Ariela L.; Zhai, Rihong; Hooshmand, Susanne M.; Asomaning, Kofi; Su, Li; Shepherd, Frances A.; Lynch, Thomas J.; Wain, John C.; Christiani, David C.; Liu, Geoffrey

    2011-01-01

    Objectives Genetic variations or polymorphisms within genes of the nucleotide excision repair (NER) pathway alter DNA repair capacity. Reduced DNA repair (NER) capacity may result in tumors that are more susceptible to cisplatin chemotherapy, which functions by causing DNA damage. We investigated the potential predictive significance of functional NER single nucleotide polymorphisms in esophageal cancer patients treated with (n = 262) or without (n = 108) cisplatin. Methods Four NER polymorphisms XPD Asp312Asn; XPD Lys751Gln, ERCC1 8092C/A, and ERCC1 codon 118C/T were each assessed in polymorphism–cisplatin treatment interactions for overall survival (OS), with progression-free survival (PFS) as a secondary endpoint. Results No associations with ERCC1 118 were found. Polymorphism–cisplatin interactions were highly significant in both OS (P = 0.002, P = 0.0001, and P < 0.0001) and PFS (P = 0.006, P = 0.008, and P = 0.0007) for XPD 312, XPD 751, and ERCC1 8092, respectively. In cisplatin-treated patients, variant alleles of XPD 312, XPD 751, and ERCC1 8092 were each associated with significantly improved OS (and PFS): adjusted hazard ratios of homozygous variants versus wild-type ranged from 0.22 [95% confidence interval (CI): 0.1–0.5] to 0.31 (95% CI: 0.1–0.7). In contrast, in patients who did not receive cisplatin, variant alleles of XPD 751 and ERCC1 8092 had significantly worse survival, with adjusted hazard ratios of homozygous variants ranging from 2.47 (95% CI: 1.1–5.5) to 3.73 (95% CI: 1.6–8.7). Haplotype analyses affirmed these results. Conclusion DNA repair polymorphisms are associated with OS and PFS, and if validated may predict for benefit from cisplatin therapy in patients with esophageal cancer. PMID:19620936

  19. Uncoupling protein 2 gene polymorphisms are associated with obesity

    PubMed Central

    2012-01-01

    Background Uncoupling protein 2 (UCP2) gene polymorphisms have been reported as genetic risk factors for obesity and type 2 diabetes mellitus (T2DM). We examined the association of commonly observed UCP2 G(−866)A (rs659366) and Ala55Val (C > T) (rs660339) single nucleotide polymorphisms (SNPs) with obesity, high fasting plasma glucose, and serum lipids in a Balinese population. Methods A total of 603 participants (278 urban and 325 rural subjects) were recruited from Bali Island, Indonesia. Fasting plasma glucose (FPG), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) were measured. Obesity was determined based on WHO classifications for adult Asians. Participants were genotyped for G(−866)A and Ala55Val polymorphisms of the UCP2 gene. Results Obesity prevalence was higher in urban subjects (51%) as compared to rural subjects (23%). The genotype, minor allele (MAF), and heterozygosity frequencies were similar between urban and rural subjects for both SNPs. All genotype frequencies were in Hardy-Weinberg equilibrium. A combined analysis of genotypes and environment revealed that the urban subjects carrying the A/A genotype of the G(−866)A SNP have higher BMI than the rural subjects with the same genotype. Since the two SNPs showed strong linkage disequilibrium (D’ = 0.946, r2 = 0.657), a haplotype analysis was performed. We found that the AT haplotype was associated with high BMI only when the urban environment was taken into account. Conclusions We have demonstrated the importance of environmental settings in studying the influence of the common UCP2 gene polymorphisms in the development of obesity in a Balinese population. PMID:22533685

  20. Nuclear gene indicates coat-color polymorphism in mammoths.

    PubMed

    Römpler, Holger; Rohland, Nadin; Lalueza-Fox, Carles; Willerslev, Eske; Kuznetsova, Tatyana; Rabeder, Gernot; Bertranpetit, Jaume; Schöneberg, Torsten; Hofreiter, Michael

    2006-07-07

    By amplifying the melanocortin type 1 receptor from the woolly mammoth, we can report the complete nucleotide sequence of a nuclear-encoded gene from an extinct species. We found two alleles and show that one allele produces a functional protein whereas the other one encodes a protein with strongly reduced activity. This finding suggests that mammoths may have been polymorphic in coat color, with both dark- and light-haired individuals co-occurring.

  1. Vitamin D receptor polymorphisms in patients with cutaneous melanoma.

    PubMed

    Orlow, Irene; Roy, Pampa; Reiner, Anne S; Yoo, Sarah; Patel, Himali; Paine, Susan; Armstrong, Bruce K; Kricker, Anne; Marrett, Loraine D; Millikan, Robert C; Thomas, Nancy E; Gruber, Stephen B; Anton-Culver, Hoda; Rosso, Stefano; Gallagher, Richard P; Dwyer, Terence; Kanetsky, Peter A; Busam, Klaus; From, Lynn; Begg, Colin B; Berwick, Marianne

    2012-01-15

    The vitamin D receptor (VDR) gene has been associated with cancer risk, but only a few polymorphisms have been studied in relation to melanoma risk and the results have been inconsistent. We examined 38 VDR gene single nucleotide polymorphisms (SNPs) in a large international multicenter population-based case-control study of melanoma. Buccal DNAs were obtained from 1,207 people with incident multiple primary melanoma and 2,469 with incident single primary melanoma. SNPs with known or suspected impact on VDR activity, haplotype tagging SNPs with ≥ 10% minor allele frequency in Caucasians, and SNPs reported as significant in other association studies were examined. Logistic regression was used to calculate the relative risks conferred by the individual SNP. Eight of 38 SNPs in the promoter, coding, and 3' gene regions were individually significantly associated with multiple primary melanoma after adjusting for covariates. The estimated increase in risk for individuals who were homozygous for the minor allele ranged from 25 to 33% for six polymorphisms: rs10875712 (odds ratios [OR] 1.28; 95% confidence interval (CI), 1.01-1.62), rs4760674 (OR 1.33; 95% CI, 1.06-1.67), rs7139166 (OR 1.26; 95%CI, 1.02-1.56), rs4516035 (OR 1.25; 95%CI, 1.01-1.55), rs11168287 (OR 1.27; 95%CI, 1.03-1.57) and rs1544410 (OR 1.30; 95%CI, 1.04-1.63); for two polymorphisms, homozygous carriers had a decreased risk: rs7305032 (OR 0.81; 95%CI 0.65-1.02) and rs7965281 (OR, 0.78; 95%CI, 0.62-0.99). We recognize the potential false positive findings because of multiple comparisons; however, the eight significant SNPs in our study outnumbered the two significant tests expected to occur by chance. The VDR may play a role in melanomagenesis.

  2. Association between serotonin transporter gene polymorphism and recurrent aphthous stomatitis

    PubMed Central

    Manchanda, Aastha; Iyengar, Asha R.; Patil, Seema

    2016-01-01

    Background: Anxiety-related traits have been attributed to sequence variability in the genes coding for serotonin transmission in  the brain. Two alleles, termed long (L) and short (S) differing by 44 base pairs, are found in a polymorphism identified in the promoter region of serotonin transporter gene. The presence of the short allele  and SS and LS genotypes is found to be associated with the reduced expression of this gene decreasing the uptake of serotonin in the brain leading to various anxiety-related traits. Recurrent aphthous stomatitis (RAS) is an oral mucosal disease with varied etiology including the presence of stress, anxiety, and genetic influences. The present study aimed to determine this serotonin transporter gene polymorphism in patients with RAS and compare it with normal individuals. Materials and Methods: This study included 20 subjects with various forms of RAS and 20 normal healthy age- and gender-matched individuals. Desquamated oral mucosal cells were collected for DNA extraction and subjected to polymerase chain reaction for studying insertion/deletion in the 5-HTT gene-linked polymorphic region. Cross tabulations followed by Chi-square tests were performed to compare the significance of findings, P < 0.05 was considered statistically significant. Results: The LS genotype was the most common genotype found in the subjects with aphthous stomatitis (60%) and controls (40%). The total percentage of LS and SS genotypes and the frequency of S allele were found to be higher in the subjects with aphthous stomatitis as compared to the control group although a statistically significant correlation could not be established, P = 0.144 and 0.371, respectively. Conclusion: Within the limitations of this study, occurrence of RAS was not found to be associated with polymorphic promoter region in serotonin transporter gene. PMID:27274339

  3. Polymorphic microsatellite markers isolated from the neptune whelk Neptunea arthritica.

    PubMed

    Azuma, N; Miranda, R M; Goshima, S; Abe, S

    2009-01-01

    Eight polymorphic microsatellite DNA loci were isolated from the neptune whelk Neptunea arthritica, which is an important fishery resource in northern Japan. The number of alleles at the loci ranged from two to six, with observed and expected heterozygosities of 0.192-0.807 and 0.233-0.738, respectively. The observed variations suggest that these loci can be used as markers for population and kinship analyses in this species.

  4. Association between IL-1β polymorphisms and gastritis risk

    PubMed Central

    Sun, Xiaoming; Cai, Hongxing; Li, Zhouru; Li, Shanshan; Yin, Wenjiang; Dong, Guokai; Kuai, Jinxia; He, Yihui; Jia, Jing

    2017-01-01

    Abstract Background: Helicobacter pylori (H. pylori) infection of the human stomach regularly leads to chronic gastric inflammation. The cytokine gene interleukin (IL)-1β has been implicated in influencing the pathology of inflammation induced by H. pylori infection. Currently, several studies have been carried out to investigate the association of IL-1β-511 (rs16944) and IL-1β-31 (rs1143627) polymorphisms with gastritis risk; however, the results are inconsistent and inconclusive. To assess the effect of IL-1β polymorphisms on gastritis susceptibility, we conducted a meta-analysis. Methods: Up to March 15, 2016, 2205 cases and 2289 controls were collected from 12 published case–control studies. Summarized odds ratios and corresponding 95% confidence intervals (CIs) for IL-1β-511 and IL-1β-31 polymorphisms and gastritis risk were estimated using fixed- or random-effects models when appropriate. Heterogeneity was assessed by chi-squared-based Q-statistic test, and the sources of heterogeneity were explored by subgroup analyses and logistic meta-regression analyses. Publication bias was evaluated by Begg funnel plot and Egger test. Sensitivity analyses were also performed. Results: The results provided evidences that the single nucleotide polymorphisms (SNPs) in IL-1β-31 might be associated with the gastritis risk, especially in the Caucasian population, while SNPs in the IL-1β-511 might not be. Conclusion: Our studies may be helpful in supplementing the disease monitoring of gastritis in the future, and additional studies to determine the exact molecular mechanisms might inspire interventions to protect the susceptible subgroups. PMID:28151895

  5. Rhesus macaque IFITM3 gene polymorphisms and SIV infection

    PubMed Central

    Winkler, Michael; Gärtner, Sabine; Wrensch, Florian; Krawczak, Michael; Sauermann, Ulrike

    2017-01-01

    Interferon-induced transmembrane proteins (IFITMs) have been recognized as important antiviral effectors of the innate immune system, both in cell culture and in infected humans. In particular, polymorphisms of the human IFITM3 gene have been shown to affect disease severity and progression in influenza A virus (FLUAV) and human immunodeficiency virus (HIV) infection, respectively. Rhesus macaques (Macaca mulatta) are commonly used to model human infections and the experimental inoculation of these animals with simian immunodeficiency virus (SIV) is one of the best models for HIV/AIDS in humans. However, information on the role of IFITM3 in SIV infection of rhesus macaques is currently lacking. We show that rhesus macaque (rh) IFITM3 inhibits SIV and FLUAV entry in cell culture, although with moderately reduced efficiency as compared to its human counterpart. We further report the identification of 16 polymorphisms in the rhIFITM3 gene, three of which were exonic and synonymous while the remainder was located in non-coding regions. Employing previously characterized samples from two cohorts of SIV-infected rhesus macaques, we investigated the relationship between these rhIFITM3 polymorphisms and both AIDS-free survival time and virus load. In cohort 1, several intronic polymorphisms were significantly associated with virus load or survival. However, an association with both parameters was not observed and significance was lost in most cases when animals were stratified for the presence of MHC allele Mamu-A1*001. Moreover, no significant genotype-phenotype associations were detected in cohort 2. These results suggest that, although IFITM3 can inhibit SIV infection in cell culture, genetic variation in rhIFITM3 might have only a minor impact on the course of SIV infection in experimentally infected animals. PMID:28257482

  6. The relationship between MAOA gene polymorphism and test anxiety.

    PubMed

    Liu, Yangyang; Lu, Zuhong

    2013-12-01

    In a sample of 569 Chinese high school students, the present findings indicated that students with the 4-repeat genotype showed a higher level of test anxiety. Furthermore, the prediction of academic performance on test anxiety was stronger among students with the 3-repeat genotype than those with the 4-repeat genotype. The present findings suggest that mono-amine-oxidase type A gene polymorphism is significantly related to test anxiety.

  7. Solid solution hardening of molecular crystals: tautomeric polymorphs of omeprazole.

    PubMed

    Mishra, Manish Kumar; Ramamurty, Upadrasta; Desiraju, Gautam R

    2015-02-11

    In the context of processing of molecular solids, especially pharmaceuticals, hardness is an important property that often determines the manufacturing steps employed. Through nanoindentation studies on a series of omeprazole polymorphs, in which the proportions of the 5- and 6-methoxy tautomers vary systematically, we demonstrate that solid-solution strengthening can be effectively employed to engineer the hardness of organic solids. High hardness can be attained by increasing lattice resistance to shear sliding of molecular layers during plastic deformation.

  8. Heparin-induced thrombocytopenia: the role of platelets genetic polymorphisms.

    PubMed

    Pamela, Scarparo; Anna Maria, Lombardi; Elena, Duner; Giovanni, Malerba; Emanuele, Allemand; Silvia, Vettore; Carmen, Blumentritt; Andreas, Greinacher; Fabrizio, Fabris

    2013-01-01

    Heparin-induced thrombocytopenia (HIT) is a severe complication of heparin therapy, characterized by thrombocytopenia and an increased risk for thrombotic complications secondary to the formation of IgG antibodies (Ab), recognizing a complex of heparin (H) and PF4. Using the 4T clinical score for HIT and the presence of heparin-associated Ab assayed by enzyme-linked immunosorbent assay and heparin-induced platelet aggregation, we define the phenotype of three groups of patients: 51 H/PF4/Ab patients with antibodies and without thrombocytopenia; 50 patients with thrombocytopenia (HIT) and 53 patients with thrombosis (HITT). In these patients we studied four polymorphisms: FcγRIIA-H131R, GpIIb/IIIa-HP-1, PECAM1-L125V (in linkage-disequilibrium with S563N and R670G), and FcγRIIIA-F158V, to understand if these variations may influence the different phenotypes of the patients. There were no difference in genotype or allele frequencies between controls and the three groups of patients. Afterward, we created a genotype score for multiple risk alleles for thrombosis considering as risk genotype FcγRIIA R/R131, HPA-1a/b, and PECAM1-V/V125. These polymorphisms were overrepresented in HITT patients, ascertained by a permutation test (10 000 replicates) p = 0.0198 for the two-single-nucleotide polymorphism (SNP) model and p = 0.0119 for the three-SNP model. The calculated odds ratio for thrombosis was 4.01[CI: 2.30-6.96] in the case of the presence of two at risk genotypes and 8.002 [CI: 4.59-13.93] if all the three at risk genotypes were present. In conclusion these polymorphisms could contribute to the risk of thrombotic complications in HIT.

  9. Ribosomal DNA polymorphisms in the yeast Geotrichum candidum.

    PubMed

    Alper, Iraz; Frenette, Michel; Labrie, Steve

    2011-12-01

    The dimorphic yeast Geotrichum candidum (teleomorph: Galactomyces candidus) is commonly used to inoculate washed-rind and bloomy-rind cheeses. However, little is known about the phylogenetic lineage of this microorganism. We have sequenced the complete 18S, 5.8S, 26S ribosomal RNA genes and their internal transcribed spacers (ITS1) and ITS2 regions (5126 nucleotides) from 18 G. candidum strains from various environmental niches, with a focus on dairy strains. Multiple sequence alignments revealed the presence of 60 polymorphic sites, which is generally unusual for ribosomal DNA (rDNA) within a given species because of the concerted evolution mechanism. This mechanism drives genetic homogenization to prevent the divergent evolution of rDNA copies within individuals. While the polymorphisms observed were mainly substitutions, one insertion/deletion (indel) polymorphism was detected in ITS1. No polymorphic sites were detected downstream from this indel site, that is, in 5.8S and ITS2. More surprisingly, many sequence electrophoregrams generated during the sequencing of the rDNA had dual peaks, suggesting that many individuals exhibited intragenomic rDNA variability. The ITS1-5.8S-ITS2 regions of four strains were cloned. The sequence analysis of 68 clones revealed 32 different ITS1-5.8S-ITS2 variants within these four strains. Depending on the strain, from four to twelve variants were detected, indicating that multiple rDNA copies were present in the genomes of these G. candidum strains. These results contribute to the debate concerning the use of the ITS region for barcoding fungi and suggest that community profiling techniques based on rDNA should be used with caution.

  10. A new polymorph of Lu(PO(3))(3).

    PubMed

    Bejaoui, Anis; Horchani-Naifer, Karima; Férid, Mokhtar

    2008-07-19

    A new polymorph of lutetium polyphosphate, Lu(PO(3))(3), was found to be isotypic with the trigonal form of Yb(PO(3))(3). Two of the three Lu atoms occupy special positions (Wyckoff positions 3a and 3b, site symmetry ). The atomic arrangement consists of infinite helical polyphosphate chains running along the c axis, with a repeat period of 12 PO(4) tetra-hedra, joined with LuO(6) octa-hedra.

  11. A monoclinic polymorph of KY(PO(3))(4).

    PubMed

    Horchani-Naifer, Karima; Jouini, Anis; Férid, Mokhtar

    2008-05-17

    The title compound, potassium yttrium polyphosphate, KY(PO(3))(4), was synthesized using the flux method. The atomic arrangement consists of an infinite long-chain polyphosphate organization. Chains, with a period of four PO(4) tetra-hedra, run along the a-axis direction. Two other polymorphs of this phosphate are known, in space groups P21/n and C2/c.

  12. A monoclinic polymorph of KY(PO3)4

    PubMed Central

    Horchani-Naifer, Karima; Jouini, Anis; Férid, Mokhtar

    2008-01-01

    The title compound, potassium yttrium polyphosphate, KY(PO3)4, was synthesized using the flux method. The atomic arrangement consists of an infinite long-chain polyphosphate organization. Chains, with a period of four PO4 tetra­hedra, run along the a-axis direction. Two other polymorphs of this phosphate are known, in space groups P21/n and C2/c. PMID:21202436

  13. DNA Repair Gene Polymorphisms in Hereditary and Sporadic Breast Cancer

    DTIC Science & Technology

    2006-03-01

    polymorphisms will then be tested in an existing epidemiological breast cancer study, a funded NIH and DOD case-control study of breast cancer from the... tested for the 3 founder mutations. If the patient was not Jewish, then Myriad did full sequencing. If a non-Jewish patient has a relative that...has already tested positive for a BRCA1 mutation, then the patient is only tested for the mutation that has already been identified in her relative

  14. Ethnicity and lipoprotein(a) polymorphism in Native Mexican populations

    PubMed Central

    Cardoso-Saldaña, Guillermo; De La Peña-Díaz, Aurora; Zamora-González, José; Gomez-Ortega, Rocio; Posadas-Romero, Carlos; Izaguirre-Avila, Raul; Malvido-Miranda, Elsa; Morales-Anduaga, Maria Elena; Angles-Cano, Eduardo

    2006-01-01

    Background Lp(a) is a lipoparticle of unknown function mainly present in primates and humans. It consists of a low-density lipoprotein and apo(a), a polymorphic glycoprotein. Apo(a) shares sequence homology and fibrin-binding with plasminogen inhibiting its fibrinolytic properties. Lp(a) is considered a link between atherosclerosis and thrombosis. Marked inter-ethnic differences in Lp(a) concentration related to the genetic polymorphism of apo(a), have been reported in several populations. Aim To study the structural and functional features of Lp(a) in three Native Mexican populations (Mayos, Mazahuas and Mayas) and in Mestizo subjects. Methods We determined the plasma concentration of Lp(a) by immunonephelometry, apo(a) isoforms by Western blot, Lp(a) fibrin-binding by immuno-enzymatic assay and STR polymorphic markers genetic analysis by capillary electrophoresis. Results Mestizos presented the less skewed distribution and the highest median Lp(a) concentration (13.25 mg/dL) relative to Mazahuas (8.2 mg/dL), Mayas (8.25 mg/dL) and Mayos (6.5 mg/dL). Phenotype distribution was different in Mayas and Mazahuas as compared to the Mestizo group. The higher Lp(a) fibrin-binding capacity was found in the Maya population. There was an inverse relationship between the size of apo(a) polymorphs and both Lp(a) levels and Lp(a) fibrin binding. Conclusion There is evidence of significative differences in Lp(a) plasma concentration and phenotype distribution in Native Mexican and the Mestizo group. PMID:16684693

  15. Genetic polymorphism of xenobiotic metabolising enzymes, diet and cancer susceptibility.

    PubMed

    Reszka, Edyta; Wasowicz, Wojciech; Gromadzinska, Jolanta

    2006-10-01

    There is increasing evidence identifying the crucial role of numerous dietary components in modifying the process of carcinogenesis. The varied effects exerted by nutrient and non-nutrient dietary compounds on human health and cancer risk are one of the new challenges for nutritional sciences. In the present paper, an attempt is made to review the most recent epidemiological data on interactions between dietary factors and metabolic gene variants in terms of cancer risk. The majority of case-control studies indicate the significant relationship between cancer risk and polymorphic xenobiotic metabolising enzymes in relation to dietary components. The risk of colorectal cancer is associated not only with CYP2E1 high-activity alleles, but also GSTA1 low-activity alleles, among consumers of red or processed meat. Genetic polymorphisms of NAT1 and NAT2 may be also a breast-cancer susceptibility factor among postmenopausal women with a high intake of well-done meat. On the other hand, phytochemicals, especially isothiocyanates, have a protective effect against colorectal and lung cancers in individuals lacking GST genes. Moreover, polymorphism of GSTM1 seems to be involved in the dietary regulation of DNA damage. The European Prospective Investigation into Cancer and Nutrition study shows a significant inverse association between the polycyclic aromatic hydrocarbon-DNA adduct level and dietary antioxidants only among GSTM1-null individuals. However, the absence of a modulatory effect of polymorphic xenobiotic metabolising enzymes and diet on the development of cancer has been indicated by some epidemiological investigations. Studies of interactions between nutrients and genes may have great potential for exploring mechanisms, identifying susceptible populations/individuals and making practical use of study results to develop preventive strategies beneficial to human health.

  16. Salting out the polar polymorph: analysis by alchemical solvent transformation.

    PubMed

    Duff, Nathan; Dahal, Yuba Raj; Schmit, Jeremy D; Peters, Baron

    2014-01-07

    We computationally examine how adding NaCl to an aqueous solution with α- and γ-glycine nuclei alters the structure and interfacial energy of the nuclei. The polar γ-glycine nucleus in pure aqueous solution develops a melted layer of amorphous glycine around the nucleus. When NaCl is added, a double layer is formed that stabilizes the polar glycine polymorph and eliminates the surface melted layer. In contrast, the non-polar α-glycine nucleus is largely unaffected by the addition of NaCl. To quantify the stabilizing effect of NaCl on γ-glycine nuclei, we alchemically transform the aqueous glycine solution into a brine solution of glycine. The alchemical transformation is performed both with and without a nucleus in solution and for nuclei of α-glycine and γ-glycine polymorphs. The calculations show that adding 80 mg/ml NaCl reduces the interfacial free energy of a γ-glycine nucleus by 7.7 mJ/m(2) and increases the interfacial free energy of an α-glycine nucleus by 3.1 mJ/m(2). Both results are consistent with experimental reports on nucleation rates which suggest: J(α, brine) < J(γ, brine) < J(α, water). For γ-glycine nuclei, Debye-Hückel theory qualitatively, but not quantitatively, captures the effect of salt addition. Only the alchemical solvent transformation approach can predict the results for both polar and non-polar polymorphs. The results suggest a general "salting out" strategy for obtaining polar polymorphs and also a general approach to computationally estimate the effects of solvent additives on interfacial free energies for nucleation.

  17. Study of process induced polymorphic transformations in fluconazole drug.

    PubMed

    Desai, Satish R; Dharwadkar, Sanjiv R

    2009-01-01

    The polymorphic form-I of the fluconazole drug commonly crystallized from the solution phase could be obtained by the solid state transformation of form-II employing different process parameters. As received fluconazole-II drug melted at 138.4 degrees C. The molten drug undercooled almost to ambient temperature of 30 degrees C and solidified to a glassy mass which, on ageing for 48 h transformed to a white powder which could be identified as fluconazole-I. The same glassy mass on heating at 5 degrees C/min, without ageing, also underwent polymorphic transformation to fluconazole-I above 81 degrees C. The application of uniaxial pressure of 200 kg/cm2 on as received fluconazole-II sample also yielded form-I of the drug. This phase transformation was enhanced by the application of pressure (200 kg/cm2) on the as received sample aged for 36 months. The phase transformation was concluded from the difference in differential scanning calorimetric (DSC) curves of the original sample (form-II) and the products obtained by adopting the different processing routes. The DSC patterns of fluconozole-I obtained by different methods were found to be identical. The phase transformation in the as received drug (form-II) induced by different process parameters, concluded from the DSC data was corroborated by X- ray diffraction (XRD) studies and scanning electron microscope (SEM) photographs of the two polymorphic forms. The intrinsic dissolution rates of polymorphic form-I and -II and the influence of crystal habit on the drug dissolution process have also been studied.

  18. Extensive polymorphism in Cryptosporidium parvum identified by multilocus microsatellite analysis.

    PubMed

    Feng, X; Rich, S M; Akiyoshi, D; Tumwine, J K; Kekitiinwa, A; Nabukeera, N; Tzipori, S; Widmer, G

    2000-08-01

    Restriction fragment length polymorphism and DNA sequence analysis discern two main types of Cryptosporidium parvum. We present a survey of length polymorphism at several microsatellite loci for type 1 and type 2 isolates. A total of 14 microsatellite loci were identified from C. parvum DNA sequences deposited in public databases. All repeats were mono-, di-, and trinucleotide repeats of A, AT, and AAT, reflecting the high AT content of the C. parvum genome. Several of these loci showed significant length polymorphism, with as many as seven alleles identified for a single locus. Differences between alleles ranged from 1 to 27 bp. Karyotype analysis using probes flanking three microsatellites localized each marker to an individual chromosomal band, suggesting that these markers are single copy. In a sample of 19 isolates for which at least three microsatellites were typed, a majority of isolates displayed a unique multilocus fingerprint. Microsatellite analysis of isolates passaged between different host species identified genotypic changes consistent with changes in parasite populations.

  19. NBN Gene Polymorphisms and Cancer Susceptibility: A Systemic Review

    PubMed Central

    Berardinelli, Francesco; di Masi, Alessandra; Antoccia, Antonio

    2013-01-01

    The relationship between DNA repair failure and cancer is well established as in the case of rare, high penetrant genes in high cancer risk families. Beside this, in the last two decades, several studies have investigated a possible association between low penetrant polymorphic variants in genes devoted to DNA repair pathways and risk for developing cancer. This relationship would be also supported by the observation that DNA repair processes may be modulated by sequence variants in DNA repair genes, leading to susceptibility to environmental carcinogens. In this framework, the aim of this review is to provide the reader with the state of the art on the association between common genetic variants and cancer risk, limiting the attention to single nucleotide polymorphisms (SNPs) of the NBN gene and providing the various odd ratios (ORs). In this respect, the NBN protein, together with MRE11 and RAD50, is part of the MRN complex which is a central player in the very early steps of sensing and processing of DNA double-strand breaks (DSBs), in telomere maintenance, in cell cycle control, and in genomic integrity in general. So far, many papers were devoted to ascertain possible association between common synonymous and non-synonymous NBN gene polymorphisms and increased cancer risk. However, the results still remain inconsistent and inconclusive also in meta-analysis studies for the most investigated E185Q NBN miscoding variant. PMID:24396275

  20. Linkage disequilibrium of polymorphic RAET1 genes in Thais.

    PubMed

    Rareongjai, S; Romphruk, A; Romphruk, A V; Sakuntabhai, A; Leelayuwat, C

    2010-09-01

    Retinoic acid early transcripts-1 (RAET1) or unique long 16 (UL-16) binding proteins (ULBPs) is a gene cluster encoding for molecules acting as ligands to natural killer group 2 D (NKG2D), a receptor expressed on immune cells. Binding of these ligands to the receptor activates immune cells leading to killing of tumor cells and also viral-infected cells. The information on polymorphism of RAET1 is limited. In this report, we analyze the linkages between four polymorphic RAET1 genes: RAET1E, RAET1G, RAET1H and RAET1L, in 318 unrelated Thais. The strongest linkage disequilibrium was found between RAET1E and RAET1G, with P-value, D' and r(2) of <5.0 x 10(-5), 0.707 and 0.840, respectively. RAET1E(*)001 was found to be in linkage disequilibrium with RAET1G(*)002, and RAET1E(*)002 with RAET1G(*)001. Evidently, there were possible RAET1 haplotypes with haplotype frequencies of more than 10% consisting of RAET1E(*)001; RAET1G(*)002; RAET1H(*)001; RAET1L(*)001 and RAET1E(*)002; RAET1G(*)001; RAET1H(*)002; RAET1L(*)003. This study provides basic information on polymorphisms of RAET1 and possible RAET1 haplotypes in Thais.

  1. Contribution of ALDH2 polymorphism to alcoholism-associated hypertension.

    PubMed

    Hu, Nan; Zhang, Yingmei; Nair, Sreejayan; Culver, Bruce W; Ren, Jun

    2014-01-01

    Chronic alcohol intake is considered as an independent lifestyle factor that may influence the risk of a number of cardiovascular anomalies including hypertension. In healthy adults, binge drinking and chronic alcohol ingestion lead to the onset and development of hypertension although the precise mechanism(s) remains obscure. Although oxidative stress and endothelial injury have been postulated to play a major contributing role to alcoholism-induced hypertension, recent evidence depicted a rather unique role for the genotype of the acetaldehyde-metabolizing enzyme mitochondrial aldehyde dehydrogenase (ALDH2), which is mainly responsible for detoxifying ethanol consumed, in alcoholism-induced elevation of blood pressure. Genetic polymorphism of ALDH2 in human results in altered ethanol pharmacokinetic properties and ethanol metabolism, leading to accumulation of the ethanol metabolite acetaldehyde following alcohol intake. The unfavorable consequence of the ALDH2 variants is believed to be governed by the accumulation of the ethanol metabolite acetaldehyde. Presence of the mutant or inactive ALDH2*2 gene often results in an increased risk of hypertension in human. Such association between blood pressure and ALDH2 enzymatic activity may be affected by the interplay between gene and environment, such as life style and ethnicity. The aim of this mini-review is to summarize the possible contribution of ALDH2 genetic polymorphism in the onset and development of alcoholism-related development of hypertension. Furthermore, the double-edged sword of ALDH2 gene and genetic polymorphism in alcoholism and alcoholic tissue damage and relevant patents will be discussed.

  2. Association of chicken growth hormone polymorphisms with egg production.

    PubMed

    Su, Y J; Shu, J T; Zhang, M; Zhang, X Y; Shan, Y J; Li, G H; Yin, J M; Song, W T; Li, H F; Zhao, G P

    2014-07-04

    Growth hormone (GH) has diverse functions in animals, together with other hormones from the somatotropic axis. Here, chicken GH (cGH) was investigated in recessive white chickens and Qingyuan partridge chickens as a candidate gene affecting egg production traits. Chicken egg production traits were studied in association with 4 selected single nucleotide polymorphisms (T185G, G662A, T3094C, and C3199T). Genotyping was performed by the polymerase chain reaction-ligase detection reaction method. T185G was significantly associated with the egg production traits of body weight at first egg (BW), egg weight at first egg (EW), and the total egg production of 300-day old birds (EN 300). T3094C was also significantly associated with certain egg production traits; however, it affected the 2 breeds differently. Haplotypes of the 4 single nucleotide polymorphisms were also significantly associated with egg production traits of chicken age at first egg laying, BW, EW, and EN 300. H1H6 was the most advantageous diplotype for egg production. We putatively concluded that polymorphisms in the cGH gene and its haplotypes could be used as potential molecular markers for egg production traits to enhance the breeding programs of indigenous chickens.

  3. Templated Sequence Insertion Polymorphisms in the Human Genome

    PubMed Central

    Onozawa, Masahiro; Aplan, Peter D.

    2016-01-01

    Templated Sequence Insertion Polymorphism (TSIP) is a recently described form of polymorphism recognized in the human genome, in which a sequence that is templated from a distant genomic region is inserted into the genome, seemingly at random. TSIPs can be grouped into two classes based on nucleotide sequence features at the insertion junctions; Class 1 TSIPs show features of insertions that are mediated via the LINE-1 ORF2 protein, including (1) target-site duplication (TSD), (2) polyadenylation 10–30 nucleotides downstream of a “cryptic” polyadenylation signal, and (3) preference for insertion at a 5′-TTTT/A-3′ sequence. In contrast, class 2 TSIPs show features consistent with repair of a DNA double-strand break (DSB) via insertion of a DNA “patch” that is derived from a distant genomic region. Survey of a large number of normal human volunteers demonstrates that most individuals have 25–30 TSIPs, and that these TSIPs track with specific geographic regions. Similar to other forms of human polymorphism, we suspect that these TSIPs may be important for the generation of human diversity and genetic diseases. PMID:27900318

  4. Polymorphism in self-assembled AB6 binary nanocrystal superlattices.

    PubMed

    Ye, Xingchen; Chen, Jun; Murray, Christopher B

    2011-03-02

    We report the formation and systematic struc-tural characterization of a new AB(6) polymorph with the body-centered cubic (bcc) symmetry in binary nanocrystal superlattices (BNSLs). The bcc-AB(6) phase, lacking any atomic analogue, is isomorphic to certain alkali-metal intercalation compounds of fullerene C(60) (e.g., K(6)C(60)). On the basis of the space-filling principle, we further tailor the relative phase stability of the two AB(6) polymorphs-CaB(6) and bcc-AB(6)-from coexistence to phase-pure bcc-AB(6), highlighting the entropic effect as the main driving-force of the self-organization of BNSLs. We also discuss the implication of surface topology studies and the observation of twinning and preferential orientation in bcc-AB(6) on the growth mechanism of BNSLs. Furthermore, the connection between the bcc-AB(6) phase and the (3(2).4.3.4) Archimedean tiling shows the promise of further exploration on the structural diversity (both periodic and aperiodic) in this emerging class of metamaterials. The identification and the ability to tune the relative phase stability of polymorphic structures provide a unique opportunity to engineer the interparticle coupling through controlled clustering and/or interconnectivity of sublattice in BNSLs with identical stoichiometry.

  5. Count on dopamine: influences of COMT polymorphisms on numerical cognition

    PubMed Central

    Júlio-Costa, Annelise; Antunes, Andressa M.; Lopes-Silva, Júlia B.; Moreira, Bárbara C.; Vianna, Gabrielle S.; Wood, Guilherme; Carvalho, Maria R. S.; Haase, Vitor G.

    2013-01-01

    Catechol-O-methyltransferase (COMT) is an enzyme that is particularly important for the metabolism of dopamine. Functional polymorphisms of COMT have been implicated in working memory and numerical cognition. This is an exploratory study that aims at investigating associations between COMT polymorphisms, working memory, and numerical cognition. Elementary school children from 2th to 6th grades were divided into two groups according to their COMT val158met polymorphism [homozygous for valine allele (n = 61) vs. heterozygous plus methionine homozygous children or met+ group (n = 94)]. Both groups were matched for age and intelligence. Working memory was assessed through digit span and Corsi blocks. Symbolic numerical processing was assessed through transcoding and single-digit word problem tasks. Non-symbolic magnitude comparison and estimation tasks were used to assess number sense. Between-group differences were found in symbolic and non-symbolic numerical tasks, but not in working memory tasks. Children in the met+ group showed better performance in all numerical tasks while val homozygous children presented slower development of non-symbolic magnitude representations. These results suggest COMT-related dopaminergic modulation may be related not only to working memory, as found in previous studies, but also to the development of magnitude processing and magnitude representations. PMID:23966969

  6. Twinning of cubic diamond explains reported nanodiamond polymorphs

    PubMed Central

    Németh, Péter; Garvie, Laurence A. J.; Buseck, Peter R.

    2015-01-01

    The unusual physical properties and formation conditions attributed to h-, i-, m-, and n-nanodiamond polymorphs has resulted in their receiving much attention in the materials and planetary science literature. Their identification is based on diffraction features that are absent in ordinary cubic (c-) diamond (space group: Fd-3m). We show, using ultra-high-resolution transmission electron microscope (HRTEM) images of natural and synthetic nanodiamonds, that the diffraction features attributed to the reported polymorphs are consistent with c-diamond containing abundant defects. Combinations of {113} reflection and <011> rotation twins produce HRTEM images and d-spacings that match those attributed to h-, i-, and m-diamond. The diagnostic features of n-diamond in TEM images can arise from thickness effects of c-diamonds. Our data and interpretations strongly suggest that the reported nanodiamond polymorphs are in fact twinned c-diamond. We also report a new type of twin (<11> rotational), which can give rise to grains with dodecagonal symmetry. Our results show that twins are widespread in diamond nanocrystals. A high density of twins could strongly influence their applications. PMID:26671288

  7. Eccentric muscle challenge shows osteopontin polymorphism modulation of muscle damage.

    PubMed

    Barfield, Whitney L; Uaesoontrachoon, Kitipong; Wu, Chung-Sheih; Lin, Stephen; Chen, Yue; Wang, Paul C; Kanaan, Yasmine; Bond, Vernon; Hoffman, Eric P

    2014-08-01

    A promoter polymorphism of the osteopontin (OPN) gene (rs28357094) has been associated with multiple inflammatory states, severity of Duchenne muscular dystrophy (DMD) and muscle size in healthy young adults. We sought to define the mechanism of action of the polymorphism, using allele-specific in vitro reporter assays in muscle cells, and a genotype-stratified intervention in healthy controls. In vitro reporter constructs showed the G allele to respond to estrogen treatment, whereas the T allele showed no transcriptional response. Young adult volunteers (n = 187) were enrolled into a baseline study, and subjects with specific rs28357094 genotypes enrolled into an eccentric muscle challenge intervention [n = 3 TT; n = 3 GG/GT (dominant inheritance model)]. Female volunteers carrying the G allele showed significantly greater inflammation and increased muscle volume change as determined by magnetic resonance imaging T1- and T2-weighted images after eccentric challenge, as well as greater decrement in biceps muscle force. Our data suggest a model where the G allele enables enhanced activities of upstream enhancer elements due to loss of Sp1 binding at the polymorphic site. This results in significantly greater expression of the pro-inflammatory OPN cytokine during tissue remodeling in response to challenge in G allele carriers, promoting muscle hypertrophy in normal females, but increased damage in DMD patients.

  8. Scent of a Dragonfly: Sex Recognition in a Polymorphic Coenagrionid.

    PubMed

    Frati, Francesca; Piersanti, Silvana; Conti, Eric; Rebora, Manuela; Salerno, Gianandrea

    2015-01-01

    In polymorphic damselflies discrimination of females from males is complex owing to the presence of androchrome and gynochrome females. To date there is no evidence that damselflies use sensory modalities other than vision (and tactile stimuli) in mate searching and sex recognition. The results of the present behavioural and electrophysiological investigations on Ischnura elegans, a polymorphic damselfly, support our hypothesis that chemical cues could be involved in Odonata sex recognition. The bioassays demonstrate that males in laboratory prefer female to male odour, while no significant difference was present in male behavior between stimuli from males and control. The bioassays suggest also some ability of males to distinguish between the two female morphs using chemical stimuli. The ability of male antennae to perceive odours from females has been confirmed by electrophysiological recordings. These findings are important not only to get insight into the chemical ecology of Odonata, and to shed light into the problem of olfaction in Paleoptera, but could be useful to clarify the controversial aspects of the mating behavior of polymorphic coenagrionids. Behavioural studies in the field are necessary to investigate further these aspects.

  9. Scent of a Dragonfly: Sex Recognition in a Polymorphic Coenagrionid

    PubMed Central

    Conti, Eric; Rebora, Manuela; Salerno, Gianandrea

    2015-01-01

    In polymorphic damselflies discrimination of females from males is complex owing to the presence of androchrome and gynochrome females. To date there is no evidence that damselflies use sensory modalities other than vision (and tactile stimuli) in mate searching and sex recognition. The results of the present behavioural and electrophysiological investigations on Ischnura elegans, a polymorphic damselfly, support our hypothesis that chemical cues could be involved in Odonata sex recognition. The bioassays demonstrate that males in laboratory prefer female to male odour, while no significant difference was present in male behavior between stimuli from males and control. The bioassays suggest also some ability of males to distinguish between the two female morphs using chemical stimuli. The ability of male antennae to perceive odours from females has been confirmed by electrophysiological recordings. These findings are important not only to get insight into the chemical ecology of Odonata, and to shed light into the problem of olfaction in Paleoptera, but could be useful to clarify the controversial aspects of the mating behavior of polymorphic coenagrionids. Behavioural studies in the field are necessary to investigate further these aspects. PMID:26305118

  10. Evidence of polymorphic transformations of Sn under high pressure

    NASA Astrophysics Data System (ADS)

    Jing, Qiu-Min; Cao, Yu-Hong; Zhang, Yi; Li, Shou-Rui; He, Qiang; Hou, Qi-Yue; Liu, Sheng-Gang; Liu, Lei; Bi, Yan; Geng, Hua-Yun; Wu, Qiang

    2016-12-01

    The high-pressure polymorphs and structural transformation of Sn were experimentally investigated using angle-dispersive synchrotron x-ray diffraction up to 108.9 GPa. The results show that at least at 12.8 GPa β-Sn→bct structure transformation was completed and no two-phase coexistence was found. By using a long-wavelength x-ray, we resolved the diffraction peaks splitting and discovered the formation of a new distorted orthorhombic structure bco from the bct structure at 31.8 GPa. The variation of the lattice parameters and their ratios with pressure further validate the observation of the bco polymorph. The bcc structure appears at 40.9 GPa and coexists with the bco phase throughout a wide pressure range of 40.9 GPa-73.1 GPa. Above 73.1 GPa, only the bcc polymorph is observed. The systematically experimental investigation confirms the phase transition sequence of Sn as β-Sn→bct→bco→bco+bcc→bcc upon compression to 108.9 GPa at room temperature. Project supported by the National Natural Science Foundation of China (Grant Nos. 11304294 and 11274281) and the Science Fund from the National Laboratory of Shock Wave and Detonation Physics of China (Grant Nos. 9140C670201140C67281 and 9140C670102150C67288).

  11. Polymorphism influences singlet fission rates in tetracene thin films

    DOE PAGES

    Arias, Dylan H.; Ryerson, Joseph L.; Cook, Jasper D.; ...

    2015-11-06

    Here, we report the effect of crystal structure and crystallite grain size on singlet fission (SF) in polycrystalline tetracene, one of the most widely studied SF and organic semiconductor materials. SF has been comprehensively studied in one polymoprh (Tc I), but not in the other, less stable polymorph (Tc II). Using carefully controlled thermal evaporation deposition conditions and high sensitivity ultrafast transient absorption spectroscopy, we found that for large crystallite size samples, SF in nearly pure Tc II films is significantly faster than SF in Tc I films. We also discovered that crystallite size has a minimal impact on themore » SF rate in Tc II films, but a significant influence in Tc I films. Large crystallites exhibit SF times of 125 ps and 22 ps in Tc I and Tc II, respectively, whereas small crystallites have SF times of 31 ps and 33 ps. Our results demonstrate first, that attention must be paid to polymorphism in obtaining a self-consistent rate picture for SF in tetracene and second, that control of polymorphism can play a significant role towards achieving a mechanistic understanding of SF in polycrystalline systems. In this latter context we show that conventional theory based on non-covalent tetracene couplings is insufficient, thus highlighting the need for models that capture the delocalized and highly mobile nature of excited states in elucidating the full photophysical picture.« less

  12. Polymorphism influences singlet fission rates in tetracene thin films

    SciTech Connect

    Arias, Dylan H.; Ryerson, Joseph L.; Cook, Jasper D.; Damrauer, Niels H.; Johnson, Justin C.

    2015-11-06

    Here, we report the effect of crystal structure and crystallite grain size on singlet fission (SF) in polycrystalline tetracene, one of the most widely studied SF and organic semiconductor materials. SF has been comprehensively studied in one polymoprh (Tc I), but not in the other, less stable polymorph (Tc II). Using carefully controlled thermal evaporation deposition conditions and high sensitivity ultrafast transient absorption spectroscopy, we found that for large crystallite size samples, SF in nearly pure Tc II films is significantly faster than SF in Tc I films. We also discovered that crystallite size has a minimal impact on the SF rate in Tc II films, but a significant influence in Tc I films. Large crystallites exhibit SF times of 125 ps and 22 ps in Tc I and Tc II, respectively, whereas small crystallites have SF times of 31 ps and 33 ps. Our results demonstrate first, that attention must be paid to polymorphism in obtaining a self-consistent rate picture for SF in tetracene and second, that control of polymorphism can play a significant role towards achieving a mechanistic understanding of SF in polycrystalline systems. In this latter context we show that conventional theory based on non-covalent tetracene couplings is insufficient, thus highlighting the need for models that capture the delocalized and highly mobile nature of excited states in elucidating the full photophysical picture.

  13. Polymorphisms in cyclooxygenase-2 gene in endometrial cancer patients.

    PubMed

    Torricelli, Federica; Mandato, Vincenzo Dario; Farnetti, Enrico; Abrate, Martino; Casali, Bruno; Ciarlini, Gino; Pirillo, Debora; Gelli, Maria Carolina; Costagliola, Luigi; Nicoli, Davide; Palomba, Stefano; La Sala, Giovanni Battista

    2015-09-01

    The enzyme cyclooxygenase 2 is an inducible enzyme expressed at sites of inflammation and in a variety of malignant solid tumors such as endometrial cancer (EC). In EC patients, its over-expression is correlated with progressive disease and poor prognosis. The expression is encoded by a polymorphic gene, called PTGS2. The aim of the current study was to test the hypothesis that rs5275 polymorphism of PTGS2 influence the prognosis of EC patients. This paper is a retrospective cohort study. Clinical and pathological data were extrapolated and genotypes were assessed on formalin-fixed and paraffin-embedded non-tumor tissues. A total of 159 type I EC patients were included in the final analysis. Univariate analysis indicated that patients with rs5275 genotype CC have a lower risk to develop a grade (G) 2-3 endometrial cancer. rs5275 effect on EC grading was confirmed by multivariate analysis also after data adjusting for age, BMI, parity, hypertension, and diabetes. Adjusted odds ratio (OR) confirmed that patients with rs5275 genotype CC have a risk 80 % lower (OR = 0.20, P = 0.009) to develop a G2 and/or G3 EC in comparison with patients with TT or TC genotype. Differentiation of the type 1 EC is significantly and independently influenced by rs5275 polymorphism. rs5275 CC patients have a lower risk to present a G2-G3 EC.

  14. Interaction Landscape of Inherited Polymorphisms with Somatic Events in Cancer.

    PubMed

    Carter, Hannah; Marty, Rachel; Hofree, Matan; Gross, Andy; Jensen, James; Fisch, Kathleen M; Wu, Xingyu; DeBoever, Christopher; Van Nostrand, Eric L; Song, Yan; Wheeler, Emily; Kreisberg, Jason F; Lippman, Scott M; Yeo, Gene; Gutkind, J Silvio; Ideker, Trey

    2017-02-10

    Recent studies have characterized the extensive somatic alterations that arise during cancer. However, the somatic evolution of a tumor may be significantly affected by inherited polymorphisms carried in the germline. Here, we analyze genomic data for 5954 tumors to reveal and systematically validate 412 genetic interactions between germline polymorphisms and major somatic events, including tumor formation in specific tissues and alteration of specific cancer genes. Among germline-somatic interactions, we find germline variants in RBFOX1 that increase incidence of SF3B1 somatic mutation by eight-fold via functional alterations in RNA splicing. Similarly, 19p13.3 variants are associated with a four-fold increased likelihood of somatic mutations in PTEN. In support of this association, we find that PTEN knock-down sensitizes the MTOR pathway to high expression of the 19p13.3 gene GNA11. Finally, we observe that stratifying patients by germline polymorphisms exposes distinct somatic mutation landscapes, implicating new cancer genes. This study creates a validated resource of inherited variants that govern where and how cancer develops, opening avenues for prevention research.

  15. Polymorphic robotic system controlled by an observing camera

    NASA Astrophysics Data System (ADS)

    Koçer, Bilge; Yüksel, Tugçe; Yümer, M. Ersin; Özen, C. Alper; Yaman, Ulas

    2010-02-01

    Polymorphic robotic systems, which are composed of many modular robots that act in coordination to achieve a goal defined on the system level, have been drawing attention of industrial and research communities since they bring additional flexibility in many applications. This paper introduces a new polymorphic robotic system, in which the detection and control of the modules are attained by a stationary observing camera. The modules do not have any sensory equipment for positioning or detecting each other. They are self-powered, geared with means of wireless communication and locking mechanisms, and are marked to enable the image processing algorithm detect the position and orientation of each of them in a two dimensional space. Since the system does not depend on the modules for positioning and commanding others, in a circumstance where one or more of the modules malfunction, the system will be able to continue operating with the rest of the modules. Moreover, to enhance the compatibility and robustness of the system under different illumination conditions, stationary reference markers are employed together with global positioning markers, and an adaptive filtering parameter decision methodology is enclosed. To the best of authors' knowledge, this is the first study to introduce a remote camera observer to control modules of a polymorphic robotic system.

  16. Catecholaminergic polymorphic ventricular tachycardia: An exciting new era

    PubMed Central

    Behere, Shashank P; Weindling, Steven N

    2016-01-01

    Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a highly malignant inheritable cardiac channelopathy. The past decade and a half has provided exciting new discoveries elucidating the genetic etiology and pathophysiology of CPVT. This review of the current literature on CPVT aims to summarize the state of the art in our understanding of the genetic etiology and the molecular pathogenesis of CPVT, and how these relate to our current approach to diagnosis and management. We will also shed light on groundbreaking new work that will continue to refine the management of CPVT in the future. As our knowledge of CPVT continues to grow, further studies will yield a better understanding of the efficacy and pitfalls of established diagnostic approaches and therapies as well as help shape newer diagnostic and treatment strategies. Two separate searches were run on the National Center for Biotechnology Information's (NCBI) website. The first used the medical subject headings (MeSH) database using the term “catecholaminergic polymorphic ventricular tachycardia” that was run on the PubMed database using the age filter (birth to 18 years), and it yielded 58 results. The second search using the MeSH database with the search term “catecholaminergic polymorphic ventricular tachycardia,” applying no filters yielded 178 results. The abstracts of all these articles were studied and the articles were categorized and organized. Articles of relevance were read in full. As and where applicable, relevant references and citations from the primary articles were further explored and read in full. PMID:27212848

  17. Single-strand conformation polymorphism analysis for differentiating phytoplasma strains.

    PubMed

    Musić, Martina Seruga; Skorić, Dijana

    2013-01-01

    Single-strand conformation polymorphism (SSCP) analysis is a sensitive and rapid technique for detecting DNA polymorphisms and mutations in PCR-amplified fragments. Due to its technical simplicity, it is widely used as a screening tool in various investigations, ranging from clinical diagnosis of human hereditary diseases to the characterization of microbial communities. This method can also be used successfully on phytoplasmas as a tool for the detection of molecular variability in conserved housekeeping genes such as 16S rRNA and tuf, as well as in more variable genes, revealing the presence of polymorphisms undetected by routine RFLP analyses. The reliability of SSCP has been confirmed by multiple alignments and phylogenetic analyses of representative sequences showing different SSCP profiles. However, it is not broadly applied in phytoplasma research yet. The technique provides an inexpensive, convenient, and sensitive method for determining sequence variation and to differentiate phytoplasma strains, and is particularly suitable for epidemiological studies or as a fast screening, typing tool when dealing with a large number of field samples.

  18. Templated sequence insertion polymorphisms in the human genome

    NASA Astrophysics Data System (ADS)

    Onozawa, Masahiro; Aplan, Peter

    2016-11-01

    Templated Sequence Insertion Polymorphism (TSIP) is a recently described form of polymorphism recognized in the human genome, in which a sequence that is templated from a distant genomic region is inserted into the genome, seemingly at random. TSIPs can be grouped into two classes based on nucleotide sequence features at the insertion junctions; Class 1 TSIPs show features of insertions that are mediated via the LINE-1 ORF2 protein, including 1) target-site duplication (TSD), 2) polyadenylation 10-30 nucleotides downstream of a “cryptic” polyadenylation signal, and 3) preference for insertion at a 5’-TTTT/A-3’ sequence. In contrast, class 2 TSIPs show features consistent with repair of a DNA double-strand break via insertion of a DNA “patch” that is derived from a distant genomic region. Survey of a large number of normal human volunteers demonstrates that most individuals have 25-30 TSIPs, and that these TSIPs track with specific geographic regions. Similar to other forms of human polymorphism, we suspect that these TSIPs may be important for the generation of human diversity and genetic diseases.

  19. Twinning of cubic diamond explains reported nanodiamond polymorphs

    NASA Astrophysics Data System (ADS)

    Németh, Péter; Garvie, Laurence A. J.; Buseck, Peter R.

    2015-12-01

    The unusual physical properties and formation conditions attributed to h-, i-, m-, and n-nanodiamond polymorphs has resulted in their receiving much attention in the materials and planetary science literature. Their identification is based on diffraction features that are absent in ordinary cubic (c-) diamond (space group: Fd-3m). We show, using ultra-high-resolution transmission electron microscope (HRTEM) images of natural and synthetic nanodiamonds, that the diffraction features attributed to the reported polymorphs are consistent with c-diamond containing abundant defects. Combinations of {113} reflection and <011> rotation twins produce HRTEM images and d-spacings that match those attributed to h-, i-, and m-diamond. The diagnostic features of n-diamond in TEM images can arise from thickness effects of c-diamonds. Our data and interpretations strongly suggest that the reported nanodiamond polymorphs are in fact twinned c-diamond. We also report a new type of twin (<11> rotational), which can give rise to grains with dodecagonal symmetry. Our results show that twins are widespread in diamond nanocrystals. A high density of twins could strongly influence their applications.

  20. Agouti sequence polymorphisms in coyotes, wolves and dogs suggest hybridization.

    PubMed

    Schmutz, Sheila M; Berryere, Thomas G; Barta, Jodi L; Reddick, Kimberley D; Schmutz, Josef K

    2007-01-01

    Domestic dogs have been shown to have multiple alleles of the Agouti Signal Peptide (ASIP) in exon 4 and we wished to determine the level of polymorphism in the common wild canids of Canada, wolves and coyotes, in comparison. All Canadian coyotes and most wolves have banded hairs. The ASIP coding sequence of the wolf did not vary from the domestic dog but one variant was detected in exon 4 of coyotes that did not alter the arginine at this position. Two other differences were found in the sequence flanking exon 4 of coyotes compared with the 45 dogs and 1 wolf. The coyotes also demonstrated a relatively common polymorphism in the 3' UTR sequence that could be used for population studies. One of the ASIP alleles (R96C) in domestic dogs causes a solid black coat color in homozygotes. Although some wolves are melanistic, this phenotype does not appear to be caused by this same mutation. However, one wolf, potentially a dog-wolf hybrid or descendant thereof, was heterozygous for this allele. Likewise 2 coyotes, potentially dog-coyote or wolf-coyote hybrid descendants, were heterozygous for the several polymorphisms in and flanking exon 4. We could conclude that these were coyote-dog hybrids because both were heterozygous for 2 mutations causing fawn coat color in dogs.

  1. Bionomics and polymorphism in Callosobruchus subinnotatus (Coleoptera: Bruchidae).

    PubMed

    Appleby, J H; Credland, P F

    2001-08-01

    Callosobruchus subinnotatus (Pic) is the major insect pest of stored bambara groundnuts, Vigna subterranea (L.) Verdcourt, in sub-Saharan West Africa, but little is currently known about its biology or how it may be controlled. A series of laboratory studies was performed to investigate the bionomics of and differences between two apparently different morphs of adult of each sex of this species, here termed 'active' and 'normal'. Major differences in their morphology, physiology and behaviour were identified and are described in detail for the first time. They provide clear evidence of the existence of an adult polymorphism among populations of this species, which is comparable in certain respects to that previously described for C. maculatus (Fabricius) and C. chinensis Linnaeus. Adults can be separated into the correct morph based on characteristic differences in elytral and pygidial colour and pattern. 'Normal' adults are characterized by having high fecundity, short adult life and are relatively sedentary while 'active' adults exhibit reproductive diapause (suspension of reproductive activity), are long lived, and show (at least in females) increased dispersal tendencies. These characteristics suggest adaptation of the 'active' and 'normal' morphs respectively to the different environments of field and seed stores, and the significance of the polymorphism in the life history of C. subinnotatus is discussed in this context. The design of any effective control regime for this bruchid needs to take account of and could potentially be based upon the existence of polymorphism in C. subinnotatus.

  2. Configurational entropy of hydrogen-disordered ice polymorphs

    SciTech Connect

    Herrero, Carlos P. Ramírez, Rafael

    2014-06-21

    The configurational entropy of several H-disordered ice polymorphs is calculated by means of a thermodynamic integration along a path between a totally H-disordered state and one fulfilling the Bernal-Fowler ice rules. A Monte Carlo procedure based on a simple energy model is used, so that the employed thermodynamic path drives the system from high temperatures to the low-temperature limit. This method turns out to be precise enough to give reliable values for the configurational entropy s{sub th} of different ice phases in the thermodynamic limit (number of molecules N → ∞). The precision of the method is checked for the ice model on a two-dimensional square lattice. Results for the configurational entropy are given for H-disordered arrangements on several polymorphs, including ices Ih, Ic, II, III, IV, V, VI, and XII. The highest and lowest entropy values correspond to ices VI and XII, respectively, with a difference of 3.3% between them. The dependence of the entropy on the ice structures has been rationalized by comparing it with structural parameters of the various polymorphs, such as the mean ring size. A particularly good correlation has been found between the configurational entropy and the connective constant derived from self-avoiding walks on the ice networks.

  3. Gene polymorphisms of fibrinolytic enzymes in coal workers' pneumoconiosis

    SciTech Connect

    Chang, L.C.; Tseng, J.C.; Hua, C.C.; Liu, Y.C.; Shieh, W.B.; Wu, H.P.

    2006-03-15

    The authors assessed the gene polymorphisms of missense C/T polymorphism in exon 6 of the urokinase-plasminogen activator (PLAU) gene (PLAU P141L), A/u-repeat in intron 8 of the tissue-type plasminogen activator (PLAT) gene (PLAT TPA25 Alu insertion), and 4G/5G in the promoter region of the serine proteinase inhibitor, clade E (SERPINE) or plasminogen activator inhibitor type 1 gene (SERPINE1 -675 4G/5G) in 153 healthy volunteers and 154 retired coal miners with coal miners' pneumoconiosis (CWP). The CWP subjects included 94 individuals with simple pneumoconiosis and 60 individuals with progressive massive fibrosis presenting with worse pulmonary function. The distributions of genotypes of these three genes did not differ between the control and CWP subjects or between subjects with simple pneumoconiosis and those with progressive massive fibrosis. However, by assessing duration of work and its interaction with genotypes by means of logistic regression, the authors found the missense C/T polymorphism in exon 6 of the PLAU gene to be an effect modifier of the association between work duration and the development of progressive massive fibrosis.

  4. PSCA rs2294008 Polymorphism with Increased Risk of Cancer

    PubMed Central

    Geng, Peiliang; Li, Jianjun; Wang, Ning; Ou, Juanjuan; Xie, Ganfeng; Liu, Chen; Zhao, Xiaoxin; Xiang, Lisha; Liao, Yunmei; Liang, Houjie

    2015-01-01

    Background Published data on the association between PSCA rs2294008 polymorphism and cancer risk have implicated inconclusive results. To determine the relationship and to precisely assess the effect size estimate of the association, we performed a meta-analysis. Methods We searched published literature in Embase and PubMed databases using the search terms “PSCA”, “prostate stem cell antigen”, “variants”, “polymorphism”, “polymorphisms”, and “cancer”. A total of 21 eligible articles were retrieved, with 27, 197 cancer cases and 48, 237 controls. Results On the whole, we found the association between PSCA rs2294008 polymorphism and cancer risk was statistically significant: TT vs CC: OR = 1.18, 95% CI, 1.10 to 1.27; TT + CT vs CC: OR = 1.08, 95% CI, 1.05 to 1.10; TT vs CT + CC: OR = 1.14, 95% CI, 1.07 to 1.21; T vs C: OR = 1.10, 95% CI, 1.06 to 1.14; CT vs CC: OR = 1.10, 95% CI, 1.06 to 1.13. Stratified analyses in cancer type and ethnicity showed similar results. Conclusions Based on the statistical evidence, we can draw a conclusion that the rs2294008 polymorphism of PSCA gene is likely to play a role in cancer carcinogenesis, especially in gastric cancer and bladder cancer. PMID:26308216

  5. Can paternal leakage maintain sexually antagonistic polymorphism in the cytoplasm?

    PubMed Central

    Kuijper, B; Lane, N; Pomiankowski, A

    2015-01-01

    A growing number of studies in multicellular organisms highlight low or moderate frequencies of paternal transmission of cytoplasmic organelles, including both mitochondria and chloroplasts. It is well established that strict maternal inheritance is selectively blind to cytoplasmic elements that are deleterious to males – ’mother's curse’. But it is not known how sensitive this conclusion is to slight levels of paternal cytoplasmic leakage. We assess the scope for polymorphism when individuals bear multiple cytoplasmic alleles in the presence of paternal leakage, bottlenecks and recurrent mutation. When fitness interactions among cytoplasmic elements within an individual are additive, we find that sexually antagonistic polymorphism is restricted to cases of strong selection on males. However, when fitness interactions among cytoplasmic elements are nonlinear, much more extensive polymorphism can be supported in the cytoplasm. In particular, mitochondrial mutants that have strong beneficial fitness effects in males and weak deleterious fitness effects in females when rare (i.e. ’reverse dominance’) are strongly favoured under paternal leakage. We discuss how such epistasis could arise through preferential segregation of mitochondria in sex-specific somatic tissues. Our analysis shows how paternal leakage can dampen the evolution of deleterious male effects associated with predominant maternal inheritance of cytoplasm, potentially explaining why ’mother's curse’ is less pervasive than predicted by earlier work. PMID:25653025

  6. MHC promoter polymorphism in grey wolves and domestic dogs.

    PubMed

    Berggren, Karin T; Seddon, Jennifer M

    2005-05-01

    A functional immune system requires a tight control over major histocompatibility complex (MHC) gene transcription, as the abnormal MHC expression patterns of severe immunodeficiency and autoimmune diseases demonstrate. Although the regulation of MHC expression has been well documented in humans and mice, little is known in other species. In this study, we detail the level of polymorphism in wolf and dog MHC gene promoters. The promoter regions of the DRB, DQA and DQB locus were sequenced in 90 wolves and 90 dogs. The level of polymorphism was high in the DQB promoters, with variation found within functionally relevant regions, including binding sites for transcription factors. Clear associations between DQB promoters and exon 2 alleles were noted in wolves, indicating strong linkage disequilibrium in this region. Low levels of polymorphism were found within the DRB and DQA promoter regions. However, a variable site was identified within the T box, a TNF-alpha response element, of the DQA promoter. Furthermore, we identified a previously unrecognised 18-base-pair deletion within exon 1 of the DQB locus.

  7. Flower color polymorphism maintained by overdominant selection in Sisyrinchium sp.

    PubMed

    Takahashi, Yuma; Takakura, Koh-ichi; Kawata, Masakado

    2015-11-01

    Negative frequency-dependent selection derived from positive frequency-dependent foraging is the best-known selection force maintaining genetic polymorphism within a population. However, in flowering plants, positive frequency-dependent foraging by pollinators is expected to accelerate the loss of low-frequency morphs by conferring a fitness advantage to the common morph, leading to monomorphism. In Japan, a non-native species, Sisyrinchium sp., exhibits conspicuous flower color polymorphism within a population comprising both purple morphs (homozygous recessive) and white morphs (heterozygous or homozygous dominant). Here we quantified genotype-specific reproductive success in order to reveal the contribution of overdominant selection on the maintenance of flower color polymorphism in this species. In artificial pollination experiments using individuals with identified genotypes, female reproductive success was higher in the heterozygote than in either homozygote. The frequency of purple morphs in natural populations (ca. 31%) is similar to the frequency predicted by overdominant selection (25%). Our results suggest that overdominant selection contributes to the maintenance of color morphs in the natural population of this species.

  8. Glutathione S-transferase polymorphisms in thyroid cancer patients.

    PubMed

    Hernández, Alba; Céspedes, Walkiria; Xamena, Noel; Surrallés, Jordi; Creus, Amadeu; Galofré, Pere; Marcos, Ricardo

    2003-02-10

    Glutathione S-transferases (GST) are enzymes involved in the metabolism of many carcinogens and mutagens, also acting as important free-radical scavengers. The existence of different genetic polymorphisms in human populations has proven to be a susceptibility factor for different tumours. Nevertheless, as far as we know, for thyroid cancer no study has been conducted until now linking its incidence to genetic susceptibility biomarkers. The present investigation has been conducted to detect the possible association between polymorphism at the GSTM1, GSTT1 and GSTP1 genes and thyroid cancer incidence. Thus, 134 thyroid cancer patients and 116 controls, all from the urban district of Barcelona (Spain), have been included in this study. The results indicate that, according to the calculated odds ratio, the frequencies of the different genotypes found in the group of cancer patients do not significantly differ from those values obtained in the controls. This is true for the overall data as well as for the tumour characterization as follicular and papillar types. In addition, none of the possible combinations of mutant genotypes were shown to be risk factors. Finally, when the sex of the patients, the age of tumour onset, and life-style habits were also taken into account, no influence was observed related to the different genotypes. In conclusion, the results obtained in this study clearly suggest that those susceptibility factors related to the different GST polymorphic enzymes are not a predisposing factor in thyroid cancer disease.

  9. IMPDH2 genetic polymorphism: a promoter single-nucleotide polymorphism disrupts a cyclic adenosine monophosphate responsive element.

    PubMed

    Garat, Anne; Cauffiez, Christelle; Hamdan-Khalil, Rima; Glowacki, François; Devos, Aurore; Leclerc, Julie; Lionet, Arnaud; Allorge, Delphine; Lo-Guidice, Jean-Marc; Broly, Franck

    2009-12-01

    Inosine 5'-monophosphate dehydrogenase (IMPDH), which catalyzes a key step in the de novo biosynthesis of guanine nucleotide, is mediated by two highly conserved isoforms, IMPDH1 and IMPDH2. In this study, IMPDH2 genetic polymorphism was investigated in 96 individuals of Caucasian origin. Four single-nucleotide polymorphisms were identified, comprising one previously described single base-pair substitution in the close vicinity of the consensus donor splice site of intron 7 (IVS7+10T>C), and three novel polymorphisms, one silent substitution in exon 9 (c.915C>G), one single base-pair insertion (g.6971_6972insT) within the 3'-untranslated region of the gene, and one substitution located in the promoter region (c.-95T>G) in a transcription factor binding site CRE(A) (cyclic adenosine monophosphate [cAMP] response element). Considering the nature and location of this latter polymorphism, its functional relevance was examined by transfecting HEK293 and Jurkat cell lines with constructs of the related region of IMPDH2/luciferase reporter gene. The c.-95T>G mutation leads to a significant decrease of luciferase activity (HEK293: 55% decrease, p < 0.05; Jurkat: 65% decrease, p < 0.05) compared with the wild-type promoter sequence and, therefore, is likely to determine interindividual differences in IMPDH2 transcriptional regulation. These results might contribute to a better understanding of the variability in clinical outcome and dose adjustments of certain immunosuppressors that are metabolized through the IMPDH pathway or that are IMPDH inhibitors.

  10. Bone growth in juvenile rhesus monkeys is influenced by 5HTTLPR polymorphisms and interactions between 5HTTLPR polymorphisms and fluoxetine.

    PubMed

    Golub, Mari S; Bulleri, Alicia M; Hogrefe, Casey E; Sherwood, Richard J

    2015-10-01

    Male rhesus monkeys received a therapeutic oral dose of the selective serotonin reuptake inhibitor (SSRI) fluoxetine daily from 1 to 3 years of age. Puberty is typically initiated between 2 and 3 years of age in male rhesus and reproductive maturity is reached at 4 years. The study group was genotyped for polymorphisms in the monoamine oxidase A (MAOA) and serotonin transporter (SERT) genes that affect serotonin neurotransmission. Growth was assessed with morphometrics at 4 month intervals and radiographs of long bones were taken at 12 month intervals to evaluate skeletal growth and maturation. No effects of fluoxetine, or MAOA or SERT genotype were found for growth during the first year of the study. Linear growth began to slow during the second year of the study and serotonin reuptake transporter (SERT) long polymorphic region (5HTTLPR) polymorphism effects with drug interactions emerged. Monkeys with two SERT 5HTTLPR L alleles (LL, putative greater transcription) had 25-39% less long bone growth, depending on the bone, than monkeys with one S and one L allele (SL). More advanced skeletal maturity was also seen in the LL group, suggesting earlier onset of puberty. An interaction between 5HTTLPR polymorphisms and fluoxetine was identified for femur and tibia growth; the 5HTTLPR effect was seen in controls (40% less growth for LL) but not in the fluoxetine treated group (10% less growth for LL). A role for serotonin in peripubertal skeletal growth and maturation has not previously been investigated but may be relevant to treatment of children with SSRIs.

  11. TLR-4 and VEGF Polymorphisms in Chronic Periaortitis

    PubMed Central

    Atzeni, Fabiola; Boiardi, Luigi; Vaglio, Augusto; Nicoli, Davide; Farnetti, Enrico; Palmisano, Alessandra; Pipitone, Nicolò; Martorana, Davide; Moroni, Gabriella; Longhi, Selena; Bonatti, Francesco; Buzio, Carlo; Salvarani, Carlo

    2013-01-01

    Objective Chronic periaortitis (CP) is a rare disease that is characterised by fibro-inflammatory tissue surrounding the abdominal aorta and has both non-aneurysmal (idiopathic retroperitoneal fibrosis [IRF]) and aneurysmal forms (inflammatory abdominal aortic aneurysm [IAAA]). We investigated whether toll-like receptor 4 (TLR-4) and vascular endothelial growth factor (VEGF) polymorphisms were associated with susceptibility to, and the clinical features of CP. Methods One hundred and two CP patients and 200 healthy controls were molecularly genotyped for TLR-4 gene polymorphism (+896 A/G) (rs4986790), VEGF mutations +936 C/T (rs3025039) and −634 C/G (rs2010963), and an 18 base pair (bp) insertion/deletion (I/D) polymorphism at −2549 of the VEGF promoter region. The patients were grouped on the basis of the type of CP (IRF or IAAA), and the presence or absence of established atherosclerotic disease (ischemic heart disease, cerebrovascular disease, and peripheral arterial disease). Results There were no significant differences in the distribution of the studied polymorphisms between the patients and controls. However, carriage of the +936 T allele was significantly more frequent in the patients with IRF than in those with IAAA (26.5% vs 5.3%; p = 0.046; OR 6.49 [95% CI 0.82–51.54]). There were significantly more carriers of the I allele among the patients with ureteral obstruction (83.8% vs 58.8%; p = 0.006; OR 3.63 [95% CI 1.42–9.28]) and those who received conservative treatment (48.5% vs 23.5%; p = 0.015; OR 3.06 [95% CI 1.22–7.721]) than among those without, and II homozygosity was significantly more frequent in the patients with deep vein thrombosis than in those without (30.4% vs 11.7%, p = 0.031; OR 3.31 [95% CI 1.07–10.21]). Conclusion The VEGF +936 C/T polymorphism may be associated with an increased risk of developing the non-aneurysmal IRF form of CP. Carriers of the I allele and II homozygosity are respectively at increased

  12. CXC motif chemokine receptor 4 gene polymorphism and cancer risk

    PubMed Central

    Wu, Yang; Zhang, Chun; Xu, Weizhang; Zhang, Jianzhong; Zheng, Yuxiao; Lu, Zipeng; Liu, Dongfang; Jiang, Kuirong

    2016-01-01

    Abstract Background: Previous epidemiological studies have reported the relationship between CXC motif chemokine receptor 4 (CXCR4) synonymous polymorphism (rs2228014), and risk of cancer, but the results remained conflicting and controversial. Therefore, this study was devised to evaluate the genetic effects of the rs2228014 polymorphism on cancer risk in a large meta-analysis. Methods: The computer-based databases (EMBASE, Web of Science, and PubMed) were searched for all relevant studies evaluating rs2228014 and susceptibility to cancer. In the analysis, pooled odds ratios (ORs) with its corresponding 95% confidence intervals (CIs) were calculated in 5 genetic models to assess the genetic risk. Egger regression and Begg funnel plots test were conducted to appraise the publication bias. Results: Data on rs2228014 polymorphism and overall cancer risk were available for 3684 cancer patients and 5114 healthy controls participating in 11 studies. Overall, a significantly increased risk of cancer was associated with rs2228014 polymorphism in homozygote model (OR = 2.01, 95% CI: 1.22–3.33) and in recessive model (OR = 1.97, 95% CI: 1.23–3.16). When stratified by ethnicity, the results were positive only in Asian populations (heterozygote model: OR = 1.36, 95% CI: 1.13–1.65; homozygote model: OR = 2.43, 95% CI: 1.21–4.91; dominant model: OR = 1.47, 95% CI: 1.13–1.90; recessive model: OR = 2.25, 95% CI: 1.13–4.48; and allele model: OR = 1.48, 95% CI: 1.10–1.99). Besides, in the subgroup analysis by source of control, the result was significant only in population-based control (homozygote model: OR = 2.39, 95% CI: 1.06–5.40; recessive model: pooled OR = 2.24, 95% CI: 1.02–4.96). Conclusion: In general, our results first indicated that the rs2228014 polymorphism in CXCR4 gene is correlated with an increased risk of cancer, especially among Asian ethnicity. Large, well-designed epidemiological studies are required to verify the current findings. PMID

  13. Diffuse Scattering as an Aid to the Understanding of Polymorphism in Pharmaceuticals

    NASA Astrophysics Data System (ADS)

    Welberry, T. R.; Chan, E. J.; Goossens, D. J.; Heerdegen, A. P.

    2012-05-01

    Polymorphism occurs when the same molecular compound can crystallize in more than one distinct crystal structure. Its study is a field of great interest and activity. This is largely driven by its importance in the pharmaceutical industry, but polymorphism is also an issue in the pigments, dyes, and explosives industries. The polymorph formed by a compound generally exerts a strong influence on its solid-state properties. The polymorphic form of a drug molecule may affect the ease of manufacture and processing, shelf life, and most significantly the rate of uptake of the molecule by the human body. They can even vary in toxicity; one polymorph may be safe, while a second may be toxic. In this review of recently published work, we show how diffuse scattering experiments coupled with Monte Carlo (MC) computer modeling can aid in the understanding of polymorphism. Examples of the two common pharmaceuticals, benzocaine and aspirin, both of which are bimorphic, at ambient temperatures, are discussed.

  14. Diffuse Scattering as an Aid to the Understanding of Polymorphism in Pharmaceuticals

    SciTech Connect

    Welberry, T.R.; Chan, E.J.; Goossens, D.J.; Heerdegen, A.P.

    2012-04-30

    Polymorphism occurs when the same molecular compound can crystallize in more than one distinct crystal structure. Its study is a field of great interest and activity. This is largely driven by its importance in the pharmaceutical industry, but polymorphism is also an issue in the pigments, dyes, and explosives industries. The polymorph formed by a compound generally exerts a strong influence on its solid-state properties. The polymorphic form of a drug molecule may affect the ease of manufacture and processing, shelf life, and most significantly the rate of uptake of the molecule by the human body. They can even vary in toxicity; one polymorph may be safe, while a second may be toxic. In this review of recently published work, we show how diffuse scattering experiments coupled with Monte Carlo (MC) computer modeling can aid in the understanding of polymorphism. Examples of the two common pharmaceuticals, benzocaine and aspirin, both of which are bimorphic, at ambient temperatures, are discussed.

  15. Identification of doublesex alleles associated with the female-limited Batesian mimicry polymorphism in Papilio memnon.

    PubMed

    Komata, Shinya; Lin, Chung-Ping; Iijima, Takuro; Fujiwara, Haruhiko; Sota, Teiji

    2016-10-06

    The female-limited Batesian mimicry polymorphism in Papilio butterflies is an intriguing system for investigating the mechanism of maintenance of genetic polymorphisms. In Papilio polytes, an autosomal region encompassing the sex-determinant gene doublesex controls female-limited mimicry polymorphism. In the closely related species P. memnon, which also exhibits female-limited Batesian mimicry polymorphism, we identified two allelic sequences of the doublesex gene that corresponded exactly with the mimetic and non-mimetic female phenotypes. Thus, the genetic basis of the mimicry polymorphism in P. memnon is similar to that in P. polytes. However, the mimetic and non-mimetic alleles of the two species were not identical, and the divergence of alleles occurred independently in P. memnon and P. polytes. Different mutation-selection processes may have resulted in the convergent patterns of mimicry polymorphism in these Papilio butterflies.

  16. Identification of doublesex alleles associated with the female-limited Batesian mimicry polymorphism in Papilio memnon

    PubMed Central

    Komata, Shinya; Lin, Chung-Ping; Iijima, Takuro; Fujiwara, Haruhiko; Sota, Teiji

    2016-01-01

    The female-limited Batesian mimicry polymorphism in Papilio butterflies is an intriguing system for investigating the mechanism of maintenance of genetic polymorphisms. In Papilio polytes, an autosomal region encompassing the sex-determinant gene doublesex controls female-limited mimicry polymorphism. In the closely related species P. memnon, which also exhibits female-limited Batesian mimicry polymorphism, we identified two allelic sequences of the doublesex gene that corresponded exactly with the mimetic and non-mimetic female phenotypes. Thus, the genetic basis of the mimicry polymorphism in P. memnon is similar to that in P. polytes. However, the mimetic and non-mimetic alleles of the two species were not identical, and the divergence of alleles occurred independently in P. memnon and P. polytes. Different mutation-selection processes may have resulted in the convergent patterns of mimicry polymorphism in these Papilio butterflies. PMID:27708422

  17. The Relationships Between Victim Age, Gender, and Relationship Polymorphism and Sexual Recidivism.

    PubMed

    Stephens, Skye; Seto, Michael C; Goodwill, Alasdair M; Cantor, James M

    2016-02-19

    Victim choice polymorphism refers to victim inconsistency in a series of offenses by the same perpetrator, such as in the domains of victim age, victim gender, and victim-offender relationship. Past studies have found that victim age polymorphic offenders have higher rates of sexual recidivism than offenders against adults only and offenders against children only. Few studies, however, have examined gender and relationship polymorphism, or accounted for the impact of the number of past victims. The present study analyzed the relationship between polymorphism and sexual recidivism, while controlling for the number of victims. The sample consisted of 751 male adult sexual offenders followed for an average of 10 years, 311 of whom were polymorphic (41% of the total sample). The main finding suggested that there was an association between sexual recidivism and age and relationship polymorphism; however, these associations were no longer significant after controlling for the number of victims.

  18. Intercellular Adhesion Molecule-1 (ICAM-1) Polymorphisms and Cancer Risk: A Meta-Analysis

    PubMed Central

    CHENG, Daye; LIANG, Bin

    2015-01-01

    Background: Intercellular adhesion molecule-1 (ICAM-1) Lys469Glu (K469E) polymorphism and Gly 241Arg (G241R) polymorphism might play important roles in cancer development and progression. However, the results of previous studies are inconsistent. The aim of this study was to evaluate the association between ICAM-1 K469E and G241R polymorphisms and the risk of cancer by meta-analysis. Methods: A comprehensive literature search (last search updated in November 2013) was conducted to identify case-control studies that investigated the association between ICAM-1 K469E and G241R polymorphisms and cancer risk. Results: A total of 18 case-control studies for ICAM-1 polymorphisms were included in the meta-analysis, including 4,844 cancer cases and 5,618 healthy controls. For K469E polymorphism, no significant association was found between K469E polymorphism and cancer risk. However, subgroup analysis by ethnicity revealed one genetic comparison (GG vs. AA) presented the relationship with cancer risk in Asian subgroup, and two genetic models (GG+GA vs. AA and GA vs. AA) in European subgroup, respectively. For G241R polymorphism, G241R polymorphism was significantly association with cancer risk in overall analysis. The subgroup analysis by ethnicity showed that G241R polymorphism was significantly associated with cancer risk in European subgroup. Conclusion: ICAM-1 G241R polymorphism might be associated with cancer risk, especially in European populations, but the results doesn’t support ICAM-1 K469E polymorphism as a risk factor for cancer. PMID:26284202

  19. Association between three exonuclease 1 polymorphisms and cancer risks: a meta-analysis

    PubMed Central

    Chen, Zi-Yu; Zheng, Si-Rong; Zhong, Jie-Hui; Zhuang, Xiao-Duan; Zhou, Jue-Yu

    2016-01-01

    To date, the results of studies exploring the relation between exonuclease 1 (Exo1) polymorphisms and cancer risks have differed. In this study, we performed a meta-analysis to investigate the effect of the three most extensively studied Exo1 polymorphisms (Pro757Leu, Glu589Lys, and Glu670Gly) on cancer susceptibility. The related studies published before August 5, 2015, were collected by searching the PubMed and EMBASE databases. We found 16 publications containing studies that were eligible for our study, including 10 studies for Pro757Leu polymorphism (4,093 cases and 3,834 controls), 12 studies for Glu589Lys polymorphism (6,479 cases and 6,550 controls), and 7 studies for Glu670Gly polymorphism (3,700 cases and 3,496 controls). Pooled odds ratios and 95% confidence intervals were used to assess the strength of the associations, and all the statistical analyses were calculated using the software program STATA version 12.0. Our results revealed that the Pro757Leu polymorphism was significantly associated with a reduced cancer risk, whereas an inverse association was found for the Glu589Lys polymorphism. Furthermore, subgroup analysis of smoking status indicated that the Glu589Lys polymorphism was significantly associated with an increased cancer risk in smokers, but not in nonsmokers. However, no evidence was found for an association between the Glu670Gly polymorphism and cancer risk. In conclusion, this meta-analysis suggests that the Pro757Leu polymorphism may provide protective effects against cancer, while the Glu589Lys polymorphism may be a risk factor for cancer. Moreover, the Glu670Gly polymorphism may have no influence on cancer susceptibility. In the future, large-scaled and well-designed studies are needed to achieve a more precise and comprehensive result. PMID:26966378

  20. CYP1B1 Polymorphism as a Risk Factor for Race-Related Prostate Cancer

    DTIC Science & Technology

    2008-06-01

    AD_________________ Award Number: W81XWH-04-1-0579 TITLE: CYP1B1 Polymorphism as a Risk Factor...TITLE AND SUBTITLE CYP1B1 Polymorphism as a Risk Factor for Race-Related Prostate Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-04-1-0579...collected; as well as further experimentation with aim #1to be performed. 15. SUBJECT TERMS CYP1B1 , Polymorphism , Prostate cancer, Race-related

  1. CYP1B1 Polymorphism as a Risk Factor for Race-Related Prostate Cancer

    DTIC Science & Technology

    2005-06-01

    AD Award Number: W81XWH-04-1-0579 TITLE: CYP1B1 Polymorphism as a Risk Factor for Race-Related Prostate Cancer PRINCIPAL INVESTIGATOR: Yuichiro...2005 Annual 1 Jun 2004 - 31 May 2005 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER CYP IB I Polymorphism as a Risk Factor for Race-Related Prostate Cancer...Approved for Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT- SEE ATTACHED PAGE 15. SUBJECT TERMS CYPIBI, Polymorphism

  2. CYP1B1 Polymorphism as a Risk Factor for Race-Related Prostate Cancer

    DTIC Science & Technology

    2006-06-01

    AD_________________ Award Number: W81XWH-04-1-0579 TITLE: CYP1B1 Polymorphism as a Risk Factor...TITLE AND SUBTITLE CYP1B1 Polymorphism as a Risk Factor for Race-Related Prostate Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-04-1-0579...hypothesis, single nucleotide polymorphisms (SNPs) at three codons (119, 432, and 453) of CYP1B1 have been evaluated to determine if they are risk factors

  3. Triclinic polymorph of 4-[4-(4-formyl-phen-oxy)but-oxy]benzaldehyde.

    PubMed

    Balić, Tomislav; Marković, Berislav; Balić, Ivana

    2013-01-01

    The title compound, C18H18O4, is a triclinic polymorph of the previously reported monoclinic polymorph [Han & Zhen (2005 ▶). Acta Cryst. E61, o4358-o4359]. In the crystal of the triclinic polymorph, molecules are linked by two pairs of C-H⋯O hydrogen bonds, forming a two-dimensional network parallel to (102), and enclosing loops with graph set motifs of R2(2)(8) and R2(2)(6).

  4. Polymorphism control of p-aminobenzoic acid by isothermal anti-solvent crystallization

    NASA Astrophysics Data System (ADS)

    Garg, Rakesh Kumar; Sarkar, Debasis

    2016-11-01

    We report, for the first time, the control of polymorphism of p-aminobenzoic acid by isothermal anti-solvent crystallization using ethanol as solvent and water as anti-solvent. p-aminobenzoic (p-ABA) acid crystallizes in two distinct polymorphic forms: the α-polymorph, which is commercially available form and appears as long fibrous needles; and the β-polymorph, which appears in the form of prisms. The solubility of p-ABA was determined gravimetrically for various water/ethanol mixtures at 15 °C and isothermal anti-solvent crystallization experiments were conducted at 15 °C over a range of supersaturation ratio from 1.01 to 1.30 and at different anti-solvent addition rates of 4, 6, 8, and10 ml/h. The needle-type α-polymorph was always obtained at higher supersaturation ratio and higher flow-rates of anti-solvent addition. The prismatic β-polymorph was obtained at lower supersaturation range of 1.01-1.06 when anti-solvent was added at 4 and 6 ml/h. The obtained polymorphs were characterized using scanning electron microscopy, powder x-ray diffraction, and differential scanning calorimetry. The region of occurrence of each polymorph with respect to supersaturation ratio and anti-solvent wt% is presented for these addition rates. The careful selection of supersaturation ratio and anti-solvent addition rate can produce desired polymorph of p-ABA by anti-solvent crystallization.

  5. Synthesis of chiral polymorph A-enriched zeolite Beta with an extremely concentrated fluoride route

    PubMed Central

    Tong, Mingquan; Zhang, Daliang; Fan, Weibin; Xu, Jun; Zhu, Liangkui; Guo, Wen; Yan, Wenfu; Yu, Jihong; Qiu, Shilun; Wang, Jianguo; Deng, Feng; Xu, Ruren

    2015-01-01

    Chiral zeolitic materials with intrinsically chiral frameworks are highly desired because they can combine both shape selectivity and enantioselectivity. In the field of zeolite, the synthesis of chiral polymorph A of zeolite Beta or chiral polymorph A-enriched zeolite Beta is one of the biggest challenges. We demonstrate here a generalized extremely concentrated fluoride route for the synthesis of chiral polymorph A-enriched zeolite Beta in the presence of five achiral organic structure-directing agents. The polymorph A-enriched Ti-Beta shows a higher enantioselectivity for the asymmetric epoxidation of alkenes than the normal Ti-Beta. PMID:26096214

  6. Nucleation control and separation of paracetamol polymorphs through swift cooling crystallization process

    NASA Astrophysics Data System (ADS)

    Sudha, C.; Srinivasan, K.

    2014-09-01

    Polymorphic nucleation behavior of pharmaceutical solid paracetamol has been investigated by performing swift cooling crystallization process. Saturated aqueous solution prepared at 318 K was swiftly cooled to 274 K in steps of every 1 K in the temperature range from 274 K to 313 K with uniform stirring of 100 rpm. The resultant supersaturation generated in the mother solution favours the nucleation of three different polymorphs of paracetamol. Lower supersaturation region σ=0.10-0.83 favours stable mono form I; the intermediate supersaturation region σ=0.92-1.28 favours metastable ortho form II and the higher supersaturation region σ=1.33-1.58 favours unstable form III polymorphic nucleation. Depending upon the level of supersaturation generated during swift cooling process and the corresponding solubility limit and metastable zone width (MSZW) of each polymorph, the nucleation of a particular polymorph occurs in the system. The type of polymorphs was identified by in-situ optical microscopy and the internal structure was confirmed by Powder X-ray diffraction (PXRD) study. By this novel approach, the preferred nucleation regions of all the three polymorphs of paracetamol are optimized in terms of different cooling ranges employed during the swift cooling process. Also solution mediated polymorphic transformations from unstable to mono and ortho to mono polymorphs have been studied by in-situ.

  7. The role of angiotensin-converting enzyme polymorphism in congestive heart failure.

    PubMed

    Pilati, Mara; Cicoira, Mariantonietta; Zanolla, Luisa; Nicoletti, Ilaria; Muraglia, Simone; Zardini, Piero

    2004-01-01

    Angiotensin-converting enzyme (ACE) is a zinc metallopeptidase, with primary known functions of converting angiotensin I into the vasoactive and aldosterone-stimulating peptide angiotensin II and inactivating bradykinin. There is high variability among individuals in ACE concentrations, mainly due to the presence of a genetic polymorphism. The ACE gene has, in fact, insertion/deletion polymorphism in intron 16, consisting of a 287-base pair Alu repeat sequence, with three genotypes: insertion polymorphism, insertion/deletion polymorphism, and deletion polymorphism. The genetic effect accounts for 47% of the total variance of serum ACE. The determination of this polymorphism has allowed researchers to study the implications of the ACE gene in many case-control studies of cardiovascular disease, including myocardial infarction and hypertrophic and dilated cardiomyopathy. We review the current knowledge about the ACE gene polymorphism and its implications in heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Interpretation of the results of studies about the role of this polymorphism are controversial. The repetition of epidemio-genetic studies and the creation of adequate experimental studies will help to definitively establish the pathogenetic role of the permanent increase in ACE expression associated with the deletion polymorphism genotype.

  8. Polymorphism in nimodipine raw materials: development and validation of a quantitative method through differential scanning calorimetry.

    PubMed

    Riekes, Manoela Klüppel; Pereira, Rafael Nicolay; Rauber, Gabriela Schneider; Cuffini, Silvia Lucia; de Campos, Carlos Eduardo Maduro; Silva, Marcos Antonio Segatto; Stulzer, Hellen Karine

    2012-11-01

    Due to the physical-chemical and therapeutic impacts of polymorphism, its monitoring in raw materials is necessary. The purpose of this study was to develop and validate a quantitative method to determine the polymorphic content of nimodipine (NMP) raw materials based on differential scanning calorimetry (DSC). The polymorphs required for the development of the method were characterized through DSC, X-ray powder diffraction (XRPD) and Raman spectroscopy and their polymorphic identity was confirmed. The developed method was found to be linear, robust, precise, accurate and specific. Three different samples obtained from distinct suppliers (NMP 1, NMP 2 and NMP 3) were firstly characterized through XRPD and DSC as polymorphic mixtures. The determination of their polymorphic identity revealed that all samples presented the Modification I (Mod I) or metastable form in greatest proportion. Since the commercial polymorph is Mod I, the polymorphic characteristic of the samples analyzed needs to be investigated. Thus, the proposed method provides a useful tool for the monitoring of the polymorphic content of NMP raw materials.

  9. Efficient isolation of polymorphic microsatellites from high-throughput sequence data based on number of repeats.

    PubMed

    Cardoso, Sara D; Gonçalves, David; Robalo, Joana I; Almada, Vitor C; Canário, Adelino V M; Oliveira, Rui F

    2013-09-01

    Transcriptome data are a good resource to develop microsatellites due to their potential in targeting candidate genes. However, developing microsatellites can be a time-consuming enterprise due to the numerous primer pairs to be tested. Therefore, the use of methodologies that make it efficient to identify polymorphic microsatellites is desirable. Here we used a 62,038 contigs transcriptome assembly, obtained from pyrosequencing a peacock blenny (Salaria pavo) multi-tissue cDNA library, to mine for microsatellites and in silico evaluation of their polymorphism. A total of 4190 microsatellites were identified in 3670 unique unigenes, and from these microsatellites, in silico polymorphism was detected in 733. We selected microsatellites based either on their in silico polymorphism and annotation results or based only on their number of repeats. Using these two approaches, 28 microsatellites were successfully amplified in twenty-six individuals, and all but 2 were found to be polymorphic, being the first genetic markers for this species. Our results showed that the strategy of selection based on number of repeats is more efficient in obtaining polymorphic microsatellites than the strategy of in silico polymorphism (allelic richness was 8.2±3.85 and 4.56±2.45 respectively). This study demonstrates that combining the knowledge of number of repeats with other predictors of variability, for example in silico microsatellite polymorphism, improves the rates of polymorphism, yielding microsatellites with higher allelic richness, and decreases the number of monomorphic microsatellites obtained.

  10. Lack of Arg972 polymorphism in the IRS1 gene in Parakanã Brazilian Indians.

    PubMed

    Bezerra, Rosângela M N; Chadid, Thiago T; Altemani, Claúdia M; Sales, Teresa S I; Menezes, Raimundo; Soares, Manoel C P; Saad, Sara T O; Saad, Mario J A

    2004-02-01

    Several polymorphisms in the insulin receptor substrate-1 (IRS1) gene have been reported in the last years. The most common IRS1 variant, a Gly --> Arg substitution at codon 972 (Arg972 IRS1), is more prevalent among subjects who have features of insulin resistance syndrome associated, or not, with type 2 diabetes in European populations. To determine whether the absence of IRS1 polymorphism is a more general characteristic of Paleo-Indian-derived populations, we examined the Arg972 IRS1 polymorphism in Parakanã Indians and found a lack of this polymorphism in the Parakanã population.

  11. Characterization and compilation of polymorphic simple sequence repeat (SSR) markers of peanut from public database

    PubMed Central

    2012-01-01

    Background There are several reports describing thousands of SSR markers in the peanut (Arachis hypogaea L.) genome. There is a need to integrate various research reports of peanut DNA polymorphism into a single platform. Further, because of lack of uniformity in the labeling of these markers across the publications, there is some confusion on the identities of many markers. We describe below an effort to develop a central comprehensive database of polymorphic SSR markers in peanut. Findings We compiled 1,343 SSR markers as detecting polymorphism (14.5%) within a total of 9,274 markers. Amongst all polymorphic SSRs examined, we found that AG motif (36.5%) was the most abundant followed by AAG (12.1%), AAT (10.9%), and AT (10.3%).The mean length of SSR repeats in dinucleotide SSRs was significantly longer than that in trinucleotide SSRs. Dinucleotide SSRs showed higher polymorphism frequency for genomic SSRs when compared to trinucleotide SSRs, while for EST-SSRs, the frequency of polymorphic SSRs was higher in trinucleotide SSRs than in dinucleotide SSRs. The correlation of the length of SSR and the frequency of polymorphism revealed that the frequency of polymorphism was decreased as motif repeat number increased. Conclusions The assembled polymorphic SSRs would enhance the density of the existing genetic maps of peanut, which could also be a useful source of DNA markers suitable for high-throughput QTL mapping and marker-assisted selection in peanut improvement and thus would be of value to breeders. PMID:22818284

  12. Association of Vascular Endothelial Growth Factor Polymorphisms with Asthma in Tunisian Children

    PubMed Central

    Lachheb, Jihene; Chelbi, Hanene; Ben Dhifallah, Imen; Ammar, Jamel; Hamzaoui, Kamel; Hamzaoui, Agnès

    2008-01-01

    Background Previous studies demonstrated that the vascular endothelial growth factor (VEGF) was being implicated in the airways inflammation and remodeling process in patients with asthma. Aims We explored the relationship of three polymorphisms in the VEGF gene with asthma in both case control and family studies. Methods We Genotyped a total of 210 children with asthma, 224 unrelated controls and 160 parents for the +936 C >T (rs3025039), −634 G > C (rs2010963) and −2549 −2567 del 18 of the VEGF promoter region. The Mutations were identified with polymerase chain reaction followed by restriction fragment length polymorphism (RFLP) analysis for the +936 C > T, and −634 G > C polymorphisms. Results Of the three polymorphisms studied, a borderline association with asthma was found for the G allele in the −634 G > C polymorphism (p = 0.059). No Statistically significant differences were observed for both +936 C > T, and −2549 −2567 del 18 polymorphisms between asthmatic patients and controls, considering either allelic or genotypic frequencies. The distribution of genotypes according to the severity status revealed a significant differences for the +936 C > T, and −2549 −2567 del 18 polymorphisms. In addition, association was found with the haplotypes inferred by the three polymorphisms and asthma susceptibility. Conclusion We suggest that VEGF Gene polymorphisms can be implicated in asthma. PMID:19787077

  13. Genetic Analysis of the Atrial Natriuretic Peptide Gene Polymorphisms among Essential Hypertensive Patients in Malaysia

    PubMed Central

    Ghodsian, Nooshin; Ismail, Patimah; Ahmadloo, Salma; Eskandarian, Narges; Etemad, Ali

    2016-01-01

    Background. Atrial natriuretic peptide (ANP) considerably influences blood pressure regulation through water and sodium homoeostasis. Several of the studies have utilized anonymous genetic polymorphic markers and made inconsequent claims about the ANP relevant disorders. Thus, we screened Insertion/Deletion (ID) and G191A polymorphisms of ANP to discover sequence variations with potential functional significance and to specify the linkage disequilibrium pattern between polymorphisms. The relationships of detected polymorphisms with EH with or without Type 2 Diabetes Mellitus (T2DM) status were tested subsequently. Method. ANP gene polymorphisms (I/D and A191G) were specified utilizing mutagenically separated Polymerase Chain Reaction (PCR) in 320 subjects including 163 EH case subjects and 157 controls. Result. This case-control study discovered a significant association between I/D polymorphisms of ANP gene in EH patient without T2DM. However, the study determined no association between G191A polymorphisms of ANP in EH with or without T2DM. In addition, sociodemographic factors in the case and healthy subjects exhibited strong differences (P < 0.05). Conclusion. As a risk factor, ANP gene polymorphisms may affect hypertension. Despite the small sample size in this study, it is the first research assessing the ANP gene polymorphisms in both EH and T2DM patients among Malaysian population. PMID:27413750

  14. Potential for Incorporation of Genetic Polymorphism Data in Human Health Risk Assessment

    EPA Science Inventory

    This overview summarizes several EPA assessment publications evaluating the potential impact of genetic polymorphisms in ten metabolizing enzymes on the variability in enzyme function across ethnically diverse populations.

  15. Synthesis of chiral polymorph A-enriched zeolite Beta with an extremely concentrated fluoride route.

    PubMed

    Tong, Mingquan; Zhang, Daliang; Fan, Weibin; Xu, Jun; Zhu, Liangkui; Guo, Wen; Yan, Wenfu; Yu, Jihong; Qiu, Shilun; Wang, Jianguo; Deng, Feng; Xu, Ruren

    2015-06-22

    Chiral zeolitic materials with intrinsically chiral frameworks are highly desired because they can combine both shape selectivity and enantioselectivity. In the field of zeolite, the synthesis of chiral polymorph A of zeolite Beta or chiral polymorph A-enriched zeolite Beta is one of the biggest challenges. We demonstrate here a generalized extremely concentrated fluoride route for the synthesis of chiral polymorph A-enriched zeolite Beta in the presence of five achiral organic structure-directing agents. The polymorph A-enriched Ti-Beta shows a higher enantioselectivity for the asymmetric epoxidation of alkenes than the normal Ti-Beta.

  16. Polymorph transformation kinetics of Ca3SiO5 with MgO

    NASA Astrophysics Data System (ADS)

    Ma, Suhua; Zhou, Weiqiang; Wang, Shaopeng; Li, Weifeng; Shen, Xiaodong

    2015-09-01

    Tricalcium silicate (Ca3SiO5 (C3S)) is the primary cement phase in Portland cement. An understanding of its transformation kinetics is important to make use of its polymorphism. In this study, X-ray diffractometry and Rietveld refinement were used to qualitatively and quantitatively analyze the phase compositions of C3S with 2.0% MgO. The results show that C3S with 2.0% MgO is a monoclinic polymorph, M3. Heat treatment changes this monoclinic polymorph to a triclinic polymorph via the precipitation of MgO. The transformation kinetics follows the first-order exponential decay function ?.

  17. The association between paraoxonase 1 gene polymorphisms and polycystic ovarian syndrome.

    PubMed

    Gu, H F; Mou, M; Liang, Z G; Sun, C; Ren, X Y; Xiao, Y B

    2016-12-30

    Some studies investigated the association of paraoxonase 1 (PON1) polymorphisms with polycystic ovarian syndrome (PCOS) risk. However, the result was still inconsistent. The aim of this study was to investigate whether there is an association between the PON1 polymorphisms and PCOS risk. Electronic databases, such as PubMed, EMBASE, and China National Knowledge Infrastructure (CNKI) databases, were searched for identification of the studies. The associations between PON1 polymorphisms and PCOS risk was quantified using ORs with 95% CIs. A total of 8 eligible studies with 2272 cases and 1811 controls were included in this meta-analysis. PON1 Leu55Met polymorphism was associated with a significantly increased risk of PCOS (OR=1.31; 95%CI, 1.10-1.55). However, no association was found in Asians and Caucasians (Table 2). We also found that PON1 Q192R polymorphism was associated with a significantly increased risk of PCOS (OR=1.81; 95%CI, 1.17-2.82). Additionally, this polymorphism increased PCOS risk in Asians (OR=1.26; 95%CI, 1.13-1.41). Furthermore, PON1 C108T polymorphism showed increased PCOS risk (OR=1.46; 95%CI, 1.08-1.97). No association between this polymorphism and PCOS risk was found in Asians and Caucasians. In conclusion, this meta-analysis suggested that PON1 polymorphisms were associated with PCOS risk.

  18. Red Blood Cell Polymorphism and Susceptibility to Plasmodium vivax

    PubMed Central

    Zimmerman, Peter A.; Ferreira, Marcelo U.; Howes, Rosalind E.; Mercereau-Puijalon, Odile

    2013-01-01

    Resistance to Plasmodium vivax blood-stage infection has been widely recognised to result from absence of the Duffy (Fy) blood group from the surface of red blood cells (RBCs) in individuals of African descent. Interestingly, recent studies from different malaria-endemic regions have begun to reveal new perspectives on the association between Duffy gene polymorphism and P. vivax malaria. In Papua New Guinea and the Americas, heterozygous carriers of a Duffy-negative allele are less susceptible to P. vivax infection than Duffy-positive homozygotes. In Brazil, studies show that the Fya antigen, compared to Fyb, is associated with lower binding to the P. vivax Duffy-binding protein and reduced susceptibility to vivax malaria. Additionally, it is interesting that numerous studies have now shown that P. vivax can infect RBCs and cause clinical disease in Duffy-negative people. This suggests that the relationship between P. vivax and the Duffy antigen is more complex than customarily described. Evidence of P. vivax Duffy-independent red cell invasion indicates that the parasite must be evolving alternative red cell invasion pathways. In this chapter, we review the evidence for P. vivax Duffy-dependent and Duffy-independent red cell invasion. We also consider the influence of further host gene polymorphism associated with malaria endemicity on susceptibility to vivax malaria. The interaction between the parasite and the RBC has significant potential to influence the effectiveness of P. vivax-specific vaccines and drug treatments. Ultimately, the relationships between red cell polymorphisms and P. vivax blood-stage infection will influence our estimates on the population at risk and efforts to eliminate vivax malaria. PMID:23384621

  19. Association between Polymorphisms in the TSHR Gene and Graves' Orbitopathy

    PubMed Central

    Jurecka-Lubieniecka, Beata; Ploski, Rafal; Kula, Dorota; Szymanski, Konrad; Bednarczuk, Tomasz; Ambroziak, Urszula; Hasse-Lazar, Kornelia; Hyla-Klekot, Lidia; Tukiendorf, Andrzej; Kolosza, Zofia; Jarzab, Barbara

    2014-01-01

    Background Graves' orbitopathy (GO) as well as Graves' disease (GD) hyperthyroidism originate from an autoimmune reaction against the common auto-antigen, thyroid-stimulating hormone receptor (TSHR). GO phenotype is associated with environmental risk factors, mainly nicotinism, as well as genetic risk factors which initiate an immunologic reaction. In some patients GO is observed before diagnosis of GD hyperthyroidism, while it can also be observed far after diagnosis. The intensity of GO symptoms varies greatly in these patients. Thus, the pathogenesis of GD and GO may correlate with different genetic backgrounds, which has been confirmed by studies of correlations between GO and polymorphisms in cytokines involved in orbit inflammation. The aim of our analysis was to assess genetic predisposition to GO in young patients (age of diagnosis ≤30 years of age), for whom environmental effects had less time to influence outcomes than in adults. Methods 768 GD patients were included in the study. 359 of them had clinically evident orbitopathy (NOSPECS ≥2). Patients were stratified by age at diagnosis. Association analyses were performed for genes with a known influence on development of GD - TSHR, HLA-DRB1, cytotoxic T-lymphocyte antigen 4 (CTLA4) and lymphoid protein tyrosine phosphatase (PTPN22). Results The rs179247 TSHR polymorphism was associated with GO in young patients only. In young GO-free patients, allele A was statistically more frequent and homozygous carriers had a considerable lower risk of disease incidence than patients with AG or GG genotypes. Those differences were not found in either elderly patients or the group analyzed as a whole. Conclusions Allele A of the rs179247 polymorphism in the TSHR gene is associated with lower risk of GO in young GD patients. PMID:25061884

  20. Analysis of microsatellite polymorphism in inbred knockout mice.

    PubMed

    Zuo, Baofen; Du, Xiaoyan; Zhao, Jing; Yang, Huixin; Wang, Chao; Wu, Yanhua; Lu, Jing; Wang, Ying; Chen, Zhenwen

    2012-01-01

    Previously, we found that the genotype of 42 out of 198 mouse microsatellite loci, which are distributed among all chromosomes except the Y chromosome, changed from monomorphism to polymorphism (CMP) in a genetically modified inbred mouse strain. In this study, we further examined whether CMP also relates to the homologous recombination in gene knockout (KO) mouse strains. The same 42 microsatellite loci were analyzed by polymerase chain reaction (PCR) in 29 KO inbred mouse strains via short tandem sequence repeat (STR) scanning and direct sequence cloning to justify microsatellite polymorphisms. The C57BL/6J and 129 mouse strains, from which these 29 KO mice were derived, were chosen as the background controls. The results indicated that 10 out of 42 (23.8%) loci showed CMP in some of these mouse strains. Except for the trinucleotide repeat locus of D3Mit22, which had microsatellite CMP in strain number 9, the core sequences of the remaining 41 loci were dinucleotide repeats, and 9 out of 41 (21.95%) showed CMPs among detected mouse strains. However, 11 out of 29 (37.9%) KO mice strains were recognized as having CMPs. The popular dinucleotide motifs in CMP were (TG)(n) (50%, 2/4), followed by (GT)(n) (27.27%, 3/11) and (CA)(n) (23.08%, 3/13). The microsatellite CMP in (CT)(n) and (AG)(n) repeats were 20% (1/5). According to cloning sequencing results, 6 KO mouse strains showed insertions of nucleotides whereas 1 showed a deletion. Furthermore, 2 loci (D13Mit3 and D14Mit102) revealed CMP in 2 strains, and mouse strain number 9 showed CMPs in two loci (D3Mit22 and D13Mit3) simultaneously. Collectively, these results indicated that microsatellite polymorphisms were present in the examined inbred KO mice.

  1. Serotonin transporter gene polymorphisms and treatment-resistant depression.

    PubMed

    Bonvicini, Cristian; Minelli, Alessandra; Scassellati, Catia; Bortolomasi, Marco; Segala, Matilde; Sartori, Riccardo; Giacopuzzi, Mario; Gennarelli, Massimo

    2010-08-16

    Major Depression Disorder (MDD) is a serious mental illness that is one of the most disabling diseases worldwide. In addition, approximately 15% of depression patients are defined treatment-resistant (TRD). Preclinical and genetic studies show that serotonin modulation dysfunction exists in patients with TRD. Some polymorphisms in the promoter region of the serotonin transporter gene (SLC6A4) are likely to be involved in the pathogenesis/treatment of MDD; however, no data are available concerning TRD. Therefore, in order to investigate the possible influence of SLC6A4 polymorphisms on the risk of TRD, we genotyped 310 DSM-IV MDD treatment-resistant patients and 284 healthy volunteers. We analysed the most studied polymorphism 5-HTTLPR (L/S) and a single nucleotide substitution, rs25531 (A/G), in relation to different functional haplotype combinations. However the correct mapping of rs25531 is still debated whether it is within or outside the insertion. Our sequencing analysis showed that rs25531 is immediately outside of the 5-HTTLPR segment. Differences in 5-HTTLPR allele (p=0.04) and in L allele carriers (p<0.05) were observed between the two groups. Concerning the estimated haplotype analyses, L(A)L(A) homozygote haplotype was more represented among the control subjects (p=0.01, OR=0.64 95%CI: 0.45-0.91). In conclusion, this study reports a protective effect of the L(A)L(A) haplotype on TRD, supporting the hypothesis that lower serotonin transporter transcription alleles are correlated to a common resistant depression mechanism.

  2. Chromosomal rearrangements maintain a polymorphic supergene controlling butterfly mimicry

    PubMed Central

    Joron, Mathieu; Frezal, Lise; Jones, Robert T.; Chamberlain, Nicola L.; Lee, Siu F.; Haag, Christoph R.; Whibley, Annabel; Becuwe, Michel; Baxter, Simon W.; Ferguson, Laura; Wilkinson, Paul A.; Salazar, Camilo; Davidson, Claire; Clark, Richard; Quail, Michael A.; Beasley, Helen; Glithero, Rebecca; Lloyd, Christine; Sims, Sarah; Jones, Matthew C.; Rogers, Jane; Jiggins, Chris D.; ffrench-Constant, Richard H.

    2013-01-01

    Supergenes are tight clusters of loci that facilitate the co-segregation of adaptive variation, providing integrated control of complex adaptive phenotypes1. Polymorphic supergenes, in which specific combinations of traits are maintained within a single population, were first described for ‘pin’ and ‘thrum’ floral types in Primula1 and Fagopyrum2, but classic examples are also found in insect mimicry3–5 and snail morphology6. Understanding the evolutionary mechanisms that generate these co-adapted gene sets, as well as the mode of limiting the production of unfit recombinant forms, remains a substantial challenge7–10. Here we show that individual wing-pattern morphs in the polymorphic mimetic butterfly Heliconius numata are associated with different genomic rearrangements at the supergene locus P. These rearrangements tighten the genetic linkage between at least two colour-pattern loci that are known to recombine in closely related species9–11, with complete suppression of recombination being observed in experimental crosses across a 400-kilobase interval containing at least 18 genes. In natural populations, notable patterns of linkage disequilibrium (LD) are observed across the entire P region. The resulting divergent haplotype clades and inversion breakpoints are found in complete association with wing-pattern morphs. Our results indicate that allelic combinations at known wing-patterning loci have become locked together in a polymorphic rearrangement at the Plocus, forming a supergene that acts as a simple switch between complex adaptive phenotypes found in sympatry. These findings highlight how genomic rearrangements can have a central role in the coexistence of adaptive phenotypes involving several genes acting in concert, by locally limiting recombination and gene flow. PMID:21841803

  3. Association of GSTs polymorphisms with risk of gestational diabetes mellitus

    PubMed Central

    Li, Yan; Li, Shaoru; Zhai, Qianqian; Hai, Jie; Wang, Di; Cao, Meng; Zhang, Qinggui

    2015-01-01

    We conducted a case-control study to investigate the association between GSTM1, GSTT1 and GSTP1 IIe105Val polymorphisms and development of gestational diabetes mellitus in a Chinese population. A total of 320 patients with gestational diabetes mellitus and 358 pregnancy subjects were consecutively collected between January 2013 and December 2014. Genotyping for detection of GSTM1, GSTT1 and GSTP1 IIe105Val was conducted by using PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphisms) method. By Fisher’s exact test, we found that the genotype distributions of GSTP1 IIe105Val were in line with the Hardy-Weinberg equilibrium in control subjects (P=0.57). By Chi-square test, we found significant differences in the genotype distributions of GSTM1 (χ2=11.49, P=0.001) and GSTT1 (χ2=18.50, P<0.001). Using unconditional logistic analysis, individuals carrying the null genotypes of GSTM1 and GSTT1 were associated with an increased risk of gestational diabetes mellitus when compared with the present genotype, and the adjusted Ors (95% CI) were 1.71 (1.24-2.36) and 2.00 (1.44-2.79), respectively. However, the GSTP1 IIe105Val polymorphism was not associated with an elevated risk of gestational diabetes mellitus. In conclusion, we suggest that the GSTM1 null genotype and GSTT1 null genotype are correlated with an increased risk of gestational diabetes mellitus in a Chinese population. PMID:26823865

  4. Characterization of a polymorphism of CD4 in miniature swine.

    PubMed

    Sundt, T M; LeGuern, C; Germana, S; Smith, C V; Nakajima, K; Lunney, J K; Sachs, D H

    1992-05-15

    A polymorphism of CD4 in miniature swine has been identified by failure of cells from some animals to react with mAb 74-12-4. The phenotypic, molecular genetic, and functional characteristics of these animals have been defined. Cells from heterozygous animals bear approximately 50% the number of 74-12-4-reactive molecules on their surface as do cells from animals homozygous for the wild type. Animals of both phenotypes demonstrate similar flow cytometric profiles for CD8+ T cells. Northern blot analysis confirms the presence of mRNA for CD4 among PBL of animals failing to stain with 74-12-4. CD4 allelism is confirmed by Southern blot analysis, revealing RFLP. Function of the CD4 subset in vivo, as demonstrated by antibody production against a T cell-dependent Ag, is similar between animals of both phenotypes. Proliferative responses to PHA and alloantigen stimulation by a full haplotype mismatch or a class II mismatch alone are equivalent for animals of both phenotypes. These data suggest that the allelic form of CD4, designated CD4.2 in contrast to the wild-type CD4.1, is capable of performing normally as an accessory molecule in the generation of immune responses. Furthermore, antixenogeneic responses to C57B10.BR were equivalent, suggesting that both CD4 molecular types may be capable of interacting with xenogeneic class II molecules. Although the polymorphism includes differences in exons 3 and 4, regions thought to encode portions of the molecule interacting with MHC class II, these results imply that this naturally occurring CD4 polymorphism does not affect the interaction with class II molecules.

  5. Water flow and fin shape polymorphism in coral reef fishes.

    PubMed

    Binning, Sandra A; Roche, Dominique G

    2015-03-01

    Water flow gradients have been linked to phenotypic differences and swimming performance across a variety of fish assemblages. However, the extent to which water motion shapes patterns of phenotypic divergence within species remains unknown. We tested the generality of the functional relationship between swimming morphology and water flow by exploring the extent of fin and body shape polymorphism in 12 widespread species from three families (Acanthuridae, Labridae, Pomacentridae) of pectoral-fin swimming (labriform) fishes living across localized wave exposure gradients. The pectoral fin shape of Labridae and Acanthuridae species was strongly related to wave exposure: individuals with more tapered, higher aspect ratio (AR) fins were found on windward reef crests, whereas individuals with rounder, lower AR fins were found on leeward, sheltered reefs. Three of seven Pomacentridae species showed similar trends, and pectoral fin shape was also strongly related to wave exposure in pomacentrids when fin aspect ratios of three species were compared across flow habitats at very small spatial scales (<100 m) along a reef profile (reef slope, crest, and back lagoon). Unlike fin shape, there were no intraspecific differences in fish body fineless ratio across habitats or depths. Contrary to our predictions, there was no pattern relating species' abundances to polymorphism across habitats (i.e., abundance was not higher at sites where morphology is better adapted to the environment). This suggests that there are behavioral and/or physiological mechanisms enabling some species to persist across flow habitats in the absence of morphological differences. We suggest that functional relationships between swimming morphology and water flow not only structure species assemblages, but are yet another important variable contributing to phenotypic differences within species. The close links between fin shape polymorphism and local water flow conditions appear to be important for

  6. GSTM1 polymorphism in patients with clinical manifestations of atherosclerosis.

    PubMed

    Rodrigues, D A; Martins, J V M; E Silva, K S F; Costa, I R; Lagares, M H; Campedelli, F L; Barbosa, A M; de Morais, M P; Moura, K K V O

    2017-03-15

    Atherosclerosis is characterized by lesions, called atheroma or atheromatous plaques, in the inner layer of blood vessels, which block the vascular lumen and weaken the underlying tunica media. Several modifiable and non-modifiable risk factors for the development of atherosclerosis exist. The modifiable risk factors include hypertension, smoking, obesity, high LDL and low HDL cholesterol levels, sedentary lifestyle, and stress; the non-modifiable factors include diabetes mellitus, family history of hypertension and heart disease, thrombophilia, sex, age, and genetic factors. The association of polymorphisms in GST with coronary artery disease has been studied since the polymorphisms can affect enzyme activity and contribute to the onset of atherosclerosis. We analyzed polymorphisms in GSTM1 in individuals diagnosed with atherosclerosis as well as in healthy individuals (control group). The frequency of the GSTM1 present genotype in the atherosclerosis group was 1.2 times higher than that observed in the control group. We found no sex- or alcohol-consumption-dependent differences between the occurrences of the present and null genotypes. However, the GSTM1 present genotype occurred in 52.6% individuals with atherosclerosis who reported smoking 20 or more cigarettes per day and in 60% individuals who smoked 10 to 20 cigarettes per day (P = 0.0035). In addition, the GSTM1 present genotype was more frequent in individuals who reported being former smokers - 45.5% in individuals with atherosclerosis who smoked for more than 20 years and 50% each for individuals in the control group who smoked for less than 10 years or for 10 to 20 years, respectively (P = 0.0240).

  7. Restriction fragment length polymorphism (RFLP) analysis and tuberculosis epidemiology.

    PubMed

    Gómez Marín, J E; Rigouts, L; Villegas Londoño, L E; Portaels, F

    1995-09-01

    In order to study polymorphisms of the DNA insertion sequence 6110 (IS6110) in Mycobacterium tuberculosis strains isolated from Colombian patients, together with resistance to antituberculous medications in the Department of Quindío, Colombia, a prospective study was conducted using a consecutive sample of 59 patients with symptomatic pulmonary tuberculosis whose cases had been confirmed by bacilloscopy, both with and without a history of treatment. The patients, who were participating in the Tuberculosis Control Program of the Regional Health Institute of Quindío in Armenia, included all individuals attending local health centers and hospitals between March and July 1993 who were referred to the regional institute. Sputum specimens from each patient were cultured and subjected to drug sensitivity tests. Subsequently, restriction fragment length polymorphisms (RFLP) of IS6110 from 27 patients were analyzed. The patients' treatment histories were used to classify their cases according to WHO criteria. Forty-five cultures were found positive, 44 for M. tuberculosis and 1 for M. africanum. Initial drug resistance was observed in 4 of 42 new cases, or 9.5% (95% CI: 0.6, 18), 2 showing resistance to isoniazid (INH) and 2 to isoniazid plus streptomycin (INH-SM). Acquired resistance was observed in 2 of the 3 chronic cases and relapses, the bacteria being resistant to isoniazid, rifampicin, and streptomycin (INH-RM-SM) in one case and to isoniazid, ethambutol, rifampicin, and streptomycin (INH-EMB-RM-SM) in the other. In those 27 strains subjected to RFLP analysis, the number of copies of IS6110 ranged from 6 to 17. Similarity coefficients revealed five distinct groups of strains. Overall, the RFLP analysis permitted most of the strains to be distinguished from one another, implying that the polymorphisms involved are sufficient to permit effective employment of this technique, which appears to have considerable potential for use in epidemiologic studies and in work

  8. Low-energy tetrahedral polymorphs of carbon, silicon, and germanium

    NASA Astrophysics Data System (ADS)

    Mujica, Andrés; Pickard, Chris J.; Needs, Richard J.

    2015-06-01

    Searches for low-energy tetrahedral polymorphs of carbon and silicon have been performed using density functional theory computations and the ab initio random structure searching approach. Several of the hypothetical phases obtained in our searches have enthalpies that are lower or comparable to those of other polymorphs of group 14 elements that have either been experimentally synthesized or recently proposed as the structure of unknown phases obtained in experiments, and should thus be considered as particularly interesting candidates. A structure of P b a m symmetry with 24 atoms in the unit cell was found to be a low-energy, low-density metastable polymorph in carbon, silicon, and germanium. In silicon, P b a m is found to have a direct band gap at the zone center with an estimated value of 1.4 eV, which suggests applications as a photovoltaic material. We have also found a low-energy chiral framework structure of P 41212 symmetry with 20 atoms per cell containing fivefold spirals of atoms, whose projected topology is that of the so-called Cairo-type two-dimensional pentagonal tiling. We suggest that P 41212 is a likely candidate for the structure of the unknown phase XIII of silicon. We discuss P b a m and P 41212 in detail, contrasting their energetics and structures with those of other group 14 elements, particularly the recently proposed P 42/n c m structure, for which we also provide a detailed interpretation as a network of tilted diamondlike tetrahedra.

  9. The Importance of Polymorphism in Metal-Organic Framework Studies.

    PubMed

    Aulakh, Darpandeep; Varghese, Juby R; Wriedt, Mario

    2015-09-08

    Polymorphic phase transitions remain frequently undetected in routine metal-organic framework (MOF) studies; however, their discovery is of major importance in interpreting structure-property relationships. We herein report a reversible enantiotropic single-crystal to single-crystal polymorphic phase transition of a new microporous MOF [Eu(BDC)(NO3)(DMF)2]n (H2BDC = 1,4-benzenedicarboxylic acid; DMF = dimethylformamide). While modification 1LT at 170 K crystallizes in the monoclinic space group P21/c with unit cell dimensions of a = 17.673(2) Å, b = 20.023(2) Å, c = 10.555(9) Å, β = 90.129(4)°, modification 1HT at 290 K crystallizes in higher symmetry space group C2/c with unit cell dimensions of a = 17.200(7) Å, b = 10.737(4) Å, c = 10.684(4) Å, β = 90.136(2)°. This temperature-induced phase transition is accompanied by a small change in the solvent-accessible voids from 46.8 in 1LT to 49.8% in 1HT, which triggers a significant change in the adsorption properties as compared to a reported isostructural compound. Detailed investigations on the phase transition were studied with variable-temperature single-crystal X-ray diffraction (SCXRD), powder X-ray diffraction, and differential scanning calorimetry measurements. The herein-presented investigations emphasize the importance of polymorphic phase transitions in routine MOF studies originating from low-temperature SCXRD data and high-temperature physical property characterizations in avoiding the use of a wrong structure in interpreting structure-property relationships.

  10. Analysis of Microsatellite Polymorphism in Inbred Knockout Mice

    PubMed Central

    Zhao, Jing; Yang, Huixin; Wang, Chao; Wu, Yanhua; Lu, Jing; Wang, Ying; Chen, Zhenwen

    2012-01-01

    Previously, we found that the genotype of 42 out of 198 mouse microsatellite loci, which are distributed among all chromosomes except the Y chromosome, changed from monomorphism to polymorphism (CMP) in a genetically modified inbred mouse strain. In this study, we further examined whether CMP also relates to the homologous recombination in gene knockout (KO) mouse strains. The same 42 microsatellite loci were analyzed by polymerase chain reaction (PCR) in 29 KO inbred mouse strains via short tandem sequence repeat (STR) scanning and direct sequence cloning to justify microsatellite polymorphisms. The C57BL/6J and 129 mouse strains, from which these 29 KO mice were derived, were chosen as the background controls. The results indicated that 10 out of 42 (23.8%) loci showed CMP in some of these mouse strains. Except for the trinucleotide repeat locus of D3Mit22, which had microsatellite CMP in strain number 9, the core sequences of the remaining 41 loci were dinucleotide repeats, and 9 out of 41 (21.95%) showed CMPs among detected mouse strains. However, 11 out of 29 (37.9%) KO mice strains were recognized as having CMPs. The popular dinucleotide motifs in CMP were (TG)n (50%, 2/4), followed by (GT)n (27.27%, 3/11) and (CA)n (23.08%, 3/13). The microsatellite CMP in (CT)n and (AG)n repeats were 20% (1/5). According to cloning sequencing results, 6 KO mouse strains showed insertions of nucleotides whereas 1 showed a deletion. Furthermore, 2 loci (D13Mit3 and D14Mit102) revealed CMP in 2 strains, and mouse strain number 9 showed CMPs in two loci (D3Mit22 and D13Mit3) simultaneously. Collectively, these results indicated that microsatellite polymorphisms were present in the examined inbred KO mice. PMID:22509320

  11. Vitamin D receptor polymorphisms in patients with cutaneous melanoma

    PubMed Central

    Orlow, Irene; Roy, Pampa; Reiner, Anne S.; Yoo, Sarah; Patel, Himali; Paine, Susan; Armstrong, Bruce K.; Kricker, Anne; Marrett, Loraine D.; Millikan, Robert C.; Thomas, Nancy E.; Gruber, Stephen B.; Anton-Culver, Hoda; Rosso, Stefano; Gallagher, Richard P.; Dwyer, Terence; Kanetsky, Peter A.; Busam, Klaus; From, Lynn; Begg, Colin B.; Berwick, Marianne

    2011-01-01

    The vitamin D receptor (VDR) gene has been associated with cancer risk, but only a few polymorphisms have been studied in relation to melanoma risk and the results have been inconsistent. We examined 38 VDR gene SNPs in a large international multi-center population-based case-control study of melanoma. Buccal DNAs were obtained from 1207 people with incident multiple primary melanoma and 2469 with incident single primary melanoma. SNPs with known or suspected impact on VDR activity, htSNPs with ≥10% MAF in Caucasians, and SNPs reported as significant in other association studies were examined. Logistic regression was used to calculate the relative risks conferred by the individual SNP. Eight of 38 SNPs in the promoter, coding, and 3’ gene regions were individually significantly associated with multiple primary melanoma after adjusting for covariates. The estimated increase in risk for individuals who were homozygous for the minor allele ranged from 25% to 33% for 6 polymorphisms: rs10875712 (OR 1.28; 95%CI, 1.01–1.62), rs4760674 (OR 1.33; 95% CI, 1.06–1.67), rs7139166 (OR 1.26; 95%CI, 1.02–1.56), rs4516035 (OR 1.25; 95%CI, 1.01–1.55), rs11168287 (OR 1.27; 95%CI, 1.03–1.57), rs1544410 (OR 1.30; 95%CI, 1.04–1.63); for 2 polymorphisms, homozygous carriers had a decreased risk: rs7305032 (OR 0.81; 95%CI 0.65–1.02), rs7965281 (OR, 0.78; 95%CI, 0.62–0.99). We recognize the potential false positive findings due to multiple comparisons; however the 8 significant SNPs in this study outnumbered the 2 significant tests expected to occur by chance. The vitamin D receptor may play a role in melanomagenesis. PMID:21365644

  12. Estrogen receptor alpha polymorphisms and the risk of malignancies.

    PubMed

    Anghel, Andrei; Narita, Diana; Seclaman, Edward; Popovici, Emilian; Anghel, Mariana; Tamas, Liviu

    2010-12-01

    Estrogens represent risk factors for endocrine-related cancers and play also an important role in the development and progression of other malignancies. In order to analyze the associations between estrogen receptor gene alpha polymorphisms and cancers susceptibility, we genotyped six single nucleotide polymorphisms (SNPs) in 163 Caucasian cancer patients--103 breast cancers and 60 other malignancies (colorectal, bladder, hepatocellular carcinoma and acute myeloid leukemia)--and 114 healthy controls using hybridization probes. We performed Armitage`s association trend-test to evaluate the risk. Linkage disequilibrium (LD) was assessed for each pair of markers. The genotypes CC and CT of rs3798577 were significantly associated with the cancers risk (p-trend breast = 4 × 10(-5); p-trend cancers = 1 × 10(-5)); in discrepancy with breast cancer where the C-allele represented the risk allele, for bladder, hepatocellular carcinomas and leukemia, the T allele seems to confer susceptibility. The minor G allele of rs1801132 was protective in our cases (p = 1 × 10(-4)); for rs2228480, the heterozygous frequency was higher for cancer groups (p = 0.03); the SNP pairs rs2228480&rs3798577 and rs2234693&rs9340799 were in low LD; the haplotypes T-A of rs2234693&rs9340799 and G-C of rs2228480&rs3798577 showed a trend to be higher represented in breast cancers; T allele of rs2234693 was higher expressed in breast, colon cancers and leukemia; rs2077647 was associated with colon (p = 0.008, C-risk allele) and bladder (p = 0.01, T-risk allele) cancers. We concluded that ESR1 polymorphisms may have distinct impact in carcinogenesis and further genotyping will establish whether these findings remain significant in larger cohorts.

  13. Genome skimming identifies polymorphism in tern populations and species

    PubMed Central

    2012-01-01

    Background Terns (Charadriiformes: Sterninae) are a lineage of cosmopolitan shorebirds with a disputed evolutionary history that comprises several species of conservation concern. As a non-model system in genetics, previous study has left most of the nuclear genome unexplored, and population-level studies are limited to only 15% of the world's species of terns and noddies. Screening of polymorphic nuclear sequence markers is needed to enhance genetic resolution because of supposed low mitochondrial mutation rate, documentation of nuclear insertion of hypervariable mitochondrial regions, and limited success of microsatellite enrichment in terns. Here, we investigated the phylogenetic and population genetic utility for terns and relatives of a variety of nuclear markers previously developed for other birds and spanning the nuclear genome. Markers displaying a variety of mutation rates from both the nuclear and mitochondrial genome were tested and prioritized according to optimal cross-species amplification and extent of genetic polymorphism between (1) the main tern clades and (2) individual Royal Terns (Thalasseus maxima) breeding on the US East Coast. Results Results from this genome skimming effort yielded four new nuclear sequence-based markers for tern phylogenetics and 11 intra-specific polymorphic markers. Further, comparison between the two genomes indicated a phylogenetic conflict at the base of terns, involving the inclusion (mitochondrial) or exclusion (nuclear) of the Angel Tern (Gygis alba). Although limited mitochondrial variation was confirmed, both nuclear markers and a short tandem repeat in the mitochondrial control region indicated the presence of considerable genetic variation in Royal Terns at a regional scale. Conclusions These data document the value of intronic markers to the study of terns and allies. We expect that these and additional markers attained through next-generation sequencing methods will accurately map the genetic origin and

  14. Impact of vitamin D receptor polymorphisms in centenarians.

    PubMed

    Gussago, Cristina; Arosio, Beatrice; Guerini, Franca Rosa; Ferri, Evelyn; Costa, Andrea Saul; Casati, Martina; Bollini, Elisa Mariadele; Ronchetti, Francesco; Colombo, Elena; Bernardelli, Giuseppina; Clerici, Mario; Mari, Daniela

    2016-08-01

    Vitamin D is a seco-sterol produced endogenously in the skin or obtained from certain foods. It exerts its action through binding to intracellular vitamin D receptor (VDR). Lately, the role of vitamin D has been revised regarding its potential advantage on delaying the process of aging. The aim of this study was to assess the contribution of VDR gene polymorphisms in healthy aging and longevity. We evaluated the frequency of four polymorphisms of the VDR gene (FokI, BsmI, ApaI, and TaqI) in centenarians (102 subjects, mean age: 102.3 ± 0.3 years), compared to septuagenarians (163 subjects, mean age: 73.0 ± 0.6 years) and we analyzed a variety of pathophysiologically relevant functions in centenarians. BsmI and ApaI provided a significant association with longevity: there was a highly significant difference in the frequency of BsmI genotypes (p = 0.037), ApaI genotypes (p = 0.022), and ApaI alleles (p = 0.050) in centenarians versus septuagenarians. Furthermore, we found a significant correlation of all the VDR gene polymorphisms in centenarians with some measured variables such as hand grip strength, body mass index, blood pressure, HDL cholesterol, and mini-mental state examination. We also found a correlation with the prevalence of medical history of hypertension, acute myocardial infarction, angina, venous insufficiency, dementia, chronic obstructive pulmonary disease, and arthrosis. In conclusion, this study proposes a new scenario in which the variability of the VDR gene is relevant in the aging process and emphasizes the role of VDR genetic background in determining healthy aging.

  15. Triclinic Polymorph of Bis(triphenylsilyl) Oxide Toluene Disolvate

    DTIC Science & Technology

    2012-01-01

    Triclinic polymorph of bis(triphenylsilyl) oxide toluene disolvate Andrew P. Purdy,a* Emily Smoot,a‡ Ray J. Butcherb and Andrew Kerrc aNaval Research... triclinic (P1) instead of possessing the previously reported rhombohedral symmetry [Hönle et al. (1990). Acta Cryst. C46, 1982–1984]. Each of the –SiPh3... structures of related compounds, see: Glidewell & Liles (1978); Morosin & Harrah (1981); Suwińska et al. (1986). For the determination by IR

  16. The polymorphic and mesomorphic behavior of four esters of cholesterol.

    NASA Technical Reports Server (NTRS)

    Merritt, W. G.; Cole, G. D.; Walker, W. W.

    1971-01-01

    The techniques of differential scanning calorimetry, X-ray powder diffractometry, and positron annihilation have been used to study the polymorphic and mesomorphic behavior of the following esters of cholesterol: cholesteryl formate, cholesteryl butyrate, cholesteryl benzoate, and cholesteryl cinnamate. Each of these compounds exhibits a single mesophase of the cholesteric type. The solid phase formed from the melt for each ester was observed to be structurally different from the solid phase obtained from solution. Solvents from which the solution-grown samples were crystallized were as follows: cholesteryl formate and cholesteryl butyrate from acetone, cholesteryl benzoate from benzene, and cholesteryl cinnamate from 2-butanone.

  17. Polymorphic microsatellite markers in Euryale ferox Salisb. (Nymphaeaceae).

    PubMed

    Quan, Zhiwu; Pan, Lei; Ke, Weidong; Ding, Yi

    2009-01-01

    Eleven polymorphic microsatellite markers were isolated and identified in the aquatic plant Euryale ferox Salisb. (Nymphaeaceae). This species, which belongs to basal Magnoliophyta, reproduces sexually. All of these 11 microsatellite markers yielded 25 alleles in a survey of a wild population of 34 individuals. Two or three alleles per locus were detected, with expected heterozygosity ranging from 0.056 to 0.634 and observed heterozygosity from 0.000 to 0.088. These simple sequence repeat markers will be useful for evaluating the genetic structure of the E. ferox population in the future.

  18. Polymorphisms in Endothelin System Genes, Arsenic Levels and Obesity Risk

    PubMed Central

    Martínez-Barquero, Vanesa; de Marco, Griselda; Martínez-Hervas, Sergio; Rentero, Pilar; Galan-Chilet, Inmaculada; Blesa, Sebastian; Morchon, David; Morcillo, Sonsoles; Rojo, Gemma; Ascaso, Juan Francisco; Real, José Tomás; Martín-Escudero, Juan Carlos; Chaves, Felipe Javier

    2015-01-01

    Background/Objectives Obesity has been linked to morbidity and mortality through increased risk for many chronic diseases. Endothelin (EDN) system has been related to endothelial function but it can be involved in lipid metabolism regulation: Receptor type A (EDNRA) activates lipolysis in adipocytes, the two endothelin receptors mediate arsenic-stimulated adipocyte dysfunction, and endothelin system can regulate adiposity by modulating adiponectin activity in different situations and, therefore, influence obesity development. The aim of the present study was to analyze if single nucleotide polymorphisms (SNPs) in the EDN system could be associated with human obesity. Subjects/Methods We analyzed two samples of general-population-based studies from two different regions of Spain: the VALCAR Study, 468 subjects from the area of Valencia, and the Hortega Study, 1502 subjects from the area of Valladolid. Eighteen SNPs throughout five genes were analyzed using SNPlex. Results We found associations for two polymorphisms of the EDNRB gene which codifies for EDN receptor type B. Genotypes AG and AA of the rs5351 were associated with a lower risk for obesity in the VALCAR sample (p=0.048, OR=0.63) and in the Hortega sample (p=0.001, OR=0.62). Moreover, in the rs3759475 polymorphism, genotypes CT and TT were also associated with lower risk for obesity in the Hortega sample (p=0.0037, OR=0.66) and in the VALCAR sample we found the same tendency (p=0.12, OR=0.70). Furthermore, upon studying the pooled population, we found a stronger association with obesity (p=0.0001, OR=0.61 and p=0.0008, OR=0.66 for rs5351 and rs3759475, respectively). Regarding plasma arsenic levels, we have found a positive association for the two SNPs studied with obesity risk in individuals with higher arsenic levels in plasma: rs5351 (p=0.0054, OR=0.51) and rs3759475 (p=0.009, OR=0.53) Conclusions Our results support the hypothesis that polymorphisms of the EDNRB gene may influence the susceptibility to

  19. Association between polymorphisms in interleukins and oral lichen planus

    PubMed Central

    Shi, Quan; Zhang, Tong; Huo, Na; Huang, Yang; Xu, Juan; Liu, Hongchen

    2017-01-01

    Abstract Background: More and more studies have suggested that single-nucleotide polymorphisms (SNPs) in interleukin (IL) genes are correlated with an increased risk of developing oral lichen planus (OLP). However, these results were inconsistent. Therefore, the aim of this meta-analysis is to retrieve and comprehensively analyze all related clinical studies to investigate the association of ILs gene polymorphisms with the OLP risk. Methods: PubMed, Embase, and the Cochrane Library were searched for eligible studies to evaluate the association between IL polymorphisms and the OLP. The odds ratios (ORs) and 95% confidence intervals (CIs) from each study were pooled to estimate the strength of the association. Statistical analyses were performed by using STATA software. Results: In all 6 studies, including 4 SNPs (IL6-174G/C, IL10-592C/A, IL10-819C/T, and IL10-1082G/A), 362 OLP patients and 622 non-OLP control subjects from five different countries were investigated. As for the IL6-174G/C, IL10-819C/T, and IL10-1082G/A, no evidence was found to support the association between SNP and OLP susceptibility in any genetic models. However, as for IL10-592C/A, a significant relationship between them was identified in all of comparison models (C vs A: OR = 0.724, 95% CI = 0.585–0.897, P = 0.003; CC vs AA: OR = 0.447, 95% CI = 0.276–0.722, P = 0.001; AC vs AA: OR = 0.585, 95% CI = 0.387–0.883, P = 0.011; CC+AC vs AA: OR = 0.544, 95% CI = 0.365–0.809, P = 0.003; CC vs AA+AC: OR = 0.715, 95% CI = 0.515–0.994, P = 0.046). Conclusion: With the presently available evidence, this meta-analysis fails to show the statistical associations between IL6-174G/C, IL10-819C/T, and IL10-1082G/A and OLP susceptibility in any genetic models. However, the A allele and AA genotype in IL10-592C/A polymorphism may increase the risk of OLP. In the future, more well-designed studies with larger sample sizes are needed. PMID

  20. A new polymorph of Lu(PO3)3

    PubMed Central

    Bejaoui, Anis; Horchani-Naifer, Karima; Férid, Mokhtar

    2008-01-01

    A new polymorph of lutetium polyphosphate, Lu(PO3)3, was found to be isotypic with the trigonal form of Yb(PO3)3. Two of the three Lu atoms occupy special positions (Wyckoff positions 3a and 3b, site symmetry ). The atomic arrangement consists of infinite helical polyphosphate chains running along the c axis, with a repeat period of 12 PO4 tetra­hedra, joined with LuO6 octa­hedra. PMID:21202991

  1. Modification of Tamoxifen Effectiveness by Gene Polymorphisms and Other Drugs

    DTIC Science & Technology

    2010-05-01

    Metoclopramide A03FA01 12/5 12/ 1 Ondansetron A04AA01 2/0 0/0 Antifungal Terbinafine D01BA02 0/2 0/ 1 Antiarrythmia Flecainid C01BC04 1 /0 0/0 Amiodarone...AD_________________ AWARD NUMBER: W81XWH-08- 1 -0300 TITLE: Modification of Tamoxifen Effectiveness by Gene Polymorphisms and Other Drugs...No. 0704-0188 Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for

  2. Random amplified polymorphic DNA analysis of genetically modified organisms.

    PubMed

    Yoke-Kqueen, Cheah; Radu, Son

    2006-12-15

    Randomly amplified polymorphic DNA (RAPD) was used to analyzed 78 samples comprises of certified reference materials (soya and maize powder), raw seeds (soybean and maize), processed food and animal feed. Combination assay of two arbitrary primers in the RAPD analysis enable to distinguish genetically modified organism (GMO) reference materials from the samples tested. Dendrogram analysis revealed 13 clusters at 45% similarity from the RAPD. RAPD analysis showed that the maize and soybean samples were clustered differently besides the GMO and non-GMO products.

  3. Polymorphic microsatellite loci for Japanese Spanish mackerel (Scomberomorus niphonius).

    PubMed

    Lin, L; Zhu, L; Liu, S-F; Tang, Q-S; Su, Y-Q; Zhuang, Z-M

    2012-05-08

    We isolated and characterized 21 polymorphic microsatellite loci in Japanese Spanish mackerel (Scomberomorus niphonius) using a (GT)(13)-enriched genomic library. Forty individuals were collected from Qingdao, China. We found 3 to 24 alleles per locus, with a mean of 8.8. The observed and expected heterozygosities ranged from 0.263 to 0.975 and from 0.385 to 0.946, with means of 0.655 and 0.685, respectively. Deviation from Hardy-Weinberg proportions was detected at three loci. Two loci showed evidence for null alleles. These microsatellite markers will be useful for population genetic analysis of Japanese Spanish mackerel.

  4. Polymorphic trial in oxidative damage of arsenic exposed Vietnamese

    SciTech Connect

    Fujihara, Junko; Soejima, Mikiko; Yasuda, Toshihiro; Koda, Yoshiro; Kunito, Takashi; Iwata, Hisato; Tanabe, Shinsuke; Takeshita, Haruo

    2011-10-15

    Arsenic causes DNA damage and changes the cellular capacity for DNA repair. Genes in the base excision repair (BER) pathway influence the generation and repair of oxidative lesions. Single nucleotide polymorphisms (SNPs) in human 8-oxoguanine DNA glycosylase (hOGG1) Ser326Cys; apurinic/apyrimidinic endonuclease (APE1) Asp148Glu; X-ray and repair and cross-complementing group 1 (XRCC1) Arg280His and Arg399Gln in the BER genes were analyzed, and the relationship between these 4 SNPs and the urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) concentrations of 100 Vietnamese population exposed to arsenic was investigated. Individuals with hOGG1 326Cys/Cys showed significantly higher urinary 8-OHdG concentrations than did those with 326 Ser/Cys and Ser/Ser. As for APE1 Asp148Glu, heterozygous subjects showed significantly higher urinary 8-OHdG concentrations than did those homozygous for Asp/Asp. Moreover, global ethnic comparison of the allelic frequencies of the 4SNPs was performed in 10 population and previous reported data. The mutant allele frequencies of hOGG1 Ser326Cys in the Asian populations were higher than those in the African and Caucasian populations. As for APE1 Asp148Glu, Caucasians showed higher mutant frequencies than those shown by African and Asian populations. Among Asian populations, the Bangladeshi population showed relatively higher mutant allele frequencies of the APE1 Asp148Glu polymorphism. This study is the first to demonstrate the existence of genetic heterogeneity in a worldwide distribution of SNPs (hOGG1 Ser326Cys, APE1 Asp148Glu, XRCC1 Arg280His, and XRCC1 Arg399Gln) in the BER genes. - Highlights: > We showed that hOGG1 and APE1 are associated with urinary 8-OHdG concentrations. > We showed the existence of inter-ethnic differences in hOGG1 and APE1 polymorphism. > These polymorphisms is a genetic marker of susceptibility to oxidative stress.

  5. Polymorphic DNA marker on X chromosome and manic depression.

    PubMed

    Mendlewicz, J; Simon, P; Sevy, S; Charon, F; Brocas, H; Legros, S; Vassart, G

    1987-05-30

    Heredity is an important factor in vulnerability to manic depression. A genetic linkage has been demonstrated between manic depression and coagulation factor IX at Xq27 with a TaqI polymorphism at the F9 locus in DNA samples from peripheral leucocytes of manic depressive probands and relatives in 10 informative families. Statistical analysis of the pedigrees gave a maximum lod score of 3.10 at a recombination fraction of 0.11, demonstrating a linkage between a manic depressive locus and the F9 locus in the Xq27 region.

  6. Polymorphous hemangioendothelioma in a child with acquired immunodeficiency syndrome (AIDS).

    PubMed

    Paul, Stephan R; Hurford, Matthew T; Miettinen, Markku M; Aronoff, Stephen C; Delvecchio, Michael; Grewal, Harsh; Tuluc, Madalina

    2008-03-01

    Polymorphous hemangioendotheliomas (PH) are rare and borderline malignant tumors that are among the wide range of vascular tumors. We report here a 13-year-old male presenting with a history of weight loss, opportunistic infections, and lymphadenopathy. He was determined to be HIV positive and to have acquired immunodeficiency syndrome (AIDS). A biopsy of a femoral node was diagnostic of PH. His systemic lymphadenopathy appeared to resolve with anti-retroviral therapy. This tumor should be considered within the differential diagnoses of pediatric and immunocompromised patients.

  7. N-Acetyltransferase 1 Polymorphism and Breast Cancer Risk

    DTIC Science & Technology

    2009-10-01

    endonucleases, Apa I and Sph I (New England Biolabs, Ipswich, MA), followed by ligation with T4 Ligase (Invitrogen). Polyadenylation Site Removal NATa...ligated into pcDNA5/FRT using T4 ligase . In this report, these two constructs are referred to as NATa 1*4 and NATb 1*4. NATa and NATb NAT1*10, NAT1*11...NAT1*11 DNA was selected using restriction fragment length polymorphism (RFLP) and ligated into the vector using T4 ligase . NATa and NATb 1*14

  8. Brain Penetration and Efficacy of Different Mebendazole Polymorphs in a Mouse Brain Tumor Model

    PubMed Central

    Wanjiku, Teresia; Rudek, Michelle A; Joshi, Avadhut; Gallia, Gary L.; Riggins, Gregory J.

    2015-01-01

    Purpose Mebendazole (MBZ), first used as an antiparasitic drug, shows preclinical efficacy in models of glioblastoma and medulloblastoma. Three different MBZ polymorphs (A, B and C) exist and a detailed assessment of the brain penetration, pharmacokinetics and anti-tumor properties of each individual MBZ polymorph is necessary to improve mebendazole-based brain cancer therapy. Experimental Design and Results In this study, various marketed and custom-formulated MBZ tablets were analyzed for their polymorph content by IR spectroscopy and subsequently tested in orthotopic GL261 mouse glioma model for efficacy and tolerability. The pharmacokinetics and brain concentration of MBZ polymorphs and two main metabolites were analyzed by LC-MS. We found that polymorph B and C both increased survival in a GL261 glioma model, as B exhibited greater toxicity. Polymorph A showed no benefit. Both, polymorph B and C, reached concentrations in the brain that exceeded the IC50 in GL261 cells 29-fold. In addition, polymorph C demonstrated an AUC0-24h brain-to-plasma (B/P) ratio of 0.82, whereas B showed higher plasma AUC and lower B/P ratio. In contrast, polymorph A presented markedly lower levels in the plasma and brain. Furthermore, the combination with elacridar was able to significantly improve the efficacy of polymorph C in GL261 glioma and D425 medulloblastoma models in mice. Conclusion Among MBZ polymorphs, C reaches therapeutically effective concentrations in the brain tissue and tumor with less side effects and is the better choice for brain cancer therapy. Its efficacy can be further enhanced by combination with elacridar. PMID:25862759

  9. Current Progress in Sports Genomics.

    PubMed

    Ahmetov, Ildus I; Fedotovskaya, Olga N

    2015-01-01

    Understanding the genetic architecture of athletic performance is an important step in the development of methods for talent identification in sport. Research concerned with molecular predictors has highlighted a number of potentially important DNA polymorphisms contributing to predisposition to success in certain types of sport. This review summarizes the evidence and mechanistic insights on the associations between DNA polymorphisms and athletic performance. A literature search (period: 1997-2014) revealed that at least 120 genetic markers are linked to elite athlete status (77 endurance-related genetic markers and 43 power/strength-related genetic markers). Notably, 11 (9%) of these genetic markers (endurance markers: ACE I, ACTN3 577X, PPARA rs4253778 G, PPARGC1A Gly482; power/strength markers: ACE D, ACTN3 Arg577, AMPD1 Gln12, HIF1A 582Ser, MTHFR rs1801131 C, NOS3 rs2070744 T, PPARG 12Ala) have shown positive associations with athlete status in three or more studies, and six markers (CREM rs1531550 A, DMD rs939787 T, GALNT13 rs10196189 G, NFIA-AS1 rs1572312 C, RBFOX1 rs7191721 G, TSHR rs7144481 C) were identified after performing genome-wide association studies (GWAS) of African-American, Jamaican, Japanese, and Russian athletes. On the other hand, the significance of 29 (24%) markers was not replicated in at least one study. Future research including multicenter GWAS, whole-genome sequencing, epigenetic, transcriptomic, proteomic, and metabolomic profiling and performing meta-analyses in large cohorts of athletes is needed before these findings can be extended to practice in sport.

  10. Folate and Breast Cancer: Role of Intake, Blood Levels and Metabolic Gene Polymorphisms

    DTIC Science & Technology

    2003-06-01

    those with MTHFR , MTR, and MTRR polymorphisms. The specific aims of this postdoctoral training proposal are 1) further methodological training in the...analysis of gene-gene and gene-environment interactions by studying folate intake and folate metabolic gene polymorphisms ( MTHFR , MTR, MTRR) using data

  11. Genetic polymorphisms as determinants for disease preventive effects of vitamin E

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Polymorphisms in genes involved in vitamin E uptake, distribution, metabolism and molecular action may be important determinants for the protective effects of vitamin E supplementation. The haptoglobin 2-2 polymorphism is associated with increased production of oxygen free radicals and the consequen...

  12. PTX3 Polymorphisms and Invasive Mold Infections After Solid Organ Transplant.

    PubMed

    Wójtowicz, Agnieszka; Lecompte, T Doco; Bibert, Stephanie; Manuel, Oriol; Rüeger, Sina; Berger, Christoph; Boggian, Katia; Cusini, Alexia; Garzoni, Christian; Hirsch, Hans; Khanna, Nina; Mueller, Nicolas J; Meylan, Pascal R; Pascual, Manuel; van Delden, Christian; Bochud, Pierre-Yves

    2015-08-15

    Donor PTX3 polymorphisms were shown to influence the risk of invasive aspergillosis among hematopoietic stem cell transplant recipients. Here, we show that PTX3 polymorphisms are independent risk factors for invasive mold infections among 1101 solid organ transplant recipients, thereby strengthening their role in mold infection pathogenesis and patients' risk stratification.

  13. Combined crystal structure prediction and high-pressure crystallization in rational pharmaceutical polymorph screening

    PubMed Central

    Neumann, M. A.; van de Streek, J.; Fabbiani, F. P. A.; Hidber, P.; Grassmann, O.

    2015-01-01

    Organic molecules, such as pharmaceuticals, agro-chemicals and pigments, frequently form several crystal polymorphs with different physicochemical properties. Finding polymorphs has long been a purely experimental game of trial-and-error. Here we utilize in silico polymorph screening in combination with rationally planned crystallization experiments to study the polymorphism of the pharmaceutical compound Dalcetrapib, with 10 torsional degrees of freedom one of the most flexible molecules ever studied computationally. The experimental crystal polymorphs are found at the bottom of the calculated lattice energy landscape, and two predicted structures are identified as candidates for a missing, thermodynamically more stable polymorph. Pressure-dependent stability calculations suggested high pressure as a means to bring these polymorphs into existence. Subsequently, one of them could indeed be crystallized in the 0.02 to 0.50 GPa pressure range and was found to be metastable at ambient pressure, effectively derisking the appearance of a more stable polymorph during late-stage development of Dalcetrapib. PMID:26198974

  14. Associations of five polymorphisms in the CD44 gene with cancer susceptibility in Asians

    PubMed Central

    Qi, Qichao; Wang, Jiwei; Chen, Anjing; Huang, Bin; Li, Gang; Li, Xingang; Wang, Jian

    2016-01-01

    CD44 polymorphisms have been previously associated with cancer risk. However, the results between independent studies were inconsistent. Here, a meta-analysis was performed to systematically evaluate associations between CD44 polymorphisms and cancer susceptibility. A comprehensive literature search conducted in PubMed, Embase, and Web of Science databases through August 10, 2016 yielded 11 eligible publications consisting of 5,788 cancer patients and 5,852 controls. Overall, odds ratios (OR) calculated with 95% confidence intervals (CI) identified a significant association between CD44 polymorphism rs13347 and cancer susceptibility under all genetic models. Additionally, the minor allele of polymorphism rs11821102 was associated with a decreased susceptibility to cancer in allele contrast, dominant, and heterozygous models, while no significant association was identified for polymorphisms rs10836347, rs713330, or rs1425802. Subgroup analysis by ethnicity revealed rs13347 was significantly associated with cancer susceptibility for Chinese but not for Indians. Linkage disequilibrium (LD) between different polymorphisms varied across diverse ethnic populations. In conclusion, the results indicate that CD44 polymorphism rs13347 acts as a risk factor for cancer, especially in Chinese, while the minor allele of polymorphism rs11821102 may be associated with a decreased susceptibility to cancer. Nevertheless, further studies on a larger population covering different ethnicities are warranted. PMID:28000766

  15. Polymorphisms in Dopamine System Genes Are Associated with Individual Differences in Attention in Infancy

    ERIC Educational Resources Information Center

    Holmboe, Karla; Nemoda, Zsofia; Fearon, R. M. Pasco; Csibra, Gergely; Sasvari-Szekely, Maria; Johnson, Mark H.

    2010-01-01

    Knowledge about the functional status of the frontal cortex in infancy is limited. This study investigated the effects of polymorphisms in four dopamine system genes on performance in a task developed to assess such functioning, the Freeze-Frame task, at 9 months of age. Polymorphisms in the catechol-O-methyltransferase ("COMT") and the…

  16. The ABCG5 Polymorphism Contributes to Individual Responses to Dietary Cholesterol and Carotenoids in Eggs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The ATP binding cassette G5 (ABCG5) polymorphisms have been postulated to play a role in the response to dietary cholesterol. The objective of this study was to examine the contribution of the ABCG5 polymorphism on the plasma response to consumption of cholesterol and carotenoids from eggs. For this...

  17. Polymorphisms in the control region of mitochondrial DNA associated with elite Japanese athlete status.

    PubMed

    Mikami, E; Fuku, N; Takahashi, H; Ohiwa, N; Pitsiladis, Y P; Higuchi, M; Kawahara, T; Tanaka, M

    2013-10-01

    The control region of mitochondrial DNA (mtDNA) contains the main regulatory elements for mtDNA replication and transcription. Certain polymorphisms in this region would, therefore, contribute to elite athletic performance, because mitochondrial function is one of determinants of physical performance. The present study was undertaken to examine the effect of polymorphisms in this region on elite athlete status by sequencing the mtDNA control region. Subjects comprised 185 elite Japanese athletes who had represented Japan at international competitions (i.e., 100 endurance/middle-power athletes: EMA; 85 sprint/power athletes: SPA), and 672 Japanese controls (CON). The mtDNA control region was analyzed by direct sequencing. Frequency differences of polymorphisms (minor allele frequency ≥ 0.05) in the mtDNA control region between EMA, SPA, and CON were examined. EMA displayed excess of three polymorphisms [m.152T>C, m.514(CA)n repeat (n ≥ 5), and poly-C stretch at m.568-573 (C ≥ 7)] compared with CON. On the other hand, SPA showed greater frequency of the m.204T>C polymorphism compared with CON. In addition, none of the SPA had m.16278C>T polymorphism, whereas the frequencies of this polymorphism in CON and EMA were 8.3% and 10.0%, respectively. These findings imply that several polymorphisms detected in the control region of mtDNA may influence physical performance probably in a functional manner.

  18. p53 codon 72 polymorphism in vulval cancer and vulval intraepithelial neoplasia

    PubMed Central

    Rosenthal, A N; Ryan, A; Hopster, D; Jacobs, I J

    2000-01-01

    p53 codon 72 polymorphism was analysed in UK women with human papillomavirus (HPV)-associated vulval intraepithelial neoplasia and vulval squamous cell carcinoma. Arginine homozygotes were significantly less common in either group compared with controls. We conclude that the arginine polymorphism may confer protection against the development of HPV-associated vulval neoplasia. © 2000 Cancer Research Campaign PMID:11044351

  19. HFE, MTHFR, and FGFR4 genes polymorphisms and breast cancer in Brazilian women.

    PubMed

    Batschauer, Anna P; Cruz, Nathalia G; Oliveira, Vanessa C; Coelho, Fernanda F; Santos, Izabela R; Alves, Michelle T; Fernandes, Ana P; Carvalho, Maria G; Gomes, Karina B

    2011-11-01

    Genetic factors related to cancer have been extensively studied and several polymorphisms have been associated to breast cancer. The FGFR4, MTHFR, and HFE genes have been associated with neoplastic diseases development. The current report outlines the analysis of the polymorphisms G388A (FGFR4), C677T (MTHFR), C282Y, and H63D (HFE) in Brazilian breast cancer patients. We studied 68 patients with invasive ductal and operable breast carcinoma and 85 women as a control group. The polymorphism frequencies in the breast cancer and control groups were analyzed, but no significant difference was observed by comparing the two groups. The presence of each polymorphism was analyzed according to the clinical features and markers already established as prognostic in the breast cancer group. The C677T, H63D, and G388A polymorphisms were not associated to histological grade, age of diagnosis, expression of HER2 receptor, or estrogen and progesterone receptor. The H63D polymorphism showed a significant association (P = 0.02) with the presence of p53 mutations, and C667T showed association to lymph node involvement (P = 0.05). Lymph node involvement, G388A polymorphism, and histological grade were independently associated to metastasis/death. Our data suggests that the polymorphisms G388A, C677T, and H63D are not useful in breast cancer diagnosis, but they may be significant additional prognostic markers related to breast cancer survival.

  20. 5-Methyltetrahydrofolate-homocysteine methyltransferase gene polymorphism (MTR) and risk of head and neck cancer.

    PubMed

    Galbiatti, A L S; Ruiz, M T; Biselli-Chicote, P M; Chicote-Biselli, P M; Raposo, L S; Maniglia, J V; Pavarino-Bertelli, E C; Goloni-Bertollo, E M

    2010-05-01

    The functional effect of the A>G transition at position 2756 on the MTR gene (5-methyltetrahydrofolate-homocysteine methyltransferase), involved in folate metabolism, may be a risk factor for head and neck squamous cell carcinoma (HNSCC). The frequency of MTR A2756G (rs1805087) polymorphism was compared between HNSCC patients and individuals without history of neoplasias. The association of this polymorphism with clinical histopathological parameters was evaluated. A total of 705 individuals were included in the study. The polymerase chain reaction-restriction fragment length polymorphism technique was used to genotype the polymorphism. For statistical analysis, the chi-square test (univariate analysis) was used for comparisons between groups and multiple logistic regression (multivariate analysis) was used for interactions between the polymorphism and risk factors and clinical histopathological parameters. Using univariate analysis, the results did not show significant differences in allelic or genotypic distributions. Multivariable analysis showed that tobacco and alcohol consumption (P < 0.05), AG genotype (P = 0.019) and G allele (P = 0.028) may be predictors of the disease and a higher frequency of the G polymorphic allele was detected in men with HNSCC compared to male controls (P = 0.008). The analysis of polymorphism regarding clinical histopathological parameters did not show any association with the primary site, aggressiveness, lymph node involvement or extension of the tumor. In conclusion, our data provide evidence that supports an association between the polymorphism and the risk of HNSCC.

  1. THE CRYSTAL STRUCTURE OF THE NEW SILICON CARBIDE POLYMORPH 69R,

    DTIC Science & Technology

    The 69R polymorph is one of the 32 silicon carbide polymorphs recently discovered by us. The space group is R3m and the unit cell is hexagonal with...and in two industrial silicon carbide crystal plates. They all pair with the fundamental type 6H. The five ways of pairing are: 6H + 69R + 87R, 6H

  2. Genetic Susceptibility to Multiple Sclerosis: The Role of FOXP3 Gene Polymorphism

    PubMed Central

    IŞIK, Nihal; YILDIZ MANUKYAN, Nüket; AYDIN CANTÜRK, İlknur; CANDAN, Fatma; ÜNSAL ÇAKMAK, Ayşen; SARU HAN DİRESKENELİ, Güher

    2014-01-01

    Introduction It is well recognized that both genetic and environmental factors play an important role in the pathogenesis of multiple sclerosis (MS). Immune pathogenesis of MS focuses on pathogenic CD4+ T lymphocytes. CD4+CD25+ regulatory T cells have suppressive function in this cell group. FOXP3 (forkhead boxP3) transcription factor is a key structure in the development and function of regulatory cells. Functional alterations in FOXP3 gene expression have been observed in various autoimmune diseases. Methods We screened a non-synonymous coding single nucleotide polymorphism (exon +2710 C/T) (rs2232369) of human FOXP3 gene in 148 MS patients (118 with Relapsing Remitting MS, 30 with Secondary Progressive MS) and 102 age- and sex-matched healthy controls. The association of polymorphisms with susceptibility, and course of the disease was evaluated. Results We could not detect any single nucleotide polymorphism in MS patients, however, polymorphic allele was detected in 3% of the control group. Consequently, a genetic association between the FOXP3 gene polymorphism and MS was not revealed. Conclusion The distribution of this polymorphism has not been screened in any other MS populations before. Although we could not succeed to find any association between susceptibility to MS and screened FOXP3 gene polymorphisms, we suggest that this particular polymorphism is not appropriate for these kind of studies in the future.

  3. Polymorphisms in folate-related enzyme genes in idiopathic infertile Brazilian men.

    PubMed

    Gava, Marcello M; Kayaki, Erika A; Bianco, Bianca; Teles, Juliana S; Christofolini, Denise M; Pompeo, Antonio C L; Glina, Sidney; Barbosa, Caio P

    2011-12-01

    The aim of the study was to analyze the distribution of the methylenetetrahydrofolate reductase (MTHFR), methionine synthase reductase (MTRR), and methionine synthase (MTR) polymorphisms in idiopathic infertile Brazilian men and fertile men. Case-control study comprising 133 idiopathic infertile Brazilian men with nonobstructive azoospermia ([NOA] n = 55) or severe oligozoospermia ([SO] n = 78) and 173 fertile men as controls. MTHFR C677T, A1298C, and G1793A; MTRR A66G; and MTR A2756G polymorphisms were studied by quantitative polymerase chain reaction (qPCR). The results were analyzed statistically and a P value <.05 was considered significant. Single-marker analysis revealed a significant association among MTHFR C677T polymorphism and both NOA group (P = .018) and SO group (P < .001). Considering the MTHFR A1298C, MTHFR G1793A, and MTRR A66G polymorphisms, no difference was found between NOA group and SO group. Regarding the MTR A2756G polymorphism, a significant difference was found between NOA and controls, P = .017. However, statistical analysis revealed no association between SO group and controls. Combined genotypes of 3 MTHFR polymorphisms did not identify a haplotype associated with idiopathic infertility. The combinatory analysis of the 3 polymorphisms MTHFR, MTRR, and MTR did not show difference between cases and controls. The findings suggest the MTHFR C677T and MTR A2756G polymorphisms could be an important genetic factor predisposing to idiopathic infertility in Brazilian men.

  4. Detection and validation of single feature polymorphisms using RNA expression data from a rice genome array

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A large number of genetic variations have been identified in rice. Such variations must in many cases control phenotypic differences in abiotic stress tolerance and other traits. A single feature polymorphism (SFP) is an oligonucleotide array-based polymorphism which can be used for identification o...

  5. Associations between heat shock protein 70 genetic polymorphisms and calving traits in crossbred Brahman cows

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Stressors such as heat, cold, toxins, and oxygen deprivation are known to induce heat shock proteins. Genetic polymorphisms associated with heat shock protein genes have been associated with decreased male and female fertility. Our objectives were to 1) confirm single nucleotide polymorphisms (SNP) ...

  6. (14) N nuclear quadrupole resonance study of piroxicam: confirmation of new polymorphic form V.

    PubMed

    Lavrič, Zoran; Pirnat, Janez; Lužnik, Janko; Puc, Uroš; Trontelj, Zvonko; Srčič, Stane

    2015-06-01

    A new polymorphic crystal form of piroxicam was discovered while preparing crystalline samples of piroxicam for (14) N nuclear quadrupole resonance (NQR) analysis. The new crystal form, designated as V, was prepared by evaporative recrystallization from dichloromethane. Three known polymorphic forms (I, II, and III) were also prepared. Our aim was to apply (14) N NQR to characterize the new polymorphic form of piroxicam and compare the results with those of the other known polymorphic forms. Additional analytical methods used for characterization were X-ray powder diffraction (XRPD), thermal analysis, and vibrational spectroscopy. For the first time, a complete set of nine characteristic (14) N NQR frequencies was found for each prepared polymorph of piroxicam. The consistent set of measured frequencies and calculated characteristic quadrupole parameters found for the new polymorphic form V is a convincing evidence that we are dealing with a new form. The already known piroxicam polymorphic forms were characterized similarly. The XRPD results were in accordance with the conclusions of (14) N NQR analysis. The performed study clearly demonstrates a strong potential of (14) N NQR method to be applied as a highly discriminative spectroscopic analytical tool to characterize polymorphic forms.

  7. Single-Feature Polymorphism Discovery by Computing Probe Affinity Shape Powers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Single-feature polymorphism (SFP) discovery is a rapid and cost-effective approach for plant genomic polymorphism studies. However, either a high false positive rate or low sensitivity was reported in previous SFP detection methods. An alternative method was developed for genome-wide SFP discovery b...

  8. Cytokine gene polymorphisms and outcome after traumatic brain injury.

    PubMed

    Waters, Ryan J; Murray, Gordon D; Teasdale, Graham M; Stewart, Janice; Day, Ian; Lee, Robert J; Nicoll, James A R

    2013-10-15

    Clinical outcome after traumatic brain injury (TBI) is variable and cannot easily be predicted. There is increasing evidence to suggest that there may be genetic influences on outcome. Cytokines play an important role in mediating the inflammatory response provoked within the central nervous system after TBI. This study was designed to identify associations between cytokine gene polymorphisms and clinical outcome 6 months after head injury. A prospectively identified cohort of patients (n=1096, age range 0-93 years, mean age 37) was used. Clinical outcome at 6 months was assessed using the Glasgow Outcome Scale. In an initial screen of 11 cytokine gene single nucleotide polymorphisms (SNPs) previously associated with disease susceptibility or outcome (TNFA -238 and -308, IL6 -174, -572 and -597, IL1A -889, IL1B -31, -511 and +3953, and TGFB -509 and -800), TNFA -308 was identified as having a likely association. The TNFA -308 SNP was further evaluated, and a significant association was identified, with 39% of allele 2 carriers having an unfavorable outcome compared with 31% of non-carriers (adjusted odds ratio 1.67, confidence interval 1.19-2.35, p=0.003). These findings are consistent with experimental and clinical data suggesting that neuroinflammation has an impact on clinical outcome after TBI and that tumor necrosis factor alpha plays an important role in this process.

  9. Xeroderma pigmentosum complementation group f polymorphisms influence risk of glioma.

    PubMed

    Cheng, Hong-Bin; Xie, Chen; Zhang, Ru-You; Hu, Shao-Shan; Wang, Zhi; Yue, Wu

    2013-01-01

    We conducted an exploratory investigation of whether variation in six common SNPs of xeroderma pigmentosum complementation group F (XPF) is associated with risk of glioma in a Chinese population. Six single nucleotide polymorphisms (SNPs) were genotyped in 207 glioma cases and 236 cancer-free controls by a 384-well plate format on the Sequenom MassARRAY platform (Sequenom, San Diego, USA). The rs1800067 G and rs2276466 G allele frequencies were significantly higher in the glioma group than controls. Individuals with the rs1800067 GG genotype were at greater risk of glioma when compared with the A/A genotype in the codominant model, with an OR (95% CI) of 2.63 (1.04-7.25). The rs2276466 polymorphism was significantly associated with moderate increased risk of glioma in codominant and dominant models, with ORs (95% CI) of 1.90 (1.05-3.44) and 1.55 (1.07-2.47), respectively. The combination genotype of rs1800067 G and rs2276466 G alleles was associated with a reduced risk of glioma (OR=0.44, 95% CI=0.19-0.98). These findings indicate that genetic variants of the XPF gene have critical functions in the development of glioma.

  10. Calcium carbonate polymorph control using droplet-based microfluidics.

    PubMed

    Yashina, Alexandra; Meldrum, Fiona; Demello, Andrew

    2012-06-01

    Calcium carbonate (CaCO(3)) is one of the most abundant minerals and of high importance in many areas of science including global CO(2) exchange, industrial water treatment energy storage, and the formation of shells and skeletons. Industrially, calcium carbonate is also used in the production of cement, glasses, paints, plastics, rubbers, ceramics, and steel, as well as being a key material in oil refining and iron ore purification. CaCO(3) displays a complex polymorphic behaviour which, despite numerous experiments, remains poorly characterised. In this paper, we report the use of a segmented-flow microfluidic reactor for the controlled precipitation of calcium carbonate and compare the resulting crystal properties with those obtained using both continuous flow microfluidic reactors and conventional bulk methods. Through combination of equal volumes of equimolar aqueous solutions of calcium chloride and sodium carbonate on the picoliter scale, it was possible to achieve excellent definition of both crystal size and size distribution. Furthermore, highly reproducible control over crystal polymorph could be realised, such that pure calcite, pure vaterite, or a mixture of calcite and vaterite could be precipitated depending on the reaction conditions and droplet-volumes employed. In contrast, the crystals precipitated in the continuous flow and bulk systems comprised of a mixture of calcite and vaterite and exhibited a broad distribution of sizes for all reaction conditions investigated.

  11. Risk of prostate cancer and thrombosis-related factor polymorphisms

    PubMed Central

    GHASEMI, SOMAYEHSADAT; TAVAKOLI, AYDIN; MOGHADAM, MOHAMAD; ZARGAR, MOHAMAD ALI; ABBASPOUR, MARYAM; HATAMNEJADIAN, NASIM; EBRAHIMI, AHMAD

    2014-01-01

    Venous thromboembolism (VTE) is a complication commonly encountered in cancer patients and is considered to be a major cause of morbidity and mortality. The genetic polymorphisms of thrombophilic factors in cancer patients have been focused on during the last few years. However, the number of available studies on the association between prostate cancer and thromboembolic diseases is limited. Prostate cancer is one of the four major types of cancer and its development is affected by a variety of environmental and genetic factors. In the present study we aimed to focus on the effects of thromboembolic factor gene variations on the risk of prostate cancer. In order to conduct our prospective study, we used amplification-refractory mutation system-polymerase chain reaction to investigate three polymorphisms [factor V Leiden (FVL) G1691A, factor II (prothrombin, PTH) G20210A and methylenetetrahydrofolate reductase (MTHFR) C677T] in prostate cancer patients, via comparison with normal individuals. The results demonstrated no significant differences in FVL and PTH gene variations between cases and controls (P>0.05). Although some cases with the T allele of MTHFR 677 were identified, no significant solidarity was established by statistical analysis (P>0.05). Therefore, non-genetic factors that may disturb homeostatic balance should also be considered in future studies, in order to determine the exact association between VTE and prostate cancer. PMID:24649068

  12. Correlation analysis of gene polymorphisms and β-lactam allergy*

    PubMed Central

    Li, Jing; Liu, Xin-yue; Li, Lin-jing; You, Chong-ge; Shi, Lei; Zhang, Shang-di; Liu, Qian; Wang, Jun; Liu, Ze-jing; Lv, Ting-hong

    2015-01-01

    A total of 64 patients with β-lactam allergy and 30 control subjects were enrolled in a case-control study. This study is aimed to analyze the relationship between β-lactam allergy and 10 single nucleotide polymorphisms (SNPs) in interleukin-10 (IL-10), IL-13, IL-4Rα, high-affinity immunoglobulin E-receptor β chain (FcεRIβ), interferon γ receptor 2 (IFNGR2), and CYP3A4, and within the Han Chinese population of Northwest China. Genotyping for the SNPs was conducted using the Sequenom MassARRAY®platform. SPSS 17.0 was employed to analyze the statistical data and SHEsis was used to perform the haplotype reconstruction and analyze linkage disequilibrium of SNPs of IL-10 and IL-13. The results showed that the genotype distribution of CYP3A4 rs2242480/CT differed significantly between case and control groups of males (P=0.022; odds ratio (OR)=0.167, 95% confidence interval (CI): 0.032–0.867). Further analysis showed that CCA, CCG, and TAA haplotypes of IL-10 had no significant correlation in patients with β-lactam allergy. The correlation between CCT and CAC haplotypes of IL-13 and β-lactam allergy needs to be further studied. The analysis did not reveal any differences in the distribution of others gene polymorphisms between cases and controls. PMID:26160721

  13. Amplified Fragment Length Polymorphism Diversity in Cephalosporium maydis from Egypt.

    PubMed

    Saleh, Amgad A; Zeller, Kurt A; Ismael, Abou-Serie M; Fahmy, Zeinab M; El-Assiuty, Elhamy M; Leslie, John F

    2003-07-01

    ABSTRACT Cephalosporium maydis, the causal agent of late wilt of maize, was first described in Egypt in the 1960s, where it can cause yield losses of up to 40% in susceptible plantings. We characterized 866 isolates of C. maydis collected from 14 governates in Egypt, 7 in the Nile River Delta and 7 in southern (Middle and Upper) Egypt, with amplified fragment length polymorphism (AFLP) markers. The four AFLP primer-pair combinations generated 68 bands, 25 of which were polymorphic, resulting in 52 clonal haplotypes that clustered the 866 isolates into four phylogenetic lineages. Three lineages were found in both the Nile River Delta and southern Egypt. Lineage IV, the most diverse group (20 haplotypes), was recovered only from governates in the Nile River Delta. In some locations, one lineage dominated (up to 98% of the isolates recovered) and, from some fields, only a single haplotype was recovered. Under field conditions in Egypt, there is no evidence that C. maydis reproduces sexually. The nonuniform geographic distribution of the pathogen lineages within the country could be due to differences in climate or in the farming system, because host material differs in susceptibility and C. maydis lineages differ in pathogenicity.

  14. Deadly proposal: a case of catecholaminergic polymorphic ventricular tachycardia.

    PubMed

    Heiner, Jason D; Bullard-Berent, Jeffrey H; Inbar, Shmuel

    2011-11-01

    Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare adrenergically mediated arrhythmogenic disorder classically induced by exercise or emotional stress and found in structurally normal hearts. It is an important cause of cardiac syncope and sudden death in childhood. Catecholaminergic polymorphic ventricular tachycardia is a genetic cardiac channelopathy with known mutations involving genes affecting intracellular calcium regulation. We present a case of a 14-year-old boy who had cardiopulmonary arrest after an emotionally induced episode of CPVT while attempting to invite a girl to the school dance. Review of his presenting cardiac rhythm, induction of concerning ventricular arrhythmias during an exercise stress test, and genetic testing confirmed the diagnosis of CPVT. He recovered fully and was treated with β-blocker therapy and placement of an implantable cardioverter-defibrillator. In this report, we discuss this rare but important entity, including its molecular foundation, clinical presentation, basics of diagnosis, therapeutic options, and implications of genetic testing for family members. We also compare CPVT to other notable cardiomyopathic and channelopathic causes of sudden death in youth including hypertrophic cardiomyopathy, arrhythmogenic right ventricular dysplasia, long QT syndrome, short QT syndrome, and Brugada syndrome.

  15. Murine Prkdc Polymorphisms Impact DNA-PKcs Function

    PubMed Central

    Fabre, Kristin M.; Ramaiah, Lila; Dregalla, Ryan C.; Desaintes, Christian; Weil, Michael M.; Bailey, Susan M.; Ullrich, Robert L.

    2011-01-01

    Polymorphic variants of DNA repair genes can increase the carcinogenic potential of exposure to ionizing radiation. Two single nucleotide polymorphisms (SNPs) in Prkdc, the gene encoding the DNA-dependent protein kinase catalytic subunit (DNA-PKcs), have been identified in BALB/c mice and linked to reduced DNA-PKcs activity and mammary cancer susceptibility. We examined three additional mouse strains to better define the roles of the BALB/c Prkdc SNPs (R2140C and M3844V). One is a congenic strain (C.B6) that has the C57BL/6 Prkdc allele on a BALB/c background, and the other is a congenic strain (B6.C) that has the BALB/c variant Prkdc allele on a C57BL/6 background. We also examined the LEWES mouse strain, which possesses only one of the BALB/c Prkdc SNPs (M3844V). Our results demonstrate that both Prkdc SNPs are responsible for deficient DNA-PKcs protein expression, DNA repair and telomere function, while the LEWES SNP affects only DNA-PKcs expression and repair capacity. These studies provide insight into the separation of function between the two BALB/c SNPs as well as direct evidence that SNPs positioned within Prkdc can significantly influence DNA-PKcs function involving DNA repair capacity, telomere end-capping, and potentially cancer susceptibility. PMID:21265624

  16. Novel Polymorphic Multilocus Microsatellite Markers to Distinguish Candida tropicalis Isolates

    PubMed Central

    Chen, Sharon; Kong, Fanrong; Wang, He; Zhang, Li; Hou, Xin; Xu, Ying-Chun

    2016-01-01

    Candida tropicalis is an important pathogen. Here we developed and evaluated a polymorphic multilocus microsatellite scheme employing novel genetic markers for genotyping of C. tropicalis. Using 10 isolates from 10 unique (separate) patients to screen over 4000 tandem repeats from the C. tropicalis genome (strain MYA-3404), six new candidate microsatellite loci (ctm1, ctm3, ctm8, ctm18, ctm24 and ctm26) were selected according to amplification success, observed polymorphisms and stability of flanking regions by preliminary testing. Two known microsatellite loci CT14 and URA3 were also studied. The 6-locus scheme was then tested against a set of 82 different isolates from 32 patients. Microsatellite genotypes of isolates from the same patient (two to five isolates per patient) were identical. The six loci produced eight to 17 allele types and identified 11 to 24 genotypes amongst 32 patients’ isolates, achieving a discriminatory power (DP) of 0.76 to 0.97 (versus 0.78 for both CT14 and URA3 loci, respectively). Testing of a combination of only three loci, ctm1, ctm3 and ctm24, also achieved maximum typing efficiency (DP = 0.99, 29 genotypes). The microsatellite typing scheme had good correlation compared with pulsed-field gel electrophoresis, although was slightly less discriminatory. The new six-locus microsatellite typing scheme is a potentially valuable tool for genotyping and investigating microevolution of C. tropicalis. PMID:27820850

  17. Polymorphous low grade adenocarcinoma: review and case report.

    PubMed

    Pintor, María Fernanda; Figueroa, Liberto; Martínez, Benjamín

    2007-12-01

    Polymorphous Low-Grade Adenocarcinoma is a rare, malignant salivary gland tumor, which is found almost exclusively in minor salivary glands. It is more frequent in the age range from 30 to 70, with a clear female predilection in a 2:1 ratio. It is usually located in the hard or soft palate, although it may be found in the rest of the oral cavity too. It is rare in major salivary glands. In general it has good prognosis, with recurrence rates in the range of 17% - 24%. Although rare, metastasis to regional lymph nodes may occur in 9% of the cases. This report describes the case of a patient that consulted at the Military Odontological Center (Central Odontológica del Ejército) due to an esthetic alteration of her dental prosthesis, which had been made 8 years before. The patient was sent to the Maxillofacial Surgery Service, where the intraoral examination showed a big mass compromising the hard palate and the alveolar ridge. During examination, a dent in her prosthesis was found to correspond to the tumor mass; it was therefore concluded that the tumor had at least an eight-year-old evolution. An incisional biopsy was carried out, and once the polymorphous low-grade adenocarcinoma diagnosis had been stated, the patient was sent to the Head and Neck Surgery Service of the Military Hospital, where the lesion was treated by wide surgical excision followed by radiation therapy.

  18. MHC and KIR Polymorphisms in Rhesus Macaque SIV Infection

    PubMed Central

    Walter, Lutz; Ansari, Aftab A.

    2015-01-01

    Natural killer lymphocytes are essentially involved as the first line of defense against agents such as viruses and malignant cells. The activity of these cells is regulated via interaction of specific and diverse killer cell immunoglobulin-like receptors (KIR) with the highly polymorphic cognate MHC class I proteins on target cells. Genetic variability of both KIR and MHC-I ligands has been shown to be associated with resistance to many diseases, including infection with the immunodeficiency virus. Disease course and progression to AIDS after infection with human immunodeficiency virus-1 (HIV-1) is essentially influenced by the presence of the stimulatory KIR3DS1 receptor in combination with HLA-Bw4. Knowledge of such genetic interactions that contribute to not only disease resistance but also susceptibility are just as important. Such combined genetic factors were recently reported in the rhesus macaque AIDS model. Here, we review the rhesus macaque MHC class I and KIR gene systems and the role of their polymorphisms in the SIV infection model. PMID:26557119

  19. Genome-Wide Association Study of Polymorphisms Predisposing to Bronchiolitis

    PubMed Central

    Pasanen, Anu; Karjalainen, Minna K.; Bont, Louis; Piippo-Savolainen, Eija; Ruotsalainen, Marja; Goksör, Emma; Kumawat, Kuldeep; Hodemaekers, Hennie; Nuolivirta, Kirsi; Jartti, Tuomas; Wennergren, Göran; Hallman, Mikko; Rämet, Mika; Korppi, Matti

    2017-01-01

    Bronchiolitis is a major cause of hospitalization among infants. Severe bronchiolitis is associated with later asthma, suggesting a common genetic predisposition. Genetic background of bronchiolitis is not well characterized. To identify polymorphisms associated with bronchiolitis, we conducted a genome-wide association study (GWAS) in which 5,300,000 single nucleotide polymorphisms (SNPs) were tested for association in a Finnish–Swedish population of 217 children hospitalized for bronchiolitis and 778 controls. The most promising SNPs (n = 77) were genotyped in a Dutch replication population of 416 cases and 432 controls. Finally, we used a set of 202 Finnish bronchiolitis cases to further investigate candidate SNPs. We did not detect genome-wide significant associations, but several suggestive association signals (p < 10−5) were observed in the GWAS. In the replication population, three SNPs were nominally associated (p < 0.05). Of them, rs269094 was an expression quantitative trait locus (eQTL) for KCND3, previously shown to be associated with occupational asthma. In the additional set of Finnish cases, the association for another SNP (rs9591920) within a noncoding RNA locus was further strengthened. Our results provide a first genome-wide examination of the genetics underlying bronchiolitis. These preliminary findings require further validation in a larger sample size. PMID:28139761

  20. High-Throughput Genotyping with Single Nucleotide Polymorphisms

    PubMed Central

    Ranade, Koustubh; Chang, Mau-Song; Ting, Chih-Tai; Pei, Dee; Hsiao, Chin-Fu; Olivier, Michael; Pesich, Robert; Hebert, Joan; Chen, Yii-Der I.; Dzau, Victor J.; Curb, David; Olshen, Richard; Risch, Neil; Cox, David R.; Botstein, David

    2001-01-01

    To make large-scale association studies a reality, automated high-throughput methods for genotyping with single-nucleotide polymorphisms (SNPs) are needed. We describe PCR conditions that permit the use of the TaqMan or 5′ nuclease allelic discrimination assay for typing large numbers of individuals with any SNP and computational methods that allow genotypes to be assigned automatically. To demonstrate the utility of these methods, we typed >1600 individuals for a G-to-T transversion that results in a glutamate-to-aspartate substitution at position 298 in the endothelial nitric oxide synthase gene, and a G/C polymorphism (newly identified in our laboratory) in intron 8 of the 11–β hydroxylase gene. The genotyping method is accurate—we estimate an error rate of fewer than 1 in 2000 genotypes, rapid—with five 96-well PCR machines, one fluorescent reader, and no automated pipetting, over one thousand genotypes can be generated by one person in one day, and flexible—a new SNP can be tested for association in less than one week. Indeed, large-scale genotyping has been accomplished for 23 other SNPs in 13 different genes using this method. In addition, we identified three “pseudo-SNPs” (WIAF1161, WIAF2566, and WIAF335) that are probably a result of duplication. PMID:11435409

  1. Neonatal infections in Saudi Arabia: Association with cytokine gene polymorphisms.

    PubMed

    Allam, Gamal; Alsulaimani, Adnan A; Alzaharani, Ali K; Nasr, Amre

    2015-01-01

    In recent years, many studies have reported potential associations between cytokine gene polymorphisms and the development, course, and outcome of sepsis, often with apparently conflicting results. The objective of this study was to investigate single nucleotide polymorphism (SNP) in the interleukin (IL)-1β -31 T/C, IL-6 -174 G/C, tumor necrosis factor α (TNF-α) -308 G/A, and interferon γ (IFN-γ) +874 A/T genes for their possible association with susceptibility to early onset sepsis (EOS) in Saudi newborn infants. A total of 205 newborn infants aged 1-2 days were consecutively enrolled onto the study having met the inclusion criteria (as per the research protocol). DNA was extracted from filter papers using the Chelex-100 method. The cytokines SNP were genotyping using Taqman 5' nuclease allelic discrimination. For cytokine measurements we used the commercially available Enzyme-Linked Immunosorbent Assay (ELISA) kit. Our results show that the circulating IL-1β, IL-6, TNF-α, and IFN-γ were significantly (p < 0.001) elevated in EOS patients compared to suspected and sepsis-free control groups; and IL-1β -31C, IL-6 -174G, TNF-α -308G, and IFN-γ +874A alleles were associated with EOS in Saudi infants. In conclusion, analysis of cytokines concentrations and SNP for the four tested genes can be used as a predictor of sepsis outcome in newborns.

  2. MTHFR C677 T gene polymorphism in lymphoproliferative diseases.

    PubMed

    Deligezer, Ugur; Akisik, Ebru E; Yaman, Fulya; Erten, Nilgün; Dalay, Nejat

    2006-01-01

    Methylenetetrahydrofolate reductase (MTHFR), a key enzyme in folate metabolism, has been implicated in cancer risk. In the present study we used a melting curve analysis to investigate the association of the common MTHFR C677 T polymorphism with lymphoproliferative diseases. Patients (n=117) were compared with age- and sex-matched control subjects (n=154). Our results indicate that the 677 T variant occurred less frequently in patients (26%) than in the control group (33.7%; P=0.05). Investigation of the variant allele (677 T) frequency in the subgroups with Hodgkin's lymphoma (HL) and B-cell neoplasms (BCNs) revealed that this difference was a result of the significantly lower distribution of the variant allele in patients with HL (20.5%; P=0.01). This was accompanied by a significantly higher frequency of the homozygote normal genotype (677CC) among the patients with HL. In patients with BCNs the distribution of the variant allele (30.3%) was comparable to that in the control group (P=0.47). However, the difference between HL (20.5%) and BCNs (30.3%) did not reach statistical significance (P=0.09). Our results suggest that the distribution of the C677 T polymorphism may vary among lymphoproliferative diseases.

  3. Drug polymorphism and dosage form design: a practical perspective.

    PubMed

    Singhal, Dharmendra; Curatolo, William

    2004-02-23

    Formulators are charged with the responsibility to formulate a product which is physically and chemically stable, manufacturable, and bioavailable. Most drugs exhibit structural polymorphism, and it is preferable to develop the most thermodynamically stable polymorph of the drug to assure reproducible bioavailability of the product over its shelf life under a variety of real-world storage conditions. There are occasional situations in which the development of a metastable crystalline or amorphous form is justified because a medical benefit is achieved. Such situations include those in which a faster dissolution rate or higher concentration are desired, in order to achieve rapid absorption and efficacy, or to achieve acceptable systemic exposure for a low-solubility drug. Another such situation is one in which the drug remains amorphous despite extensive efforts to crystallize it. If there is no particular medical benefit, there is less justification for accepting the risks of intentional development of a metastable crystalline or amorphous form. Whether or not there is medical benefit, the risks associated with development of a metastable form must be mitigated by laboratory work which provides assurance that (a) the largest possible form change will have no substantive effect on product quality or bioavailability, and/or (b) a change will not occur under all reasonable real-world storage conditions, and/or (c) analytical methodology and sampling procedures are in place which assure that a problem will be detected before dosage forms which have compromised quality or bioavailability can reach patients.

  4. FGFR4 polymorphic variants modulate phenotypic features of Cushing disease.

    PubMed

    Nakano-Tateno, Tae; Tateno, Toru; Hlaing, Maw Maw; Zheng, Lei; Yoshimoto, Katsuhiko; Yamada, Shozo; Asa, Sylvia L; Ezzat, Shereen

    2014-04-01

    Cushing disease is a potentially lethal condition resulting from hormone excess, usually due to a small pituitary tumor that fails to respond to negative feedback inhibition. A minority of patients develop larger, more aggressive tumors of the same lineage but with modest hormone excess. Here we show that a common polymorphism in the fibroblast growth factor receptor 4 (FGFR4) transmembrane domain yields receptor isoforms with distinct properties that mediate these biological differences. Forced expression of the major FGFR4-G388 variant allele supports pY-signal transducer and activator of transcription (STAT3) responses. In contrast, expression of the minor FGFR4-R388 allele enhances STAT3 serine phosphorylation, driving cellular growth. In addition, FGFR4-R388 enhances glucocorticoid receptor phosphorylation and nuclear translocation. Consistent with these findings, glucocorticoid administration resulted in enhanced hormone negative feedback in mice with knock-in of the FGFR4 variant allele. Moreover, clinical data from patients with pituitary tumors revealed that those homozygous for the R388 allele have a higher frequency of silent corticotroph macroadenomas than FGFR4-G388 carriers, who were more likely to have small but hormonally active microadenomas. These findings demonstrate that the FGFR4 transmembrane polymorphic variants can modulate cellular growth and sensitivity to glucocorticoid hormone negative feedback through distinct STAT3 modifications of relevance to the human forms of Cushing disease.

  5. The role of genetic polymorphisms in environmental health.

    PubMed Central

    Kelada, Samir N; Eaton, David L; Wang, Sophia S; Rothman, Nathaniel R; Khoury, Muin J

    2003-01-01

    Interest is increasing in the role of variations in the human genome (polymorphisms) in modifying the effect of exposures to environmental health hazards (often referred to as gene-environment interaction), which render some individuals or groups in the population more or less likely to develop disease after exposure. This review is intended for an audience of environmental health practitioners and students and is designed to raise awareness about this rapidly growing field of research by presenting established and novel examples of gene-environment interaction that illustrate the major theme of effect modification. Current data gaps are identified and discussed to illustrate limitations of past research and the need for the application of more robust methods in future research projects. Two primary benefits of incorporating genetics into the existing environmental health research framework are illustrated: a) the ability to detect different levels of risk within the population, and b) greater understanding of etiologic mechanisms. Both offer opportunities for developing new methods of disease prevention. Finally, we describe a basic framework for researchers interested in pursuing health effects research that incorporates genetic polymorphisms. PMID:12826477

  6. Genetic polymorphism as a background of animal behavior.

    PubMed

    Inoue-Murayama, Miho

    2009-04-01

    Various studies have shown the associations between differences in human behavioral traits and genetic polymorphism of neurotransmitter-related proteins such as receptors, transporters and monoamine oxidase. To clarify the genetic background of animal behavior, corresponding regions in animals have been analyzed. The study has been especially focused on primates, as the evolutionally closest animal to humans, and on dogs, as the socially closest animal to humans. In primates, polymorphisms were discovered between or within species, and the functional effects on neural transmission were found to be different by alleles. Even in apes, the closest species to humans, function was different from that in humans. In dogs, allele distributions of several genes were different among breeds showing different behavioral traits, and genes associated with individual differences in aggressiveness and aptitude of working dogs were surveyed. The survey of behavior-related genes has also been carried out in other mammals such as horses and cetaceans. Genes controlling various behaviors in birds have also been reported. The marker genes for behavior will provide useful information for human evolution, welfare of zoo animals and effective selection of working dogs and industry animals.

  7. Diversity and Relatedness Enhance Survival in Colour Polymorphic Grasshoppers

    PubMed Central

    Caesar, Sofia; Karlsson, Magnus; Forsman, Anders

    2010-01-01

    Evolutionary theory predicts that different resource utilization and behaviour by alternative phenotypes may reduce competition and enhance productivity and individual performance in polymorphic, as compared with monomorphic, groups of individuals. However, firm evidence that members of more heterogeneous groups benefit from enhanced survival has been scarce or lacking. Furthermore, benefits associated with phenotypic diversity may be counterbalanced by costs mediated by reduced relatedness, since closely related individuals typically are more similar. Pygmy grasshoppers (Tetrix subulata) are characterized by extensive polymorphism in colour pattern, morphology, behaviour and physiology. We studied experimental groups founded by different numbers of mothers and found that survival was higher in low than in high density, that survival peaked at intermediate colour morph diversity in high density, and that survival was independent of diversity in low density where competition was less intense. We further demonstrate that survival was enhanced by relatedness, as expected if antagonistic and competitive interactions are discriminately directed towards non-siblings. We therefore also performed behavioural observations and staged encounters which confirmed that individuals recognized and responded differently to siblings than to non-siblings. We conclude that negative effects associated with competition are less manifest in diverse groups, that there is conflicting selection for and against genetic diversity occurring simultaneously, and that diversity and relatedness may facilitate the productivity and ecological success of groups of interacting individuals. PMID:20526364

  8. Genetic diversity and chemical polymorphism of some Thymus species.

    PubMed

    Rustaiee, Ali Reza; Yavari, Alireza; Nazeri, Vahideh; Shokrpour, Majid; Sefidkon, Fatemeh; Rasouli, Musa

    2013-06-01

    To ascertain whether there are chemical and genetic relationships among some Thymus species and also to determine correlation between these two sets of data, the essential-oil composition and genetic variability of six populations of Thymus including: T. daenensis ČELAK. (two populations), T. fallax FISCH. & C.A.MEY., T. fedtschenkoi RONNIGER, T. migricus KLOKOV & DES.-SHOST., and T. vulgaris L. were analyzed by GC and GC/MS, and also by randomly amplified polymorphic DNA (RAPD). Thus, 27 individuals were analyzed using 16 RAPD primers, which generated 264 polymorphic scorable bands and volatiles isolated by distillation extraction were subjected to GC and GC/MS analyses. The yields of oils ranged from 2.1 to 3.8% (v/w), and 34 components were identified, amounting to a total percentage of 97.8-99.9%. RAPD Markers allowed a perfect distinction between the different species based on their distinctive genetic background. However, they did not show identical clustering with the volatile-oil profiles.

  9. ACE and AGTR1 polymorphisms in elite rhythmic gymnastics.

    PubMed

    Di Cagno, Alessandra; Sapere, Nadia; Piazza, Marina; Aquino, Giovanna; Iuliano, Enzo; Intrieri, Mariano; Calcagno, Giuseppe

    2013-02-01

    In the angiotensin-converting enzyme (ACE) gene, Alu deletion, in intron 16, is associated with higher concentrations of ACE serum activity and this may be associated with elite sprint and power performance. The Alu insertion is associated with lower ACE levels and this could lead to endurance performance. Moreover, recent studies have identified a single-nucleotide polymorphism of the angiotensin type 1 receptor gene AGTR1, which seems to be related to ACE activity. The aim of this study was to examine the involvement of the ACE and the AGTR1 gene polymorphisms in 28 Italian elite rhythmic gymnasts (age range 21 ± 7.6 years), and compare them to 23 middle level rhythmic gymnasts (age range 17 ± 10.9 years). The ACE D allele was significantly more frequent in elite athletes than in the control population (χ(2)=4.07, p=0.04). Comparisons between the middle level and elite athletes revealed significant differences (p<0.0001) for the ACE DD genotype (OR=6.48, 95% confidence interval=1.48-28.34), which was more frequent in elite athletes. There were no significant differences in the AGTR1 A/C genotype or allele distributions between the middle level and elite athletes. In conclusion, the ACE D allele genotype could be a contributing factor to high-performance rhythmic gymnastics that should be considered in athlete development and could help to identify which skills should be trained for talent promotion.

  10. Human ACE gene polymorphism and distilled water induced cough

    PubMed Central

    Morice, A. H.; Turley, A. J.; Linton, T. K.

    1997-01-01

    BACKGROUND: Inhibitors of angiotensin converting enzyme (ACE) cause a non-productive cough. The insertion/deletion polymorphism of ACE was used as a genetic marker to investigate the relationship between ACE genotype and cough sensitivity. METHODS: A double blind cough challenge was performed in 66 normotensive subjects (34 men) of mean age 34.8 years (range 18-80) using aerosols of distilled water. The number of coughs during the one minute exposure to water was recorded. DNA samples from venous blood were amplified by the polymerase chain reaction and resolved on a 1% agarose gel. They were analysed for the presence of a polymorphism in intron 16 of the ACE gene consisting of an insertion (I) or deletion (D) of an Alu repetitive sequence 287 base pairs long. RESULTS: The distribution of genotypes was 20 II, 26 ID, and 20 DD. The cough response was significantly (p < 0.01) related to the ACE genotype, the mean number of coughs being 15.8, 11.3, and 9.6, respectively, in subjects with the II, ID, and DD genotypes. CONCLUSIONS: The observation that cough challenge is dependent on ACE genotype in normal subjects is evidence of a link between ACE activity and the cough reflex. 


 PMID:9059468

  11. Susceptibility to basal cell carcinoma: associations with PTCH polymorphisms.

    PubMed

    Strange, R C; El-Genidy, N; Ramachandran, S; Lovatt, T J; Fryer, A A; Smith, A G; Lear, J T; Wong, C; Jones, P W; Ichii-Jones, F; Hoban, P R

    2004-11-01

    Loss of function of the human patched gene (PTCH) is common and critical in basal cell carcinoma (BCC) development. Indirect evidence suggests polymorphism in PTCH mediates BCC risk. We studied 659 BCC cases and 300 controls to determine if exon 2(318), 3(429), 11(1552), 12(1665), 12(1686), 14(2199) and 23(3944) and intron 9(1336-135) and 15(2560+9)PTCH variants were sufficiently common for use in case-control studies, and if selected markers were associated with risk. Intron 15(2560+9) and exon 23(3944) variants were studied further. Their genotype frequencies were not significantly different in controls and cases, though frequency of the G(2560+9)-C(3944) haplotype was lower in all cases (odds ratio=0.44, p=0.009) and those stratified by BCC site and rate of development of further tumours. This association was not mediated by the extent of UVR exposure. We confirmed the robustness of these findings by showing these associations demonstrated similar odds ratios in two groups of randomly selected cases and controls, and using the false positive report probability (FPRP) approach described by Wacholder et al. (2004). The FPRP value (0.168) was in the noteworthy category. These data, showing for the first time that PTCH polymorphism mediates susceptibility, are compatible with reports showing that PTCH haploinsufficiency influences development of BCC precursor lesions.

  12. Polymorphism analysis of csd gene in six Apis mellifera subspecies.

    PubMed

    Wang, Zilong; Liu, Zhiyong; Wu, Xiaobo; Yan, Weiyu; Zeng, Zhijiang

    2012-03-01

    The complementary sex determination (csd) gene is the primary gene determining the gender of honey bees (Apis spp). In this study we analyzed the polymorphism of csd gene in six Apis mellifera subspecies. The genomic region 3 of csd gene in these six A. mellifera was cloned, and identified. A total of 79 haplotypes were obtained from these six subspecies. Analysis showed that region 3 of csd gene has a high level of polymorphism in all the six A. mellifera subspecies. The A. m. anatolica subspecies has a slightly higher nucleotide diversity (π) than other subspecies, while the π values showed no significant difference among the other five subspecies. The phylogenetic tree showed that all the csd haplotypes from different A. mellifera subspecies are scattered throughout the tree, without forming six different clades. Population differentiation analysis showed that there are significant genetic differentiations among some of the subspecies. The NJ phylogenetic tree showed that the A. m. caucasica and A. m. carnica have the closest relationship, followed by A. m. ssp, A. m. ligustica, A. m. carpatica and A. m. anatolica that were gathered in the tree in turn.

  13. Polymorphisms of Saccharomyces cerevisiae genes involved in wine production.

    PubMed

    Vigentini, Ileana; Fracassetti, Daniela; Picozzi, Claudia; Foschino, Roberto

    2009-03-01

    The setting up of new molecular methods for Saccharomyces cerevisiae typing is valuable in enology. Actually, the ability to discriminate different strains in wine making can have a benefit both for the control of the fermentation process and for the preservation of wine typicity. This study focused on the screening of single-nucleotide polymorphisms in genes involved in wine production that could evolve rapidly considering the selective pressure of the isolation environment. Preliminary screening of 30 genes in silico was performed, followed by the selection of 10 loci belonging to 8 genes. The sequence analysis showed a low polymorphism and a degree of heterozygosity. However, a new potential molecular target was recognized in the TPS1 gene coding for the trehalose-6-phosphate synthase enzyme involved in the ethanol resistance mechanism. This gene showed a 1.42% sequence diversity with seven different nucleotide substitutions. Moreover, classic techniques were applied to a collection of 50 S. cerevisiae isolates, mostly with enologic origin. Our results confirmed that the wine making was not carried out only by the inoculated commercial starter because indigenous strains of S. cerevisiae present during fermentation were detected. In addition, a high genetic relationship among some commercial cultures was found, highlighting imprecision or fraudulent practices by starter manufacturers.

  14. Y-chromosome polymorphism: Possible largest Y chromosome in man?

    SciTech Connect

    Murthy, D.S.K.; Al-Awadi, S.A.; Bastaki, L.

    1994-09-01

    The role of variations (inversions/deletion or duplication) in the heterochromatin in gonadal development and function, reproductive fitness, and malignant disease has been extensively studied. However, the causal-relationship of large Y (Yqh+) and repeated fetal loss has not been established unequivocally. An Arab couple (?Bedouin origin) with a history of repeated abortions were investigated. Karyotype analysis of the husband showed a very large Y chromosome, confirmed by GTG-, QFQ- and CBG-banding techniques. C-banding showed discontinuous distribution of the heterochromatin blocks separated by pale bands. The origin of the large heterochromatin segment could be due to tandem duplication of the Yq region or translocation (Yq:Yq). No other relatives (males) of the propositus have been available for investigation. Polymorphism of the Y chromosome could be attributed to evolutionary changes from an ancestral type, either by deletion or duplication of the heterochromatin segment. More detailed studies on isolated, aboriginal/tribal human populations will enable us to better understand the significance of the Y chromosome polymorphism.

  15. Pharmaceutical Salts of Carvedilol: Polymorphism and Physicochemical Properties.

    PubMed

    Hiendrawan, Stevanus; Widjojokusumo, Edward; Veriansyah, Bambang; Tjandrawinata, Raymond R

    2016-09-06

    We report novel pharmaceutical salts of an anti-hypertensive drug carvedilol (CVD) with pharmaceutically acceptable salt formers, including oxalic acid (OXA), fumaric acid (FUMA), benzoic acid (BZA), and mandelic acid (MDA) via conventional solvent evaporation technique. The pKa difference between CVD and selected acids was greater than 3, thus suggesting salt formation. Two polymorphic forms of CVD/MDA salts and one p-Dioxane solvate of CVD/FUMA salt were also reported in this paper. The salts were characterized by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). Stability of the salts was assessed by storage at 40°C/75% RH for 1 month. All CVD salts exhibited higher solubility in phosphate buffer solution pH 6.8 compared to the parent drug CVD and showed good stability in accelerated ICH conditions at 40°C/75% RH for 1 month. CVD/FUMA salt showed the highest solubility (1.78 times). Based on thermal analysis and slurry experiment, it was found that CVD/MDA polymorphs were related monotropically with Form 1 as the stable form. The results suggested that salt formation could be an alternative method to improve CVD solubility.

  16. Characterization of the COL2A1 VNTR polymorphism

    SciTech Connect

    Berg, E.S.; Olaisen, B.

    1993-05-01

    The variable number of tandem repeat (VNTR) region 3{prime} to the collagen type II gene (COL2A1) was amplified in vitro by the polymerase chain reaction. Subsequent high-resolution gel electrophoresis showed that the five earlier reported alleles could be further subtyped. A total of 17 allelic variants with a heterozygosity of 73.0% were found in 202 unrelated Norwegians. DNA sequencing of 19 COL2A1 alleles has been performed. The internal organization of the VNTR was common for all alleles, as previously shown for a few alleles. Moreover, the polymorphism in the COL2A1 locus is mainly due to variation in the numbers of copies of two repeat units, containing 34 and 31 bp, respectively, and/or to small deletions in either of the two units. DNA sequencing of alleles with the same electrophoretic size revealed no heterogeneity such as an alternating order of the different units, a feature that might have been expected to be the result of unequal crossing-over events. The observed ordered structure of the VNTR and the possibility of single-stranded DNA from the cores in the VNTR forming hairpins and loops suggest that the COL2A1 polymorphism may have evolved mainly by replication slippage mechanisms. 23 refs., 2 figs., 3 tabs.

  17. Genetic Polymorphism and Expression of CXCR4 in Breast Cancer

    PubMed Central

    Okuyama Kishima, Marina; Brajão de Oliveira, Karen; Ariza, Carolina Batista; de Oliveira, Carlos Eduardo Coral; Losi Guembarovski, Roberta; Banin Hirata, Bruna Karina; de Almeida, Felipe Campos; Vitiello, Glauco Akelinghton Freire; Trugilo, Kleber Paiva; Guembarovski, Alda Fiorina Maria Losi; Jorge Sobrinho, Walter; Campos, Clodoaldo Zago; Watanabe, Maria Angelica Ehara

    2015-01-01

    CXCR4 genetic polymorphisms, as well as their expression level, have been associated with cancer development and prognosis. The present study aimed to investigate the influence of CXCR4 rs2228014 polymorphism on its mRNA and protein expression in breast cancer samples. It was observed that patients presented higher CXCR4 mRNA relative expression (5.7-fold) than normal mammary gland, but this expression was not correlated with patients clinicopathological features (nuclear grade, nodal status, ER status, PR status, p53 staining, Ki67 index, and HER-2 status). Moreover, CXCR4 mRNA relative expression also did not differ regarding the presence or absence of T allele (p = 0.301). In the immunohistochemical assay, no difference was observed for CXCR4 cytoplasmic protein staining in relation to different genotypes (p = 0.757); however, high cytoplasmic CXCR4 staining was verified in invasive breast carcinoma (p < 0.01). All in all, the results from present study indicated that rs2228014 genetic variant does not alter CXCR4 mRNA or protein expression. However, this receptor was more expressed in tumor compared to normal tissue, in both RNA and protein levels, suggesting its promising applicability in the general context of mammary carcinogenesis. PMID:26576337

  18. A comprehensive map of mobile element insertion polymorphisms in humans.

    PubMed

    Stewart, Chip; Kural, Deniz; Strömberg, Michael P; Walker, Jerilyn A; Konkel, Miriam K; Stütz, Adrian M; Urban, Alexander E; Grubert, Fabian; Lam, Hugo Y K; Lee, Wan-Ping; Busby, Michele; Indap, Amit R; Garrison, Erik; Huff, Chad; Xing, Jinchuan; Snyder, Michael P; Jorde, Lynn B; Batzer, Mark A; Korbel, Jan O; Marth, Gabor T

    2011-08-01

    As a consequence of the accumulation of insertion events over evolutionary time, mobile elements now comprise nearly half of the human genome. The Alu, L1, and SVA mobile element families are still duplicating, generating variation between individual genomes. Mobile element insertions (MEI) have been identified as causes for genetic diseases, including hemophilia, neurofibromatosis, and various cancers. Here we present a comprehensive map of 7,380 MEI polymorphisms from the 1000 Genomes Project whole-genome sequencing data of 185 samples in three major popula