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Sample records for chromosome 9p21 snps

  1. Association of chromosome 9p21 SNPs with cardiovascular phenotypes in morbid obesity using electronic health record data

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    Wood, G. Craig; Still, Christopher D.; Chu, Xin; Susek, Meghan; Erdman, Robert; Hartman, Christina; Yeager, Stephanie; Blosky, Mary Ann; Krum, Wanda; Carey, David J.; Skelding, Kimberly A; Benotti, Peter; Stewart, Walter F.; Gerhard, Glenn S.

    2008-01-01

    Genomic medicine research requires substantial time and resources to obtain phenotype data. The electronic health record offers potential efficiencies in addressing these temporal and economic challenges, but few studies have explored the feasibility of using such data for genetics research. The main objective of this study was to determine the association of two genetic variants located on chromosome 9p21 conferring susceptibility to coronary heart disease and type 2 diabetes with a variety ...

  2. INK4/ARF transcript expression is associated with chromosome 9p21 variants linked to atherosclerosis.

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    Yan Liu

    Full Text Available Genome-wide association studies (GWAS have linked common single nucleotide polymorphisms (SNPs on chromosome 9p21 near the INK4/ARF (CDKN2A/B tumor suppressor locus with risk of atherosclerotic diseases and type 2 diabetes mellitus. To explore the mechanism of this association, we investigated whether expression of proximate transcripts (p16(INK4a, p15(INK4b, ARF, ANRIL and MTAP correlate with genotype of representative 9p21 SNPs.We analyzed expression of 9p21 transcripts in purified peripheral blood T-cells (PBTL from 170 healthy donors. Samples were genotyped for six selected disease-related SNPs spanning the INK4/ARF locus. Correlations among these variables were determined by univariate and multivariate analysis. Significantly reduced expression of all INK4/ARF transcripts (p15(INK4b, p16(INK4a, ARF and ANRIL was found in PBTL of individuals harboring a common SNP (rs10757278 associated with increased risk of coronary artery disease, stroke and aortic aneurysm. Expression of MTAP was not influenced by rs10757278 genotype. No association of any these transcripts was noted with five other tested 9p21 SNPs.Genotypes of rs10757278 linked to increased risk of atherosclerotic diseases are also associated with decreased expression in PBTL of the INK4/ARF locus, which encodes three related anti-proliferative transcripts of known importance in tumor suppression and aging.

  3. Common variants on chromosome 9p21 are associated with normal tension glaucoma.

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    Mitsuko Takamoto

    Full Text Available Although intraocular pressure (IOP is the most definitive cause of glaucoma, a subtype of open angle glaucoma (OAG termed normal tension glaucoma (NTG, which occurs in spite of normal IOP, accounts for a large part of glaucoma cases, especially in Japan. To find common genetic variants contributing to NTG in Japanese patients, we conducted a genome-wide association study (GWAS. We performed the first screening for 531,009 autosomal SNPs with a discovery cohort of 286 cases and 557 controls, and then a second screening for the top 30 suggestive loci in an independent cohort of 183 cases and 514 controls. Our findings identified a significantly associated SNP; rs523096 [combined p-value = 7.40× 10(-8, odds ratio (OR= 2.00 with 95% confidence interval (CI 1.55-2.58] located 10 kbp upstream of CDKN2B on chromosome 9p21. Moreover, analysis of another independent case-control set successfully replicated the results of the screening studies (combined values of all 3 stages p = 4.96 × 10(-11, OR= 2.13 with 95% CI 1.69-2.68. The SNPs near rs523096 were recently reported to be associated with OAG associated with elevated IOP in primary open-angle glaucoma (POAG, the predominant subtype of glaucoma in Caucasian populations. Our results revealed that the 9p21 locus is also associated with NTG in Japanese. In addition, we identified SNPs more strongly associated with NTG.

  4. Association Between the Chromosome 9p21 Locus and Angiographic Coronary Artery Disease Burden

    Science.gov (United States)

    Chan, Kenneth; MPharm; Patel, Riyaz S.; Newcombe, Paul; Nelson, Christopher P.; Qasim, Atif; Epstein, Stephen E.; Burnett, Susan; Vaccarino, Viola L.; Zafari, A. Maziar; Shah, Svati H.; Anderson, Jeffrey L.; Carlquist, John F.; Hartiala, Jaana; Allayee, Hooman; Hinohara, Kunihiko; Lee, Bok-Soo; Erl, Anna; Ellis, Katrina L.; Goel, Anuj; Schaefer, Arne S.; El Mokhtari, Nour Eddine; Goldstein, Benjamin A.; Hlatky, Mark A.; Go, Alan S.; Shen, Gong-Qing; Gong, Yan; Pepine, Carl; Laxton, Ross C.; Whittaker, John C.; Tang, W.H. Wilson; Johnson, Julie A.; Wang, Qing K.; Assimes, Themistocles L.; Nöthlings, Ute; Farrall, Martin; Watkins, Hugh; Richards, A. Mark; Cameron, Vicky A.; Muendlein, Axel; Drexel, Heinz; Koch, Werner; Park, Jeong Euy; Kimura, Akinori; Shen, Wei-feng; Simpson, Iain A.; Hazen, Stanley L.; Horne, Benjamin D.; Hauser, Elizabeth R.; Quyyumi, Arshed A.; Reilly, Muredach P.; Samani, Nilesh J.; Ye, Shu

    2013-01-01

    Objectives This study sought to ascertain the relationship of 9p21 locus with: 1) angiographic coronary artery disease (CAD) burden; and 2) myocardial infarction (MI) in individuals with underlying CAD. Background Chromosome 9p21 variants have been robustly associated with coronary heart disease, but questions remain on the mechanism of risk, specifically whether the locus contributes to coronary atheroma burden or plaque instability. Methods We established a collaboration of 21 studies consisting of 33,673 subjects with information on both CAD (clinical or angiographic) and MI status along with 9p21 genotype. Tabular data are provided for each cohort on the presence and burden of angiographic CAD, MI cases with underlying CAD, and the diabetic status of all subjects. Results We first confirmed an association between 9p21 and CAD with angiographically defined cases and control subjects (pooled odds ratio [OR]: 1.31, 95% confidence interval [CI]: 1.20 to 1.43). Among subjects with angiographic CAD (n = 20,987), random-effects model identified an association with multivessel CAD, compared with those with single-vessel disease (OR: 1.10, 95% CI: 1.04 to 1.17)/copy of risk allele). Genotypic models showed an OR of 1.15, 95% CI: 1.04 to 1.26 for heterozygous carrier and OR: 1.23, 95% CI: 1.08 to 1.39 for homozygous carrier. Finally, there was no significant association between 9p21 and prevalent MI when both cases (n = 17,791) and control subjects (n = 15,882) had underlying CAD (OR: 0.99, 95% CI: 0.95 to 1.03)/risk allele. Conclusions The 9p21 locus shows convincing association with greater burden of CAD but not with MI in the presence of underlying CAD. This adds further weight to the hypothesis that 9p21 locus primarily mediates an atherosclerotic phenotype. PMID:23352782

  5. Validated context-dependent associations of coronary heart disease risk with genotype variation in the chromosome 9p21 region

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    Lusk, Christine M; Dyson, Greg; Clark, Andrew G;

    2014-01-01

    Markers of the chromosome 9p21 region are regarded as the strongest and most reliably significant genome-wide association study (GWAS) signals for Coronary heart disease (CHD) risk; this was recently confirmed by the CARDIoGRAMplusC4D Consortium meta-analysis. However, while these associations...... genotypes in the 9p21 region were strongest in a sub-group of hypertensives. We subsequently validated the effect of the region in an independent sample from the Copenhagen City Heart Study. Our study suggests that marker SNPs identified as predictors of CHD risk in large population based GWAS may have...... their greatest utility in explaining risk of disease in particular sub-groups characterized by biological and environmental effects measured by the traditional CHD risk factors....

  6. Deletion breakpoint mapping on chromosome 9p21 in breast cancer cell line MCF-7

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    Hua-ping XIE

    2012-05-01

    Full Text Available Objective  To map the deletion breakpoint of chromosome 9p21 in breast cancer cell line MCF-7. Methods  The deletion of chromosome 9p21 was checked by Multiplex Ligation-dependent Probe Amplification (MLPA in MCF-7. Subsequently, the deletion breakpoint was amplified by long range PCR and the deletion region was narrowed by primer walking. Finally, the deletion position was confirmed by sequencing. Results  The deletion was found starting within the MTAP gene and ending within CDKN2A gene by MLPA. Based on long range PCR and primer walking, the deletion was confirmed to cover the region from chr9:21819532 to chr9:21989622 by sequencing, with a deletion size of 170kb, starting within the intron 4 of MTAP and ending within the intron 1 near exon 1β of CDKN2A. Conclusions  Long range PCR is an efficient way to detect deletion breakpoints. In MCF-7, the deletion has been confirmed to be 170kb, starting within the MTAP gene and ending within the CDKN2A gene. The significance of the deletion warrants further research.

  7. Genetic Variant rs10757278 on Chromosome 9p21 Contributes to Myocardial Infarction Susceptibility

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    Guangyuan Chen

    2015-05-01

    Full Text Available Large-scale genome-wide association studies (GWAS have revealed that rs10757278 polymorphism (or its proxy rs1333049 on chromosome 9p21 is associated with myocardial infarction (MI susceptibility in individuals of Caucasian ancestry. Following studies in other populations investigated this association. However, some of these studies reported weak or no significant association. Here, we reevaluated this association using large-scale samples by searching PubMed and Google Scholar databases. Our results showed significant association between rs10757278 polymorphism and MI with p = 6.09 × 10−22, odds ratio (OR = 1.29, 95% confidence interval (CI 1.22–1.36 in pooled population. We further performed a subgroup analysis, and found significant association between rs10757278 polymorphism and MI in Asian and Caucasian populations. We identified that the association between rs10757278 polymorphism and MI did not vary substantially by excluding any one study. However, the heterogeneity among the selected studies varies substantially by excluding the study from the Pakistan population. We found even more significant association between rs10757278 polymorphism and MI in pooled population, p = 3.55 × 10−53, after excluding the study from the Pakistan population. In summary, previous studies reported weak or no significant association between rs10757278 polymorphism and MI. Interestingly, our analysis suggests that rs10757278 polymorphism is significantly associated with MI susceptibility by analyzing large-scale samples.

  8. The Chromosome 9p21 CVD- and T2D-Associated Regions in a Norwegian Population (The HUNT2 Survey

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    Øyvind Helgeland

    2015-01-01

    Full Text Available Background. Two adjacent regions upstream CDKN2B on chromosome 9p21 have been associated with type 2 diabetes (T2D and progression of cardiovascular disease (CVD. The precise location and number of risk variants have not been completely delineated and a possible synergistic relationship between the adjacent regions is not fully addressed. By a population based cross-sectional case-control design, we genotyped 18 SNPs upstream of CDKN2B tagging 138 kb in and around two LD-blocks associated with CVD and T2D and investigated associations with T2D, angina pectoris (AP, myocardial infarction (MI, coronary heart disease (CHD; AP or AMI, and stroke using 5,564 subjects from HUNT2. Results. Single point and haplotype analysis showed evidence for only one common T2D risk haplotype (rs10757282∣rs10811661: OR = 1.19, P=2.0×10-3 in the region. We confirmed the strong association between SNPs in the 60 kb CVD region with AP, MI, and CHD (P<0.01. Conditioning on the lead SNPs in the region, we observed two suggestive independent single SNP association signals for MI, rs2065501  (P=0.03 and rs3217986  (P=0.04. Conclusions. We confirmed the association of known variants within the 9p21 interval with T2D and CHD. Our results further suggest that additional CHD susceptibility variants exist in this region.

  9. Smoking modifies the associated increased risk of future cardiovascular disease by genetic variation on chromosome 9p21.

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    Viktor Hamrefors

    Full Text Available AIMS: Genetic predisposition for cardiovascular disease (CVD is likely to be modified by environmental exposures. We tested if the associated risk of CVD and CVD-mortality by the single nucleotide polymorphism rs4977574 on chromosome 9p21 is modified by life-style factors. METHODS AND RESULTS: A total of 24,944 middle-aged subjects (62% females from the population-based Malmö-Diet-and-Cancer-Cohort were genotyped. Smoking, education and physical activity-levels were recorded. Subjects were followed for 15 years for incidence of coronary artery disease (CAD; N = 2309, ischemic stroke (N = 1253 and CVD-mortality (N = 1156. Multiplicative interactions between rs4977574 and life-style factors on endpoints were tested in Cox-regression-models. We observed an interaction between rs4977574 and smoking on incident CAD (P = 0.035 and CVD-mortality (P = 0.012. The hazard ratios (HR per risk allele of rs4977574 were highest in never smokers (N = 9642 for CAD (HR = 1.26; 95% CI 1.13-1.40; P<0.001 and for CVD-mortality (HR = 1.40; 95% CI 1.20-1.63; P<0.001, whereas the risk increase by rs4977574 was attenuated in current smokers (N = 7000 for both CAD (HR = 1.05; 95%CI 0.95-1.16; P = 0.326 and CVD-mortality (HR = 1.08; 95%CI 0.94-1.23; P = 0.270. A meta-analysis supported the finding that the associated increased risk of CAD by the risk-allele was attenuated in smokers. Neither education nor physical activity-levels modified the associated risk of CAD, ischemic stroke and CVD mortality conferred by rs4977574. CONCLUSION: Smoking may modify the associated risk of CAD and CVD-mortality conferred by genetic variation on chromosome 9p21. Whether the observed attenuation of the genetic risk reflects a pathophysiological mechanism or is a result of smoking being such a strong risk-factor that it may eliminate the associated genetic effect, requires further investigation.

  10. Chromosome 9p21 and ABCA1 Genetic Variants and Their Interactions on Coronary Heart Disease and Ischemic Stroke in a Chinese Han Population

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    Xiao-Li Cao

    2016-04-01

    Full Text Available The single nucleotide polymorphisms (SNPs related to both coronary heart disease (CHD and ischemic stroke (IS in Chinese individuals have not been identified definitely. This study was developed to evaluate the genetic susceptibility to CHD and IS on the chromosome 9p21 and the adenosine triphosphate (ATP-binding cassette transporter A1 genes (ABCA1 in a Chinese Han population. Genotypes of the rs1333040, rs1333042, rs4977574, rs2066715 and rs2740483 SNPs were determined in 1134 unrelated patients (CHD, 565 and IS, 569 and 541 controls. The frequencies of the rs4977574 genotypes and alleles between CHD and control groups, and the rs2740483 genotypes and alleles between IS and control groups were different (p = 0.006–0.001. The subjects with rs1333042GG genotype and the carriers of the rs4977574G allele were associated with increased risk of CHD. The carriers of the rs4977574G allele were associated with increased risk of IS. However, the carriers of the rs2740483C allele had lower risk of IS than the non-carriers of the rs2740483C allele after controlling for potential confounders. The rs4977574GG-age (>60 year interaction increased the risk of CHD (p = 0.022, whereas the rs2740483CG/CC-body mass index (>24 kg/m2 interaction decreased the risk of IS (p = 0.035. The interactions of rs1333040-rs1333042 on the risk of CHD and IS were relatively strong, whereas the interactions of rs1333040-rs1333042-rs2066715 and rs1333040-rs1333042-rs2066715-rs2740483 on the risk of CHD, and rs1333040-rs1333042-rs4977574 and rs1333040-rs1333042-rs4977574-rs2740483 on the risk of IS were relatively weak. These findings suggest that some common variants on the chromosome 9p21 and ABCA1 and their interactions may significantly modify the risk of CHD and IS independent of effects on serum lipid levels.

  11. Ocular expression and distribution of products of the POAG-associated chromosome 9p21 gene region.

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    Glyn Chidlow

    Full Text Available It has recently been shown that there are highly significant associations for common single nucleotide polymorphisms (SNPs near the CDKN2B-AS1 gene region at the 9p21 locus with primary open angle glaucoma (POAG, a leading cause of irreversible blindness. This gene region houses the CDKN2B/p15(INK4B , CDKN2A/p16(INK4A and p14ARF (rat equivalent, p19(ARF tumour suppressor genes and is adjacent to the S-methyl-5'-thioadenosine phosphorylase (MTAP gene. In order to understand the ocular function of these genes and, therefore, how they may be involved in the pathogenesis of POAG, we studied the distribution patterns of each of their products within human and rat ocular tissues. MTAP mRNA was detected in the rat retina and optic nerve and its protein product was localised to the corneal epithelium, trabecular meshwork and retinal glial cells in both human and rat eyes. There was a very low level of p16(INK4A mRNA present within the rat retina and slightly more in the optic nerve, although no protein product could be detected in either rat or human eyes with any of the antibodies tested. P19(ARF mRNA was likewise only present at very low levels in rat retina and slightly higher levels in the optic nerve. However, no unambiguous evidence was found to indicate expression of specific P19(ARF/p14(ARF proteins in either rat or human eyes, respectively. In contrast, p15(INK4B mRNA was detected in much higher amounts in both retina and optic nerve compared with the other genes under analysis. Moreover, p15(INK4B protein was clearly localised to the retinal inner nuclear and ganglion cell layers and the corneal epithelium and trabecular meshwork in rat and human eyes. The presented data provide the basis for future studies that can explore the roles that these gene products may play in the pathogenesis of glaucoma and other models of optic nerve damage.

  12. Behavioral variant frontotemporal lobar degeneration with amyotrophic lateral sclerosis with a chromosome 9p21 hexanucleotide repeat

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    Robert eFriedland

    2012-10-01

    Full Text Available To determine the genetic basis of familial frontotemporal lobar degeneration (FTLD with amyotrophic lateral sclerosis (ALS we performed a clinical and genetic analysis of an affected family. A 51-year-old man with behavioral variant frontotemporal lobar degeneration with amyotrophic lateral sclerosis had a family history of the disease suggestive of autosomal dominant inheritance with incomplete penetrance. Genetic studies in this patient demonstrated the presence of an amplified hexanucleotide repeat (>30 polymorphism in the chromosome 9 open reading frame 72 (C9ORF72 gene which was previously identified as a cause of FTLD. Five others unaffecteds from the family were negative (all had less than 11 repeats. We did not find association of single nucleotide polymorphisms (SNPs in C9ORF72 gene with Alzheimer’s disease (AD risk using a large genome wide association study dataset. Bioinformatic analysis of C9ORF72 using the Gene Expression Omnibus database showed expression differences in patients with muscular dystrophy, neural tube defects and schizophrenia. We also report analysis of gene expression in brain regions using the Allen Human Brain Atlas. Defects in this recently reported gene are now believed to be the most common cause of inherited ALS and an important cause of inherited FTLD. Our work suggests that the gene may also be important in other neurological conditions.

  13. Polymorphism on chromosome 9p21.3 contributes to early-onset and severity of coronary artery disease in non-diabetic and type 2 diabetic patients

    Institute of Scientific and Technical Information of China (English)

    WANG Wei; PENG Wen-hui; LU Lin; ZHANG Rui-yan; ZHANG Qi; WANG Ling-jie; CHEN Qiu-jing; SHEN Wei-feng

    2011-01-01

    Background Susceptibility to coronary artery disease (CAD) and diabetes is encoded by distinct, tightly-linked single nucleotide polymorphisms on chromosome 9p21. This study aimed to examine the association of variant rs1333049 on chromosome 9p21.3 with early-onset and severity of CAD in Chinese patients with and without type 2 diabetes, and to determine the possible impact of rs1333049 on glucose metabolism and inflammation pathways.Methods Genotyping of variant rs1333049 on chromosome 9p21.3 was performed in 2387 patients with and without diabetes who were undergoing coronary angiography to evaluate suspected or established CAD. Serum levels of glucose, glycosylated hemoglobin A1c (HbA1c), insulin, high-sensitivity C-reactive protein, tumor necrosis factor-α, and interleukin-6 were also measured, and compared with each patient's genotype.Results The homozygous CC genotype of rs1333049 was significantly associated with CAD in diabetic (OR:1.270,P=0.044) and non-diabetic (OR: 1.369, P=0.011) patients after adjusting for traditional risk factors. There was an association between CC genotype and number of diseased vessels in diabetics (P=0.019), but not in non-diabetics (P=0.126). Among diabetic patients, CC genotype carriers had an increased risk of early-onset CAD (OR:. 2.367, P=0.008)and greater cumulative atherosclerotic burden compared with non-CC genotype carriers (Gensini score: 31.80±17.20 vs.23.09±21.63, P=0.039). No significant differences were observed between genotypes of rs1333049 in serum levels of glucose, insulin, HbA1c, or inflammatory cytokines for diabetic or non-diabetic patients with CAD.Conclusions This study demonstrated a significant association of rs1333049 polymorphism on chromosome 9p21.3 with CAD in Chinese diabetic and non-diabetic patients. The homozygous CC genotype of rs1333049 confers a magnified risk of early-onset and more severe CAD in diabetic patients through a novel biological pathway unrelated to glucose metabolism or

  14. Molecular definition of a chromosome 9p21 germ-line deletion in a woman with multiple melanomas and a plexiform neurofibroma: implications for 9p tumor-suppressor gene(s).

    Science.gov (United States)

    Petty, E M; Gibson, L H; Fountain, J W; Bolognia, J L; Yang-Feng, T L; Housman, D E; Bale, A E

    1993-01-01

    Cutaneous malignant melanoma (CMM) is often familial, but the mode of inheritance and the chromosomal location of melanoma susceptibility locus are controversial. Identification of a 34-year-old woman with eight primary malignant melanomas, multiple atypical moles, and a de novo constitutional cytogenetic rearrangement involving chromosomes 5p and 9p suggested the presence of a melanoma predisposition gene at one of these locations. A high-resolution karyotype showed a partial deletion of a dark-staining Giemsa band, either 5p14 or 9p21. The patient was heterozygous for five 5p14 RFLPs. In situ hybridization with D9S3 indicated that this 9p21 marker was deleted. Gene dosage studies demonstrated the deletion of two more distal 9p21 markers, D9S126 and IFNA. In addition, she was hemizygous for the more proximal 9p21 short tandem-repeat polymorphism at D9S104. D9S18, D9S19, and D9S33 were retained, localizing the deletion to 9p21 between D9S19 on the proximal side and D9S33 on the distal side. Pulsed-field gel electrophoresis with D9S19 and D9S33 did not reveal any junction fragments in the patient's DNA. This germ-line deletion suggests that mutations in a 9p21 gene may initiate melanoma tumorigenesis. Images Figure 1 Figure 2 Figure 3 PMID:8317504

  15. Molecular definition of a chromosome 9p21 germ-line deletion in a woman with multiple melanomas and a plexiform neurofibroma: Implications for 9p tumor-suppressor gene(s)

    Energy Technology Data Exchange (ETDEWEB)

    Petty, E.M.; Gibson, L.H.; Yang-Feng, T.L.; Bale, A.E.; Bolognia, J.L. (Yale Univ. School of Medicine, New Haven, CT (United States)); Fountain, J.W.; Housman, D.E. (Massachusetts Institute of Technology, Cambridge (United States))

    1993-07-01

    Cutaneous malignant melanoma (CMM) is often familial, but the mode of inheritance and the chromosomal location of a melanoma susceptibility locus are controversial. Identification of a 34-year-old woman with eight primary malignant melanomas, multiple atypical moles, and a de novo constitutional cytogenetic rearrangement involving chromosomes 5p and 9p suggested the presence of a melanoma predisposition gene at one of these locations. A high-resolution karyotype showed a partial deletion of a dark-staining Giemsa band, either 5p14 or 9p21. The patient was heterozygous for five 5p14 RFLPs. In situ hybridization with D9S3 indicated that this 9p21 marker was deleted. Gene dosage studies demonstrated the deletion of two more distal 9p21 markers, D9S126 and IFNA. In addition, she was hemizygous for the more proximal 9p21 short tandem-repeat polymorphism at D9S104. D9S18, D9S19, and D9S33 were retained, localizing the deletion to 9p21 between D9S19 on the proximal side and D9S33 on the distal side. Pulsed-field gel electrophoresis with D9S19 and D9S33 did not reveal any junction fragments in the patient's DNA. This germ-line deletion suggests that mutations in a 9p21 gene may initiate melanoma tumorigenesis. 39 refs., 4 figs., 1 tab.

  16. A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD.

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    Renton, Alan E; Majounie, Elisa; Waite, Adrian; Simón-Sánchez, Javier; Rollinson, Sara; Gibbs, J Raphael; Schymick, Jennifer C; Laaksovirta, Hannu; van Swieten, John C; Myllykangas, Liisa; Kalimo, Hannu; Paetau, Anders; Abramzon, Yevgeniya; Remes, Anne M; Kaganovich, Alice; Scholz, Sonja W; Duckworth, Jamie; Ding, Jinhui; Harmer, Daniel W; Hernandez, Dena G; Johnson, Janel O; Mok, Kin; Ryten, Mina; Trabzuni, Danyah; Guerreiro, Rita J; Orrell, Richard W; Neal, James; Murray, Alex; Pearson, Justin; Jansen, Iris E; Sondervan, David; Seelaar, Harro; Blake, Derek; Young, Kate; Halliwell, Nicola; Callister, Janis Bennion; Toulson, Greg; Richardson, Anna; Gerhard, Alex; Snowden, Julie; Mann, David; Neary, David; Nalls, Michael A; Peuralinna, Terhi; Jansson, Lilja; Isoviita, Veli-Matti; Kaivorinne, Anna-Lotta; Hölttä-Vuori, Maarit; Ikonen, Elina; Sulkava, Raimo; Benatar, Michael; Wuu, Joanne; Chiò, Adriano; Restagno, Gabriella; Borghero, Giuseppe; Sabatelli, Mario; Heckerman, David; Rogaeva, Ekaterina; Zinman, Lorne; Rothstein, Jeffrey D; Sendtner, Michael; Drepper, Carsten; Eichler, Evan E; Alkan, Can; Abdullaev, Ziedulla; Pack, Svetlana D; Dutra, Amalia; Pak, Evgenia; Hardy, John; Singleton, Andrew; Williams, Nigel M; Heutink, Peter; Pickering-Brown, Stuart; Morris, Huw R; Tienari, Pentti J; Traynor, Bryan J

    2011-10-20

    The chromosome 9p21 amyotrophic lateral sclerosis-frontotemporal dementia (ALS-FTD) locus contains one of the last major unidentified autosomal-dominant genes underlying these common neurodegenerative diseases. We have previously shown that a founder haplotype, covering the MOBKL2b, IFNK, and C9ORF72 genes, is present in the majority of cases linked to this region. Here we show that there is a large hexanucleotide (GGGGCC) repeat expansion in the first intron of C9ORF72 on the affected haplotype. This repeat expansion segregates perfectly with disease in the Finnish population, underlying 46.0% of familial ALS and 21.1% of sporadic ALS in that population. Taken together with the D90A SOD1 mutation, 87% of familial ALS in Finland is now explained by a simple monogenic cause. The repeat expansion is also present in one-third of familial ALS cases of outbred European descent, making it the most common genetic cause of these fatal neurodegenerative diseases identified to date.

  17. SNP in the genome-wide association study hotspot on chromosome 9p21 confers susceptibility to diabetic nephropathy in type 1 diabetes

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    Fagerholm, E; Ahlqvist, E; Forsblom, C

    2012-01-01

    Parental type 2 diabetes mellitus increases the risk of diabetic nephropathy in offspring with type 1 diabetes mellitus. Several single nucleotide polymorphisms (SNPs) that predispose to type 2 diabetes mellitus have recently been identified. It is, however, not known whether such SNPs also confer...

  18. Association between 9p21 genetic variants and mortality risk in a prospective cohort of patients with type 2 diabetes (ZODIAC-15)

    NARCIS (Netherlands)

    van Vliet-Ostaptchouk, J.V.; Kleefstra, N.; van Hateren, K.J.J.; Drion, I.; Groenier, K.H.; Gans, R.O.B.; Snieder, H.; Hofker, M.H.; Bilo, H.J.G.; Landman, G.

    2012-01-01

    The genomic region at 9p21 chromosome near the CDKN2A/CDKN2B genes is associated with type 2 diabetes(T2D) and cardiovascular disease(CVD). The effect of the 9p21 locus on long-term mortality in patients with T2D has yet to be determined. We examined three single nucleotide polymorphisms (SNPs) on 9

  19. Genetic aberration in primary hepatocellular carcinoma:correlation between p53 gene mutation and loss—of—heterozygosity on chromosome 16q21—q23 and 9p21—p23

    Institute of Scientific and Technical Information of China (English)

    WANGGANG; CHANGHUIHUANG; 等

    2000-01-01

    To elucidate the molecular pathology underlying the development of hepatocellular carcinoma (HCC),we used 41 highly polymorphic microsatellite markers to examine 55 HCC and corresponding non-tumor liver tissues on chromosome 9,16 and 17.Loss-of-heterozygosity(LOH) is observed with high frequency on chromosomal region 17p13(36k/55,65%),9q21-p23(28/55,51%),16q21-23(27/55,49%) in tumors.Meanwhile,microsatellite instability is rarely found in these microsatellite loci.Direct sequencing was performed to detect the tentative mutation of tumor wuppressor genes in these regions:p53,MTS1/p16,and CDH1/E-cadherin.Wihin exon 5-9 of p53 gene,14 out of 55 HCC specimens(24%) have somatic mutations,and nucleotide deletion of this gene is reported in HCC for the first time.Mutation in MTS1/p16 is found only in one tumor case.We do not find mutations in CDH1/E-cadherin.Furthermore,a statistically significant correlation is present between p53 gene mutation and loss of chromosome region 16q21-q23 and 9p21-p23,which indicates that synergism between p53 inactivation and deletion of 16q21-q23 and 9p21-p23 may play a role in the pathogenesis of HCC.

  20. Study of 25 X-chromosome SNPs in the Portuguese

    DEFF Research Database (Denmark)

    Pereira, Vania; Tomas Mas, Carmen; Amorim, António

    2011-01-01

    The importance of X-chromosome markers in individual identifications, population genetics, forensics and kinship testing is getting wide recognition. In this work, we studied the distributions of 25 X-chromosome single nucleotide polymorphisms (X-SNPs) in population samples from Northern, Central...

  1. Multiplex PCR and minisequencing of SNPs--a model with 35 Y chromosome SNPs

    DEFF Research Database (Denmark)

    Sanchez, Juan J; Børsting, Claus; Hallenberg, Charlotte;

    2003-01-01

    We have developed a robust single nucleotide polymorphism (SNPs) typing assay with co-amplification of 25 DNA-fragments and the detection of 35 human Y chromosome SNPs. The sizes of the PCR products ranged from 79 to 186 base pairs. PCR primers were designed to have a theoretical Tm of 60 +/- 5...... degrees C at a salt concentration of 180 mM. The sizes of the primers ranged from 19 to 34 nucleotides. The concentration of amplification primers was adjusted to obtain balanced amounts of PCR products in 8mM MgCl2. For routine purposes, 1 ng of genomic DNA was amplified and the lower limit...... was approximately 100 pg DNA. The minisequencing reactions were performed simultaneously for all 35 SNPs with fluorescently labelled dideoxynucleotides. The size of the minisequencing primers ranged from 19 to 106 nucleotides. The minisequencing reactions were analysed by capillary electrophoresis and multicolour...

  2. Typing of Y chromosome SNPs with multiplex PCR methods

    DEFF Research Database (Denmark)

    Sanchez Sanchez, Juan Jose; Børsting, Claus; Morling, Niels

    2005-01-01

    We describe a method for the simultaneous typing of Y-chromosome single nucleotide polymorphism (SNP) markers by means of multiplex polymerase chain reaction (PCR) strategies that allow the detection of 35 Y chromosome SNPs on 25 amplicons from 100 to 200 pg of chromosomal deoxyribonucleic acid...... (DNA). Multiplex PCR amplification of the DNA was performed with slight modifications of standard PCR conditions. Single-base extension (SBE) was performed using the SNaPshot kit containing fluorescently labeled ddNTPs. The extended primers were detected on an ABI 3100 sequencer. The most important...... factors for the creation of larger SNP typing PCR multiplexes include careful selection of primers for the primary amplification and the SBE reaction, use of DNA primers with homogenous composition, and balancing the primer concentrations for both the amplification and the SBE reactions....

  3. Association between 9p21 genetic variants and mortality risk in a prospective cohort of patients with type 2 diabetes (ZODIAC-15

    Directory of Open Access Journals (Sweden)

    Landman Gijs WD

    2012-11-01

    Full Text Available Abstract The genomic region at 9p21 chromosome near the CDKN2A/CDKN2B genes is associated with type 2 diabetes(T2D and cardiovascular disease(CVD. The effect of the 9p21 locus on long-term mortality in patients with T2D has yet to be determined. We examined three single nucleotide polymorphisms (SNPs on 9p21, consistently and independently associated with T2D (rs10811661 or CVD (rs10757278, rs2383206, in relation to the risk of total and cardiovascular mortality in diabetic patients. We also aimed to replicate the previously observed interaction between rs2383206 and glycemic control on mortality. Genotypes for three SNPs were determined in 914 individuals from a prospective cohort of T2D patients of Dutch origin. Associations with mortality were assessed using Cox proportional hazard analyses. After a median follow-up of 9.5 years, 358 out of 914 patients had died. The hazard ratio (HR for total mortality among individuals homozygous for the T2D-risk allele of rs10811661 compared to non-homozygous individuals was 0.74(95%CI 0.59-0.93. For the carriers of both CVD-risk alleles of rs10757278, the HR for total mortality was 1.31(95%CI 1.01-1.70. We found a significant interaction between rs2383206 and HbA1c on mortality, which was higher among patients with two CVD-risk alleles in the two lowest HbA1c tertiles (HR 1.68(95%CI 1.08-2.63; HR 1.48(95%CI 1.01-2.18. In conclusion, common variants on 9p21 were associated with mortality in patients with T2D in a Dutch population. The T2D SNP was inversely associated with mortality, while the CVD SNP increased the risk for mortality. We confirmed a possible, although different, synergistic relationship between HbA1c and rs2383206 on total mortality.

  4. AB048. X-chromosomal SNPs variation in populations of Russia

    OpenAIRE

    Stepanov, Vadim; Vagaitseva, Kseniya; Kharkov, Vladimir

    2015-01-01

    X-chromosome markers are informative tool for studying a genetic diversity in human populations and have become a useful in DNA identification when certain complex kinship cases need to be unravelled. In this work we present population genetic data on X-chromosome-wide SNPs in North Eurasian populations and report XSNP multiplex system for forensic genetics. A total of 2,867 X-chromosomal SNPs were genotyped in 12 populations using Illumina microarray platform. Twelve populations under study ...

  5. Utility of X-chromosome SNPs in relationship testing

    DEFF Research Database (Denmark)

    Tomas, Carmen; Sanchez, Juan Jose; Castro, J.A.;

    2008-01-01

    X-chromosome markers may complement the results obtained from other genetic markers in complex relationship cases. Until now, reports on relationship testing using X-chromosome markers have mainly included data of short tandem repeats (STRs) while little data on single nucleotide polymorphisms (S...

  6. Comments on: Association Study between Coronary Artery Disease and rs1333049 and rs10757274 Polymorphisms at 9p21 Locus in South-West Iran

    Directory of Open Access Journals (Sweden)

    Michael H. Preuß

    2016-02-01

    Full Text Available Foroughmand et al. (1 have recently reported association between coronary artery disease (CAD and two well-known single nucleotide polymorphisms (SNPs on chromosome 9p21.3 in subjects from South-West Iran. We doubt the validity of their findings. Genotyping was done using ARMS-PCR for rs1333049 and rs10757274 in their study. When we first looked at the genotype frequencies, we observed a substantial excess of heterozygote subjects for both SNPs. Specifically, the relative excess of heterozygosity (REH (2, a measure for the strength of deviation from Hardy-Weinberg equilibrium (HWE, was approximately 137% for rs1333049 in controls (REH=2.3688, Table 1. In contrast, we did not observe any deviation from HWE in our own studies (3, 4. We additionally conducted a short literature search to identify other studies from Asia, which reported genotype frequencies in controls for rs1333049. These studies are summarized in table 1. None of these studies shows a deviation from HWE in their control groups (all P>0.05. In summary, only the recent study by Foroughmand and colleagues (1 shows a marked deviation from HWE in controls with this deviation observed for both reported SNPs. Possible reasons for deviations from HWE have been summarized, e.g., in Ziegler et al. (2. The most likely cause for such a strong deviation from HWE is genotyping errors, especially because genotyping by ARMS-PCR plus gel electrophoresis is prone to such errors. However, REH could also be caused by population specifics, which has been discussed by Namipashaki et al. (5. In any case, we (2 and others (5 recommend the investigation of HWE in population-based genetic association studies to improve quality and reliability of the research results.

  7. Clustering of SNPs along a chromosome can the neutral model be rejected?

    CERN Document Server

    Eriksson, A; Mehlig, B

    2002-01-01

    Single nucleotide polymorphisms (SNPs) often appear in clusters along the length of a chromosome. This is due to variation in local coalescent times caused by,for example, selection or recombination. Here we investigate whether recombination alone (within a neutral model) can cause statistically significant SNP clustering. We measure the extent of SNP clustering as the ratio between the variance of SNPs found in bins of length $l$, and the mean number of SNPs in such bins, $\\sigma^2_l/\\mu_l$. For a uniform SNP distribution $\\sigma^2_l/\\mu_l=1$, for clustered SNPs $\\sigma^2_l/\\mu_l > 1$. Apart from the bin length, three length scales are important when accounting for SNP clustering: The mean distance between neighboring SNPs, $\\Delta$, the mean length of chromosome segments with constant time to the most recent common ancestor, $\\el$, and the total length of the chromosome, $L$. We show that SNP clustering is observed if $\\Delta < \\el \\ll L$. Moreover, if $l\\ll \\el \\ll L$, clustering becomes independent of ...

  8. Association of rs10757274 and rs2383206 Polymorphisms on 9p21 locus with Coronary Artery Disease in Turkish Population

    Science.gov (United States)

    Okyay, Kaan; Yılmaz, Akın; Şahinarslan, Asife; Yar Sağlam, Atiye Seda; Eyiol, Azmi; Bolayır, Hasan Ata; Sezenöz, Burak; Menevşe, Sevda; Çengel, Atiye

    2016-01-01

    Background and Objectives Genetic predisposition is an important risk factor for coronary artery disease (CAD). In this study, we aimed to evaluate the impact of rs10757274 and rs2383206 polymorphisms in chromosome 9p21 on presence and severity of CAD in a Turkish population. Subjects and Methods A total of 646 patients who underwent coronary angiography were included in this study. Coronary vessel score and Gensini score were calculated to assess the angiographic severity of CAD. Alleles of AA, AG, and GG were determined for rs10757274 (polymorphism-1) and rs2383206 (polymorphism-2) polymorphisms located in chromosome 9p21 from the blood samples. Results There was a significant difference between the alleles in polymorphism-1 in the presence of coronary artery disease (38.9% in AA, 48.0% in GG and 56.4% in AG, p=0.017). However, there was no difference between the alleles in polymorphism-2. According to vessel scores, there was a significant difference between the alleles in polymorphism-1 (AA 0.71±1.04, GG 0.88±1.07, AG 1.06±1.12, p=0.018). In polymorphism-2, vessel scores did not show a difference between the alleles. In polymorphism-1, there was a significant difference in Gensini score (p=0.041). Gensini scores did not differ between the alleles in polymorphism-2 (p>0.05 for all). In multivariate analyses, none of the alleles was an independent factor for presence of CAD. Conclusion The presence of rs10757274 polymorphism including AG allele in chromosome 9p21 was related to CAD. However, this relationship was not independent of other cardiovascular risk factors. PMID:27721851

  9. Targeted deletion of the 9p21 noncoding coronary artery disease risk interval in mice

    Energy Technology Data Exchange (ETDEWEB)

    Visel, Axel; Zhu, Yiwen; May, Dalit; Afzal, Veena; Gong, Elaine; Attanasio, Catia; Blow, Matthew J.; Cohen, Jonathan C.; Rubin, Edward M.; Pennacchio, Len A.

    2010-01-01

    Sequence polymorphisms in a 58kb interval on chromosome 9p21 confer a markedly increased risk for coronary artery disease (CAD), the leading cause of death worldwide 1,2. The variants have a substantial impact on the epidemiology of CAD and other life?threatening vascular conditions since nearly a quarter of Caucasians are homozygous for risk alleles. However, the risk interval is devoid of protein?coding genes and the mechanism linking the region to CAD risk has remained enigmatic. Here we show that deletion of the orthologous 70kb noncoding interval on mouse chromosome 4 affects cardiac expression of neighboring genes, as well as proliferation properties of vascular cells. Chr4delta70kb/delta70kb mice are viable, but show increased mortality both during development and as adults. Cardiac expression of two genes near the noncoding interval, Cdkn2a and Cdkn2b, is severely reduced in chr4delta70kb/delta70kb mice, indicating that distant-acting gene regulatory functions are located in the noncoding CAD risk interval. Allelespecific expression of Cdkn2b transcripts in heterozygous mice revealed that the deletion affects expression through a cis-acting mechanism. Primary cultures of chr4delta70kb/delta70kb aortic smooth muscle cells exhibited excessive proliferation and diminished senescence, a cellular phenotype consistent with accelerated CAD pathogenesis. Taken together, our results provide direct evidence that the CAD risk interval plays a pivotal role in regulation of cardiac Cdkn2a/b expression and suggest that this region affects CAD progression by altering the dynamics of vascular cell proliferation.

  10. AB048. X-chromosomal SNPs variation in populations of Russia

    Science.gov (United States)

    Stepanov, Vadim; Vagaitseva, Kseniya; Kharkov, Vladimir

    2015-01-01

    X-chromosome markers are informative tool for studying a genetic diversity in human populations and have become a useful in DNA identification when certain complex kinship cases need to be unravelled. In this work we present population genetic data on X-chromosome-wide SNPs in North Eurasian populations and report XSNP multiplex system for forensic genetics. A total of 2,867 X-chromosomal SNPs were genotyped in 12 populations using Illumina microarray platform. Twelve populations under study (Komi, Mordva, Russians, Kirghiz, Kazakh, Uzbek, Buryat, Yakut, Evenk, Tuva, Khanty, Ket) represent various language families and geographic regions of North Eurasia (Eastern Europe, Central Asia, Siberia and North Asia). North Eurasian populations are highly genetically differentiated with respect to XSNPs allele frequencies. Average level of genetic differentiation (Gst) for 12 populations is 6.03% and ranged from 1.05% to 30.05% per individual SNP. Principal component analysis of allele frequencies demonstrated geographic pattern of population clustering, as well as longitudinal gradient in genetic diversity. The 66 XSNPs characterized by high expected heterozygosity and linkage equilibrium in populations under study were selected for constructing a panel for forensic genetic applications. Average heterozygosity of selected SNPs varied from 0.4925 to 0.4958. Overall values of power of discrimination for males and females (PDm and PDf) obtained with these XSNPs set are several magnitude higher than those for standard forensic STR panels. Protocol for multiplex amplification of 66 XSNPs in two separate multiplex PCR reactions and MALDI-TOF mass spectrometry genotyping was developed. North Eurasian populations demonstrate high level of genetic diversity and differentiation for X-chromosome-wide SNPs. Based on obtained population genetic data, highly informative multiplex XSNPs panel for forensic genetics was developed.

  11. Genetic variants in loci 1p13 and 9p21 and fatal coronary heart disease in a Norwegian case-cohort study.

    Science.gov (United States)

    Jansen, Mona Dverdal; Knudsen, Gun Peggy; Myhre, Ronny; Høiseth, Gudrun; Mørland, Jørg; Næss, Øyvind; Tambs, Kristian; Magnus, Per

    2014-05-01

    Single nucleotide polymorphisms (SNPs) in loci 1p13 and 9p21 have previously been found to be associated with incident coronary heart disease (CHD). This study aimed to investigate whether these SNPs show associations with fatal CHD in a population-based cohort study after adjustment for socioeconomic- and lifestyle-related CHD risk factors not commonly included in genetic association studies. Using the population-based Cohort of Norway (CONOR), a nested case-cohort study was set up and DNA from 2,953 subjects (829 cases and 2,124 non-cases) were genotyped. The association with fatal CHD was estimated for four SNPs, three from locus 1p13 and one from locus 9p21. Multivariable Cox regression was used to estimate unstratified and gender-stratified hazard ratios while adjusting for major CHD risk factors. The associations between three SNPs from locus 1p13 and non-HDL cholesterol levels were also estimated. Men homozygous for the risk alleles on rs1333049 (9p21) and rs14000 (1p13) were found to have significantly increased hazard ratios in crude and adjusted models, and the hazard ratios remained statistically significant when both genders were analyzed together. Adjustment for additional socioeconomic- and lifestyle-related CHD risk factors influenced the association estimates only slightly. No significant associations were observed between the other two SNPs in loci 1p13 (rs599839 and rs646776) and CHD mortality in either gender. Both rs599839 and rs646776 showed significant, gradual increases in non-HDL cholesterol levels with increasing number of risk alleles. This study confirms the association between 9p21 (rs1333049) and fatal CHD in a Norwegian population-based cohort. The effect was not influenced by several socioeconomic- and lifestyle-related risk factors. Our results show that 1p13 (rs14000) may also be associated with fatal CHD. SNPs at 1p13 (rs599839 and rs646776) were associated with non-HDL cholesterol levels.

  12. p16 overexpression and 9p21 deletion are linked to unfavorable tumor phenotype in breast cancer.

    Science.gov (United States)

    Lebok, Patrick; Roming, Magdalena; Kluth, Martina; Koop, Christina; Özden, Cansu; Taskin, Berivan; Hussein, Khakan; Lebeau, Annette; Witzel, Isabell; Wölber, Linn; Geist, Stefan; Paluchowski, Peter; Wilke, Christian; Heilenkötter, Uwe; Müller, Volkmar; Schmalfeldt, Barbara; Simon, Ronald; Sauter, Guido; Terracciano, Luigi; Krech, Rainer Horst; von der Assen, Albert; Burandt, Eike

    2016-12-06

    Overexpression of the p16 tumor suppressor, but also deletion of its gene locus 9p21, is linked to unfavorable tumor phenotype and poor prognosis in breast cancer. To better understand these contradictory observations, and to clarify the prognostic impact of p16 expression and 9p21 deletion, a tissue microarray (TMA) with 2,197 breast cancers was analyzed by fluorescence in-situ hybridization and immunohistochemistry (FISH) for 9p21 deletion and p16 expression. p16 immunostaining was weak in 25.6%, moderate in 7.1%, and strong in 12.7% of 1,684 evaluable cancers. Strong p16 staining was linked to advanced tumor stage (p = 0.0003), high-grade (p p16 expression was absent in cancers harboring homozygous 9p21 deletions, but no difference in p16 expression was found between cancers with (59.2% p16 positive) and without heterozygous 9p21 deletion (51.3% p16 positive, p = 0.0256). In summary, p16 expression is unrelated to partial 9p21 deletion, but both alterations are linked to aggressive breast cancer phenotype. High-level p16 expression is a strong predictor of unfavorable disease course in breast cancer.

  13. CDKN2B expression and subcutaneous adipose tissue expandability: Possible influence of the 9p21 atherosclerosis locus

    Energy Technology Data Exchange (ETDEWEB)

    Svensson, Per-Arne; Wahlstrand, Björn; Olsson, Maja [Institute of Medicine, The Sahlgrenska Academy at University of Gothenburg (Sweden); Froguel, Philippe; Falchi, Mario [Department of Genomics of Common Disease, School of Public Health, Imperial College London (United Kingdom); Bergman, Richard N. [Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA (United States); McTernan, Philip G. [Division of Metabolic and Vascular Health, Warwick Medical School, University of Warwick, Coventry (United Kingdom); Hedner, Thomas; Carlsson, Lena M.S. [Institute of Medicine, The Sahlgrenska Academy at University of Gothenburg (Sweden); Jacobson, Peter, E-mail: peter.jacobson@medfak.gu.se [Institute of Medicine, The Sahlgrenska Academy at University of Gothenburg (Sweden)

    2014-04-18

    Highlights: • The tumor suppressor gene CDKN2B is highly expressed in human adipose tissue. • Risk alleles at the 9p21 locus modify CDKN2B expression in a BMI-dependent fashion. • There is an inverse relationship between expression of CDKN2B and adipogenic genes. • CDKN2B expression influences to postprandial triacylglycerol clearance. • CDKN2B expression in adipose tissue is linked to markers of hepatic steatosis. - Abstract: Risk alleles within a gene desert at the 9p21 locus constitute the most prevalent genetic determinant of cardiovascular disease. Previous research has demonstrated that 9p21 risk variants influence gene expression in vascular tissues, yet the biological mechanisms by which this would mediate atherosclerosis merits further investigation. To investigate possible influences of this locus on other tissues, we explored expression patterns of 9p21-regulated genes in a panel of multiple human tissues and found that the tumor suppressor CDKN2B was highly expressed in subcutaneous adipose tissue (SAT). CDKN2B expression was regulated by obesity status, and this effect was stronger in carriers of 9p21 risk alleles. Covariation between expression of CDKN2B and genes implemented in adipogenesis was consistent with an inhibitory effect of CDKN2B on SAT proliferation. Moreover, studies of postprandial triacylglycerol clearance indicated that CDKN2B is involved in down-regulation of SAT fatty acid trafficking. CDKN2B expression in SAT correlated with indicators of ectopic fat accumulation, including markers of hepatic steatosis. Among genes regulated by 9p21 risk variants, CDKN2B appears to play a significant role in the regulation of SAT expandability, which is a strong determinant of lipotoxicity and therefore might contribute to the development of atherosclerosis.

  14. A variant at 9p21.3 functionally implicates CDKN2B in paediatric B-cell precursor acute lymphoblastic leukaemia aetiology

    Science.gov (United States)

    Hungate, Eric A.; Vora, Sapana R.; Gamazon, Eric R.; Moriyama, Takaya; Best, Timothy; Hulur, Imge; Lee, Younghee; Evans, Tiffany-Jane; Ellinghaus, Eva; Stanulla, Martin; Rudant, Jéremie; Orsi, Laurent; Clavel, Jacqueline; Milne, Elizabeth; Scott, Rodney J.; Pui, Ching-Hon; Cox, Nancy J.; Loh, Mignon L.; Yang, Jun J.; Skol, Andrew D.; Onel, Kenan

    2016-01-01

    Paediatric B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) is the most common cancer of childhood, yet little is known about BCP-ALL predisposition. In this study, in 2,187 cases of European ancestry and 5,543 controls, we discover and replicate a locus indexed by rs77728904 at 9p21.3 associated with BCP-ALL susceptibility (Pcombined=3.32 × 10−15, OR=1.72) and independent from rs3731217, the previously reported ALL-associated variant in this region. Of correlated SNPs tagged by this locus, only rs662463 is significant in African Americans, suggesting it is a plausible causative variant. Functional analysis shows that rs662463 is a cis-eQTL for CDKN2B, with the risk allele associated with lower expression, and suggests that rs662463 influences BCP-ALL risk by regulating CDKN2B expression through CEBPB signalling. Functional analysis of rs3731217 suggests it is associated with BCP-ALL by acting within a splicing regulatory element determining CDKN2A exon 3 usage (P=0.01). These findings provide new insights into the critical role of the CDKN2 locus in BCP-ALL aetiology. PMID:26868379

  15. Chromosome 5p Region SNPs Are Associated with Risk of NSCLC among Women

    Directory of Open Access Journals (Sweden)

    Alison L. Van Dyke

    2009-01-01

    Full Text Available In a population-based case-control study, we explored the associations between 42 polymorphisms in seven genes in this region and non-small cell lung cancer (NSCLC risk among Caucasian (364 cases; 380 controls and African American (95 cases; 103 controls women. Two TERT region SNPs, rs2075786 and rs2853677, conferred an increased risk of developing NSCLC, especially among African American women, and TERT-rs2735940 was associated with a decreased risk of lung cancer among African Americans. Five of the 20 GHR polymorphisms and SEPP1-rs6413428 were associated with a marginally increased risk of NSCLC among Caucasians. Random forest analysis reinforced the importance of GHR among Caucasians and identified AMACR, TERT, and GHR among African Americans, which were also significant using gene-based risk scores. Smoking-SNP interactions were explored, and haplotypes in TERT and GHR associated with NSCLC risk were identified. The roles of TERT, GHR, AMACR and SEPP1 genes in lung carcinogenesis warrant further exploration.

  16. An updated phylogeny of the human Y-chromosome lineage O2a-M95 with novel SNPs.

    Directory of Open Access Journals (Sweden)

    Xiaoming Zhang

    Full Text Available Though the Y-chromosome O2a-M95 lineage is one of the major haplogroups present in eastern Asian populations, especially among Austro-Asiatic speaking populations from Southwestern China and mainland Southeast Asia, to date its phylogeny lacks structure due to only one downstream SNP marker (M88 assigned to the lineage. A recent array-capture-based Y chromosome sequencing of Asian samples has yielded a variety of novel SNPs purportedly belonging to the O2a-M95 lineage, but their phylogenetic positions have yet to be determined. In this study, we sampled 646 unrelated males from 22 Austro-Asiatic speaking populations from Cambodia, Thailand and Southwestern China, and genotyped 12 SNP makers among the sampled populations, including 10 of the newly reported markers. Among the 646 males, 343 belonged to the O2a-M95 lineage, confirming the supposed dominance of this Y chromosome lineage in Austro-Asiatic speaking populations. We further characterized the phylogeny of O2a-M95 by defining 5 sub-branches: O2a1*-M95, O2a1a-F789, O2a1b*-F1252, O2a1b1*-M88 and O2a1b1a -F761. This updated phylogeny not only improves the resolution of this lineage, but also allows for greater tracing of the prehistory of human populations in eastern Asia and the Pacific, which may yield novel insights into the patterns of language diversification and population movement in these regions.

  17. An updated phylogeny of the human Y-chromosome lineage O2a-M95 with novel SNPs.

    Science.gov (United States)

    Zhang, Xiaoming; Kampuansai, Jatupol; Qi, Xuebin; Yan, Shi; Yang, Zhaohui; Serey, Bun; Sovannary, Tuot; Bunnath, Long; Aun, Hong Seang; Samnom, Ham; Kutanan, Wibhu; Luo, Xin; Liao, Shiyu; Kangwanpong, Daoroong; Jin, Li; Shi, Hong; Su, Bing

    2014-01-01

    Though the Y-chromosome O2a-M95 lineage is one of the major haplogroups present in eastern Asian populations, especially among Austro-Asiatic speaking populations from Southwestern China and mainland Southeast Asia, to date its phylogeny lacks structure due to only one downstream SNP marker (M88) assigned to the lineage. A recent array-capture-based Y chromosome sequencing of Asian samples has yielded a variety of novel SNPs purportedly belonging to the O2a-M95 lineage, but their phylogenetic positions have yet to be determined. In this study, we sampled 646 unrelated males from 22 Austro-Asiatic speaking populations from Cambodia, Thailand and Southwestern China, and genotyped 12 SNP makers among the sampled populations, including 10 of the newly reported markers. Among the 646 males, 343 belonged to the O2a-M95 lineage, confirming the supposed dominance of this Y chromosome lineage in Austro-Asiatic speaking populations. We further characterized the phylogeny of O2a-M95 by defining 5 sub-branches: O2a1*-M95, O2a1a-F789, O2a1b*-F1252, O2a1b1*-M88 and O2a1b1a -F761. This updated phylogeny not only improves the resolution of this lineage, but also allows for greater tracing of the prehistory of human populations in eastern Asia and the Pacific, which may yield novel insights into the patterns of language diversification and population movement in these regions.

  18. Common variants at 9p21 and 8q22 are associated with increased susceptibility to optic nerve degeneration in glaucoma.

    Directory of Open Access Journals (Sweden)

    Janey L Wiggs

    Full Text Available Optic nerve degeneration caused by glaucoma is a leading cause of blindness worldwide. Patients affected by the normal-pressure form of glaucoma are more likely to harbor risk alleles for glaucoma-related optic nerve disease. We have performed a meta-analysis of two independent genome-wide association studies for primary open angle glaucoma (POAG followed by a normal-pressure glaucoma (NPG, defined by intraocular pressure (IOP less than 22 mmHg subgroup analysis. The single-nucleotide polymorphisms that showed the most significant associations were tested for association with a second form of glaucoma, exfoliation-syndrome glaucoma. The overall meta-analysis of the GLAUGEN and NEIGHBOR dataset results (3,146 cases and 3,487 controls identified significant associations between two loci and POAG: the CDKN2BAS region on 9p21 (rs2157719 [G], OR = 0.69 [95%CI 0.63-0.75], p = 1.86×10⁻¹⁸, and the SIX1/SIX6 region on chromosome 14q23 (rs10483727 [A], OR = 1.32 [95%CI 1.21-1.43], p = 3.87×10⁻¹¹. In sub-group analysis two loci were significantly associated with NPG: 9p21 containing the CDKN2BAS gene (rs2157719 [G], OR = 0.58 [95% CI 0.50-0.67], p = 1.17×10⁻¹² and a probable regulatory region on 8q22 (rs284489 [G], OR = 0.62 [95% CI 0.53-0.72], p = 8.88×10⁻¹⁰. Both NPG loci were also nominally associated with a second type of glaucoma, exfoliation syndrome glaucoma (rs2157719 [G], OR = 0.59 [95% CI 0.41-0.87], p = 0.004 and rs284489 [G], OR = 0.76 [95% CI 0.54-1.06], p = 0.021, suggesting that these loci might contribute more generally to optic nerve degeneration in glaucoma. Because both loci influence transforming growth factor beta (TGF-beta signaling, we performed a genomic pathway analysis that showed an association between the TGF-beta pathway and NPG (permuted p = 0.009. These results suggest that neuro-protective therapies targeting TGF-beta signaling could be effective for

  19. IMPACT OF LOCUS 9P21.3 SINGLE NUCLEOTIDE POLYMORPHISMS ON CORONARY ATHEROSCLEROSIS SEVERITY AND LONG-TERM OUTCOMES AFTER PERCUTANEOUS CORONARY INTERVENTION IN PATIENT WITH MYOCARDIAL INFARCTION

    Directory of Open Access Journals (Sweden)

    P. A. Shesternya

    2013-01-01

    Full Text Available Aim. To investigate association between 9p21.3 locus single nucleotide polymorphisms (SNPs and coronary atherosclerosis severity and long-term outcomes after percutaneous coronary intervention (PCI in patients with myocardial infarction (MI.Material and methods. A total of 255 Caucasian patients (211 male, 44 female; aged up to 65 years, on the average 52.56±7.98 years with MI were recruited into the study from 01.01.2009 to 30.06.2010. All participants were included into the study after written informed consent. Genome DNA was extracted from leukocytes of venous blood by the phenol-chloroform extraction method. Two SNPs rs10757278 and rs1333049 (locus 9p21.3 were tested by real-time polymerase chain reaction (PCR according to protocol (probes TaqMan, Applied Biosystems, 7900HT. The coronary angiograms were reviewed by independent angiographers who were blinded to the results of the genotyp- ing (Philips Allura Xper FD10. The total number of lesions, Gensini score and SYNTAX score were derived. Follow-up lasted two years.Results. Locus 9р21.3 genotypes CC rs1333049 and GG rs10757278 demonstrated a direct strong association with severity of coronary atheromatous burden (left main coro- nary artery stenosis, total number of lesions, Gensini score. There are not influence of locus 9p21.3 on mortality, recurrent MI, hospitalization due to unstable angina, repeated PCI, stroke during follow-up period (6, 12, 24 months. Frequency of the genotype СС rs1333049 among patients with recurrent MI was 20% (without recurrent MI — 27.4%; р=0.54; with hospitalization due to unstable angina — 27.5% (without hospitalization — 26.4%; р=0.82; with repeated PCI — 24.0% (without repeated PCI — 27.2%; р=0.97; among died patients — 29.8% (among survived ones — 26.4%; р=0.76. Frequencies of the genotype GG rs10757278 were similar: recurrent MI (yes — 18.8%; no — 26.4%; р=0.49; hospitalization due to unstable angina (yes — 28%; no — 25

  20. The contribution of a 9p21.3 variant, a KIF6 variant, and C-reactive protein to predicting risk of myocardial infarction in a prospective study

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    Tracy Russell P

    2011-03-01

    Full Text Available Abstract Background Genetic risk factors might improve prediction of coronary events. Several variants at chromosome 9p21.3 have been widely reported to be associated with coronary heart disease (CHD in prospective and case-control studies. A variant of KIF6 (719Arg has also been reported to be associated with increased risk of CHD in large prospective studies, but not in case-control studies. We asked whether the addition of genetic information (the 9p21.3 or KIF6 variants or a well-established non-genetic risk factor (C-reactive protein [CRP] can improve risk prediction by the Framingham Risk Score (FRS in the Cardiovascular Health Study (CHS--a prospective observational study of risk factors for cardiovascular disease among > 5,000 participants aged 65 or older. Methods Improvement of risk prediction was assessed by change in the area under the receiver-operator characteristic curve (AUC and by net reclassification improvement (NRI. Results Among white participants the FRS was improved by addition of KIF6 719Arg carrier status among men as assessed by the AUC (from 0.581 to 0.596, P = 0.03 but not by NRI (NRI = 0.027, P = 0.32. Adding both CRP and 719Arg carrier status to the FRS improved risk prediction by the AUC (0.608, P = 0.02 and NRI (0.093, P = 0.008 in men, but not women (P ≥ 0.24. Conclusions While none of these risk markers individually or in combination improved risk prediction among women, a combination of KIF6 719Arg carrier status and CRP levels modestly improved risk prediction among white men; although this improvement is not significant after multiple-testing correction. These observations should be investigated in other prospective studies.

  1. The rs10757278 polymorphism of the 9p21.3 locus is associated with premature coronary artery disease in Polish patients.

    Science.gov (United States)

    Niemiec, Pawel; Gorczynska-Kosiorz, Sylwia; Iwanicki, Tomasz; Krauze, Jolanta; Trautsolt, Wanda; Grzeszczak, Wladyslaw; Bochenek, Andrzej; Zak, Iwona

    2012-09-01

    Recently, genome-wide association studies have revealed a locus associated with coronary artery disease (CAD) and myocardial infarction, namely, 9p21.3. Its participation in the conditioning of the disease has been proven in many populations of European descent, but not yet in Slavs. Allelic variants of the rs10757278 polymorphism functionally affect the activity of the 9p21.3 locus; therefore, we conducted a study to determine whether the rs10757278 is associated with premature CAD in Polish patients. We studied 320 subjects aged 25-55 years, divided into two groups matched by sex and age: (1) patients with angiographically proven premature CAD (n=160), and (2) blood donors as a control group (n=160). The rs10757278 was genotyped using the method of fluorescently labeled allele-specific oligonucleotides. The frequency of the G allele was significantly higher in patients than in controls (58.2% vs. 42.8%, respectively, p=0.011) and was similar to the frequency of the GG homozygotes (30.6% vs. 17.5%, respectively, p=0.006). Both the GG homozygosity (odds ratio [OR]=2.08, 95% confidence interval [CI]: 1.19-3.66) as well as the G allele (OR=1.49, 95% CI: 1.08-2.07) have been associated with CAD in the analyzed population. These variants may be considered as risk factors, also in the Polish population.

  2. Association Between Chromosome 9p21 Variants and the Ankle-Brachial Index Identified by a Meta-Analysis of 21 Genome-Wide Association Studies

    NARCIS (Netherlands)

    Murabito, Joanne M.; White, Charles C.; Kavousi, Maryam; Sun, Yan V.; Feitosa, Mary F.; Nambi, Vijay; Lamina, Claudia; Schillert, Arne; Coassin, Stefan; Bis, Joshua C.; Broer, Linda; Crawford, Dana C.; Franceschini, Nora; Frikke-Schmidt, Ruth; Haun, Margot; Holewijn, Suzanne; Huffman, Jennifer E.; Hwang, Shih-Jen; Kiechl, Stefan; Kollerits, Barbara; Montasser, May E.; Nolte, Ilja M.; Rudock, Megan E.; Senft, Andrea; Teumer, Alexander; van der Harst, Pim; Vitart, Veronique; Waite, Lindsay L.; Wood, Andrew R.; Wassel, Christina L.; Absher, Devin M.; Allison, Matthew A.; Amin, Najaf; Arnold, Alice; Asselbergs, Folkert W.; Aulchenko, Yurii; Bandinelli, Stefania; Barbalic, Maja; Boban, Mladen; Brown-Gentry, Kristin; Couper, David J.; Criqui, Michael H.; Dehghan, Abbas; den Heijer, Martin; Dieplinger, Benjamin; Ding, Jingzhong; Doerr, Marcus; Espinola-Klein, Christine; Felix, Stephan B.; Ferrucci, Luigi; Folsom, Aaron R.; Fraedrich, Gustav; Gibson, Quince; Goodloe, Robert; Gunjaca, Grgo; Haltmayer, Meinhard; Heiss, Gerardo; Hofman, Albert; Kieback, Arne; Kiemeney, Lambertus A.; Kolcic, Ivana; Kullo, Iftikhar J.; Kritchevsky, Stephen B.; Lackner, Karl J.; Li, Xiaohui; Lieb, Wolfgang; Lohman, Kurt; Meisinger, Christa; Melzer, David; Mohler, Emile R.; Mudnic, Ivana; Mueller, Thomas; Navis, Gerjan; Oberhollenzer, Friedrich; Olin, Jeffrey W.; O'Connell, Jeff; O'Donnell, Christopher J.; Palmas, Walter; Penninx, Brenda W.; Petersmann, Astrid; Polasek, Ozren; Psaty, Bruce M.; Rantner, Barbara; Rice, Ken; Rivadeneira, Fernando; Rotter, Jerome I.; Seldenrijk, Adrie; Stadler, Marietta; Summerer, Monika; Tanaka, Toshiko; Tybjaerg-Hansen, Anne; Uitterlinden, Andre G.; van Gilst, Wiek H.; Vermeulen, Sita H.; Wild, Sarah H.; Wild, Philipp S.; Willeit, Johann; Zeller, Tanja; Zemunik, Tatijana; Zgaga, Lina; Assimes, Themistocles L.; Blankenberg, Stefan; Campbell, Harry; Boerwinkle, Eric; Cooke, John P.; de Graaf, Jacqueline; Herrington, David; Kardia, Sharon L. R.; Mitchell, Braxton D.; Murray, Anna; Muenzel, Thomas; Newman, Anne B.; Oostra, Ben A.; Rudan, Igor; Shuldiner, Alan R.; Snieder, Harold; van Duijn, Cornelia M.; Voelker, Uwe; Wright, Alan F.; Wichmann, H. -Erich; Wilson, James F.; Witteman, Jacqueline C. M.; Liu, Yongmei; Hayward, Caroline; Borecki, Ingrid B.; Ziegler, Andreas; North, Kari E.; Cupples, L. Adrienne; Kronenberg, Florian; Dorr, M.; Munzel, T.; Volker, U.

    2012-01-01

    Background-Genetic determinants of peripheral arterial disease (PAD) remain largely unknown. To identify genetic variants associated with the ankle-brachial index (ABI), a noninvasive measure of PAD, we conducted a meta-analysis of genome-wide association study data from 21 population-based cohorts.

  3. Association Between Chromosome 9p21 Variants and the Ankle-Brachial Index Identified by a Meta-Analysis of 21 Genome-Wide Association Studies

    DEFF Research Database (Denmark)

    Murabito, Joanne M; White, Charles C; Kavousi, Maryam

    2012-01-01

    BACKGROUND: -Genetic determinants of peripheral arterial disease (PAD) remain largely unknown. To identify genetic variants associated with the ankle-brachial index (ABI), a noninvasive measure of PAD, we conducted a meta-analysis of genome-wide association study data from 21 population-based coh...

  4. An evaluation of the performance of HapMap SNP data in a Shanghai Chinese population: Analyses of allele frequency, linkage disequilibrium pattern and tagging SNPs transferability on chromosome 1q21-q25

    OpenAIRE

    2008-01-01

    Abstract Background The HapMap project aimed to catalog millions of common single nucleotide polymorphisms (SNPs) in the human genome in four major populations, in order to facilitate association studies of complex diseases. To examine the transferability of Han Chinese in Beijing HapMap data to the Southern Han Chinese in Shanghai, we performed comparative analyses between genotypes from over 4,500 SNPs in a 21 Mb region on chromosome 1q21-q25 in 80 unrelated Shanghai Chinese and 45 HapMap C...

  5. An evaluation of the performance of HapMap SNP data in a Shanghai Chinese population: Analyses of allele frequency, linkage disequilibrium pattern and tagging SNPs transferability on chromosome 1q21-q25

    Directory of Open Access Journals (Sweden)

    Wang Jie

    2008-02-01

    Full Text Available Abstract Background The HapMap project aimed to catalog millions of common single nucleotide polymorphisms (SNPs in the human genome in four major populations, in order to facilitate association studies of complex diseases. To examine the transferability of Han Chinese in Beijing HapMap data to the Southern Han Chinese in Shanghai, we performed comparative analyses between genotypes from over 4,500 SNPs in a 21 Mb region on chromosome 1q21-q25 in 80 unrelated Shanghai Chinese and 45 HapMap Chinese data. Results Three thousand and forty-two SNPs were analyzed after removal of SNPs that failed quality control and those not in the HapMap panel. We compared the allele frequency distributions, linkage disequilibrium patterns, haplotype frequency distributions and tagging SNP sets transferability between the HapMap population and Shanghai Chinese population. Among the four HapMap populations, Beijing Chinese showed the best correlation with Shanghai population on allele frequencies, linkage disequilibrium and haplotype frequencies. Tagging SNP sets selected from four HapMap populations at different thresholds were evaluated in the Shanghai sample. Under the threshold of r2 equal to 0.8 or 0.5, both HapMap Chinese and Japanese data showed better coverage and tagging efficiency than Caucasian and African data. Conclusion Our study supported the applicability of HapMap Beijing Chinese SNP data to the study of complex diseases among southern Chinese population.

  6. Common variants at 12p11, 12q24, 9p21, 9q31.2 and in ZNF365 are associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers

    NARCIS (Netherlands)

    Antoniou, Antonis C.; Kuchenbaecker, Karoline B.; Soucy, Penny; Beesley, Jonathan; Chen, Xiaoqing; McGuffog, Lesley; Lee, Andrew; Barrowdale, Daniel; Healey, Sue; Sinilnikova, Olga M.; Caligo, Maria A.; Loman, Niklas; Harbst, Katja; Lindblom, Annika; Arver, Brita; Rosenquist, Richard; Karlsson, Per; Nathanson, Kate; Domchek, Susan; Rebbeck, Tim; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Zlowowcka-Perlowska, Elzbieta; Osorio, Ana; Duran, Mercedes; Andres, Raquel; Benitez, Javier; Hamann, Ute; Hogervorst, Frans B.; van Os, Theo A.; Verhoef, Senno; Meijers-Heijboer, Hanne E. J.; Wijnen, Juul; Garcia, Encarna B. Gomez; Ligtenberg, Marjolijn J.; Kriege, Mieke; Collee, Margriet; Ausems, Margreet G. E. M.; Oosterwijk, Jan C.; Peock, Susan; Frost, Debra; Ellis, Steve D.; Platte, Radka; Fineberg, Elena; Evans, D. Gareth; Lalloo, Fiona; Jacobs, Chris; Eeles, Ros; Adlard, Julian; Davidson, Rosemarie; Cole, Trevor; Cook, Jackie; Paterson, Joan; Douglas, Fiona; Brewer, Carole; Hodgson, Shirley; Morrison, Patrick J.; Walker, Lisa; Rogers, Mark T.; Donaldson, Alan; Dorkins, Huw; Godwin, Andrew K.; Bove, Betsy; Stoppa-Lyonnet, Dominique; Houdayer, Claude; Buecher, Bruno; de Pauw, Antoine; Mazoyer, Sylvie; Calender, Alain; Leone, Melanie; Bressac-de Paillerets, Brigitte; Caron, Olivier; Sobol, Hagay; Frenay, Marc; Prieur, Fabienne; Ferrer, Sandra Fert; Mortemousque, Isabelle; Buys, Saundra; Daly, Mary; Miron, Alexander; Terry, Mary Beth; Hopper, John L.; John, Esther M.; Southey, Melissa; Goldgar, David; Singer, Christian F.; Fink-Retter, Anneliese; Tea, Muy-Kheng; Kaulich, Daphne Geschwantler; Hansen, Thomas V. O.; Nielsen, Finn C.; Barkardottir, Rosa B.; Gaudet, Mia; Kirchhoff, Tomas; Joseph, Vijai; Dutra-Clarke, Ana; Offit, Kenneth; Piedmonte, Marion; Kirk, Judy; Cohn, David; Hurteau, Jean; Byron, John; Fiorica, James; Toland, Amanda E.; Montagna, Marco; Oliani, Cristina; Imyanitov, Evgeny; Isaacs, Claudine; Tihomirova, Laima; Blanco, Ignacio; Lazaro, Conxi; Teule, Alex; Del Valle, J.; Gayther, Simon A.; Odunsi, Kunle; Gross, Jenny; Karlan, Beth Y.; Olah, Edith; Teo, Soo-Hwang; Ganz, Patricia A.; Beattie, Mary S.; Dorfling, Cecelia M.; van Rensburg, Elizabeth Jansen; Diez, Orland; Kwong, Ava; Schmutzler, Rita K.; Wappenschmidt, Barbara; Engel, Christoph; Meindl, Alfons; Ditsch, Nina; Arnold, Norbert; Heidemann, Simone; Niederacher, Dieter; Preisler-Adams, Sabine; Gadzicki, Dorothea; Varon-Mateeva, Raymonda; Deissler, Helmut; Gehrig, Andrea; Sutter, Christian; Kast, Karin; Fiebig, Britta; Schaefer, Dieter; Caldes, Trinidad; de la Hoya, Miguel; Nevanlinna, Heli; Muranen, Taru A.; Lesperance, Bernard; Spurdle, Amanda B.; Neuhausen, Susan L.; Ding, Yuan C.; Wang, Xianshu; Fredericksen, Zachary; Pankratz, Vernon S.; Lindor, Noralane M.; Peterlongo, Paolo; Manoukian, Siranoush; Peissel, Bernard; Zaffaroni, Daniela; Bonanni, Bernardo; Bernard, Loris; Dolcetti, Riccardo; Papi, Laura; Ottini, Laura; Radice, Paolo; Greene, Mark H.; Loud, Jennifer T.; Andrulis, Irene L.; Ozcelik, Hilmi; Mulligan, Anna Marie; Glendon, Gord; Thomassen, Mads; Gerdes, Anne-Marie; Jensen, Uffe B.; Skytte, Anne-Bine; Kruse, Torben A.; Chenevix-Trench, Georgia; Couch, Fergus J.; Simard, Jacques; Easton, Douglas F.

    2012-01-01

    Introduction: Several common alleles have been shown to be associated with breast and/or ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Recent genome-wide association studies of breast cancer have identified eight additional breast cancer susceptibility loci: rs1011970 (9p21, CDKN2A/B),

  7. Common variants at 12p11, 12q24, 9p21, 9q31.2 and in ZNF365 are associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers

    DEFF Research Database (Denmark)

    Antoniou, Antonis C; Kuchenbaecker, Karoline B; Soucy, Penny

    2012-01-01

    Several common alleles have been shown to be associated with breast and/or ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Recent genome-wide association studies of breast cancer have identified eight additional breast cancer susceptibility loci: rs1011970 (9p21, CDKN2A/B), rs10995190...

  8. A Novel Cryptic Three-Way Translocation t(2;9;18)(p23.2;p21.3;q21.33) with Deletion of Tumor Suppressor Genes in 9p21.3 and 13q14 in a T-Cell Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Othman, Moneeb A K; Rincic, Martina; Melo, Joana B; Carreira, Isabel M; Alhourani, Eyad; Hunstig, Friederike; Glaser, Anita; Liehr, Thomas

    2014-01-01

    Acute leukemia often presents with pure chromosomal resolution; thus, aberrations may not be detected by banding cytogenetics. Here, a case of 26-year-old male diagnosed with T-cell acute lymphoblastic leukemia (T-ALL) and a normal karyotype after standard GTG-banding was studied retrospectively in detail by molecular cytogenetic and molecular approaches. Besides fluorescence in situ hybridization (FISH), multiplex ligation-dependent probe amplification (MLPA) and high resolution array-comparative genomic hybridization (aCGH) were applied. Thus, cryptic chromosomal aberrations not observed before were detected: three chromosomes were involved in a cytogenetically balanced occurring translocation t(2;9;18)(p23.2;p21.3;q21.33). Besides a translocation t(10;14)(q24;q11) was identified, an aberration known to be common in T-ALL. Due to the three-way translocation deletion of tumor suppressor genes CDKN2A/INK4A/p16, CDKN2B/INK4B/p15, and MTAP/ARF/p14 in 9p21.3 took place. Additionally RB1 in 13q14 was deleted. This patient, considered to have a normal karyotype after low resolution banding cytogenetics, was treated according to general protocol of anticancer therapy (ALL-BFM 95).

  9. A Novel Cryptic Three-Way Translocation t(2;9;18(p23.2;p21.3;q21.33 with Deletion of Tumor Suppressor Genes in 9p21.3 and 13q14 in a T-Cell Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Moneeb A. K. Othman

    2014-01-01

    Full Text Available Acute leukemia often presents with pure chromosomal resolution; thus, aberrations may not be detected by banding cytogenetics. Here, a case of 26-year-old male diagnosed with T-cell acute lymphoblastic leukemia (T-ALL and a normal karyotype after standard GTG-banding was studied retrospectively in detail by molecular cytogenetic and molecular approaches. Besides fluorescence in situ hybridization (FISH, multiplex ligation-dependent probe amplification (MLPA and high resolution array-comparative genomic hybridization (aCGH were applied. Thus, cryptic chromosomal aberrations not observed before were detected: three chromosomes were involved in a cytogenetically balanced occurring translocation t(2;9;18(p23.2;p21.3;q21.33. Besides a translocation t(10;14(q24;q11 was identified, an aberration known to be common in T-ALL. Due to the three-way translocation deletion of tumor suppressor genes CDKN2A/INK4A/p16, CDKN2B/INK4B/p15, and MTAP/ARF/p14 in 9p21.3 took place. Additionally RB1 in 13q14 was deleted. This patient, considered to have a normal karyotype after low resolution banding cytogenetics, was treated according to general protocol of anticancer therapy (ALL-BFM 95.

  10. Chromosome

    Science.gov (United States)

    Chromosomes are structures found in the center (nucleus) of cells that carry long pieces of DNA. DNA ... is the building block of the human body. Chromosomes also contain proteins that help DNA exist in ...

  11. SNPs & indels Schizophyllum commune

    NARCIS (Netherlands)

    Nieuwenhuis, B.P.S.; Aanen, D.K.

    2013-01-01

    This description accompanies four files containing SNPs and indels found in two sets of isolates of Schizophyllum commune. This dataset was created for and used in Nieuwenhuis, Nieuwhof and Aanen (2013) On the asymmetry of mating in natural populations of the mushroom fungus Schizophyllum commune. F

  12. A new locus (SPG46) maps to 9p21.2-q21.12 in a Tunisian family with a complicated autosomal recessive hereditary spastic paraplegia with mental impairment and thin corpus callosum.

    Science.gov (United States)

    Boukhris, Amir; Feki, Imed; Elleuch, Nizar; Miladi, Mohamed Imed; Boland-Augé, Anne; Truchetto, Jérémy; Mundwiller, Emeline; Jezequel, Nadia; Zelenika, Diana; Mhiri, Chokri; Brice, Alexis; Stevanin, Giovanni

    2010-10-01

    Hereditary spastic paraplegia (HSP) with thin corpus callosum (TCC) and mental impairment is a frequent subtype of complicated HSP, often inherited as an autosomal recessive (AR) trait. It is clear from molecular genetic analyses that there are several underlying causes of this syndrome, with at least six genetic loci identified to date. However, SPG11 and SPG15 are the two major genes for this entity. To map the responsible gene in a large AR-HSP-TCC family of Tunisian origin, we investigated a consanguineous family with a diagnosis of AR-HSP-TCC excluded for linkage to the SPG7, SPG11, SPG15, SPG18, SPG21, and SPG32 loci. A genome-wide scan was undertaken using 6,090 SNP markers covering all chromosomes. The phenotypic presentation in five patients was suggestive of a complex HSP that associated an early-onset spastic paraplegia with mild handicap, mental deterioration, congenital cataract, cerebellar signs, and TCC. The genome-wide search identified a single candidate region on chromosome 9, exceeding the LOD score threshold of +3. Fine mapping using additional markers narrowed the candidate region to a 45.1-Mb interval (15.4 cM). Mutations in three candidate genes were excluded. The mapping of a novel AR-HSP-TCC locus further demonstrates the extensive genetic heterogeneity of this condition. We propose that testing for this locus should be performed, after exclusion of mutations in SPG11 and SPG15 genes, in AR-HSP-TCC families, especially when cerebellar ataxia and cataract are present.

  13. Genome bioinformatic analysis of nonsynonymous SNPs

    Directory of Open Access Journals (Sweden)

    Todd John A

    2007-08-01

    Full Text Available Abstract Background Genome-wide association studies of common diseases for common, low penetrance causal variants are underway. A proportion of these will alter protein sequences, the most common of which is the non-synonymous single nucleotide polymorphism (nsSNP. It would be an advantage if the functional effects of an nsSNP on protein structure and function could be predicted, both for the final identification process of a causal variant in a disease-associated chromosome region, and in further functional analyses of the nsSNP and its disease-associated protein. Results In the present report we have compared and contrasted structure- and sequence-based methods of prediction to over 5500 genes carrying nearly 24,000 nsSNPs, by employing an automatic comparative modelling procedure to build models for the genes. The nsSNP information came from two sources, the OMIM database which are rare (minor allele frequency, MAF, 0.05, have no known link to a disease. For over 40% of the nsSNPs, structure-based methods predicted which of these sequence changes are likely to either disrupt the structure of the protein or interfere with the function or interactions of the protein. For the remaining 60%, we generated sequence-based predictions. Conclusion We show that, in general, the prediction tools are able distinguish disease causing mutations from those mutations which are thought to have a neutral affect. We give examples of mutations in genes that are predicted to be deleterious and may have a role in disease. Contrary to previous reports, we also show that rare mutations are consistently predicted to be deleterious as often as commonly occurring nsSNPs.

  14. SNPs Array Karyotyping in Non-Hodgkin Lymphoma

    Directory of Open Access Journals (Sweden)

    Maryam Etebari

    2015-11-01

    Full Text Available The traditional methods for detection of chromosomal aberrations, which included cytogenetic or gene candidate solutions, suffered from low sensitivity or the need for previous knowledge of the target regions of the genome. With the advent of single nucleotide polymorphism (SNP arrays, genome screening at global level in order to find chromosomal aberrations like copy number variants, DNA amplifications, deletions, and also loss of heterozygosity became feasible. In this review, we present an update of the knowledge, gained by SNPs arrays, of the genomic complexity of the most important subtypes of non-Hodgkin lymphomas.

  15. Chromosomal imbalances in successive moments of human bladder urothelial carcinoma

    DEFF Research Database (Denmark)

    Nascimento e Pontes, Merielen Garcia; da Silveira, Sara Martorelli; Trindade Filho, José Carlos de Souza;

    2013-01-01

    in 16p12, in line with suggestions that these chromosome regions contain genes critical for urinary bladder carcinogenesis. Within a same patient, tumors and their respective recurrences showed common genomic losses and gains, which implies that the genomic profile acquired by primary tumors...... cells expressing the p53 protein, suggesting that the apparently normal urothelium was genomically unstable. No numerical alterations of the chromosomes 7, 17, and 9p21 region were found by FISH during the periods "free-of-neoplasia." Our data are informative for further studies to better understand...

  16. Testing SNPs and sets of SNPs for importance in association studies

    OpenAIRE

    Schwender, Holger; Ruczinski, Ingo; Ickstadt, Katja

    2010-01-01

    A major goal of genetic association studies concerned with single nucleotide polymorphisms (SNPs) is the detection of SNPs exhibiting an impact on the risk of developing a disease. Typically, this problem is approached by testing each of the SNPs individually. This, however, can lead to an inaccurate measurement of the influence of the SNPs on the disease risk, in particular, if SNPs only show an effect when interacting with other SNPs, as the multivariate structure of the data is ignored. In...

  17. Chromosome 9 ALS and FTD locus is probably derived from a single founder.

    Science.gov (United States)

    Mok, Kin; Traynor, Bryan J; Schymick, Jennifer; Tienari, Pentti J; Laaksovirta, Hannu; Peuralinna, Terhi; Myllykangas, Liisa; Chiò, Adriano; Shatunov, Aleksey; Boeve, Bradley F; Boxer, Adam L; DeJesus-Hernandez, Mariely; Mackenzie, Ian R; Waite, Adrian; Williams, Nigel; Morris, Huw R; Simón-Sánchez, Javier; van Swieten, John C; Heutink, Peter; Restagno, Gabriella; Mora, Gabriele; Morrison, Karen E; Shaw, Pamela J; Rollinson, Pamela Sara; Al-Chalabi, Ammar; Rademakers, Rosa; Pickering-Brown, Stuart; Orrell, Richard W; Nalls, Michael A; Hardy, John

    2012-01-01

    We and others have recently reported an association between amyotrophic lateral sclerosis (ALS) and single nucleotide polymorphisms on chromosome 9p21 in several populations. Here we show that the associated haplotype is the same in all populations and that several families previously shown to have genetic linkage to this region also share this haplotype. The most parsimonious explanation of these data are that there is a single founder for this form of disease.

  18. How well do HapMap SNPs capture the untyped SNPs?

    Directory of Open Access Journals (Sweden)

    Yang Yuchen

    2006-09-01

    Full Text Available Abstract Background The recent advancement in human genome sequencing and genotyping has revealed millions of single nucleotide polymorphisms (SNP which determine the variation among human beings. One of the particular important projects is The International HapMap Project which provides the catalogue of human genetic variation for disease association studies. In this paper, we analyzed the genotype data in HapMap project by using National Institute of Environmental Health Sciences Environmental Genome Project (NIEHS EGP SNPs. We first determine whether the HapMap data are transferable to the NIEHS data. Then, we study how well the HapMap SNPs capture the untyped SNPs in the region. Finally, we provide general guidelines for determining whether the SNPs chosen from HapMap may be able to capture most of the untyped SNPs. Results Our analysis shows that HapMap data are not robust enough to capture the untyped variants for most of the human genes. The performance of SNPs for European and Asian samples are marginal in capturing the untyped variants, i.e. approximately 55%. Expectedly, the SNPs from HapMap YRI panel can only capture approximately 30% of the variants. Although the overall performance is low, however, the SNPs for some genes perform very well and are able to capture most of the variants along the gene. This is observed in the European and Asian panel, but not in African panel. Through observation, we concluded that in order to have a well covered SNPs reference panel, the SNPs density and the association among reference SNPs are important to estimate the robustness of the chosen SNPs. Conclusion We have analyzed the coverage of HapMap SNPs using NIEHS EGP data. The results show that HapMap SNPs are transferable to the NIEHS SNPs. However, HapMap SNPs cannot capture some of the untyped SNPs and therefore resequencing may be needed to uncover more SNPs in the missing region.

  19. The hare and the tortoise: one small step for four SNPs, one giant leap for SNP-kind

    Science.gov (United States)

    Xue, Yali; Tyler-Smith, Chris

    2012-01-01

    A recently-published study has used next-gen sequencing technology to resequence two Y chromosomes separated by 13 generations and discovered four single-base differences in ~10 Mb DNA, suggesting that the Y chromosome euchromatin accumulates around one mutation per generation. Y-SNPs therefore now offer the best resolution of Y haplotypes and promise to distinguish almost every Y chromosome. This work illustrates the promise of current sequencing technology for forensically-relevant applications. PMID:20129461

  20. Gene expression meta-analysis identifies chromosomal regions involved in ovarian cancer survival

    DEFF Research Database (Denmark)

    Thomassen, Mads; Jochumsen, Kirsten M; Mogensen, Ole;

    2009-01-01

    the relation of gene expression and chromosomal position to identify chromosomal regions of importance for early recurrence of ovarian cancer. By use of *Gene Set Enrichment Analysis*, we have ranked chromosomal regions according to their association to survival. Over-representation analysis including 1......Ovarian cancer cells exhibit complex karyotypic alterations causing deregulation of numerous genes. Some of these genes are probably causal for cancer formation and local growth, whereas others are causal for metastasis and recurrence. By using publicly available data sets, we have investigated......-4 consecutive cytogenetic bands identified regions with increased expression for chromosome 5q12-14, and a very large region of chromosome 7 with the strongest signal at 7p15-13 among tumors from short-living patients. Reduced gene expression was identified at 4q26-32, 6p12-q15, 9p21-q32, and 11p14-11. We...

  1. A new translocation between chromosomes 6 and 9 helps to establish diagnosis of renal oncocytoma.

    Science.gov (United States)

    Hudacko, Rachel; May, Michael; Aviv, Hana

    2011-08-01

    Renal oncocytomas are benign epithelial tumors of the kidney. Histologically, they resemble certain malignant renal tumors, such as chromophobe renal cell carcinoma and the eosinophilic or granular form of clear cell renal carcinoma. It is, therefore, important to be able to differentiate among these tumors. Cytogenetic analysis is an important adjunct to the diagnosis of renal tumors, as the various subtypes have specific acquired chromosome abnormalities. Oncocytomas present either with loss of chromosome 1 and a sex chromosome, or with recurring translocations involving chromosome 11. We describe 2 patients with renal oncocytoma and a new translocation between chromosomes 6 and 9. The tumors in both patients were histologically virtually identical. The t(6;9)(p21;p23) may be a new translocation associated with renal oncocytomas.

  2. SNPs and MALDI-TOF MS: tools for DNA typing in forensic paternity testing and anthropology.

    Science.gov (United States)

    Petkovski, Elizabet; Keyser-Tracqui, Christine; Hienne, Rémi; Ludes, Bertrand

    2005-05-01

    DNA markers used for individual identification in forensic sciences are based on repeat sequences in nuclear DNA and the mitochondrial DNA hypervariable regions 1 and 2. An alternative to these markers is the use of single nucleotide polymorphisms (SNPs). These have a particular advantage in the analysis of degraded or poor samples, which are often all that is available in forensics or anthropology. In order to study the potential of SNP analysis in these fields, 41 SNPs were selected on the basis of following criteria: conservation, lack of phenotypic expression, and frequency of occurrence in populations. Thirty-six autosomal SNPs were used for genotyping 21 inclusionary and 3 exclusionary paternity cases. The behavior of 5 X-chromosome SNPs was analyzed in a French representative population. Our approach to SNP typing is a multiplex PCR based amplification followed by simultaneous detection by primer extension (PEX) analyzed by Matrix Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS). The selected autosomal SNPs showed independent inheritance and gave clear results in paternity investigation. All X-SNPs were useful as both paternity and identification markers. PEX and MALDI-TOF MS, with their high sensitivity, precision and speed, gave a powerful method for forensic and anthropological exploitation of biallelic markers.

  3. V-MitoSNP: visualization of human mitochondrial SNPs

    Directory of Open Access Journals (Sweden)

    Tsui Ke-Hung

    2006-08-01

    Full Text Available Abstract Background Mitochondrial single nucleotide polymorphisms (mtSNPs constitute important data when trying to shed some light on human diseases and cancers. Unfortunately, providing relevant mtSNP genotyping information in mtDNA databases in a neatly organized and transparent visual manner still remains a challenge. Amongst the many methods reported for SNP genotyping, determining the restriction fragment length polymorphisms (RFLPs is still one of the most convenient and cost-saving methods. In this study, we prepared the visualization of the mtDNA genome in a way, which integrates the RFLP genotyping information with mitochondria related cancers and diseases in a user-friendly, intuitive and interactive manner. The inherent problem associated with mtDNA sequences in BLAST of the NCBI database was also solved. Description V-MitoSNP provides complete mtSNP information for four different kinds of inputs: (1 color-coded visual input by selecting genes of interest on the genome graph, (2 keyword search by locus, disease and mtSNP rs# ID, (3 visualized input of nucleotide range by clicking the selected region of the mtDNA sequence, and (4 sequences mtBLAST. The V-MitoSNP output provides 500 bp (base pairs flanking sequences for each SNP coupled with the RFLP enzyme and the corresponding natural or mismatched primer sets. The output format enables users to see the SNP genotype pattern of the RFLP by virtual electrophoresis of each mtSNP. The rate of successful design of enzymes and primers for RFLPs in all mtSNPs was 99.1%. The RFLP information was validated by actual agarose electrophoresis and showed successful results for all mtSNPs tested. The mtBLAST function in V-MitoSNP provides the gene information within the input sequence rather than providing the complete mitochondrial chromosome as in the NCBI BLAST database. All mtSNPs with rs number entries in NCBI are integrated in the corresponding SNP in V-MitoSNP. Conclusion V-MitoSNP is a web

  4. Novel and efficient tag SNPs selection algorithms.

    Science.gov (United States)

    Chen, Wen-Pei; Hung, Che-Lun; Tsai, Suh-Jen Jane; Lin, Yaw-Ling

    2014-01-01

    SNPs are the most abundant forms of genetic variations amongst species; the association studies between complex diseases and SNPs or haplotypes have received great attention. However, these studies are restricted by the cost of genotyping all SNPs; thus, it is necessary to find smaller subsets, or tag SNPs, representing the rest of the SNPs. In fact, the existing tag SNP selection algorithms are notoriously time-consuming. An efficient algorithm for tag SNP selection was presented, which was applied to analyze the HapMap YRI data. The experimental results show that the proposed algorithm can achieve better performance than the existing tag SNP selection algorithms; in most cases, this proposed algorithm is at least ten times faster than the existing methods. In many cases, when the redundant ratio of the block is high, the proposed algorithm can even be thousands times faster than the previously known methods. Tools and web services for haplotype block analysis integrated by hadoop MapReduce framework are also developed using the proposed algorithm as computation kernels.

  5. Utilizing HapMap and tagging SNPs.

    Science.gov (United States)

    Haiman, Christopher A; Stram, Daniel O

    2008-01-01

    Advancements in our understanding of variation in the human genome and rapid improvements in high-throughput genotyping technology have made it feasible to study most of the human genetic diversity that is due to common variations in relation to observable phenotypes. Over the past few years, public SNP databases have matured and empirical genome-wide SNP data, such as that generated by the International HapMap Project, have shown the utility and efficiency of selecting and testing informative markers ("tag SNPs") that exploit redundancies among nearby polymorphisms due to linkage disequilibrium (LD). In this chapter, we will demonstrate how to use the HapMap resource and the Haploview program to process and analyze genetic data from HapMap, to evaluate LD relations between SNPs, and to select tagging SNPs to be examined in disease association studies.

  6. An evaluation of the performance of tag SNPs derived from HapMap in a Caucasian population.

    Directory of Open Access Journals (Sweden)

    2006-03-01

    Full Text Available The Haplotype Map (HapMap project recently generated genotype data for more than 1 million single-nucleotide polymorphisms (SNPs in four population samples. The main application of the data is in the selection of tag single-nucleotide polymorphisms (tSNPs to use in association studies. The usefulness of this selection process needs to be verified in populations outside those used for the HapMap project. In addition, it is not known how well the data represent the general population, as only 90-120 chromosomes were used for each population and since the genotyped SNPs were selected so as to have high frequencies. In this study, we analyzed more than 1,000 individuals from Estonia. The population of this northern European country has been influenced by many different waves of migrations from Europe and Russia. We genotyped 1,536 randomly selected SNPs from two 500-kbp ENCODE regions on Chromosome 2. We observed that the tSNPs selected from the CEPH (Centre d'Etude du Polymorphisme Humain from Utah (CEU HapMap samples (derived from US residents with northern and western European ancestry captured most of the variation in the Estonia sample. (Between 90% and 95% of the SNPs with a minor allele frequency of more than 5% have an r2 of at least 0.8 with one of the CEU tSNPs. Using the reverse approach, tags selected from the Estonia sample could almost equally well describe the CEU sample. Finally, we observed that the sample size, the allelic frequency, and the SNP density in the dataset used to select the tags each have important effects on the tagging performance. Overall, our study supports the use of HapMap data in other Caucasian populations, but the SNP density and the bias towards high-frequency SNPs have to be taken into account when designing association studies.

  7. An evaluation of the performance of tag SNPs derived from HapMap in a Caucasian population.

    Science.gov (United States)

    Montpetit, Alexandre; Nelis, Mari; Laflamme, Philippe; Magi, Reedik; Ke, Xiayi; Remm, Maido; Cardon, Lon; Hudson, Thomas J; Metspalu, Andres

    2006-03-01

    The Haplotype Map (HapMap) project recently generated genotype data for more than 1 million single-nucleotide polymorphisms (SNPs) in four population samples. The main application of the data is in the selection of tag single-nucleotide polymorphisms (tSNPs) to use in association studies. The usefulness of this selection process needs to be verified in populations outside those used for the HapMap project. In addition, it is not known how well the data represent the general population, as only 90-120 chromosomes were used for each population and since the genotyped SNPs were selected so as to have high frequencies. In this study, we analyzed more than 1,000 individuals from Estonia. The population of this northern European country has been influenced by many different waves of migrations from Europe and Russia. We genotyped 1,536 randomly selected SNPs from two 500-kbp ENCODE regions on Chromosome 2. We observed that the tSNPs selected from the CEPH (Centre d'Etude du Polymorphisme Humain) from Utah (CEU) HapMap samples (derived from US residents with northern and western European ancestry) captured most of the variation in the Estonia sample. (Between 90% and 95% of the SNPs with a minor allele frequency of more than 5% have an r2 of at least 0.8 with one of the CEU tSNPs.) Using the reverse approach, tags selected from the Estonia sample could almost equally well describe the CEU sample. Finally, we observed that the sample size, the allelic frequency, and the SNP density in the dataset used to select the tags each have important effects on the tagging performance. Overall, our study supports the use of HapMap data in other Caucasian populations, but the SNP density and the bias towards high-frequency SNPs have to be taken into account when designing association studies.

  8. Co-regulated transcripts associated to cooperating eSNPs define Bi-fan motifs in human gene networks.

    Directory of Open Access Journals (Sweden)

    Anat Kreimer

    2014-09-01

    Full Text Available Associations between the level of single transcripts and single corresponding genetic variants, expression single nucleotide polymorphisms (eSNPs, have been extensively studied and reported. However, most expression traits are complex, involving the cooperative action of multiple SNPs at different loci affecting multiple genes. Finding these cooperating eSNPs by exhaustive search has proven to be statistically challenging. In this paper we utilized availability of sequencing data with transcriptional profiles in the same cohorts to identify two kinds of usual suspects: eSNPs that alter coding sequences or eSNPs within the span of transcription factors (TFs. We utilize a computational framework for considering triplets, each comprised of a SNP and two associated genes. We examine pairs of triplets with such cooperating source eSNPs that are both associated with the same pair of target genes. We characterize such quartets through their genomic, topological and functional properties. We establish that this regulatory structure of cooperating quartets is frequent in real data, but is rarely observed in permutations. eSNP sources are mostly located on different chromosomes and away from their targets. In the majority of quartets, SNPs affect the expression of the two gene targets independently of one another, suggesting a mutually independent rather than a directionally dependent effect. Furthermore, the directions in which the minor allele count of the SNP affects gene expression within quartets are consistent, so that the two source eSNPs either both have the same effect on the target genes or both affect one gene in the opposite direction to the other. Same-effect eSNPs are observed more often than expected by chance. Cooperating quartets reported here in a human system might correspond to bi-fans, a known network motif of four nodes previously described in model organisms. Overall, our analysis offers insights regarding the fine motif structure

  9. Restriction enzyme mining for SNPs in genomes.

    Science.gov (United States)

    Chuang, Li-Yeh; Yang, Cheng-Hong; Tsui, Ke-Hung; Cheng, Yu-Huei; Chang, Phei-Lang; Wen, Cheng-Hao; Chang, Hsueh-Wei

    2008-01-01

    Many different single nucleotide polymorphisms (SNPs) genotyping methods have been developed recently. However, most of them are expensive. Using restriction enzymes for SNP genotyping is a cost-effective method. However, restriction enzyme mining for SNPs in a genome sequence is still challenging for researchers who do not have a background in genomics and bioinformatics. In this review, the basic bioinformatics tools used for restriction enzyme mining for SNP genotyping are summarized and described. The objectives of this paper include: i) the introduction of SNPs, genotyping and PCR-restriction fragment length polymorphism (RFLP); ii) a review of components for genotyping software, including tools for primer design only or restriction enzyme mining only; iii) a review of software providing the flanking sequence for primer design; iv) recent advances in PCR-RFLP tools and natural and mutagenic PCR-RFLP; v) highlighting the strategy for restriction enzyme mining for SNP genotyping; vi) a discussion of potential problems for multiple PCR-RFLP. The different implications for restriction enzymes on sense and antisense strands are also discussed. Our PCR-RFLP freeware, SNP-RFLPing, is included in this review to illustrate many characteristics of PCR-RFLP software design. Future developments will include further sophistication of PCR-RFLP software in order to provide better visualization and a more interactive environment for SNP genotyping and to integrate the software with other tools used in association studies.

  10. Human SNPs resulting in premature stop codons and protein truncation

    OpenAIRE

    Savas Sevtap; Tuzmen Sukru; Ozcelik Hilmi

    2006-01-01

    Abstract Single nucleotide polymorphisms (SNPs) constitute the most common type of genetic variation in humans. SNPs introducing premature termination codons (PTCs), herein called X-SNPs, can alter the stability and function of transcripts and proteins and thus are considered to be biologically important. Initial studies suggested a strong selection against such variations/mutations. In this study, we undertook a genome-wide systematic screening to identify human X-SNPs using the dbSNP databa...

  11. Marker chromosomes.

    Science.gov (United States)

    Rao, Kiran Prabhaker; Belogolovkin, Victoria

    2013-04-01

    Marker chromosomes are a morphologically heterogeneous group of structurally abnormal chromosomes that pose a significant challenge in prenatal diagnosis. Phenotypes associated with marker chromosomes are highly variable and range from normal to severely abnormal. Clinical outcomes are very difficult to predict when marker chromosomes are detected prenatally. In this review, we outline the classification, etiology, cytogenetic characterization, and clinical consequences of marker chromosomes, as well as practical approaches to prenatal diagnosis and genetic counseling.

  12. Estimating the proportion of variation in susceptibility to schizophrenia captured by common SNPs

    DEFF Research Database (Denmark)

    Lee, S Hong; DeCandia, Teresa R; Ripke, Stephan;

    2012-01-01

    of schizophrenia is the same in males and females, and that a disproportionate proportion of variation is attributable to a set of 2,725 genes expressed in the central nervous system (CNS; P = 7.6 × 10(-8)). These results are consistent with a polygenic genetic architecture and imply more individual SNP......Schizophrenia is a complex disorder caused by both genetic and environmental factors. Using 9,087 affected individuals, 12,171 controls and 915,354 imputed SNPs from the Schizophrenia Psychiatric Genome-Wide Association Study (GWAS) Consortium (PGC-SCZ), we estimate that 23% (s.e. = 1......%) of variation in liability to schizophrenia is captured by SNPs. We show that a substantial proportion of this variation must be the result of common causal variants, that the variance explained by each chromosome is linearly related to its length (r = 0.89, P = 2.6 × 10(-8)), that the genetic basis...

  13. Multiple ant colony algorithm method for selecting tag SNPs.

    Science.gov (United States)

    Liao, Bo; Li, Xiong; Zhu, Wen; Li, Renfa; Wang, Shulin

    2012-10-01

    The search for the association between complex disease and single nucleotide polymorphisms (SNPs) or haplotypes has recently received great attention. Finding a set of tag SNPs for haplotyping in a great number of samples is an important step to reduce cost for association study. Therefore, it is essential to select tag SNPs with more efficient algorithms. In this paper, we model problem of selection tag SNPs by MINIMUM TEST SET and use multiple ant colony algorithm (MACA) to search a smaller set of tag SNPs for haplotyping. The various experimental results on various datasets show that the running time of our method is less than GTagger and MLR. And MACA can find the most representative SNPs for haplotyping, so that MACA is more stable and the number of tag SNPs is also smaller than other evolutionary methods (like GTagger and NSGA-II). Our software is available upon request to the corresponding author.

  14. New native South American Y chromosome lineages.

    Science.gov (United States)

    Jota, Marilza S; Lacerda, Daniela R; Sandoval, José R; Vieira, Pedro Paulo R; Ohasi, Dominique; Santos-Júnior, José E; Acosta, Oscar; Cuellar, Cinthia; Revollo, Susana; Paz-Y-Miño, Cesar; Fujita, Ricardo; Vallejo, Gustavo A; Schurr, Theodore G; Tarazona-Santos, Eduardo M; Pena, Sergio Dj; Ayub, Qasim; Tyler-Smith, Chris; Santos, Fabrício R

    2016-07-01

    Many single-nucleotide polymorphisms (SNPs) in the non-recombining region of the human Y chromosome have been described in the last decade. High-coverage sequencing has helped to characterize new SNPs, which has in turn increased the level of detail in paternal phylogenies. However, these paternal lineages still provide insufficient information on population history and demography, especially for Native Americans. The present study aimed to identify informative paternal sublineages derived from the main founder lineage of the Americas-haplogroup Q-L54-in a sample of 1841 native South Americans. For this purpose, we used a Y-chromosomal genotyping multiplex platform and conventional genotyping methods to validate 34 new SNPs that were identified in the present study by sequencing, together with many Y-SNPs previously described in the literature. We updated the haplogroup Q phylogeny and identified two new Q-M3 and three new Q-L54*(xM3) sublineages defined by five informative SNPs, designated SA04, SA05, SA02, SA03 and SA29. Within the Q-M3, sublineage Q-SA04 was mostly found in individuals from ethnic groups belonging to the Tukanoan linguistic family in the northwest Amazon, whereas sublineage Q-SA05 was found in Peruvian and Bolivian Amazon ethnic groups. Within Q-L54*, the derived sublineages Q-SA03 and Q-SA02 were exclusively found among Coyaima individuals (Cariban linguistic family) from Colombia, while Q-SA29 was found only in Maxacali individuals (Jean linguistic family) from southeast Brazil. Furthermore, we validated the usefulness of several published SNPs among indigenous South Americans. This new Y chromosome haplogroup Q phylogeny offers an informative paternal genealogy to investigate the pre-Columbian history of South America.Journal of Human Genetics advance online publication, 31 March 2016; doi:10.1038/jhg.2016.26.

  15. Chromosomal and Genetic Analysis of a Human Lung Adenocarcinoma Cell Line OM

    Institute of Scientific and Technical Information of China (English)

    Yong-Wu Li; Lin Bai; Lyu-Xia Dai; Xu He; Xian-Ping Zhou

    2016-01-01

    Background: Lung cancer has become the leading cause of death in many regions.Carcinogenesis is caused by the stepwise accumulation of genetic and chromosomal changes.The aim of this study was to investigate the chromosome and gene alterations in the human lung adenocarcinoma cell line OM.Methods: We used Giemsa banding and multiplex fluorescence in situ hybridization focusing on the human lung adenocarcinoma cell line OM to analyze its chromosome alterations.In addition, the gains and losses in the specific chromosome regions were identified by comparative genomic hybridization (CGH) and the amplifications of cancer-related genes were also detected by polymerase chain reaction (PCR).Results: We identified a large number of chromosomal numerical alterations on all chromosomes except chromosome X and 19.Chromosome 10 is the most frequently involved in translocations with six different interchromosomal translocations.CGH revealed the gains on chromosome regions of 3q25.3-28, 5p13, 12q22-23.24, and the losses on 3p25-26, 6p25, 6q26-27, 7q34-36, 8p22-23, 9p21-24, 10q25-26.3, 12p 13.31-13.33 and 17p 13.1-13.3.And PCR showed the amplification of genes: Membrane metalloendopeptidase (MME), sucrase-isomaltase (SI), butyrylcholinesterase (BCHE), and kininogen (KNG).Conclusions: The lung adenocarcinoma cell line OM exhibited multiple complex karyotypes, and chromosome 10 was frequently involved in chromosomal translocation, which may play key roles in tumorigenesis.We speculated that the oncogenes may be located at 3q25.3-28, 5p13, 12q22-23.24, while tumor suppressor genes may exist in 3p25-26, 6p25, 6q26-27, 7q34-36, 8p22-23, 9p21-24, 10q25-26.3, 12p 13.31-13.33, and 17p 13.1-13.3.Moreover, at least four genes (MME, SI, BCHE, and KNG) may be involved in the human lung adenocarcinoma cell line OM.

  16. A functional link between FOXA1 and breast cancer SNPs

    OpenAIRE

    Katika, Madhumohan R; Hurtado, Antoni

    2013-01-01

    Genome-wide association studies have revealed a multitude of breast cancer-associated SNPs. The majority of these SNPs are located in noncoding regions of the genome. Yet how they contribute to breast cancer development is unknown. Recently, a groundbreaking study by the Lupien group has shown that risk-associated SNPs of breast cancer are enriched for FOXA1 binding sites, which influences the function of this transcription factor.

  17. Consortium analysis of 7 candidate SNPs for ovarian cancer

    DEFF Research Database (Denmark)

    Ramus, S.J.; Vierkant, R.A.; Johnatty, S.E.

    2008-01-01

    The Ovarian Cancer Association Consortium selected 7 candidate single nucleotide polymorphisms (SNPs), for which there is evidence from previous studies of an association with variation in ovarian cancer or breast cancer risks. The SNPs selected for analysis were F31I (rs2273535) in AURKA, N372H...... for SNPs identified from relatively large initial studies shows the importance of replicating associations by a consortium approach Udgivelsesdato: 2008/7/15...

  18. Identification of Pyrus single nucleotide polymorphisms (SNPs) and evaluation for genetic mapping in European pear and interspecific Pyrus hybrids.

    Science.gov (United States)

    Montanari, Sara; Saeed, Munazza; Knäbel, Mareike; Kim, YoonKyeong; Troggio, Michela; Malnoy, Mickael; Velasco, Riccardo; Fontana, Paolo; Won, KyungHo; Durel, Charles-Eric; Perchepied, Laure; Schaffer, Robert; Wiedow, Claudia; Bus, Vincent; Brewer, Lester; Gardiner, Susan E; Crowhurst, Ross N; Chagné, David

    2013-01-01

    We have used new generation sequencing (NGS) technologies to identify single nucleotide polymorphism (SNP) markers from three European pear (Pyrus communis L.) cultivars and subsequently developed a subset of 1096 pear SNPs into high throughput markers by combining them with the set of 7692 apple SNPs on the IRSC apple Infinium® II 8K array. We then evaluated this apple and pear Infinium® II 9K SNP array for large-scale genotyping in pear across several species, using both pear and apple SNPs. The segregating populations employed for array validation included a segregating population of European pear ('Old Home'×'Louise Bon Jersey') and four interspecific breeding families derived from Asian (P. pyrifolia Nakai and P. bretschneideri Rehd.) and European pear pedigrees. In total, we mapped 857 polymorphic pear markers to construct the first SNP-based genetic maps for pear, comprising 78% of the total pear SNPs included in the array. In addition, 1031 SNP markers derived from apple (13% of the total apple SNPs included in the array) were polymorphic and were mapped in one or more of the pear populations. These results are the first to demonstrate SNP transferability across the genera Malus and Pyrus. Our construction of high density SNP-based and gene-based genetic maps in pear represents an important step towards the identification of chromosomal regions associated with a range of horticultural characters, such as pest and disease resistance, orchard yield and fruit quality.

  19. Identification of Pyrus single nucleotide polymorphisms (SNPs and evaluation for genetic mapping in European pear and interspecific Pyrus hybrids.

    Directory of Open Access Journals (Sweden)

    Sara Montanari

    Full Text Available We have used new generation sequencing (NGS technologies to identify single nucleotide polymorphism (SNP markers from three European pear (Pyrus communis L. cultivars and subsequently developed a subset of 1096 pear SNPs into high throughput markers by combining them with the set of 7692 apple SNPs on the IRSC apple Infinium® II 8K array. We then evaluated this apple and pear Infinium® II 9K SNP array for large-scale genotyping in pear across several species, using both pear and apple SNPs. The segregating populations employed for array validation included a segregating population of European pear ('Old Home'×'Louise Bon Jersey' and four interspecific breeding families derived from Asian (P. pyrifolia Nakai and P. bretschneideri Rehd. and European pear pedigrees. In total, we mapped 857 polymorphic pear markers to construct the first SNP-based genetic maps for pear, comprising 78% of the total pear SNPs included in the array. In addition, 1031 SNP markers derived from apple (13% of the total apple SNPs included in the array were polymorphic and were mapped in one or more of the pear populations. These results are the first to demonstrate SNP transferability across the genera Malus and Pyrus. Our construction of high density SNP-based and gene-based genetic maps in pear represents an important step towards the identification of chromosomal regions associated with a range of horticultural characters, such as pest and disease resistance, orchard yield and fruit quality.

  20. Forensic usefulness of a 25 X-chromosome single-nucleotide polymorphism marker set

    DEFF Research Database (Denmark)

    Tomas, Carmen; Sanchez, Juan J; Castro, Jose Aurelio

    2010-01-01

    BACKGROUND: The analysis of X-chromosome markers can be valuable in particular situations, for example, deficiency kinship cases, where the putative father cannot be typed. X-chromosome short-tandem repeats (X-STRs) are widely used in forensic genetics, while the use of X-chromosome single....... The usefulness of X-chromosome markers was particularly illustrative in Case 1, where the typing of 25 X-SNPs would have been sufficient to exclude paternity. CONCLUSION: The high level of polymorphism, low degree of linkage disequilibrium, and very low probability of mutation of the 25 X-SNPs makes this set...

  1. The molecular marker for new type--SNPs%新型的分子标记--SNPs

    Institute of Scientific and Technical Information of China (English)

    吴春太; 叶水英; 李雄; 方团

    2003-01-01

    SNPs(Single nucleotide polymorphisms)是近年来发展起来的最有效的新一代分子标记.本文对SNPs的发展、基本原理、检测,以及在确定疾病相关基因研究中的应用进行了介绍和评述.

  2. Performance of random forest when SNPs are in linkage disequilibrium

    Directory of Open Access Journals (Sweden)

    Cupples L Adrienne

    2009-03-01

    Full Text Available Abstract Background Single nucleotide polymorphisms (SNPs may be correlated due to linkage disequilibrium (LD. Association studies look for both direct and indirect associations with disease loci. In a Random Forest (RF analysis, correlation between a true risk SNP and SNPs in LD may lead to diminished variable importance for the true risk SNP. One approach to address this problem is to select SNPs in linkage equilibrium (LE for analysis. Here, we explore alternative methods for dealing with SNPs in LD: change the tree-building algorithm by building each tree in an RF only with SNPs in LE, modify the importance measure (IM, and use haplotypes instead of SNPs to build a RF. Results We evaluated the performance of our alternative methods by simulation of a spectrum of complex genetics models. When a haplotype rather than an individual SNP is the risk factor, we find that the original Random Forest method performed on SNPs provides good performance. When individual, genotyped SNPs are the risk factors, we find that the stronger the genetic effect, the stronger the effect LD has on the performance of the original RF. A revised importance measure used with the original RF is relatively robust to LD among SNPs; this revised importance measure used with the revised RF is sometimes inflated. Overall, we find that the revised importance measure used with the original RF is the best choice when the genetic model and the number of SNPs in LD with risk SNPs are unknown. For the haplotype-based method, under a multiplicative heterogeneity model, we observed a decrease in the performance of RF with increasing LD among the SNPs in the haplotype. Conclusion Our results suggest that by strategically revising the Random Forest method tree-building or importance measure calculation, power can increase when LD exists between SNPs. We conclude that the revised Random Forest method performed on SNPs offers an advantage of not requiring genotype phase, making it a

  3. Transposon Insertions, Structural Variations, and SNPs Contribute to the Evolution of the Melon Genome.

    Science.gov (United States)

    Sanseverino, Walter; Hénaff, Elizabeth; Vives, Cristina; Pinosio, Sara; Burgos-Paz, William; Morgante, Michele; Ramos-Onsins, Sebastián E; Garcia-Mas, Jordi; Casacuberta, Josep Maria

    2015-10-01

    The availability of extensive databases of crop genome sequences should allow analysis of crop variability at an unprecedented scale, which should have an important impact in plant breeding. However, up to now the analysis of genetic variability at the whole-genome scale has been mainly restricted to single nucleotide polymorphisms (SNPs). This is a strong limitation as structural variation (SV) and transposon insertion polymorphisms are frequent in plant species and have had an important mutational role in crop domestication and breeding. Here, we present the first comprehensive analysis of melon genetic diversity, which includes a detailed analysis of SNPs, SV, and transposon insertion polymorphisms. The variability found among seven melon varieties representing the species diversity and including wild accessions and highly breed lines, is relatively high due in part to the marked divergence of some lineages. The diversity is distributed nonuniformly across the genome, being lower at the extremes of the chromosomes and higher in the pericentromeric regions, which is compatible with the effect of purifying selection and recombination forces over functional regions. Additionally, this variability is greatly reduced among elite varieties, probably due to selection during breeding. We have found some chromosomal regions showing a high differentiation of the elite varieties versus the rest, which could be considered as strongly selected candidate regions. Our data also suggest that transposons and SV may be at the origin of an important fraction of the variability in melon, which highlights the importance of analyzing all types of genetic variability to understand crop genome evolution.

  4. Genomics and introgression: discovery and mapping of thousands of species-diagnostic SNPs using RAD sequencing

    Science.gov (United States)

    Hand, Brian K; Hether, Tyler D; Kovach, Ryan P.; Muhlfeld, Clint C.; Amish, Stephen J.; Boyer, Matthew C.; O’Rourke, Sean M.; Miller, Michael R.; Lowe, Winsor H.; Hohenlohe, Paul A.; Luikart, Gordon

    2015-01-01

    Invasive hybridization and introgression pose a serious threat to the persistence of many native species. Understanding the effects of hybridization on native populations (e.g., fitness consequences) requires numerous species-diagnostic loci distributed genome-wide. Here we used RAD sequencing to discover thousands of single-nucleotide polymorphisms (SNPs) that are diagnostic between rainbow trout (RBT, Oncorhynchus mykiss), the world’s most widely introduced fish, and native westslope cutthroat trout (WCT, O. clarkii lewisi) in the northern Rocky Mountains, USA. We advanced previous work that identified 4,914 species-diagnostic loci by using longer sequence reads (100 bp vs. 60 bp) and a larger set of individuals (n = 84). We sequenced RAD libraries for individuals from diverse sampling sources, including native populations of WCT and hatchery broodstocks of WCT and RBT. We also took advantage of a newly released reference genome assembly for RBT to align our RAD loci. In total, we discovered 16,788 putatively diagnostic SNPs, 10,267 of which we mapped to anchored chromosome locations on the RBT genome. A small portion of previously discovered putative diagnostic loci (325 of 4,914) were no longer diagnostic (i.e., fixed between species) based on our wider survey of non-hybridized RBT and WCT individuals. Our study suggests that RAD loci mapped to a draft genome assembly could provide the marker density required to identify genes and chromosomal regions influencing selection in admixed populations of conservation concern and evolutionary interest.

  5. High throughput sequencing in mice: a platform comparison identifies a preponderance of cryptic SNPs

    Directory of Open Access Journals (Sweden)

    Darakjian Priscila

    2009-08-01

    Full Text Available Abstract Background Allelic variation is the cornerstone of genetically determined differences in gene expression, gene product structure, physiology, and behavior. However, allelic variation, particularly cryptic (unknown or not annotated variation, is problematic for follow up analyses. Polymorphisms result in a high incidence of false positive and false negative results in hybridization based analyses and hinder the identification of the true variation underlying genetically determined differences in physiology and behavior. Given the proliferation of mouse genetic models (e.g., knockout models, selectively bred lines, heterogeneous stocks derived from standard inbred strains and wild mice and the wealth of gene expression microarray and phenotypic studies using genetic models, the impact of naturally-occurring polymorphisms on these data is critical. With the advent of next-generation, high-throughput sequencing, we are now in a position to determine to what extent polymorphisms are currently cryptic in such models and their impact on downstream analyses. Results We sequenced the two most commonly used inbred mouse strains, DBA/2J and C57BL/6J, across a region of chromosome 1 (171.6 – 174.6 megabases using two next generation high-throughput sequencing platforms: Applied Biosystems (SOLiD and Illumina (Genome Analyzer. Using the same templates on both platforms, we compared realignments and single nucleotide polymorphism (SNP detection with an 80 fold average read depth across platforms and samples. While public datasets currently annotate 4,527 SNPs between the two strains in this interval, thorough high-throughput sequencing identified a total of 11,824 SNPs in the interval, including 7,663 new SNPs. Furthermore, we confirmed 40 missense SNPs and discovered 36 new missense SNPs. Conclusion Comparisons utilizing even two of the best characterized mouse genetic models, DBA/2J and C57BL/6J, indicate that more than half of naturally

  6. Evaluating the transferability of Hapmap SNPs to a Singapore Chinese population

    Directory of Open Access Journals (Sweden)

    Wang De Yun

    2010-05-01

    Full Text Available Abstract Background The International Hapmap project serves as a valuable resource for human genome variation data, however its applicability to other populations has yet to be exhaustively investigated. In this paper, we use high density genotyping chips and resequencing strategies to compare the Singapore Chinese population with the Hapmap populations. First we compared 1028 and 114 unrelated Singapore Chinese samples genotyped using the Illumina Human Hapmap 550 k chip and Affymetrix 500 k array respectively against the 270 samples from Hapmap. Secondly, data from 20 candidate genes on 5q31-33 resequenced for an asthma candidate gene based study was also used for the analysis. Results A total of 237 SNPs were identified through resequencing of which only 95 SNPs (40% were in Hapmap; however an additional 56 SNPs (24% were not genotyped directly but had a proxy SNP in the Hapmap. At the genome-wide level, Singapore Chinese were highly correlated with Hapmap Han Chinese with correlation of 0.954 and 0.947 for the Illumina and Affymetrix platforms respectively with deviant SNPs randomly distributed within and across all chromosomes. Conclusions The high correlation between our population and Hapmap Han Chinese reaffirms the applicability of Hapmap based genome-wide chips for GWA studies. There is a clear population signature for the Singapore Chinese samples and they predominantly resemble the southern Han Chinese population; however when new migrants particularly those with northern Han Chinese background were included, population stratification issues may arise. Future studies needs to address population stratification within the sample collection while designing and interpreting GWAS in the Chinese population.

  7. The distribution of SNPs in human gene regulatory regions

    Directory of Open Access Journals (Sweden)

    Guo Yongjian

    2005-10-01

    Full Text Available Abstract Background As a result of high-throughput genotyping methods, millions of human genetic variants have been reported in recent years. To efficiently identify those with significant biological functions, a practical strategy is to concentrate on variants located in important sequence regions such as gene regulatory regions. Results Analysis of the most common type of variant, single nucleotide polymorphisms (SNPs, shows that in gene promoter regions more SNPs occur in close proximity to transcriptional start sites than in regions further upstream, and a disproportionate number of those SNPs represent nucleotide transversions. Additionally, the number of SNPs found in the predicted transcription factor binding sites is higher than in non-binding site sequences. Conclusion Current information about transcription factor binding site sequence patterns may not be exhaustive, and SNPs may be actively involved in influencing gene expression by affecting the transcription factor binding sites.

  8. Modeling Chromosomes

    Science.gov (United States)

    Robertson, Carol

    2016-01-01

    Learning about chromosomes is standard fare in biology classrooms today. However, students may find it difficult to understand the relationships among the "genome", "chromosomes", "genes", a "gene locus", and "alleles". In the simple activity described in this article, which follows the 5E approach…

  9. In Silico Analysis of FMR1 Gene Missense SNPs.

    Science.gov (United States)

    Tekcan, Akin

    2016-06-01

    The FMR1 gene, a member of the fragile X-related gene family, is responsible for fragile X syndrome (FXS). Missense single-nucleotide polymorphisms (SNPs) are responsible for many complex diseases. The effect of FMR1 gene missense SNPs is unknown. The aim of this study, using in silico techniques, was to analyze all known missense mutations that can affect the functionality of the FMR1 gene, leading to mental retardation (MR) and FXS. Data on the human FMR1 gene were collected from the Ensembl database (release 81), National Centre for Biological Information dbSNP Short Genetic Variations database, 1000 Genomes Browser, and NHLBI Exome Sequencing Project Exome Variant Server. In silico analysis was then performed. One hundred-twenty different missense SNPs of the FMR1 gene were determined. Of these, 11.66 % of the FMR1 gene missense SNPs were in highly conserved domains, and 83.33 % were in domains with high variety. The results of the in silico prediction analysis showed that 31.66 % of the FMR1 gene SNPs were disease related and that 50 % of SNPs had a pathogenic effect. The results of the structural and functional analysis revealed that although the R138Q mutation did not seem to have a damaging effect on the protein, the G266E and I304N SNPs appeared to disturb the interaction between the domains and affect the function of the protein. This is the first study to analyze all missense SNPs of the FMR1 gene. The results indicate the applicability of a bioinformatics approach to FXS and other FMR1-related diseases. I think that the analysis of FMR1 gene missense SNPs using bioinformatics methods would help diagnosis of FXS and other FMR1-related diseases.

  10. Potentially functional SNPs (pfSNPs as novel genomic predictors of 5-FU response in metastatic colorectal cancer patients.

    Directory of Open Access Journals (Sweden)

    Jingbo Wang

    Full Text Available 5-Fluorouracil (5-FU and its pro-drug Capecitabine have been widely used in treating colorectal cancer. However, not all patients will respond to the drug, hence there is a need to develop reliable early predictive biomarkers for 5-FU response. Here, we report a novel potentially functional Single Nucleotide Polymorphism (pfSNP approach to identify SNPs that may serve as predictive biomarkers of response to 5-FU in Chinese metastatic colorectal cancer (CRC patients. 1547 pfSNPs and one variable number tandem repeat (VNTR in 139 genes in 5-FU drug (both PK and PD pathway and colorectal cancer disease pathways were examined in 2 groups of CRC patients. Shrinkage of liver metastasis measured by RECIST criteria was used as the clinical end point. Four non-responder-specific pfSNPs were found to account for 37.5% of all non-responders (P<0.0003. Five additional pfSNPs were identified from a multivariate model (AUC under ROC = 0.875 that was applied for all other pfSNPs, excluding the non-responder-specific pfSNPs. These pfSNPs, which can differentiate the other non-responders from responders, mainly reside in tumor suppressor genes or genes implicated in colorectal cancer risk. Hence, a total of 9 novel SNPs with potential functional significance may be able to distinguish non-responders from responders to 5-FU. These pfSNPs may be useful biomarkers for predicting response to 5-FU.

  11. Linking SNPs to CAG repeat length in Huntington's disease patients.

    Science.gov (United States)

    Liu, Wanzhao; Kennington, Lori A; Rosas, H Diana; Hersch, Steven; Cha, Jang-Ho; Zamore, Phillip D; Aronin, Neil

    2008-11-01

    Allele-specific silencing using small interfering RNAs targeting heterozygous single-nucleotide polymorphisms (SNPs) is a promising therapy for human trinucleotide repeat diseases such as Huntington's disease. Linking SNP identities to the two HTT alleles, normal and disease-causing, is a prerequisite for allele-specific RNA interference. Here we describe a method, SNP linkage by circularization (SLiC), to identify linkage between CAG repeat length and nucleotide identity of heterozygous SNPs using Huntington's disease patient peripheral blood samples.

  12. Investigation of SNPs in the porcine desmoglein 1 gene

    Directory of Open Access Journals (Sweden)

    Andresen Lars

    2007-03-01

    Full Text Available Abstract Background Desmoglein 1 (DSG1 is the target protein in the skin disease exudative epidermitis in pigs caused by virulent strains of Staphylococcus hyicus. The exfoliative toxins produced by S. hyicus digest the porcine desmoglein 1 (PIGDSG1 by a very specific reaction. This study investigated the location of single nucleotide polymorphisms (SNPs in the porcine desmoglein 1 gene (PIGDSG1 in correlation to the cleavage site as well as if the genotype of the SNPs is correlated to susceptibility or resistance to the disease. Results DNA from 32 affected and 32 unaffected piglets with exudative epidermitis were diagnosed clinically as affected or unaffected. Two regions of the desmoglein 1 gene were sequenced and genotypes of the SNPs were established. Seven SNPs (823T>C, 828A>G, 829A>G, 830A>T, 831A>T, 838A>C and 1139C>T were found in the analysed sequences and the allele frequencies were determined for the SNPs resulting in amino acid change. Four of the seven polymorphisms were situated in the motif known to be important for toxin cleavage. The distribution of the genotypes between affected and unaffected animals was analysed. Conclusion The study indicated a possible correlation between the genotypes of two out of seven SNPs found in the porcine desmoglein 1 gene and the susceptibility to exudative epidermitis.

  13. SNPs in Multi-Species Conserved Sequences (MCS as useful markers in association studies: a practical approach

    Directory of Open Access Journals (Sweden)

    Pericak-Vance Margaret A

    2007-08-01

    Full Text Available Abstract Background Although genes play a key role in many complex diseases, the specific genes involved in most complex diseases remain largely unidentified. Their discovery will hinge on the identification of key sequence variants that are conclusively associated with disease. While much attention has been focused on variants in protein-coding DNA, variants in noncoding regions may also play many important roles in complex disease by altering gene regulation. Since the vast majority of noncoding genomic sequence is of unknown function, this increases the challenge of identifying "functional" variants that cause disease. However, evolutionary conservation can be used as a guide to indicate regions of noncoding or coding DNA that are likely to have biological function, and thus may be more likely to harbor SNP variants with functional consequences. To help bias marker selection in favor of such variants, we devised a process that prioritizes annotated SNPs for genotyping studies based on their location within Multi-species Conserved Sequences (MCSs and used this process to select SNPs in a region of linkage to a complex disease. This allowed us to evaluate the utility of the chosen SNPs for further association studies. Previously, a region of chromosome 1q43 was linked to Multiple Sclerosis (MS in a genome-wide screen. We chose annotated SNPs in the region based on location within MCSs (termed MCS-SNPs. We then obtained genotypes for 478 MCS-SNPs in 989 individuals from MS families. Results Analysis of our MCS-SNP genotypes from the 1q43 region and comparison to HapMap data confirmed that annotated SNPs in MCS regions are frequently polymorphic and show subtle signatures of selective pressure, consistent with previous reports of genome-wide variation in conserved regions. We also present an online tool that allows MCS data to be directly exported to the UCSC genome browser so that MCS-SNPs can be easily identified within genomic regions of

  14. Diagnosis of a constitutional five-chromosome rearrangement by fluorescent in situ hybridization (FISH)

    Energy Technology Data Exchange (ETDEWEB)

    Tsien, F.; Shapira, E. [Tulane Univ. School of Medicine, New Orleans, LA (United States); Carvalho, T. [Hospital Sarah Kubitschek, Brasilia (Brazil)] [and others

    1994-09-01

    Complex chromosomal rearrangements are structural rearrangements involving at least three chromosomes and three or more chromosome breakpoints. Such karyotypes are often acquired during cancer multi-step development and in chromosome instability syndromes. However, extremely rare constitutional forms have been reported, most of which are incompatible with life. We present a 2-year-old female with de novo complex rearrangement consisting of five chromosomes and nine breakpoints. Clinical evaluation at two years of age revealed a weight of 5 kg, length of 66 cm, and had circumference of 38 cm, all below the 5th percentile, microcephaly, trigonocephaly, epicanthal folds, inguinal hernia, left clubfoot, hypertonicity, and developmental delay. The neurological examination revealed chorea-acanthocytosis and psychomotor delay. Cultured lymphocytes and fibroblasts revealed a karyotype consisting of five derivative chromosomes. The metaphases were further analyzed by FISH using chromosome-specific libraries and telomeric probes in order to delineate the composition of the rearranged chromosomes; FISH results demonstrated a karyotype of: 46,XX,1pter{r_arrow}1q25::1q42.1{r_arrow}1qter, 2pter{r_arrow}q32.3::1q32.3{r_arrow}2q41::2q37.3{r_arrow}2qter, 7qter{r_arrow}7q21.2::6q22.3{r_arrow}6qter::1q31{r_arrow}1q32.3::6p23{r_arrow}6q22.3, 7pter{r_arrow}7q21.1::6p23{r_arrow}6pter, 2q33{r_arrow}2q37, 1::9p21{r_arrow}9qter. This analysis demonstrates the usefulness of FISH in characterizing complex chromosome rearrangements otherwise difficult to correctly interpret using classical cytogenetics alone.

  15. Proteasome Modulator 9 SNPs are linked to hypertension in type 2 diabetes families

    Directory of Open Access Journals (Sweden)

    Gragnoli Claudia

    2011-08-01

    Full Text Available Abstract Background Chromosome 12q24 was recently associated with hypertension. Proteasome Modulator 9 (PSMD9 lies in the 12q24 locus and is in linkage with MODY3, type 2 diabetes (T2D, microvascular and macrovascular pathology, carpal tunnel syndrome, and hypercholesterolemia in Italian families. Aims Our goal was to determine whether PSMD9 is linked to elevated blood pressure/hypertension in T2D families. Methods We characterized the Italian T2D families' members for presence and/or absence of elevated blood pressure (≥ 130/80 and/or hypertension. The phenotypes were described as unknown in all cases in which the diagnosis was either unclear or the data were not available for the subject studied. We tested in the 200 Italians families for the presence of the linkage of the PSMD9 T2D risk single nucleotide polymorphisms (SNPs IVS3+nt460 A > G, IVS3+nt437 T > C and E197G A > G with elevated blood pressure/hypertension. The non-parametric linkage analysis was performed for this qualitative phenotype by using the Merlin software; the Lod score and correspondent P-value were calculated. Parametric linkage analysis was also performed. For the significant linkage score, 1000 replicates were run to calculate the empirical P-value. Results The PSMD9 gene SNPs studied are in linkage with elevated blood pressure/hypertension in our Italian families. Conclusions We conclude that the PSMD9 gene and/or any variant in linkage disequilibrium with the SNPs studied contribute to the linkage to hypertension within our family dataset. This is the first report of PSMD9 linkage to hypertension within the 12q24 locus.

  16. Synthetic chromosomes.

    Science.gov (United States)

    Schindler, Daniel; Waldminghaus, Torsten

    2015-11-01

    What a living organism looks like and how it works and what are its components-all this is encoded on DNA, the genetic blueprint. Consequently, the way to change an organism is to change its genetic information. Since the first pieces of recombinant DNA have been used to transform cells in the 1970s, this approach has been enormously extended. Bigger and bigger parts of the genetic information have been exchanged or added over the years. Now we are at a point where the construction of entire chromosomes becomes a reachable goal and first examples appear. This development leads to fundamental new questions, for example, about what is possible and desirable to build or what construction rules one needs to follow when building synthetic chromosomes. Here we review the recent progress in the field, discuss current challenges and speculate on the appearance of future synthetic chromosomes.

  17. Seeing the wood for the trees: a minimal reference phylogeny for the human Y chromosome.

    Science.gov (United States)

    van Oven, Mannis; Van Geystelen, Anneleen; Kayser, Manfred; Decorte, Ronny; Larmuseau, Maarten H D

    2014-02-01

    During the last few decades, a wealth of studies dedicated to the human Y chromosome and its DNA variation, in particular Y-chromosome single-nucleotide polymorphisms (Y-SNPs), has led to the construction of a well-established Y-chromosome phylogeny. Since the recent advent of new sequencing technologies, the discovery of additional Y-SNPs is exploding and their continuous incorporation in the phylogenetic tree is leading to an ever higher resolution. However, the large and increasing amount of information included in the "complete" Y-chromosome phylogeny, which now already includes many thousands of identified Y-SNPs, can be overwhelming and complicates its understanding as well as the task of selecting suitable markers for genotyping purposes in evolutionary, demographic, anthropological, genealogical, medical, and forensic studies. As a solution, we introduce a concise reference phylogeny whereby we do not aim to provide an exhaustive tree that includes all known Y-SNPs but, rather, a quite stable reference tree aiming for optimal global discrimination capacity based on a strongly reduced set that includes only the most resolving Y-SNPs. Furthermore, with this reference tree, we wish to propose a common standard for Y-marker as well as Y-haplogroup nomenclature. The current version of our tree is based on a core set of 417 branch-defining Y-SNPs and is available online at http://www.phylotree.org/Y.

  18. Genetic Mapping of Millions of SNPs in Safflower (Carthamus tinctorius L. via Whole-Genome Resequencing

    Directory of Open Access Journals (Sweden)

    John E. Bowers

    2016-07-01

    Full Text Available Accurate assembly of complete genomes is facilitated by very high density genetic maps. We performed low-coverage, whole-genome shotgun sequencing on 96 F6 recombinant inbred lines (RILs of a cross between safflower (Carthamus tinctorius L. and its wild progenitor (C. palaestinus Eig. We also produced a draft genome assembly of C. tinctorius covering 866 million bp (∼two-thirds of the expected 1.35 Gbp genome after sequencing a single, short insert library to ∼21 × depth. Sequence reads from the RILs were mapped to this genome assembly to facilitate SNP identification, and the resulting polymorphisms were used to construct a genetic map. The resulting map included 2,008,196 genetically located SNPs in 1178 unique positions. A total of 57,270 scaffolds, each containing five or more mapped SNPs, were anchored to the map. This resulted in the assignment of sequence covering 14% of the expected genome length to a genetic position. Comparison of this safflower map to genetic maps of sunflower and lettuce revealed numerous chromosomal rearrangements, and the resulting patterns were consistent with a whole-genome duplication event in the lineage leading to sunflower. This sequence-based genetic map provides a powerful tool for the assembly of a low-cost draft genome of safflower, and the same general approach is expected to work for other species.

  19. Genetic Mapping of Millions of SNPs in Safflower (Carthamus tinctorius L.) via Whole-Genome Resequencing.

    Science.gov (United States)

    Bowers, John E; Pearl, Stephanie A; Burke, John M

    2016-07-07

    Accurate assembly of complete genomes is facilitated by very high density genetic maps. We performed low-coverage, whole-genome shotgun sequencing on 96 F6 recombinant inbred lines (RILs) of a cross between safflower (Carthamus tinctorius L.) and its wild progenitor (C. palaestinus Eig). We also produced a draft genome assembly of C. tinctorius covering 866 million bp (∼two-thirds) of the expected 1.35 Gbp genome after sequencing a single, short insert library to ∼21 × depth. Sequence reads from the RILs were mapped to this genome assembly to facilitate SNP identification, and the resulting polymorphisms were used to construct a genetic map. The resulting map included 2,008,196 genetically located SNPs in 1178 unique positions. A total of 57,270 scaffolds, each containing five or more mapped SNPs, were anchored to the map. This resulted in the assignment of sequence covering 14% of the expected genome length to a genetic position. Comparison of this safflower map to genetic maps of sunflower and lettuce revealed numerous chromosomal rearrangements, and the resulting patterns were consistent with a whole-genome duplication event in the lineage leading to sunflower. This sequence-based genetic map provides a powerful tool for the assembly of a low-cost draft genome of safflower, and the same general approach is expected to work for other species.

  20. In silico detection of phylogenetic informative Y-chromosomal single nucleotide polymorphisms from whole genome sequencing data.

    Science.gov (United States)

    Van Geystelen, Anneleen; Wenseleers, Tom; Decorte, Ronny; Caspers, Maarten J L; Larmuseau, Maarten H D

    2014-11-01

    A state-of-the-art phylogeny of the human Y-chromosome is an essential tool for forensic genetics. The explosion of whole genome sequencing (WGS) data due to the rapid progress of next-generation sequencing facilities is useful to optimize and to increase the resolution of the phylogenetic Y-chromosomal tree. The most interesting Y-chromosomal variants to increase the phylogeny are SNPs (Y-SNPs) especially since the software to call them in WGS data and to genotype them in forensic assays has been optimized over the past years. The PENNY software presented here detects potentially phylogenetic interesting Y-SNPs in silico based on SNP calling data files and classifies them into different types according to their position in the currently used Y-chromosomal tree. The software utilized 790 available male WGS samples of which 172 had a high SNP calling quality. In total, 1269 Y-SNPs potentially capable of increasing the resolution of the Y-chromosomal phylogenetic tree were detected based on a first run with PENNY. Based on a test panel of 57 high-quality and 618 low-quality WGS samples, we could prove that these newly added Y-SNPs indeed increased the resolution of the phylogenetic Y-chromosomal analysis substantially. Finally, we performed a second run with PENNY whereby all samples including those of the test panel are used and this resulted in 509 additional phylogenetic promising Y-SNPs. By including these additional Y-SNPs, a final update of the present phylogenetic Y-chromosomal tree which is useful for forensic applications was generated. In order to find more convincing forensic interesting Y-SNPs with this PENNY software, the number of samples and variety of the haplogroups to which these samples belong needs to increase. The PENNY software (inclusive the user manual) is freely available on the website http://bio.kuleuven.be/eeb/lbeg/software.

  1. A model-based approach to selection of tag SNPs

    Directory of Open Access Journals (Sweden)

    Sun Fengzhu

    2006-06-01

    Full Text Available Abstract Background Single Nucleotide Polymorphisms (SNPs are the most common type of polymorphisms found in the human genome. Effective genetic association studies require the identification of sets of tag SNPs that capture as much haplotype information as possible. Tag SNP selection is analogous to the problem of data compression in information theory. According to Shannon's framework, the optimal tag set maximizes the entropy of the tag SNPs subject to constraints on the number of SNPs. This approach requires an appropriate probabilistic model. Compared to simple measures of Linkage Disequilibrium (LD, a good model of haplotype sequences can more accurately account for LD structure. It also provides a machinery for the prediction of tagged SNPs and thereby to assess the performances of tag sets through their ability to predict larger SNP sets. Results Here, we compute the description code-lengths of SNP data for an array of models and we develop tag SNP selection methods based on these models and the strategy of entropy maximization. Using data sets from the HapMap and ENCODE projects, we show that the hidden Markov model introduced by Li and Stephens outperforms the other models in several aspects: description code-length of SNP data, information content of tag sets, and prediction of tagged SNPs. This is the first use of this model in the context of tag SNP selection. Conclusion Our study provides strong evidence that the tag sets selected by our best method, based on Li and Stephens model, outperform those chosen by several existing methods. The results also suggest that information content evaluated with a good model is more sensitive for assessing the quality of a tagging set than the correct prediction rate of tagged SNPs. Besides, we show that haplotype phase uncertainty has an almost negligible impact on the ability of good tag sets to predict tagged SNPs. This justifies the selection of tag SNPs on the basis of haplotype

  2. Kinship Testing Based on SNPs Using Microarray System

    Science.gov (United States)

    Cho, Sohee; Seo, Hee Jin; Lee, Jihyun; Yu, Hyung Jin; Lee, Soong Deok

    2016-01-01

    Background Kinship testing using biallelic SNP markers has been demonstrated to be a promising approach as a supplement to standard STR typing, and several systems, such as pyrosequencing and microarray, have been introduced and utilized in real forensic cases. The Affymetrix microarray containing 169 autosomal SNPs developed for forensic application was applied to our practical case for kinship analysis that had remained inconclusive due to partial STR profiles of degraded DNA and possibility of inbreeding within the population. Case Report 169 autosomal SNPs were typed on array with severely degraded DNA of two bone samples, and the kinship compared to genotypes in a reference database of their putative family members. Results Two bone samples remained unidentified through traditional STR typing with partial profiles of 10 or 14 of 16 alleles. Because these samples originated from a geographically isolated population, a cautious approach was required when analyzing and declaring true paternity only based on PI values. In a supplementary SNP typing, 106 and 78 SNPs were obtained, and the match candidates were found in each case with improved PI values than using only STRs and with no discrepant SNPs in comparison. Conclusion Our case showed that the utility of multiple SNPs on array is expected in practical forensic caseworks with an establishment of reference database. PMID:27994531

  3. Investigation of SNPs in the porcine desmoglein 1 gene

    DEFF Research Database (Denmark)

    Daugaard, L.; Andresen, Lars Ole; Fredholm, M.

    2007-01-01

    Background: Desmoglein I (DSGI) is the target protein in the skin disease exudative epidermitis in pigs caused by virulent strains of Staphylococcus hyicus. The exfoliative toxins produced by S. hyicus digest the porcine desmoglein I (PIG)DSGI by a very specific reaction. This study investigated...... epidermitis were diagnosed clinically as affected or unaffected. Two regions of the desmoglein I gene were sequenced and genotypes of the SNPs were established. Seven SNPs (823T>C, 828A>G, 829A>G, 830A>T, 831A>T, 838A>C and 1139C>T) were found in the analysed sequences and the allele frequencies were...... the genotypes of two out of seven SNPs found in the porcine desmoglein I gene and the susceptibility to exudative epidermitis....

  4. Establishment of a pipeline to analyse non-synonymous SNPs in Bos taurus

    Directory of Open Access Journals (Sweden)

    Schreiber Mark

    2006-11-01

    Full Text Available Abstract Background Single nucleotide polymorphisms (SNPs are an abundant form of genetic variation in the genome of every species and are useful for gene mapping and association studies. Of particular interest are non-synonymous SNPs, which may alter protein function and phenotype. We therefore examined bovine expressed sequences for non-synonymous SNPs and validated and tested selected SNPs for their association with measured traits. Results Over 500,000 public bovine expressed sequence tagged (EST sequences were used to search for coding SNPs (cSNPs. A total of 15,353 SNPs were detected in the transcribed sequences studied, of which 6,325 were predicted to be coding SNPs with the remaining 9,028 SNPs presumed to be in untranslated regions. Of the cSNPs detected, 2,868 were predicted to result in a change in the amino acid encoded. In order to determine the actual number of non-synonymous polymorphic SNPs we designed assays for 920 of the putative SNPs. These SNPs were then genotyped through a panel of cattle DNA pools using chip-based MALDI-TOF mass spectrometry. Of the SNPs tested, 29% were found to be polymorphic with a minor allele frequency >10%. A subset of the SNPs was genotyped through animal resources in order to look for association with age of puberty, facial eczema resistance or meat yield. Three SNPs were nominally associated with resistance to the disease facial eczema (P Conclusion We have identified 15,353 putative SNPs in or close to bovine genes and 2,868 of these SNPs were predicted to be non-synonymous. Approximately 29% of the non-synonymous SNPs were polymorphic and common with a minor allele frequency >10%. Of the SNPs detected in this study, 99% have not been previously reported. These novel SNPs will be useful for association studies or gene mapping.

  5. A periodic pattern of SNPs in the human genome

    DEFF Research Database (Denmark)

    Madsen, Bo Eskerod; Villesen, Palle; Wiuf, Carsten

    2007-01-01

    or alignment errors, for example, transposable elements (SINE, LINE, and LTR), tandem repeats, and large duplicated regions. However, we found that the pattern is almost entirely confined to what we define as "periodic DNA." Periodic DNA is a genomic region with a high degree of periodicity in nucleotide usage...... periodic DNA. Our results suggest that not all SNPs in the human genome are created by independent single nucleotide mutations, and that care should be taken in analysis of SNPs from periodic DNA. The latter may have important consequences for SNP and association studies....

  6. Inherited variants in the inner centromere protein (INCENP) gene of the chromosomal passenger complex contribute to the susceptibility of ER-negative breast cancer

    NARCIS (Netherlands)

    M. Kabisch (Maria); J.L. Bermejo (Justo Lorenzo); T. Dun̈nebier (Thomas); S. Ying (Shibo); K. Michailidou (Kyriaki); M.K. Bolla (Manjeet); Q. Wang (Qing); J. Dennis (Joe); M. Shah (Mitul); B. Perkins (Barbara); K. Czene (Kamila); H. Darabi (Hatef); M. Eriksson (Mikael); S.E. Bojesen (Stig); B.G. Nordestgaard (Børge); S.F. Nielsen (Sune); H. Flyger (Henrik); D. Lambrechts (Diether); P. Neven (Patrick); S.T.H. Peeters (Stephanie); C. Weltens (Caroline); F.J. Couch (Fergus); J.E. Olson (Janet); X. Wang (Xianshu); K. Purrington (Kristen); J. Chang-Claude (Jenny); A. Rudolph (Anja); P. Seibold (Petra); D. Flesch-Janys (Dieter); J. Peto (Julian); I. dos Santos Silva (Isabel); N. Johnson (Nichola); O. Fletcher (Olivia); H. Nevanlinna (Heli); T.A. Muranen (Taru); K. Aittomäki (Kristiina); C. Blomqvist (Carl); M.K. Schmidt (Marjanka); A. Broeks (Annegien); S. Cornelissen (Sten); F.B.L. Hogervorst (Frans); J. Li (Jingmei); J.S. Brand (Judith S.); M.K. Humphreys (Manjeet); P. Guénel (Pascal); T. Truong (Thérèse); F. Menegaux (Florence); M. Sanchez (Marie); B. Burwinkel (Barbara); F. Marme (Federick); R. Yang (Rongxi); P. Bugert (Peter); A. González-Neira (Anna); J. Benítez (Javier); M.P. Zamora (Pilar); J.I. Arias Pérez (José Ignacio); A. Cox (Angela); S.S. Cross (Simon); M.W.R. Reed (Malcolm); I.L. Andrulis (Irene); J.A. Knight (Julia); G. Glendon (Gord); S. Tchatchou (Sandrine); E.J. Sawyer (Elinor); I.P. Tomlinson (Ian); M. Kerin (Michael); N. Miller (Nicola); C.A. Haiman (Christopher); F.R. Schumacher (Fredrick); B.E. Henderson (Brian); L. Le Marchand (Loic); A. Lindblom (Annika); S. Margolin (Sara); M.J. Hooning (Maartje); A. Hollestelle (Antoinette); M. Kriege (Mieke); L.B. Koppert (Linetta); J. Hopper (John); M.C. Southey (Melissa); H. Tsimiklis (Helen); C. Apicella (Carmel); S. Slettedahl (Seth); A.E. Toland (Amanda); C. Vachon (Celine); D. Yannoukakos (Drakoulis); G.G. Giles (Graham); R.L. Milne (Roger); C.A. McLean (Catriona Ann); P.A. Fasching (Peter); M. Ruebner (Matthias); A.B. Ekici (Arif); M.W. Beckmann (Matthias); H. Brenner (Hermann); A.K. Dieffenbach (Aida Karina); V. Arndt (Volker); C. Stegmaier (Christa); A. Ashworth (Alan); N. Orr (Nick); M. Schoemaker (Minouk); A.J. Swerdlow (Anthony ); M. García-Closas (Montserrat); J.D. Figueroa (Jonine); S.J. Chanock (Stephen); J. Lissowska (Jolanta); M.S. Goldberg (Mark); F. Labrèche (France); M. Dumont (Martine); R. Winqvist (Robert); K. Pykäs (Katri); A. Jukkola-Vuorinen (Arja); M. Grip (Mervi); H. Brauch (Hiltrud); T. Brüning (Thomas); Y-D. Ko (Yon-Dschun); P. Radice (Paolo); P. Peterlongo (Paolo); G. Scuvera (Giulietta); S. Fortuzzi (S.); N.V. Bogdanova (Natalia); T. Dörk (Thilo); A. Mannermaa (Arto); V. Kataja (Vesa); V-M. Kosma (Veli-Matti); J.M. Hartikainen (J.); P. Devilee (Peter); R.A.M. Tollenaar (Robert A.M.); C.M. Seynaeve (Caroline); C.J. van Asperen (Christi); A. Jakubowska (Anna); J. Lubinski (Jan); K. Jaworska-Bieniek (Katarzyna); K. Durda (Katarzyna); W. Zheng (Wei); M. Shrubsole (Martha); Q. Cai (Qiuyin); D. Torres (Diana); H. Anton-Culver (Hoda); V. Kristensen (Vessela); F. Bacot (Francois); D.C. Tessier (Daniel C.); D. Vincent (Daniel); C. Luccarini (Craig); C. Baynes (Caroline); S. Ahmed (Shahana); M. Maranian (Melanie); J. Simard (Jacques); G. Chenevix-Trench (Georgia); P. Hall (Per); P.D.P. Pharoah (Paul); A.M. Dunning (Alison); D.F. Easton (Douglas); U. Hamann (Ute)

    2014-01-01

    textabstractThe chromosomal passenger complex (CPC) plays a pivotal role in the regulation of cell division. Therefore, inherited CPC variability could influence tumor development. The present candidate gene approach investigates the relationship between single nucleotide polymorphisms (SNPs) in gen

  7. Inherited variants in the inner centromere protein (INCENP) gene of the chromosomal passenger complex contribute to the susceptibility of ER-negative breast cancer

    DEFF Research Database (Denmark)

    Kabisch, Maria; Lorenzo Bermejo, Justo; Dünnebier, Thomas

    2015-01-01

    The chromosomal passenger complex (CPC) plays a pivotal role in the regulation of cell division. Therefore, inherited CPC variability could influence tumor development. The present candidate gene approach investigates the relationship between single nucleotide polymorphisms (SNPs) in genes encodi...

  8. Chromosome Analysis

    Science.gov (United States)

    1998-01-01

    Perceptive Scientific Instruments, Inc., provides the foundation for the Powergene line of chromosome analysis and molecular genetic instrumentation. This product employs image processing technology from NASA's Jet Propulsion Laboratory and image enhancement techniques from Johnson Space Center. Originally developed to send pictures back to earth from space probes, digital imaging techniques have been developed and refined for use in a variety of medical applications, including diagnosis of disease.

  9. Identification of SNPs in RNA-seq data of two cultivars of Glycine max (soybean differing in drought resistance

    Directory of Open Access Journals (Sweden)

    Ramon Oliveira Vidal

    2012-01-01

    Full Text Available The legume Glycine max (soybean plays an important economic role in the international commodities market, with a world production of almost 260 million tons for the 2009/2010 harvest. The increase in drought events in the last decade has caused production losses in recent harvests. This fact compels us to understand the drought tolerance mechanisms in soybean, taking into account its variability among commercial and developing cultivars. In order to identify single nucleotide polymorphisms (SNPs in genes up-regulated during drought stress, we evaluated suppression subtractive libraries (SSH from two contrasting cultivars upon water deprivation: sensitive (BR 16 and tolerant (Embrapa 48. A total of 2,222 soybean genes were up-regulated in both cultivars. Our method identified more than 6,000 SNPs in tolerant and sensitive Brazilian cultivars in those drought stress related genes. Among these SNPs, 165 (in 127 genes are positioned at soybean chromosome ends, including transcription factors (MYB, WRKY related to tolerance to abiotic stress.

  10. Identification of SNPs in RNA-seq data of two cultivars of Glycine max (soybean) differing in drought resistance.

    Science.gov (United States)

    Vidal, Ramon Oliveira; do Nascimento, Leandro Costa; Mondego, Jorge Maurício Costa; Pereira, Gonçalo Amarante Guimarães; Carazzolle, Marcelo Falsarella

    2012-06-01

    The legume Glycine max (soybean) plays an important economic role in the international commodities market, with a world production of almost 260 million tons for the 2009/2010 harvest. The increase in drought events in the last decade has caused production losses in recent harvests. This fact compels us to understand the drought tolerance mechanisms in soybean, taking into account its variability among commercial and developing cultivars. In order to identify single nucleotide polymorphisms (SNPs) in genes up-regulated during drought stress, we evaluated suppression subtractive libraries (SSH) from two contrasting cultivars upon water deprivation: sensitive (BR 16) and tolerant (Embrapa 48). A total of 2,222 soybean genes were up-regulated in both cultivars. Our method identified more than 6,000 SNPs in tolerant and sensitive Brazilian cultivars in those drought stress related genes. Among these SNPs, 165 (in 127 genes) are positioned at soybean chromosome ends, including transcription factors (MYB, WRKY) related to tolerance to abiotic stress.

  11. Analysis of multiple SNPs in genetic association studies: comparison of three multi-locus methods to prioritize and select SNPs

    NARCIS (Netherlands)

    Heidema, A.G.; Feskens, E.J.M.; Doevendans, P.A.F.M.; Ruven, H.J.T.; Houwelingen, H.C.; Mariman, E.C.M.; Boer, J.M.A.

    2007-01-01

    Nonparametric approaches have been developed that are able to analyze large numbers of single nucleotide polymorphisms (SNPs) in modest sample sizes. These approaches have different selection features and may not provide similar results when applied to the same dataset. Therefore, we compared the re

  12. Generation of meiomaps of genome-wide recombination and chromosome segregation in human oocytes

    DEFF Research Database (Denmark)

    Ottolini, Christian S; Capalbo, Antonio; Newnham, Louise

    2016-01-01

    We have developed a protocol for the generation of genome-wide maps (meiomaps) of recombination and chromosome segregation for the three products of human female meiosis: the first and second polar bodies (PB1 and PB2) and the corresponding oocyte. PB1 is biopsied and the oocyte is artificially......-nucleotide polymorphisms (SNPs) genome-wide by microarray. Informative maternal heterozygous SNPs are phased using a haploid PB2 or oocyte as a reference. A simple algorithm is then used to identify the maternal haplotypes for each chromosome, in all of the products of meiosis for each oocyte. This allows mapping...

  13. Computational screening and molecular dynamics simulation of disease associated nsSNPs in CENP-E

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Ambuj [Bioinformatics Division, School of Bio Sciences and Technology, Vellore Institute of Technology University, Vellore 632014, Tamil Nadu (India); Purohit, Rituraj, E-mail: riturajpurohit@gmail.com [Bioinformatics Division, School of Bio Sciences and Technology, Vellore Institute of Technology University, Vellore 632014, Tamil Nadu (India)

    2012-10-15

    Aneuploidy and chromosomal instability (CIN) are hallmarks of most solid tumors. Mutations in centroemere proteins have been observed in promoting aneuploidy and tumorigenesis. Recent studies reported that Centromere-associated protein-E (CENP-E) is involved in inducing cancers. In this study we investigated the pathogenic effect of 132 nsSNPs reported in CENP-E using computational platform. Y63H point mutation found to be associated with cancer using SIFT, Polyphen, PhD-SNP, MutPred, CanPredict and Dr. Cancer tools. Further we investigated the binding affinity of ATP molecule to the CENP-E motor domain. Complementarity scores obtained from docking studies showed significant loss in ATP binding affinity of mutant structure. Molecular dynamics simulation was carried to examine the structural consequences of Y63H mutation. Root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (R{sub g}), solvent accessibility surface area (SASA), energy value, hydrogen bond (NH Bond), eigenvector projection, trace of covariance matrix and atom density analysis results showed notable loss in stability for mutant structure. Y63H mutation was also shown to disrupt the native conformation of ATP binding region in CENP-E motor domain. Docking studies for remaining 18 mutations at 63rd residue position as well as other two computationally predicted disease associated mutations S22L and P69S were also carried to investigate their affect on ATP binding affinity of CENP-E motor domain. Our study provided a promising computational methodology to study the tumorigenic consequences of nsSNPs that have not been characterized and clear clue to the wet lab scientist.

  14. A consensus linkage map of the grass carp (Ctenopharyngodon idella based on microsatellites and SNPs

    Directory of Open Access Journals (Sweden)

    Li Jiale

    2010-02-01

    Full Text Available Abstract Background Grass carp (Ctenopharyngodon idella belongs to the family Cyprinidae which includes more than 2000 fish species. It is one of the most important freshwater food fish species in world aquaculture. A linkage map is an essential framework for mapping traits of interest and is often the first step towards understanding genome evolution. The aim of this study is to construct a first generation genetic map of grass carp using microsatellites and SNPs to generate a new resource for mapping QTL for economically important traits and to conduct a comparative mapping analysis to shed new insights into the evolution of fish genomes. Results We constructed a first generation linkage map of grass carp with a mapping panel containing two F1 families including 192 progenies. Sixteen SNPs in genes and 263 microsatellite markers were mapped to twenty-four linkage groups (LGs. The number of LGs was corresponding to the haploid chromosome number of grass carp. The sex-specific map was 1149.4 and 888.8 cM long in females and males respectively whereas the sex-averaged map spanned 1176.1 cM. The average resolution of the map was 4.2 cM/locus. BLAST searches of sequences of mapped markers of grass carp against the whole genome sequence of zebrafish revealed substantial macrosynteny relationship and extensive colinearity of markers between grass carp and zebrafish. Conclusions The linkage map of grass carp presented here is the first linkage map of a food fish species based on co-dominant markers in the family Cyprinidae. This map provides a valuable resource for mapping phenotypic variations and serves as a reference to approach comparative genomics and understand the evolution of fish genomes and could be complementary to grass carp genome sequencing project.

  15. SNPs and Hox gene mapping in Ciona intestinalis

    Directory of Open Access Journals (Sweden)

    Biffali Elio

    2008-01-01

    Full Text Available Abstract Background The tunicate Ciona intestinalis (Enterogona, Ascidiacea, a major model system for evolutionary and developmental genetics of chordates, harbours two cryptic species. To assess the degree of intra- and inter-specific genetic variability, we report the identification and analysis of C. intestinalis SNP (Single Nucleotide Polymorphism markers. A SNP subset was used to determine the genetic distance between Hox-5 and -10 genes. Results DNA fragments were amplified from 12 regions of C. intestinalis sp. A. In total, 128 SNPs and 32 one bp indels have been identified within 8 Kb DNA. SNPs in coding regions cause 4 synonymous and 12 non-synonymous substitutions. The highest SNP frequency was detected in the Hox5 and Hox10 intragenic regions. In C. intestinalis, these two genes have lost their archetypal topology within the cluster, such that Hox10 is located between Hox4 and Hox5. A subset of the above primers was used to perform successful amplification in C. intestinalis sp. B. In this cryptic species, 62 SNPs were identified within 3614 bp: 41 in non-coding and 21 in coding regions. The genetic distance of the Hox-5 and -10 loci, computed combining a classical backcross approach with the application of SNP markers, was found to be 8.4 cM (Haldane's function. Based on the physical distance, 1 cM corresponds to 39.5 Kb. Linkage disequilibrium between the aforementioned loci was calculated in the backcross generation. Conclusion SNPs here described allow analysis and comparisons within and between C. intestinalis cryptic species. We provide the first reliable computation of genetic distance in this important model chordate. This latter result represents an important platform for future studies on Hox genes showing deviations from the archetypal topology.

  16. Joint effect of multiple common SNPs predicts melanoma susceptibility.

    Directory of Open Access Journals (Sweden)

    Shenying Fang

    Full Text Available Single genetic variants discovered so far have been only weakly associated with melanoma. This study aims to use multiple single nucleotide polymorphisms (SNPs jointly to obtain a larger genetic effect and to improve the predictive value of a conventional phenotypic model. We analyzed 11 SNPs that were associated with melanoma risk in previous studies and were genotyped in MD Anderson Cancer Center (MDACC and Harvard Medical School investigations. Participants with ≥15 risk alleles were 5-fold more likely to have melanoma compared to those carrying ≤6. Compared to a model using the most significant single variant rs12913832, the increase in predictive value for the model using a polygenic risk score (PRS comprised of 11 SNPs was 0.07(95% CI, 0.05-0.07. The overall predictive value of the PRS together with conventional phenotypic factors in the MDACC population was 0.69 (95% CI, 0.64-0.69. PRS significantly improved the risk prediction and reclassification in melanoma as compared with the conventional model. Our study suggests that a polygenic profile can improve the predictive value of an individual gene polymorphism and may be able to significantly improve the predictive value beyond conventional phenotypic melanoma risk factors.

  17. SNPs genotyping technologies and their applications in farm animals breeding programs: review

    Directory of Open Access Journals (Sweden)

    Hamed Kharrati Koopaee

    2014-02-01

    Full Text Available Single nucleotide polymorphisms (SNPs are DNA sequence variations that occur when a single nucleotide: adenine (A, thymine (T, cytosine (C or guanine (G in the genome sequence is altered. Traditional and high throughput methods are two main strategies for SNPs genotyping. The SNPs genotyping technologies provide powerful resources for animal breeding programs.Genomic selection using SNPs is a new tool for choosing the best breeding animals. In addition, the high density maps using SNPs can provide useful genetic tools to study quantitative traits genetic variations. There are many sources of SNPs and exhaustive numbers of methods of SNP detection to be considered. For many traits in farm animals, the rate of genetic improvement can be nearly doubled when SNPs information is used compared to the current methods of genetic evaluation. The goal of this review is to characterize the SNPs genotyping methods and their applications in farm animals breeding.

  18. SNPs in the SCGB3A2 promoter are associated with susceptibility to Graves’ disease

    Institute of Scientific and Technical Information of China (English)

    梁军

    2013-01-01

    Objective To investigate the association of single nucleotide polymorphisms(SNPs) in the SCGB3A2(secretoglobin family 3A member 2) gene promoter with susceptibility of Graves’ disease. Methods One-hundred and seventy-nine SNPs within

  19. Detection of chromosomal aberrations of bladder carcinoma by fluorescence in situ hybridization%荧光原位杂交技术检测膀胱癌染色体畸变的研究

    Institute of Scientific and Technical Information of China (English)

    李晓娟; 符生苗; 刘元晓; 邓立群

    2012-01-01

    Objective To detect the common chromosomal aberrations from (he bladder transitional cell carcinoma by using M-FISH. Methods 50 urine samples were detected by FISH with centromeric probes of chromosome 17,7,3 and band probe of 9p2 l,and then the results were analyzed. Results There were four chromosomes showing a high distortion in 50 cases of bladder carcinoma group,showing significant association between chromosome 17,7,3,9p2 1 aberrations and pathological stage,grade (P<0.01). Conclusion Fluorescence in situ hybridization is an effective way for detection of chromosomal aberrations of urothelial tumors, as well as the early diagnosis of urothelial cancer.%目的 用多色荧光原位杂交(M-FISH)检测膀胱移行细胞癌中常见的染色体畸变. 方法 50例尿液标本采用FISH技术检测9p21区带及17、7、3号染色体的畸变情况,并对结果进行相应的统计学分析. 结果 50例膀胱癌病人组中,4个染色体均显示较高的畸变率.9p21以及17、7和3号染色体畸变率与病理分期、分级均有显著相关性(P<0.01).结论 用荧光原位杂交技术是检测尿路上皮肿瘤染色体畸变的有效方法,可作为早期诊断尿路上皮肿瘤的重要途径.

  20. Establishment of a pipeline to analyse non-synonymous SNPs in Bos taurus

    OpenAIRE

    Schreiber Mark; Morris Chris A; McCulloch Alan F; Dodds Ken G; Cullen Neil G; Manley Tim R; Glass Belinda C; Keane Orla M; Lee Michael A; Warren Jonathan; Zadissa Amonida; Wilson Theresa; McEwan John C

    2006-01-01

    Abstract Background Single nucleotide polymorphisms (SNPs) are an abundant form of genetic variation in the genome of every species and are useful for gene mapping and association studies. Of particular interest are non-synonymous SNPs, which may alter protein function and phenotype. We therefore examined bovine expressed sequences for non-synonymous SNPs and validated and tested selected SNPs for their association with measured traits. Results Over 500,000 public bovine expressed sequence ta...

  1. SNPs Selection using Gravitational Search Algorithm and Exhaustive Search for Association Mapping

    Science.gov (United States)

    Kusuma, W. A.; Hasibuan, L. S.; Istiadi, M. A.

    2016-01-01

    Single Nucleotide Polymorphisms (SNPs) are known having association to phenotipic variations. The study of linking SNPs to interest phenotype is refer to Association Mapping (AM), which is classified as a combinatorial problem. Exhaustive Search (ES) approach is able to be implemented to select targeted SNPs exactly since it evaluate all possible combinations of SNPs, but it is not efficient in terms of computer resources and computation time. Heuristic Search (HS) approach is an alternative to improve the performance of ES in those terms, but it still suffers high false positive SNPs in each combinations. Gravitational Search Algorithm (GSA) is a new HS algorithm that yields better performance than other nature inspired HS. This paper proposed a new method which combined GSA and ES to identify the most appropriate combination of SNPs linked to interest phenotype. Testing was conducted using dataset without epistasis and dataset with epistasis. Using dataset without epistasis with 7 targeted SNPs, the proposed method identified 7 SNPs - 6 True Positive (TP) SNPs and 1 False Positive (FP) SNP- with association value of 0.83. In addition, the proposed method could identified 3 SNPs- 2 TP SNP and 1 FP SNP with association value of 0.87 by using dataset with epistases and 5 targeted SNPs. The results showed that the method is robust in reducing redundant SNPs and identifying main markers.

  2. Comparison of information content for microsatellites and SNPs in poultry and cattle

    NARCIS (Netherlands)

    Schopen, G.C.B.; Bovenhuis, H.; Visker, M.H.P.W.; Arendonk, van J.A.M.

    2008-01-01

    Data were available for 12 poultry microsatellites and 29 poultry single nucleotide polymorphisms (SNPs), and for 34 cattle microsatellites and 36 cattle SNPs. Stochastic permutation was used to determine the number of SNPs needed to obtain the same average information content as a given number of m

  3. The contribution of the functional IL6R polymorphism rs2228145, eQTLs and other genome-wide SNPs to the heritability of plasma sIL-6R levels

    OpenAIRE

    van Dongen, Jenny; Jansen, Rick; Smit, Dirk; Hottenga, Jouke-Jan; Mbarek, Hamdi; Willemsen, Gonneke; Kluft, Cornelis; Penninx, Brenda W.J.; Ferreira, Manuel A.; Boomsma, Dorret I.; de Geus, Eco J C

    2014-01-01

    The non-synonymous SNP rs2228145 in the IL6R gene on chromosome 1q21.3 is associated with a wide range of common diseases, including asthma, rheumatoid arthritis, type 1 diabetes and coronary heart disease. We examined the contribution of this functional IL6R gene polymorphism rs2228145 versus other genome-wide SNPs to the variance of sIL-6R levels in blood plasma in a large population-based sample (N∼5000), and conducted an expression QTL (eQTL) analysis to identify SNPs associated with IL6R...

  4. Identification of candidate genes for dyslexia susceptibility on chromosome 18.

    Directory of Open Access Journals (Sweden)

    Thomas S Scerri

    Full Text Available Six independent studies have identified linkage to chromosome 18 for developmental dyslexia or general reading ability. Until now, no candidate genes have been identified to explain this linkage. Here, we set out to identify the gene(s conferring susceptibility by a two stage strategy of linkage and association analysis.Linkage analysis: 264 UK families and 155 US families each containing at least one child diagnosed with dyslexia were genotyped with a dense set of microsatellite markers on chromosome 18. Association analysis: Using a discovery sample of 187 UK families, nearly 3000 SNPs were genotyped across the chromosome 18 dyslexia susceptibility candidate region. Following association analysis, the top ranking SNPs were then genotyped in the remaining samples. The linkage analysis revealed a broad signal that spans approximately 40 Mb from 18p11.2 to 18q12.2. Following the association analysis and subsequent replication attempts, we observed consistent association with the same SNPs in three genes; melanocortin 5 receptor (MC5R, dymeclin (DYM and neural precursor cell expressed, developmentally down-regulated 4-like (NEDD4L.Along with already published biological evidence, MC5R, DYM and NEDD4L make attractive candidates for dyslexia susceptibility genes. However, further replication and functional studies are still required.

  5. Genotyping of Brucella species using clade specific SNPs

    Directory of Open Access Journals (Sweden)

    Foster Jeffrey T

    2012-06-01

    Full Text Available Abstract Background Brucellosis is a worldwide disease of mammals caused by Alphaproteobacteria in the genus Brucella. The genus is genetically monomorphic, requiring extensive genotyping to differentiate isolates. We utilized two different genotyping strategies to characterize isolates. First, we developed a microarray-based assay based on 1000 single nucleotide polymorphisms (SNPs that were identified from whole genome comparisons of two B. abortus isolates , one B. melitensis, and one B. suis. We then genotyped a diverse collection of 85 Brucella strains at these SNP loci and generated a phylogenetic tree of relationships. Second, we developed a selective primer-extension assay system using capillary electrophoresis that targeted 17 high value SNPs across 8 major branches of the phylogeny and determined their genotypes in a large collection ( n = 340 of diverse isolates. Results Our 1000 SNP microarray readily distinguished B. abortus, B. melitensis, and B. suis, differentiating B. melitensis and B. suis into two clades each. Brucella abortus was divided into four major clades. Our capillary-based SNP genotyping confirmed all major branches from the microarray assay and assigned all samples to defined lineages. Isolates from these lineages and closely related isolates, among the most commonly encountered lineages worldwide, can now be quickly and easily identified and genetically characterized. Conclusions We have identified clade-specific SNPs in Brucella that can be used for rapid assignment into major groups below the species level in the three main Brucella species. Our assays represent SNP genotyping approaches that can reliably determine the evolutionary relationships of bacterial isolates without the need for whole genome sequencing of all isolates.

  6. Tracing cattle breeds with principal components analysis ancestry informative SNPs.

    Directory of Open Access Journals (Sweden)

    Jamey Lewis

    Full Text Available The recent release of the Bovine HapMap dataset represents the most detailed survey of bovine genetic diversity to date, providing an important resource for the design and development of livestock production. We studied this dataset, comprising more than 30,000 Single Nucleotide Polymorphisms (SNPs for 19 breeds (13 taurine, three zebu, and three hybrid breeds, seeking to identify small panels of genetic markers that can be used to trace the breed of unknown cattle samples. Taking advantage of the power of Principal Components Analysis and algorithms that we have recently described for the selection of Ancestry Informative Markers from genomewide datasets, we present a decision-tree which can be used to accurately infer the origin of individual cattle. In doing so, we present a thorough examination of population genetic structure in modern bovine breeds. Performing extensive cross-validation experiments, we demonstrate that 250-500 carefully selected SNPs suffice in order to achieve close to 100% prediction accuracy of individual ancestry, when this particular set of 19 breeds is considered. Our methods, coupled with the dense genotypic data that is becoming increasingly available, have the potential to become a valuable tool and have considerable impact in worldwide livestock production. They can be used to inform the design of studies of the genetic basis of economically important traits in cattle, as well as breeding programs and efforts to conserve biodiversity. Furthermore, the SNPs that we have identified can provide a reliable solution for the traceability of breed-specific branded products.

  7. Molecular Beacon CNT-based Detection of SNPs

    Science.gov (United States)

    Egorova, V. P.; Krylova, H. V.; Lipnevich, I. V.; Veligura, A. A.; Shulitsky, B. G.; Y Fedotenkova, L.

    2015-11-01

    An fluorescence quenching effect due to few-walled carbon nanotubes chemically modified by carboxyl groups has been utilized to discriminate Single Nucleotide Polymorphism (SNP). It was shown that the complex obtained from these nanotube and singlestranded primer DNA is formed due to stacking interactions between the hexagons of the nanotubes and aromatic rings of nucleotide bases as well as due to establishing of hydrogen bonds between acceptor amine groups of nucleotide bases and donor carboxyl groups of the nanotubes. It has been demonstrated that these complexes may be used to make highly effective DNA biosensors detecting SNPs which operate as molecular beacons.

  8. Development of a multiplex PCR assay detecting 52 autosomal SNPs

    DEFF Research Database (Denmark)

    Sanchez Sanchez, Juan Jose; Phillips, C.; Børsting, Claus

    2006-01-01

    be performed. The SNPforID consortium (www.snpforid.org) was established in 2003 with the principal goal of developing a SNP-based system of DNA analysis that would have comparable discrimination power and ease of use to those of existing short tandem repeat (STR) based techniques. Here, we describe a strategy...... for amplifying 52 genomic DNA fragments, each containing one SNP, in a single tube, and accurately genotyping the PCR product mixture using two single base extension reactions. This multiplex approach reduces the cost of SNP genotyping and requires as little as 0.5 ng of genomic DNA to detect 52 SNPs. We used...

  9. ASSESSMENT OF CHAROLAIS BULLS POPULATION STRUCTURE BASED ON SNPs ANALYSES

    OpenAIRE

    Nina Moravčíková; Tomáš Minarovič; Anna Trakovická

    2014-01-01

    The aim of this study was identification of SNPs in leptin (LEP), leptin receptor (LEPR), growth hormone (GH) and specific pituitary transcription factor (Pit-1) genes in order to analyze genetic structure of Charolais bulls’ population. The total numbers of genomic DNA samples were taken from 52 breeding bulls and analyzed by PCR-RFLP method. After digestion with restriction enzymes were detected in bulls’ population alleles with frequency: LEP/Sau3AI A 0.83 and B 0.17 (±0.037); LEPR/BseGI C...

  10. Altofrequency SNPs of mitochondrial DNA in 26 Han Chinese

    Institute of Scientific and Technical Information of China (English)

    LUO Yong-jun; GAO Wen-xiang; GAO Yu-qi; CHEN Jian; TAN Xiao-ling; LIU Xin; CHEN Hai-hua

    2007-01-01

    Objective:To explore the possible mitochondrial DNA (mtDNA) polymorphism in Han Chinese.Methods:The complete mitochondrial genome of 26 unrelated healthy Han Chinese were extracted and sequenced.Results:The mtDNA nucleotide sites (2 706,7 028,8 860,11 719,and 15 326)were found totally different from the Revised Cambridge Reference Sequence (rCRS).These single nucleotide polymorphisms (SNPs) were 2 706 A→G,7 028 C→T,8 860 A→G,11 719 G→A,15 326 A→G.Conclusion:These findings provide new insights into the characteristics of Han Chinese mitochondrial genetic diversity.

  11. Analysis of 49 autosomal SNPs in an Iraqi population

    DEFF Research Database (Denmark)

    Tomas Mas, Carmen; Diez, Isabel E; Moncada, Enrique;

    2013-01-01

    Forty-nine of the 52 autosomal single nucleotide polymorphisms (SNPs) in the SNPforID 52plex were typed in 101 unrelated Iraqis living in Denmark. No significant deviation from HWE was found in all but one of the 49 SNP systems and no significant pairwise linkage disequilibrium was observed for any...... SNP pair. When 18 worldwide populations were compared (including populations in Iraq, Turkey, Israel, Pakistan, India, China, Taiwan, Japan, Siberia, Algeria, Somalia, Uganda, Mozambique, Angola, Nigeria, Denmark, Portugal, Spain), a significant global F(ST) value was obtained. All but six F...

  12. Context-dependent individualization of nucleotides and virtual genomic hybridization allow the precise location of human SNPs.

    Science.gov (United States)

    Reyes, José; Gómez-Romero, Laura; Ibarra-Soria, Ximena; Palacios-Flores, Kim; Arriola, Luis R; Wences, Alejandro; García, Delfino; Boege, Margareta; Dávila, Guillermo; Flores, Margarita; Palacios, Rafael

    2011-09-13

    We have entered the era of individual genomic sequencing, and can already see exponential progress in the field. It is of utmost importance to exclude false-positive variants from reported datasets. However, because of the nature of the used algorithms, this task has not been optimized to the required level of precision. This study presents a unique strategy for identifying SNPs, called COIN-VGH, that largely minimizes the presence of false-positives in the generated data. The algorithm was developed using the X-chromosome-specific regions from the previously sequenced genomes of Craig Venter and James Watson. The algorithm is based on the concept that a nucleotide can be individualized if it is analyzed in the context of its surrounding genomic sequence. COIN-VGH consists of defining the most comprehensive set of nucleotide strings of a defined length that map with 100% identity to a unique position within the human reference genome (HRG). Such set is used to retrieve sequence reads from a query genome (QG), allowing the production of a genomic landscape that represents a draft HRG-guided assembly of the QG. This landscape is analyzed for specific signatures that indicate the presence of SNPs. The fidelity of the variation signature was assessed using simulation experiments by virtually altering the HRG at defined positions. Finally, the signature regions identified in the HRG and in the QG reads are aligned and the precise nature and position of the corresponding SNPs are detected. The advantages of COIN-VGH over previous algorithms are discussed.

  13. Multiple SNPs in intron 41 of thyroglobulin gene are associated with autoimmune thyroid disease in the Japanese population.

    Directory of Open Access Journals (Sweden)

    Yoshiyuki Ban

    Full Text Available BACKGROUND: The etiology of the autoimmune thyroid diseases (AITDs, Graves' disease (GD and Hashimoto's thyroiditis (HT, is largely unknown. However, genetic susceptibility is believed to play a major role. Two whole genome scans from Japan and from the US identified a locus on chromosome 8q24 that showed evidence for linkage with AITD and HT. Recent studies have demonstrated an association between thyroglobulin (Tg polymorphisms and AITD in Caucasians, suggesting that Tg is a susceptibility gene on 8q24. OBJECTIVES: The objective of the study was to refine Tg association with AITD, by analyzing a panel of 25 SNPs across an extended 260 kb region of the Tg. METHODS: We studied 458 Japanese AITD patients (287 GD and 171 HT patients and 221 matched Japanese control subjects in association studies. Case-control association studies were performed using 25 Tg single nucleotide polymorphisms (SNPs chosen from a database of the Single Nucleotide Polymorphism Database (dbSNP. Haplotype analysis was undertaken using the computer program SNPAlyze version 7.0. PRINCIPAL FINDINGS AND CONCLUSIONS: In total, 5 SNPs revealed association with GD (P<0.05, with the strongest SNP associations at rs2256366 (P = 0.002 and rs2687836 (P = 0.0077, both located in intron 41 of the Tg gene. Because of the strong LD between these two strongest associated variants, we performed the haplotype analysis, and identified a major protective haplotype for GD (P = 0.001. These results suggested that the Tg gene is involved in susceptibility for GD and AITD in the Japanese.

  14. Undetected sex chromosome aneuploidy by chromosomal microarray.

    Science.gov (United States)

    Markus-Bustani, Keren; Yaron, Yuval; Goldstein, Myriam; Orr-Urtreger, Avi; Ben-Shachar, Shay

    2012-11-01

    We report on a case of a female fetus found to be mosaic for Turner syndrome (45,X) and trisomy X (47,XXX). Chromosomal microarray analysis (CMA) failed to detect the aneuploidy because of a normal average dosage of the X chromosome. This case represents an unusual instance in which CMA may not detect chromosomal aberrations. Such a possibility should be taken into consideration in similar cases where CMA is used in a clinical setting.

  15. MirSNP, a database of polymorphisms altering miRNA target sites, identifies miRNA-related SNPs in GWAS SNPs and eQTLs

    Directory of Open Access Journals (Sweden)

    Liu Chenxing

    2012-11-01

    Full Text Available Abstract Background Numerous single nucleotide polymorphisms (SNPs associated with complex diseases have been identified by genome-wide association studies (GWAS and expression quantitative trait loci (eQTLs studies. However, few of these SNPs have explicit biological functions. Recent studies indicated that the SNPs within the 3’UTR regions of susceptibility genes could affect complex traits/diseases by affecting the function of miRNAs. These 3’UTR SNPs are functional candidates and therefore of interest to GWAS and eQTL researchers. Description We developed a publicly available online database, MirSNP (http://cmbi.bjmu.edu.cn/mirsnp, which is a collection of human SNPs in predicted miRNA-mRNA binding sites. We identified 414,510 SNPs that might affect miRNA-mRNA binding. Annotations were added to these SNPs to predict whether a SNP within the target site would decrease/break or enhance/create an miRNA-mRNA binding site. By applying MirSNP database to three brain eQTL data sets, we identified four unreported SNPs (rs3087822, rs13042, rs1058381, and rs1058398, which might affect miRNA binding and thus affect the expression of their host genes in the brain. We also applied the MirSNP database to our GWAS for schizophrenia: seven predicted miRNA-related SNPs (p  Conclusion MirSNP could identify the putative miRNA-related SNPs from GWAS and eQTLs researches and provide the direction for subsequent functional researches.

  16. Next generation sequencing of SNPs using the HID-Ion AmpliSeq™ Identity Panel on the Ion Torrent PGM™ platform.

    Science.gov (United States)

    Guo, Fei; Zhou, Yishu; Song, He; Zhao, Jinling; Shen, Hongying; Zhao, Bin; Liu, Feng; Jiang, Xianhua

    2016-11-01

    The HID-Ion AmpliSeq™ Identity Panel (the HID Identity Panel) is designed to detect 124-plex single nucleotide polymorphisms (SNPs) with next generation sequencing (NGS) technology on the Ion Torrent PGM™ platform, including 90 individual identification SNPs (IISNPs) on autosomal chromosomes and 34 lineage informative SNPs (LISNPs) on Y chromosome. In this study, we evaluated performance for the HID Identity Panel to provide a reference for NGS-SNP application, focusing on locus strand balance, locus coverage balance, heterozygote balance, and background signals. Besides, several experiments were carried out to find out improvements and limitations of this panel, including studies of species specificity, repeatability and concordance, sensitivity, mixtures, case-type samples and degraded samples, population genetics and pedigrees following the Scientific Working Group on DNA Analysis Methods (SWGDAM) guidelines. In addition, Southern and Northern Chinese Han were investigated to assess applicability of this panel. Results showed this panel led to cross-reactivity with primates to some extent but rarely with non-primate animals. Repeatable and concordant genotypes could be obtained in triplicate with one exception at rs7520386. Full profiles could be obtained from 100pg input DNA, but the optimal input DNA would be 1ng-200pg with 21 initial PCR cycles. A sample with ≥20% minor contributor could be considered as a mixture by the number of homozygotes, and full profiles belonging to minor contributors could be detected between 9:1 and 1:9 mixtures with known reference profiles. Also, this assay could be used for case-type samples and degraded samples. For autosomal SNPs (A-SNPs), FST across all 90loci was not significantly different between Southern and Northern Chinese Han or between male and female samples. All A-SNP loci were independent in Chinese Han population. Except for 18loci with He Identity Panel presented high polymorphisms. Forensic parameters were

  17. Combining SNPs in latent variables to improve genomic prediction

    DEFF Research Database (Denmark)

    Heuven, Henri C M; Rosa, G J M; Janss, Luc

    The objective of this study was to develop and test hierarchical genomic models with latent variables that represent parts of the genomic values. An interaction model and a chromosome model were compared with a model based on variable selection in a simulated and real dataset. The program Bayz......: Hierarchical genetic model; Predictive value; Gibbs sampling; Variable selection....

  18. Combinations of SNPs related to signal transduction in bipolar disorder

    DEFF Research Database (Denmark)

    Koefoed, Pernille; Andreassen, Ole A; Bennike, Bente

    2011-01-01

    of complex diseases, it may be useful to look at combinations of genotypes. Genes related to signal transmission, e.g., ion channel genes, may be of interest in this respect in the context of bipolar disorder. In the present study, we analysed 803 SNPs in 55 genes related to aspects of signal transmission...... and calculated all combinations of three genotypes from the 3×803 SNP genotypes for 1355 controls and 607 patients with bipolar disorder. Four clusters of patient-specific combinations were identified. Permutation tests indicated that some of these combinations might be related to bipolar disorder. The WTCCC...... in the clusters in the two datasets. The present analyses of the combinations of SNP genotypes support a role for both genetic heterogeneity and interactions in the genetic architecture of bipolar disorder....

  19. ASSESSMENT OF CHAROLAIS BULLS POPULATION STRUCTURE BASED ON SNPs ANALYSES

    Directory of Open Access Journals (Sweden)

    Nina Moravčíková

    2014-02-01

    Full Text Available The aim of this study was identification of SNPs in leptin (LEP, leptin receptor (LEPR, growth hormone (GH and specific pituitary transcription factor (Pit-1 genes in order to analyze genetic structure of Charolais bulls’ population. The total numbers of genomic DNA samples were taken from 52 breeding bulls and analyzed by PCR-RFLP method. After digestion with restriction enzymes were detected in bulls’ population alleles with frequency: LEP/Sau3AI A 0.83 and B 0.17 (±0.037; LEPR/BseGI C 0.95 and T 0.05 (±0.021, GH/AluI L 0.62 and V 0.38 (±0.048 and Pit1/HinfI A 0.40 and B 0.60 (±0.048. Based on the observed vs. expected genotypes frequencies population across loci were in Hardy-Weinberg equilibrium (P>0.05, only in case of Pit-1 locus was detected disequilibrium. Predominant were in analyzed breeding bulls LEP/Sau3AIAA (0.69, LEPR/T945MCC (0.90, GH/AluILL (0.43 and Pit-1/HinfIAB (0.65 genotypes. The observed heterozygosity of SNPs was also transferred to the low (LEP/Sau3AI/0.248 and LEPR/T945M/0.088 or median polymorphic information content (GH/AluI/0.366 and Pit-1/HinfI/0.370. Within genetic variability estimating negative (LEPR/T945M and Pit-1/HinfI and positive values (LEP/Sau3AI and GH/AluI of fixation indexes FIS indicating slight heterozygote excess or deficiency based on analyzed genetic marker were observed.

  20. Chromosome Disorder Outreach

    Science.gov (United States)

    ... BLOG Join Us Donate You are not alone. Chromosome Disorder Outreach, Inc. is a non-profit organization, ... Support For all those diagnosed with any rare chromosome disorder. Since 1992, CDO has supported the parents ...

  1. Single nucleotide polymorphism discovery of Pinus radiata with chromosome walking PCR method

    Institute of Scientific and Technical Information of China (English)

    Wei LI; Hui LI; Xiaoyang CHEN; Harry WU

    2008-01-01

    In this paper, the basic principle of chromosome walking is presented and we used an actin gene of radiata pine (Pinus radiata) as an example to conduct upstream and downstream chromosome walking for EST sequences. The full genomic sequence (2154 bp) of the actin gene, including promoters 5' UTR, CDS and 3' UTR, was identified by chromosome walking. PCR amplification and DNA band sequencing from 200 unrelated radiata pine trees revealed a total of 21 SNPs for the actin gene, three in the promoter region, 15 in CDS and 4 in 3' UTR. The results of this experiment provide a technical framework for SNPs dis-covery in none coding regions of candidate genes.

  2. Chromosome painting in plants.

    NARCIS (Netherlands)

    Schubert, I.; Fransz, P.F.; Fuchs, J.; Jong, de J.H.

    2001-01-01

    The current 'state-of-art' as to chromosome painting in plants is reviewed. We define different situations described as painting so far: i) Genomic in situ hybridisation (GISH) with total genomic DNA to distinguish alien chromosomes on the basis of divergent dispersed repeats, ii) 'Chromosomal in si

  3. ZEBRAFISH CHROMOSOME-BANDING

    NARCIS (Netherlands)

    PIJNACKER, LP; FERWERDA, MA

    1995-01-01

    Banding techniques were carried out on metaphase chromosomes of zebrafish (Danio rerio) embryos. The karyotypes with the longest chromosomes consist of 12 metacentrics, 26 submetacentrics, and 12 subtelocentrics (2n = 50). All centromeres are C-band positive. Eight chromosomes have a pericentric C-b

  4. Computational and Structural Investigation of Deleterious Functional SNPs in Breast Cancer BRCA2 Gene

    Institute of Scientific and Technical Information of China (English)

    Rajasekaran R; George Priya Doss; Sudandiradoss C; Ramanathan K; Rituraj Purohit; Rao Sethumadhavan

    2008-01-01

    In this work, we have analyzed the genetic variation that can alter the expression and the function in BRCA2 gene using computational methods. Out of the total 534 SNPs, 101 were found to be non synonymous (nsSNPs). Among the 7 SNPs in the untranslated region, 3 SNPs were found in 5′ and 4 SNPs were found in 3′ un-translated regions (UTR). Of the nsSNPs 20.7% were found to be damaging by both SIFT and PolyPhen server among the 101 nsSNPs investigated. UTR resource tool suggested that 2 SNPs in the 5′ UTR region and 4 SNPs in the 3′ UTR regions might change the protein expression levels. The mutation from asparagine to isoleucine at the position 3124 of the native protein of BRCA2 gene was most deleterious by both SIFT and PolyPhen servers. A structural analysis of this mutated protein and the native protein was made which had an RMSD value of 0.301 nm. Based on this work, we proposed that this most deleterious nsSNP with an SNPid rs28897759 is an important candidate for the cause of breast cancer by BRCA2 gene.

  5. FGFR2 risk SNPs confer breast cancer risk by augmenting oestrogen responsiveness.

    Science.gov (United States)

    Campbell, Thomas M; Castro, Mauro A A; de Santiago, Ines; Fletcher, Michael N C; Halim, Silvia; Prathalingam, Radhika; Ponder, Bruce A J; Meyer, Kerstin B

    2016-08-01

    The fibroblast growth factor receptor 2 (FGFR2) locus is consistently the top hit in genome-wide association studies for oestrogen receptor-positive (ER(+)) breast cancer. Yet, its mode of action continues to be controversial. Here, we employ a systems biology approach to demonstrate that signalling via FGFR2 counteracts cell activation by oestrogen. In the presence of oestrogen, the oestrogen receptor (ESR1) regulon (set of ESR1 target genes) is in an active state. However, signalling by FGFR2 is able to reverse the activity of the ESR1 regulon. This effect is seen in multiple distinct FGFR2 signalling model systems, across multiple cells lines and is dependent on the presence of FGFR2. Increased oestrogen exposure has long been associated with an increased risk of breast cancer. We therefore hypothesized that risk variants should reduce FGFR2 expression and subsequent signalling. Indeed, transient transfection experiments assaying the three independent variants of the FGFR2 risk locus (rs2981578, rs35054928 and rs45631563) in their normal chromosomal context show that these single-nucleotide polymorphisms (SNPs) map to transcriptional silencer elements and that, compared with wild type, the risk alleles augment silencer activity. The presence of risk variants results in lower FGFR2 expression and increased oestrogen responsiveness. We thus propose a molecular mechanism by which FGFR2 can confer increased breast cancer risk that is consistent with oestrogen exposure as a major driver of breast cancer risk. Our findings may have implications for the clinical use of FGFR2 inhibitors.

  6. CsSNP: A Web-Based Tool for the Detecting of Comparative Segments SNPs.

    Science.gov (United States)

    Wang, Yi; Wang, Shuangshuang; Zhou, Dongjie; Yang, Shuai; Xu, Yongchao; Yang, Chao; Yang, Long

    2016-07-01

    SNP (single nucleotide polymorphism) is a popular tool for the study of genetic diversity, evolution, and other areas. Therefore, it is necessary to develop a convenient, utility, robust, rapid, and open source detecting-SNP tool for all researchers. Since the detection of SNPs needs special software and series steps including alignment, detection, analysis and present, the study of SNPs is limited for nonprofessional users. CsSNP (Comparative segments SNP, http://biodb.sdau.edu.cn/cssnp/ ) is a freely available web tool based on the Blat, Blast, and Perl programs to detect comparative segments SNPs and to show the detail information of SNPs. The results are filtered and presented in the statistics figure and a Gbrowse map. This platform contains the reference genomic sequences and coding sequences of 60 plant species, and also provides new opportunities for the users to detect SNPs easily. CsSNP is provided a convenient tool for nonprofessional users to find comparative segments SNPs in their own sequences, and give the users the information and the analysis of SNPs, and display these data in a dynamic map. It provides a new method to detect SNPs and may accelerate related studies.

  7. SNPs in PPARG associate with type 2 diabetes and interact with physical activity

    DEFF Research Database (Denmark)

    Oskari Kilpeläinen, Tuomas; Lakka, Timo A; Laaksonen, David E

    2008-01-01

    To study the associations of seven single-nucleotide polymorphisms (SNPs) in the peroxisome proliferator-activated receptor gamma (PPARG) gene with the conversion from impaired glucose tolerance (IGT) to type 2 diabetes (T2D), and the interactions of the SNPs with physical activity (PA)....

  8. Data mining of public SNP databases for the selection of intragenic SNPs

    NARCIS (Netherlands)

    Aerts, J.; Wetzels, Y.; Cohen, N.; Aerssens, J.

    2002-01-01

    Different strategies to search public single nucleotide polymorphism (SNP) databases for intragenic SNPs were evaluated. First, we assembled a strategy to annotate SNPs onto candidate genes based on a BLAST search of public SNP databases (Intragenic SNP Annotation by BLAST, ISAB). Only BLAST hits th

  9. The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm

    DEFF Research Database (Denmark)

    Helgadottir, Anna; Thorleifsson, Gudmar; Magnusson, Kristinn P

    2008-01-01

    . Here we report that rs10757278-G is associated with, in addition to CAD, abdominal aortic aneurysm (AAA; odds ratio (OR) = 1.31, P = 1.2 x 10(-12)) and intracranial aneurysm (OR = 1.29, P = 2.5 x 10(-6)), but not with T2D. This variant is the first to be described that affects the risk of AAA...... and intracranial aneurysm in many populations. The association of rs10811661-T to T2D replicates in our samples, but the variant does not associate with any of the five arterial diseases examined. These findings extend our insight into the role of the sequence variant tagged by rs10757278-G and show...

  10. Chromosomal instability in meningiomas.

    Science.gov (United States)

    van Tilborg, Angela A G; Al Allak, Bushra; Velthuizen, Sandra C J M; de Vries, Annie; Kros, Johan M; Avezaat, Cees J J; de Klein, Annelies; Beverloo, H Berna; Zwarthoff, Ellen C

    2005-04-01

    Approximately 60% of sporadic meningiomas are caused by inactivation of the NF2 tumor suppressor gene on chromosome 22. No causative gene is known for the remaining 40%. Cytogenetic analysis shows that meningiomas caused by inactivation of the NF2 gene can be divided into tumors that show monosomy 22 as the sole abnormality and tumors with a more complex karyotype. Meningiomas not caused by the NF2 gene usually have a diploid karyotype. Here we report that, besides the clonal chromosomal aberrations, the chromosome numbers in many meningiomas varied from one metaphase spread to the other, a feature that is indicative of chromosomal instability. Unexpectedly and regardless of genotype, a subgroup of tumors was observed with an average number of 44.9 chromosomes and little variation in the number of chromosomes per metaphase spread. In addition, a second subgroup was recognized with a hyperdiploid number of chromosomes (average 48.5) and considerable variation in numbers per metaphase. However, this numerical instability resulted in a clonal karyotype with chromosomal gains and losses in addition to loss of chromosome 22 only in meningiomas caused by inactivation of the NF2 gene. In cultured cells of all tumor groups, bi- and multinucleated cells were seen, as well as anaphase bridges, residual chromatid strings, multiple spindle poles, and unseparated chromatids, suggesting defects in the mitotic apparatus or kinetochore. Thus, we conclude that even a benign and slow-growing tumor like a meningioma displays chromosomal instability.

  11. Identification of SNPs in Goats (Capra hircus using RNA-Seq Analysis

    Directory of Open Access Journals (Sweden)

    Upasna Sharma

    2012-08-01

    Full Text Available Single Nucleotide Polymorphisms (SNPs have become the marker of choice for genome-wide association studies. In order to provide the best genome coverage for the analysis of performance and production traits, a large number of relatively evenly distributed SNPs are needed. Gene-associated SNPs may fulfill these requirements of large numbers and genome wide distribution. In addition, gene-associated SNPs could themselves be causative SNPs for traits. The main objective of our work was to identify large numbers of gene-associated SNPs using high-throughput next generation sequencing. Transcriptome sequencing was conducted on 2 tissues viz. liver and kidney for 5 breeds of goat (Kanniadu, Osmanabadi, Black Bengal, Changthangi and Sirohi using Illumina next generation sequencing technology. Approximately 46.4 million reads for Black Bengal, 61.9 from Kanniadu, 58.2 from Changthangi, 47.3 from Osmanabadi, 73.2 from Sirohi were obtained by sequencing gene transcripts derived from kidney while 37, 27.2, 19.4, 56.9 and 80.7 million reads were obtained by gene transcripts derived from liver. The analysis of total number of SNPs in liver and kidney revealed that out of a total of 68597 SNPs in liver, the total number of transversions was 21300 and the number of transitions was 47297. A total of 1574 SNPs of liver were complex. Similarly for kidney the total number of 72047 SNPs were categorised into 22774 transversions and 49273 transitions. The total number of complex SNPs in kidney was 1597. The number of transitions is more than double the number of transversions in both the tissues. Further analysis of transversion revealed a preponderance of cytosine and guanine change compared to other nucleotides. 12863 and 11319 transversions out of 21300 and 22774 transversions respectively for liver and kidney revealed this bias. When multiple individuals with different genetic backgrounds were used, RNA-Seq was very effective for the identification of SNPs. The

  12. Effect of SNPs in protein kinase Czgene on gene expression in the reporter gene detection system

    Institute of Scientific and Technical Information of China (English)

    Zhuo Liu; Hong-Xia Sun; Yong-Wei Zhang; Yun-Feng Li; Jin Zuo; Yan Meng; Fu-De Fang

    2004-01-01

    AIM: To investigated the effects of the SNPs (rs411021,rs436045, rs427811, rs385039 and rs809912) on gene expression and further identify the susceptibility genes of type 2 diabetes.METHODS: Ten allele fragments (49 bp each) were synthesized according to the 5 SNPs mentioned above.These fragments were cloned into luciferase reporter gene vector and then transfected into HepG2 cells. The activity of the luciferase was assayed. Effects of the SNPs on RNA splicing were analyzed by bioinformatics.RESULTS: rs427811T allele and rs809912G allele enhanced the activity of the reporter gene expression. None of the 5 SNPs affected RNA splicing.CONCLUSION: SNPs in protein kinase Cz (PKCZ) gene probably play a role in the susceptibility to type 2 diabetes by affecting the expression level of the relevant genes.

  13. Description and interpretation of various SNPs identified by BRCA2 gene sequencing

    Directory of Open Access Journals (Sweden)

    Anca Negura

    2011-12-01

    Full Text Available Molecular diagnosis for hereditary breast and ovarian cancer (HBOC involves systematic DNA sequencing of predisposition genes like BRCA1 or BRCA2. Deleterious mutations within such genes are responsible for developing the disease, but other sequence variants can also be identified. Common Single Nucleotide Polymorphisms (SNPs are usually present in human genome, defining alleles whose frequencies widely vary in different populations. Either intragenic or intronic, silent or generating aminoacid substitutions, SNPs cannot be afforded themselves a predisposition status. However, prevalent SNPs can be used to define gene haplotypes, with also various frequencies. Since some mutation can easily be assigned to haplotypes (such is the case for BRCA1 gene, SNPs can therefore provide usual information in interpreting gene mutations effects on hereditary predisposition to cancer. Here we describe 10 BRCA2 SNPs identified by complete gene sequencing

  14. Inferring Alcoholism SNPs and Regulatory Chemical Compounds Based on Ensemble Bayesian Network.

    Science.gov (United States)

    Chen, Huan; Sun, Jiatong; Jiang, Hong; Wang, Xianyue; Wu, Lingxiang; Wu, Wei; Wang, Qh

    2016-12-20

    The disturbance of consciousness is one of the most common symptoms of those have alcoholism and may cause disability and mortality. Previous studies indicated that several single nucleotide polymorphisms (SNP) increase the susceptibility of alcoholism. In this study, we utilized the Ensemble Bayesian Network (EBN) method to identify causal SNPs of alcoholism based on the verified GAW14 data. Thirteen out of eighteen SNPs directly connected with alcoholism were found concordance with potential risk regions of alcoholism in OMIM database. As a number of SNPs were found contributing to alteration on gene expression, known as expression quantitative trait loci (eQTLs), we further sought to identify chemical compounds acting as regulators of alcoholism genes captured by causal SNPs. Chloroprene and valproic acid were identified as the expression regulators for genes C11orf66 and SALL3 which were captured by alcoholism SNPs, respectively.

  15. Association between SNPs within candidate genes and compounds related to boar taint and reproduction

    DEFF Research Database (Denmark)

    Moe, Maren; Lien, Sigbjørn; Aasmundstad, Torunn

    2009-01-01

    understanding of the complex regulation of the trait and for the purpose of identifying markers that can be used to improve the gain of breeding. The beneficial SNPs to be used in breeding would have the combinational effects of reducing levels of boar taint without affecting fertility of the animals. The aim...... of this study was to detect SNPs in boar taint candidate genes and to perform association studies for both single SNPs and haplotypes with levels of boar taint compounds and phenotypes related to reproduction. RESULTS: An association study involving 275 SNPs in 121 genes and compounds related to boar taint...... and reproduction were carried out in Duroc and Norwegian Landrace boars. Phenotypes investigated were levels of androstenone, skatole and indole in adipose tissue, levels of androstenone, testosterone, estrone sulphate and 17beta-estradiol in plasma, and length of bulbo urethralis gland. The SNPs were genotyped...

  16. Multistudy fine mapping of chromosome 2q identifies XRCC5 as a chronic obstructive pulmonary disease susceptibility gene

    DEFF Research Database (Denmark)

    Hersh, Craig P; Pillai, Sreekumar G; Zhu, Guohua

    2010-01-01

    the National Emphysema Treatment Trial and 330 community control subjects. Significant associations from the combined results across the two case-control studies were followed up in 1,839 individuals from 603 families from the International COPD Genetics Network (ICGN) and in 949 individuals from 127 families...... to the identification of chronic obstructive pulmonary disease (COPD) susceptibility genes on chromosome 2q. METHODS: Within the chromosome 2q linkage region, 2,843 SNPs were genotyped in 806 COPD cases and 779 control subjects from Norway, and 2,484 SNPs were genotyped in 309 patients with severe COPD from...... in the Boston Early-Onset COPD Study. MEASUREMENTS AND MAIN RESULTS: Merging the results of the two case-control analyses, 14 of the 790 overlapping SNPs had a combined P

  17. X-chromosome Forkhead Box P3 polymorphisms associate with atopy in girls in three Dutch birth cohorts

    NARCIS (Netherlands)

    Bottema, R. W. B.; Kerkhof, M.; Reijmerink, N. E.; Koppelman, G. H.; Thijs, C.; Stelma, F. F.; Smit, H. A.; Brunekreef, B.; van Schayck, C. P.; Postma, D. S.

    2010-01-01

    P>Background: The Forkhead Box P3 (FOXP3) gene, located on the X-chromosome, encodes a transcription factor that directs T cells toward a regulatory phenotype. Regulatory T cells may suppress development of atopy. We evaluated whether single-nucleotide polymorphisms (SNPs) of FOXP3 are associated wi

  18. X-chromosome Forkhead Box P3 polymorphisms associate with atopy in girls in three Dutch birth cohorts.

    NARCIS (Netherlands)

    Bottema, R.W.B.; Kerkhof, M.; Reijmerink, N.E.; Koppelman, G.H.; Thijs, C.; Stelma, F.F.; Smit, H.A.; Brunekreef, B.

    2010-01-01

    BACKGROUND: The Forkhead Box P3 (FOXP3) gene, located on the X-chromosome, encodes a transcription factor that directs T cells toward a regulatory phenotype. Regulatory T cells may suppress development of atopy. We evaluated whether single-nucleotide polymorphisms (SNPs) of FOXP3 are associated with

  19. Genotyping of 75 SNPs using arrays for individual identification in five population groups.

    Science.gov (United States)

    Hwa, Hsiao-Lin; Wu, Lawrence Shih Hsin; Lin, Chun-Yen; Huang, Tsun-Ying; Yin, Hsiang-I; Tseng, Li-Hui; Lee, James Chun-I

    2016-01-01

    Single nucleotide polymorphism (SNP) typing offers promise to forensic genetics. Various strategies and panels for analyzing SNP markers for individual identification have been published. However, the best panels with fewer identity SNPs for all major population groups are still under discussion. This study aimed to find more autosomal SNPs with high heterozygosity for individual identification among Asian populations. Ninety-six autosomal SNPs of 502 DNA samples from unrelated individuals of five population groups (208 Taiwanese Han, 83 Filipinos, 62 Thais, 69 Indonesians, and 80 individuals with European, Near Eastern, or South Asian ancestry) were analyzed using arrays in an initial screening, and 75 SNPs (group A, 46 newly selected SNPs; groups B, 29 SNPs based on a previous SNP panel) were selected for further statistical analyses. Some SNPs with high heterozygosity from Asian populations were identified. The combined random match probability of the best 40 and 45 SNPs was between 3.16 × 10(-17) and 7.75 × 10(-17) and between 2.33 × 10(-19) and 7.00 × 10(-19), respectively, in all five populations. These loci offer comparable power to short tandem repeats (STRs) for routine forensic profiling. In this study, we demonstrated the population genetic characteristics and forensic parameters of 75 SNPs with high heterozygosity from five population groups. This SNPs panel can provide valuable genotypic information and can be helpful in forensic casework for individual identification among these populations.

  20. Analysis of plant meiotic chromosomes by chromosome painting.

    Science.gov (United States)

    Lysak, Martin A; Mandáková, Terezie

    2013-01-01

    Chromosome painting (CP) refers to visualization of large chromosome regions, entire chromosome arms, or entire chromosomes via fluorescence in situ hybridization (FISH). For CP in plants, contigs of chromosome-specific bacterial artificial chromosomes (BAC) from the target species or from a closely related species (comparative chromosome painting, CCP) are typically applied as painting probes. Extended pachytene chromosomes provide the highest resolution of CP in plants. CP enables identification and tracing of particular chromosome regions and/or entire chromosomes throughout all meiotic stages as well as corresponding chromosome territories in premeiotic interphase nuclei. Meiotic pairing and structural chromosome rearrangements (typically inversions and translocations) can be identified by CP. Here, we describe step-by-step protocols of CP and CCP in plant species including chromosome preparation, BAC DNA labeling, and multicolor FISH.

  1. "GenotypeColour™": colour visualisation of SNPs and CNVs

    Directory of Open Access Journals (Sweden)

    Magri Chiara

    2009-02-01

    Full Text Available Abstract Background The volume of data available on genetic variations has increased considerably with the recent development of high-density, single-nucleotide polymorphism (SNP arrays. Several software programs have been developed to assist researchers in the analysis of this huge amount of data, but few can rely upon a whole genome variability visualisation system that could help data interpretation. Results We have developed GenotypeColour™ as a rapid user-friendly tool able to upload, visualise and compare the huge amounts of data produced by Affymetrix Human Mapping GeneChips without losing the overall view of the data. Some features of GenotypeColour™ include visualising the entire genome variability in a single screenshot for one or more samples, the simultaneous display of the genotype and Copy Number state for thousands of SNPs, and the comparison of large amounts of samples by producing "consensus" images displaying regions of complete or partial identity. The software is also useful for genotype analysis of trios and to show regions of potential uniparental disomy (UPD. All information can then be exported in a tabular format for analysis with dedicated software. At present, the software can handle data from 10 K, 100 K, 250 K, 5.0 and 6.0 Affymetrix chips. Conclusion We have created a software that offers a new way of displaying and comparing SNP and CNV genomic data. The software is available free at http://www.med.unibs.it/~barlati/GenotypeColour and is especially useful for the analysis of multiple samples.

  2. The Precarious Prokaryotic Chromosome

    OpenAIRE

    Kuzminov, Andrei

    2014-01-01

    Evolutionary selection for optimal genome preservation, replication, and expression should yield similar chromosome organizations in any type of cells. And yet, the chromosome organization is surprisingly different between eukaryotes and prokaryotes. The nuclear versus cytoplasmic accommodation of genetic material accounts for the distinct eukaryotic and prokaryotic modes of genome evolution, but it falls short of explaining the differences in the chromosome organization. I propose that the t...

  3. Mechanisms for chromosome segregation.

    Science.gov (United States)

    Bouet, Jean-Yves; Stouf, Mathieu; Lebailly, Elise; Cornet, François

    2014-12-01

    Bacteria face the problem of segregating their gigantic chromosomes without a segregation period restricted in time and space, as Eukaryotes do. Segregation thus involves multiple activities, general or specific of a chromosome region and differentially controlled. Recent advances show that these various mechanisms conform to a “pair and release” rule, which appears as a general rule in DNA segregation. We describe the latest advances in segregation of bacterial chromosomes with emphasis on the different pair and release mechanisms.

  4. Bacterial chromosome segregation.

    Science.gov (United States)

    Possoz, Christophe; Junier, Ivan; Espeli, Olivier

    2012-01-01

    Dividing cells have mechanisms to ensure that their genomes are faithfully segregated into daughter cells. In bacteria, the description of these mechanisms has been considerably improved in the recent years. This review focuses on the different aspects of bacterial chromosome segregation that can be understood thanks to the studies performed with model organisms: Escherichia coli, Bacillus subtilis, Caulobacter crescentus and Vibrio cholerae. We describe the global positionning of the nucleoid in the cell and the specific localization and dynamics of different chromosomal loci, kinetic and biophysic aspects of chromosome segregation are presented. Finally, a presentation of the key proteins involved in the chromosome segregation is made.

  5. Chromosome oscillations in mitosis

    Science.gov (United States)

    Campas, Otger

    2008-03-01

    Successful cell division necessitates a tight regulation of chromosome movement via the activity of molecular motors. Many of the key players at the origin of the forces generating the motion have been identified, but their spatial and temporal organization remains elusive. In animal cells, chromosomes periodically switch between phases of movement towards and away from the pole. This characteristic oscillatory behaviour cannot be explained by the current models of chromosome positioning and congression. We perform a self-contained theoretical analysis in which the motion of mono-oriented chromosomes results from the competition between the activity of the kinetochore and chromokinesin motors on the chromosome arms. Our analysis, consistent with the available experimental data, proposes that the interplay between the aster-like morphology of the spindle and the collective kinetics of molecular motors is at the origin of chromosome oscillations, positioning and congression. It provides a natural explanation for the so-called chromosome directional instability and for the mechanism by which chromosomes sense their position in space. In addition, we estimate the in vivo velocity of chromokinesins at vanishing load and propose new experiments to assess the mechanism at the origin of chromosome movement in cell division.

  6. Proteasome modulator 9 gene SNPs, responsible for anti-depressant response, are in linkage with generalized anxiety disorder.

    Science.gov (United States)

    Gragnoli, Claudia

    2014-09-01

    Proteasome modulator 9 (PSMD9) gene single nucleotide polymorphism (SNP) rs1043307/rs2514259 (E197G) is associated with significant clinical response to the anti-depressant desipramine. PSMD9 SNP rs74421874 [intervening sequence (IVS) 3 + nt460 G>A], rs3825172 (IVS3 + nt437 C>T) and rs1043307/rs2514259 (E197G A>G) are all linked to type 2 diabetes (T2D), maturity-onset-diabetes-of the young 3 (MODY3), obesity and waist circumference, hypertension, hypercholesterolemia, T2D-macrovascular and T2D-microvascular disease, T2D-neuropathy, T2D-carpal tunnel syndrome, T2D-nephropathy, T2D-retinopathy, non-diabetic retinopathy and depression. PSMD9 rs149556654 rare SNP (N166S A>G) and the variant S143G A>G also contribute to T2D. PSMD9 is located in the chromosome 12q24 locus, which per se is in linkage with depression, bipolar disorder and anxiety. In the present study, we wanted to determine whether PSMD9 is linked to general anxiety disorder in Italian T2D families. Two-hundred Italian T2D families were phenotyped for generalized anxiety disorder, using the diagnostic criteria of DSM-IV. When the diagnosis was unavailable or unclear, the trait was reported as unknown. The 200 Italians families were tested for the PSMD9 T2D risk SNPs rs74421874 (IVS3 + nt460 G>A), rs3825172 (IVS3 +nt437 T>C) and for the T2D risk and anti-depressant response SNP rs1043307/rs2514259 (E197G A>G) for evidence of linkage with generalized anxiety disorder. Non-parametric linkage analysis was executed via Merlin software. One-thousand simulation tests were performed to exclude results due to random chance. In our study, the PSMD9 gene SNPs rs74421874, rs3825172, and rs1043307/rs2514259 result in linkage to generalized anxiety disorder. This is the first report describing PSMD9 gene SNPs in linkage to generalized anxiety disorder in T2D families.

  7. Fetal chromosome analysis: screening for chromosome disease?

    DEFF Research Database (Denmark)

    Philip, J; Tabor, Ann; Bang, J

    1983-01-01

    The aim of the study was to investigate the rationale of the current indications for fetal chromosome analysis. 5372 women had 5423 amniocentesis performed, this group constituting a consecutive sample at the chromosome laboratory, Rigshospitalet, Copenhagen from March 1973 to September 1980 (Group...... to women having amniocentesis, although considered not to have any increased risk of fetal chromosome abnormality (1390 pregnancies, group B). They were also compared with 750 consecutive pregnancies in women 25-34 years of age, in whom all heritable diseases were excluded (group C). The risk of unbalanced...... with women without elevated risk. Spontaneous abortion rate and prematurity rate did not differ from rates expected without amniocentesis. It is concluded that current indications may be characterized as a mixture of evident high risk factors and factors with only a minor influence on risk. Indications...

  8. Rapid de novo evolution of X chromosome dosage compensation in Silene latifolia, a plant with young sex chromosomes.

    Science.gov (United States)

    Muyle, Aline; Zemp, Niklaus; Deschamps, Clothilde; Mousset, Sylvain; Widmer, Alex; Marais, Gabriel A B

    2012-01-01

    Silene latifolia is a dioecious plant with heteromorphic sex chromosomes that have originated only ∼10 million years ago and is a promising model organism to study sex chromosome evolution in plants. Previous work suggests that S. latifolia XY chromosomes have gradually stopped recombining and the Y chromosome is undergoing degeneration as in animal sex chromosomes. However, this work has been limited by the paucity of sex-linked genes available. Here, we used 35 Gb of RNA-seq data from multiple males (XY) and females (XX) of an S. latifolia inbred line to detect sex-linked SNPs and identified more than 1,700 sex-linked contigs (with X-linked and Y-linked alleles). Analyses using known sex-linked and autosomal genes, together with simulations indicate that these newly identified sex-linked contigs are reliable. Using read numbers, we then estimated expression levels of X-linked and Y-linked alleles in males and found an overall trend of reduced expression of Y-linked alleles, consistent with a widespread ongoing degeneration of the S. latifolia Y chromosome. By comparing expression intensities of X-linked alleles in males and females, we found that X-linked allele expression increases as Y-linked allele expression decreases in males, which makes expression of sex-linked contigs similar in both sexes. This phenomenon is known as dosage compensation and has so far only been observed in evolutionary old animal sex chromosome systems. Our results suggest that dosage compensation has evolved in plants and that it can quickly evolve de novo after the origin of sex chromosomes.

  9. Evaluating GWAS-identified SNPs for age at natural menopause among chinese women.

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    Chong Shen

    Full Text Available BACKGROUND: Age at natural menopause (ANM is a complex trait with high heritability and is associated with several major hormonal-related diseases. Recently, several genome-wide association studies (GWAS, conducted exclusively among women of European ancestry, have discovered dozens of genetic loci influencing ANM. No study has been conducted to evaluate whether these findings can be generalized to Chinese women. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated the index single nucleotide polymorphisms (SNPs in 19 GWAS-identified genetic susceptibility loci for ANM among 3,533 Chinese women who had natural menopause. We also investigated 3 additional SNPs which were in LD with the index SNP in European-ancestry but not in Asian-ancestry populations. Two genetic risk scores (GRS were calculated to summarize SNPs across multiple loci one for all SNPs tested (GRSall, and one for SNPs which showed association in our study (GRSsel. All 22 SNPs showed the same association direction as previously reported. Eight SNPs were nominally statistically significant with P≤0.05: rs4246511 (RHBDL2, rs12461110 (NLRP11, rs2307449 (POLG, rs12611091 (BRSK1, rs1172822 (BRSK1, rs365132 (UIMC1, rs2720044 (ASH2L, and rs7246479 (TMEM150B. Especially, SNPs rs4246511, rs365132, rs1172822, and rs7246479 remained significant even after Bonferroni correction. Significant associations were observed for GRS. Women in the highest quartile began menopause 0.7 years (P = 3.24×10(-9 and 0.9 years (P = 4.61×10(-11 later than those in the lowest quartile for GRSsel and GRSall, respectively. CONCLUSIONS: Among the 22 investigated SNPs, eight showed associations with ANM (P<0.05 in our Chinese population. Results from this study extend some recent GWAS findings to the Asian-ancestry population and may guide future efforts to identify genetic determination of menopause.

  10. Screening and Evaluation of Deleterious SNPs in APOE Gene of Alzheimer’s Disease

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    Tariq Ahmad Masoodi

    2012-01-01

    Full Text Available Introduction. Apolipoprotein E (APOE is an important risk factor for Alzheimer’s disease (AD and is present in 30–50% of patients who develop late-onset AD. Several single-nucleotide polymorphisms (SNPs are present in APOE gene which act as the biomarkers for exploring the genetic basis of this disease. The objective of this study is to identify deleterious nsSNPs associated with APOE gene. Methods. The SNPs were retrieved from dbSNP. Using I-Mutant, protein stability change was calculated. The potentially functional nonsynonymous (ns SNPs and their effect on protein was predicted by PolyPhen and SIFT, respectively. FASTSNP was used for functional analysis and estimation of risk score. The functional impact on the APOE protein was evaluated by using Swiss PDB viewer and NOMAD-Ref server. Results. Six nsSNPs were found to be least stable by I-Mutant 2.0 with DDG value of >−1.0. Four nsSNPs showed a highly deleterious tolerance index score of 0.00. Nine nsSNPs were found to be probably damaging with position-specific independent counts (PSICs score of ≥2.0. Seven nsSNPs were found to be highly polymorphic with a risk score of 3-4. The total energies and root-mean-square deviation (RMSD values were higher for three mutant-type structures compared to the native modeled structure. Conclusion. We concluded that three nsSNPs, namely, rs11542041, rs11542040, and rs11542034, to be potentially functional polymorphic.

  11. Geographic differences in allele frequencies of susceptibility SNPs for cardiovascular disease

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    Kullo Iftikhar J

    2011-04-01

    Full Text Available Abstract Background We hypothesized that the frequencies of risk alleles of SNPs mediating susceptibility to cardiovascular diseases differ among populations of varying geographic origin and that population-specific selection has operated on some of these variants. Methods From the database of genome-wide association studies (GWAS, we selected 36 cardiovascular phenotypes including coronary heart disease, hypertension, and stroke, as well as related quantitative traits (eg, body mass index and plasma lipid levels. We identified 292 SNPs in 270 genes associated with a disease or trait at P -8. As part of the Human Genome-Diversity Project (HGDP, 158 (54.1% of these SNPs have been genotyped in 938 individuals belonging to 52 populations from seven geographic areas. A measure of population differentiation, FST, was calculated to quantify differences in risk allele frequencies (RAFs among populations and geographic areas. Results Large differences in RAFs were noted in populations of Africa, East Asia, America and Oceania, when compared with other geographic regions. The mean global FST (0.1042 for 158 SNPs among the populations was not significantly higher than the mean global FST of 158 autosomal SNPs randomly sampled from the HGDP database. Significantly higher global FST (P FST of 2036 putatively neutral SNPs. For four of these SNPs, additional evidence of selection was noted based on the integrated Haplotype Score. Conclusion Large differences in RAFs for a set of common SNPs that influence risk of cardiovascular disease were noted between the major world populations. Pairwise comparisons revealed RAF differences for at least eight SNPs that might be due to population-specific selection or demographic factors. These findings are relevant to a better understanding of geographic variation in the prevalence of cardiovascular disease.

  12. Identifying Liver Cancer-Related Enhancer SNPs by Integrating GWAS and Histone Modification ChIP-seq Data

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    Tianjiao Zhang

    2016-01-01

    Full Text Available Many disease-related single nucleotide polymorphisms (SNPs have been inferred from genome-wide association studies (GWAS in recent years. Numerous studies have shown that some SNPs located in protein-coding regions are associated with numerous diseases by affecting gene expression. However, in noncoding regions, the mechanism of how SNPs contribute to disease susceptibility remains unclear. Enhancer elements are functional segments of DNA located in noncoding regions that play an important role in regulating gene expression. The SNPs located in enhancer elements may affect gene expression and lead to disease. We presented a method for identifying liver cancer-related enhancer SNPs through integrating GWAS and histone modification ChIP-seq data. We identified 22 liver cancer-related enhancer SNPs, 9 of which were regulatory SNPs involved in distal transcriptional regulation. The results highlight that these enhancer SNPs may play important roles in liver cancer.

  13. Identifying Liver Cancer-Related Enhancer SNPs by Integrating GWAS and Histone Modification ChIP-seq Data

    Science.gov (United States)

    Hu, Yang; Wu, Xiaoliang; Ma, Rui

    2016-01-01

    Many disease-related single nucleotide polymorphisms (SNPs) have been inferred from genome-wide association studies (GWAS) in recent years. Numerous studies have shown that some SNPs located in protein-coding regions are associated with numerous diseases by affecting gene expression. However, in noncoding regions, the mechanism of how SNPs contribute to disease susceptibility remains unclear. Enhancer elements are functional segments of DNA located in noncoding regions that play an important role in regulating gene expression. The SNPs located in enhancer elements may affect gene expression and lead to disease. We presented a method for identifying liver cancer-related enhancer SNPs through integrating GWAS and histone modification ChIP-seq data. We identified 22 liver cancer-related enhancer SNPs, 9 of which were regulatory SNPs involved in distal transcriptional regulation. The results highlight that these enhancer SNPs may play important roles in liver cancer. PMID:27429976

  14. Association of SNPs and haplotypes in GABA(A) receptor beta(2) gene with schizophrenia

    Institute of Scientific and Technical Information of China (English)

    WSLau; CFXuan; ZChan; CFFeng; GYHe; LCao; ZCLiu; HLuan; QMXue

    2005-01-01

    Disturbances in GABAergic system have been observed in schizophrenics.(1-3) In the present study, population association analysis was performed on 19 SNPs in the alpha(l), beta(2), gamma(2), epsilon and pi subunit genes of GABA(A) receptor. Five SNPs in GABRB2, namely B217G1584T, rs1816071, rs194072, rs252944 and rs187269,were found to be significantly associated, and their haplotypes in linkage disequilibrium, with schizophrenia. This represents the first report on any disease association of SNPs in the human GABA(A) receptor genes, and focuses attention on the GABAergic hypothesis of schizophrenia etiology.(3,4)

  15. Allelic expression mapping across cellular lineages to establish impact of non-coding SNPs

    OpenAIRE

    Adoue, Veronique; Schiavi, Alicia; Light, Nicholas; Carlsson Almlöf, Jonas; Lundmark, Per; Ge, Bing; Kwan, Tony; Caron, Maxime; Rönnblom, Lars; Wang, Chuan; Chen, Shu-Huang; Goodall, Alison H; Cambien, Francois; Deloukas, Panos; Ouwehand, Willem H.

    2014-01-01

    Most complex disease-associated genetic variants are located in non-coding regions and are therefore thought to be regulatory in nature. Association mapping of differential allelic expression (AE) is a powerful method to identify SNPs with direct cis-regulatory impact (cis-rSNPs). We used AE mapping to identify cis-rSNPs regulating gene expression in 55 and 63 HapMap lymphoblastoid cell lines from a Caucasian and an African population, respectively, 70 fibroblast cell lines, and 188 purified ...

  16. Complex high-resolution linkage disequilibrium and haplotype patterns of single-nucleotide polymorphisms in 2.5 Mb of sequence on human chromosome 21.

    Science.gov (United States)

    Olivier, M; Bustos, V I; Levy, M R; Smick, G A; Moreno, I; Bushard, J M; Almendras, A A; Sheppard, K; Zierten, D L; Aggarwal, A; Carlson, C S; Foster, B D; Vo, N; Kelly, L; Liu, X; Cox, D R

    2001-11-01

    One approach to identify potentially important segments of the human genome is to search for DNA regions with nonrandom patterns of human sequence variation. Previous studies have investigated these patterns primarily in and around candidate gene regions. Here, we determined patterns of DNA sequence variation in 2.5 Mb of finished sequence from five regions on human chromosome 21. By sequencing 13 individual chromosomes, we identified 1460 single-nucleotide polymorphisms (SNPs) and obtained unambiguous haplotypes for all chromosomes. For all five chromosomal regions, we observed segments with high linkage disequilibrium (LD), extending from 1.7 to>81 kb (average 21.7 kb), disrupted by segments of similar or larger size with no significant LD between SNPs. At least 25% of the contig sequences consisted of segments with high LD between SNPs. Each of these segments was characterized by a restricted number of observed haplotypes,with the major haplotype found in over 60% of all chromosomes. In contrast, the interspersed segments with low LD showed significantly more haplotype patterns. The position and extent of the segments of high LD with restricted haplotype variability did not coincide with the location of coding sequences. Our results indicate that LD and haplotype patterns need to be investigated with closely spaced SNPs throughout the human genome, independent of the location of coding sequences, to reliably identify regions with significant LD useful for disease association studies.

  17. XYY chromosome anomaly and schizophrenia.

    Science.gov (United States)

    Rajagopalan, M; MacBeth, R; Varma, S L

    1998-02-07

    Sex chromosome anomalies have been associated with psychoses, and most of the evidence is linked to the presence of an additional X chromosome. We report a patient with XYY chromosome anomaly who developed schizophrenia.

  18. Atrial Fibrillation associated chromosome 4q25 variants are not associated with PITX2c expression in human adult left atrial appendages.

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    Shamone R Gore-Panter

    Full Text Available Atrial Fibrillation (AF, the most common sustained arrhythmia, has a strong genetic component, but the mechanism by which common genetic variants lead to increased AF susceptibility is unknown. Genome-wide association studies (GWAS have identified that the single nucleotide polymorphisms (SNPs most strongly associated with AF are located on chromosome 4q25 in an intergenic region distal to the PITX2 gene. Our objective was to determine whether the AF-associated SNPs on chromosome 4q25 were associated with PITX2c expression in adult human left atrial appendages. Analysis of a lone AF GWAS identified four independent AF risk SNPs at chromosome 4q25. Human adult left atrial appendage tissue was obtained from 239 subjects of European Ancestry and used for SNP analysis of genomic DNA and determination of PITX2c RNA expression levels by quantitative PCR. Subjects were divided into three groups based on their history of AF and pre-operative rhythm. AF rhythm subjects had higher PITX2c expression than those with history of AF but in sinus rhythm. PITX2c expression was not associated with the AF risk SNPs in human adult left atrial appendages in all subjects combined or in each of the three subgroups. However, we identified seven SNPs modestly associated with PITX2c expression located in the introns of the ENPEP gene, ∼54 kb proximal to PITX2. PITX2c expression in human adult left atrial appendages is not associated with the chromosome 4q25 AF risk SNPs; thus, the mechanism by which these SNPs are associated with AF remains enigmatic.

  19. Optimisation and validation of methods to assess single nucleotide polymorphisms (SNPs) in archival histological material

    DEFF Research Database (Denmark)

    Andreassen, Christian Nicolaj; Sørensen, Flemming Brandt; Overgaard, J.;

    2004-01-01

    only archival specimens are available. This study was conducted to validate protocols optimised for assessment of SNPs based on paraffin embedded, formalin fixed tissue samples. PATIENTS AND METHODS: In 137 breast cancer patients, three TGFB1 SNPs were assessed based on archival histological specimens...... TGFB1 SNPs was used to provide an indirect validation of the genotyping results. Furthermore, two different methods for DNA extraction were compared (semi-automatic DNA extraction using the ABI Prism 6100 Nucleic Acid PrepStation versus Proteinase K digestion for 5 days followed by boiling and DNA...... precipitation). RESULTS: Assessment of SNPs based on archival histological material is encumbered by a number of obstacles and pitfalls. However, these can be widely overcome by careful optimisation of the methods used for sample selection, DNA extraction and PCR. Within 130 samples that fulfil the criteria...

  20. SNP uniqueness problem: a proof-of-principle in HapMap SNPs.

    Science.gov (United States)

    Doron, Shany; Shweiki, Dorit

    2011-04-01

    SNP-based research strongly affects our biomedical and clinically associated knowledge. Nonunique and false-positive SNP existence in commonly used datasets may thus lead to biased, inaccurate clinically associated conclusions. We designed a computational study to reveal the degree of nonunique/false-positive SNPs in the HapMap dataset. Two sets of SNP flanking sequences were used as queries for BLAT analysis against the human genome. 4.2% and 11.9% of HapMap SNPs align to the genome nonuniquely (long and short, respectively). Furthermore, an average of 7.9% nonunique SNPs are included in common commercial genotyping arrays (according to our designed probes). Nonunique SNPs identified in this study are represented to various degrees in clinically associated databases, stressing the consequence of inaccurate SNP annotation and hence SNP utilization. Unfortunately, our results question some disease-related genotyping analyses, raising a worrisome concern on their validity.

  1. No Association of SNPs in One-Carbon Metabolism Genes with Prostate Cancer Risk

    OpenAIRE

    Stevens, Victoria L.; Rodriguez, Carmen; Sun, Juzhong; Talbot, Jeffrey T.; Thun, Michael J.; Calle, Eugenia E.

    2008-01-01

    One-carbon metabolism mediates the inter-conversion of folates for the synthesis of precursors used in DNA synthesis, repair and methylation. Inadequate folate nutrition or compromised metabolism can disrupt these processes and facilitate carcinogenesis. In this study, we investigated associations of 39 candidate SNPs in nine one-carbon metabolism genes with risk of prostate cancer using 1,144 cases and 1,144 controls from the Cancer Prevention Study-II Nutrition Cohort. None of these SNPs we...

  2. Sequential cloning of chromosomes

    Science.gov (United States)

    Lacks, S.A.

    1995-07-18

    A method for sequential cloning of chromosomal DNA of a target organism is disclosed. A first DNA segment homologous to the chromosomal DNA to be sequentially cloned is isolated. The first segment has a first restriction enzyme site on either side. A first vector product is formed by ligating the homologous segment into a suitably designed vector. The first vector product is circularly integrated into the target organism`s chromosomal DNA. The resulting integrated chromosomal DNA segment includes the homologous DNA segment at either end of the integrated vector segment. The integrated chromosomal DNA is cleaved with a second restriction enzyme and ligated to form a vector-containing plasmid, which is replicated in a host organism. The replicated plasmid is then cleaved with the first restriction enzyme. Next, a DNA segment containing the vector and a segment of DNA homologous to a distal portion of the previously isolated DNA segment is isolated. This segment is then ligated to form a plasmid which is replicated within a suitable host. This plasmid is then circularly integrated into the target chromosomal DNA. The chromosomal DNA containing the circularly integrated vector is treated with a third, retrorestriction (class IIS) enzyme. The cleaved DNA is ligated to give a plasmid that is used to transform a host permissive for replication of its vector. The sequential cloning process continues by repeated cycles of circular integration and excision. The excision is carried out alternately with the second and third enzymes. 9 figs.

  3. Chromosomal mosaicism goes global

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    Yurov Yuri B

    2008-11-01

    Full Text Available Intercellular differences of chromosomal content in the same individual are defined as chromosomal mosaicism (alias intercellular or somatic genomic variations or, in a number of publications, mosaic aneuploidy. It has long been suggested that this phenomenon poorly contributes both to intercellular (interindividual diversity and to human disease. However, our views have recently become to change due to a series of communications demonstrated a higher incidence of chromosomal mosaicism in diseased individuals (major psychiatric disorders and autoimmune diseases as well as depicted chromosomal mosaicism contribution to genetic diversity, the central nervous system development, and aging. The later has been produced by significant achievements in the field of molecular cytogenetics. Recently, Molecular Cytogenetics has published an article by Maj Hulten and colleagues that has provided evidences for chromosomal mosaicism to underlie formation of germline aneuploidy in human female gametes using trisomy 21 (Down syndrome as a model. Since meiotic aneuploidy is suggested to be the leading genetic cause of human prenatal mortality and postnatal morbidity, these data together with previous findings define chromosomal mosaicism not as a casual finding during cytogenetic analyses but as a more significant biological phenomenon than previously recognized. Finally, the significance of chromosomal mosaicism can be drawn from the fact, that this phenomenon is involved in genetic diversity, normal and abnormal prenatal development, human diseases, aging, and meiotic aneuploidy, the intrinsic cause of which remains, as yet, unknown.

  4. Association of Sult4A1 SNPs with psychopathology and cognition in patients with schizophrenia or schizoaffective disorder.

    Science.gov (United States)

    Meltzer, Herbert Y; Brennan, Mark D; Woodward, Neil D; Jayathilake, Karu

    2008-12-01

    A number of genes located on chromosome 22q11-13, including catechol-O-methyltransferase (COMT), are potential schizophrenia susceptibility genes. Recently, the sulfotransferase-4A1 (Sult4A1) locus within chromosome 22q13 was reported to be linked to schizophrenia in a family TDT study. Sult4A1 is related to metabolism of monoamines, particularly dopamine and norepinephrine, both of which have been implicated in the pathophysiology of the psychopathology and cognitive dysfunction components of schizophrenia. An available, prospectively collected data base was interrogated to determine how three Sult4A1 SNPs: rs138060, rs138097, and rs138110, previously shown to be associated with schizophrenia might be associated with psychopathology, cognition, and quality of life in a sample of 86 Caucasian patients with schizophrenia or schizoaffective disorder. The majority of patients met criteria for treatment resistant schizophrenia and had been drug-free for one week or longer at the time of evaluation. The major findings were: 1) patients heterozygous (T/G) for rs138060 had significantly worse Brief Psychiatric Rating Scale (BPRS) Total and anxiety/depression sub-scale scores, and higher Scale for the Assessment of Positive Symptoms (SAPS) Total scores than G/G homozygous patients; and 2) patients heterozygous (A/G) for rs138097 demonstrated significantly worse performance on neuropsychological testing, specifically on tests of executive function and working memory, compared to patients homozygous for the G and A alleles. RS138110 was unrelated to psychopathology and cognition. These results provide the first evidence of how genetic variation in Sult4A1 may be related to clinical symptoms and cognitive function in schizophrenia, and permit future studies to attempt to replicate these potentially important findings.

  5. Characterisation of the genomic architecture of human chromosome 17q and evaluation of different methods for haplotype block definition

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    Ollier William

    2005-04-01

    Full Text Available Abstract Background The selection of markers in association studies can be informed through the use of haplotype blocks. Recent reports have determined the genomic architecture of chromosomal segments through different haplotype block definitions based on linkage disequilibrium (LD measures or haplotype diversity criteria. The relative applicability of distinct block definitions to association studies, however, remains unclear. We compared different block definitions in 6.1 Mb of chromosome 17q in 189 unrelated healthy individuals. Using 137 single nucleotide polymorphisms (SNPs, at a median spacing of 15.5 kb, we constructed haplotype block maps using published methods and additional methods we have developed. Haplotype tagging SNPs (htSNPs were identified for each map. Results Blocks were found to be shorter and coverage of the region limited with methods based on LD measures, compared to the method based on haplotype diversity. Although the distribution of blocks was highly variable, the number of SNPs that needed to be typed in order to capture the maximum number of haplotypes was consistent. Conclusion For the marker spacing used in this study, choice of block definition is not important when used as an initial screen of the region to identify htSNPs. However, choice of block definition has consequences for the downstream interpretation of association study results.

  6. Analysis of 17,576 potentially functional SNPs in three case-control studies of myocardial infarction.

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    Dov Shiffman

    Full Text Available Myocardial infarction (MI is a common complex disease with a genetic component. While several single nucleotide polymorphisms (SNPs have been reported to be associated with risk of MI, they do not fully explain the observed genetic component of MI. We have been investigating the association between MI and SNPs that are located in genes and have the potential to affect gene function or expression. We have previously published studies that tested about 12,000 SNPs for association with risk of MI, early-onset MI, or coronary stenosis. In the current study we tested 17,576 SNPs that could affect gene function or expression. In order to use genotyping resources efficiently, we staged the testing of these SNPs in three case-control studies of MI. In the first study (762 cases, 857 controls we tested 17,576 SNPs and found 1,949 SNPs that were associated with MI (P<0.05. We tested these 1,949 SNPs in a second study (579 cases and 1159 controls and found that 24 SNPs were associated with MI (1-sided P<0.05 and had the same risk alleles in the first and second study. Finally, we tested these 24 SNPs in a third study (475 cases and 619 controls and found that 5 SNPs in 4 genes (ENO1, FXN (2 SNPs, HLA-DPB2, and LPA were associated with MI in the third study (1-sided P<0.05, and had the same risk alleles in all three studies. The false discovery rate for this group of 5 SNPs was 0.23. Thus, we have identified 5 SNPs that merit further examination for their potential association with MI. One of these SNPs (in LPA, has been previously shown to be associated with risk of cardiovascular disease in other studies.

  7. All SNPs are not created equal: genome-wide association studies reveal a consistent pattern of enrichment among functionally annotated SNPs

    DEFF Research Database (Denmark)

    Schork, Andrew J; Thompson, Wesley K; Pham, Phillip;

    2013-01-01

    (TDR = 1-FDR) for strata determined by different genic categories. We show a consistent pattern of enrichment of polygenic effects in specific annotation categories across diverse phenotypes, with the greatest enrichment for SNPs tagging regulatory and coding genic elements, little enrichment...

  8. Bioinformatics Analysis for Coding SNPs of the HLADQA1 Gene Involved in Susceptibility to Cervical Cancer

    Institute of Scientific and Technical Information of China (English)

    Yanyun Li; Jun Xing; Linsheng Zhao; Yanni Li; Yuchuan Wang; Weiming Zhang

    2006-01-01

    OBJECTIVE To analyze coding SNPs of the HLA-DQA1 gene involved in susceptibility for cervical cancer by a bioinformatics approach, and to choose some SNPs that may have an association with cervical cancer.METHODS By a SNPper tool we extracted SNPs from a public database (dbSNP), exporting them in FASTA formats suitable for subsequent use.Then we used PARSESNP as a tool for the analysis of the cSNPs.RESULTS In the cSNPs of the HLA-DQA1 gene, we find that rs9272693and rs9272703, are made up of missense mutations which convert a codon for one amino acid into a codon for a different amino acid. We chose a PSSM Difference >10 as a lower level for the scores of changes predicted to be deldterious.CONCLUSION We used a bioinformatics approach for cSNPs analysis of the HLA-DQA1 gene. This method can select the variants in a conserved region, and give a PSSM Difference score. But the results need to be verified in cervical cancer patients and a control population.

  9. Verification of SNPs Associated with Growth Traits in Two Populations of Farmed Atlantic Salmon

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    Hsin Y. Tsai

    2015-12-01

    Full Text Available Understanding the relationship between genetic variants and traits of economic importance in aquaculture species is pertinent to selective breeding programmes. High-throughput sequencing technologies have enabled the discovery of large numbers of SNPs in Atlantic salmon, and high density SNP arrays now exist. A previous genome-wide association study (GWAS using a high density SNP array (132K SNPs has revealed the polygenic nature of early growth traits in salmon, but has also identified candidate SNPs showing suggestive associations with these traits. The aim of this study was to test the association of the candidate growth-associated SNPs in a separate population of farmed Atlantic salmon to verify their effects. Identifying SNP-trait associations in two populations provides evidence that the associations are true and robust. Using a large cohort (N = 1152, we successfully genotyped eight candidate SNPs from the previous GWAS, two of which were significantly associated with several growth and fillet traits measured at harvest. The genes proximal to these SNPs were identified by alignment to the salmon reference genome and are discussed in the context of their potential role in underpinning genetic variation in salmon growth.

  10. Simulation of SNPs Data of Complex Diseases and Evaluation on the Results%复杂性疾病SNPs数据模拟的实现与效果评价

    Institute of Scientific and Technical Information of China (English)

    孙远洁; 郑娟娟; 李昂; 温琪; 佟海龙; 刘艳; 赵晓雯

    2013-01-01

    目的 探讨有效的复杂性疾病单核苷酸多态性(SNPs)数据模拟方法,为疾病发病机理的研究提供帮助.方法 运用HAPC-EN2软件实现复杂性疾病SNPs数据的模拟,利用GTOOL软件和R语言实现SNPs数据格式的转换,采用LD图以及x2检验对模拟效果进行评价. 结果 利用HAPGEN2以JPT+ CHB人群的22号染色体的500、1000、5000个SNPs位点为参照,分别生成了致病位点个数为3、5、8的模拟数据.模拟数据与相对应的参照数据的LD模式基本相似,致病位点的差异显著性较为明显. 结论 HAPGEN2是一种简单有效的SNPs数据模拟软件.%Objective To explore the effective method to simulate the single nucleotide polymorphisms (SNPs) data of complex diseases, and to provide reference for the research on their pathogenesis. Methods HAPGEN2 software was used to simulate the SNPs data of complex diseases, and GTOOL software and R Language were used to convert the SNPs data formats. The simulation results were evaluated by LD diagram and chi - square test. Results With the first 500, 1,000 and 5,000 SNPs in the chromosome 22 of JPT+ CHB population as reference, pathogenic SNPs for 3, 5, 8 of the analog data were respectively made by HAPGEN2. The linkage disequilibrium (LD) maps of the simulation data and the corresponding reference data were similar. The differences of the pathogenic SNPs were obvious. Conclusions HAPGEN2 is a simple and effective software for SNPs data simulating.

  11. CHROMOSOMES OF AMERICAN MARSUPIALS.

    Science.gov (United States)

    BIGGERS, J D; FRITZ, H I; HARE, W C; MCFEELY, R A

    1965-06-18

    Studies of the chromosomes of four American marsupials demonstrated that Caluromys derbianus and Marmosa mexicana have a diploid number of 14 chromosomes, and that Philander opossum and Didelphis marsupialis have a diploid number of 22. The karyotypes of C. derbianus and M. mexicana are similar, whereas those of P. opossum and D. marsupialis are dissimilar. If the 14-chromosome karyotype represents a reduction from a primitive number of 22, these observations suggest that the change has occurred independently in the American and Australasian forms.

  12. Nonrandom distribution of interhomolog recombination events induced by breakage of a dicentric chromosome in Saccharomyces cerevisiae.

    Science.gov (United States)

    Song, Wei; Gawel, Malgorzata; Dominska, Margaret; Greenwell, Patricia W; Hazkani-Covo, Einat; Bloom, Kerry; Petes, Thomas D

    2013-05-01

    Dicentric chromosomes undergo breakage in mitosis, resulting in chromosome deletions, duplications, and translocations. In this study, we map chromosome break sites of dicentrics in Saccharomyces cerevisiae by a mitotic recombination assay. The assay uses a diploid strain in which one homolog has a conditional centromere in addition to a wild-type centromere, and the other homolog has only the wild-type centromere; the conditional centromere is inactive when cells are grown in galactose and is activated when the cells are switched to glucose. In addition, the two homologs are distinguishable by multiple single-nucleotide polymorphisms (SNPs). Under conditions in which the conditional centromere is activated, the functionally dicentric chromosome undergoes double-stranded DNA breaks (DSBs) that can be repaired by mitotic recombination with the homolog. Such recombination events often lead to loss of heterozygosity (LOH) of SNPs that are centromere distal to the crossover. Using a PCR-based assay, we determined the position of LOH in multiple independent recombination events to a resolution of ∼4 kb. This analysis shows that dicentric chromosomes have recombination breakpoints that are broadly distributed between the two centromeres, although there is a clustering of breakpoints within 10 kb of the conditional centromere.

  13. Family-Based Association Testing of OCD-associated SNPs of SLC1A1 in an autism sample.

    Science.gov (United States)

    Brune, Camille W; Kim, Soo-Jeong; Hanna, Gregory L; Courchesne, Eric; Lord, Catherine; Leventhal, Bennett L; Cook, Edwin H

    2008-04-01

    Reports identified the neuronal glutamate transporter gene, SLC1A1 (OMIM 133550, chromosome 9p24), as a positional and functional candidate gene for obsessive-compulsive disorder (OCD). The presence of obsessions and compulsions similar to OCD in autism, the identification of this region in a genome-wide linkage analysis of individuals with autism spectrum disorders (ASDs), and the hypothesized role of glutamate in ASDs make SLC1A1 a candidate gene for ASD as well. To test for association between SLC1A1 and autism, we typed three single nucleotide polymorphisms (SNPs, rs301430, rs301979, rs301434) previously associated with OCD in 86 strictly defined trios with autism. Family-Based Association Tests (FBAT) with additive and recessive models were used to check for association. Additionally, an rs301430-rs301979 haplotype identified for OCD was investigated. FBAT revealed nominally significant association between autism and one SNP under a recessive model. The G allele of rs301979 was undertransmitted (equivalent to overtransmission of the C allele under a dominant model) to individuals with autism (Z=-2.47, P=0.01). The G allele was also undertransmitted in the T-G haplotype under the recessive model (Z=-2.41, P=0.02). Both findings were also observed in the male-only sample. However, they did not withstand correction for multiple comparisons.

  14. Constructing an initial map of transmission distortion based on high density HapMap SNPs across the human autosomes.

    Science.gov (United States)

    Deng, Libin; Zhang, Dake; Richards, Elliott; Tang, Xiaoli; Fang, Jin; Long, Fei; Wang, Yan

    2009-12-01

    Transmission distortion (TD) is a significant departure from Mendelian predictions of genes or chromosomes to offspring. While many biological processes have been implicated, there is still much to be understood about TD in humans. Here we present our findings from a genome-wide scan for evidence of TD using haplotype data of 60 trio families from the International HapMap Project. Fisher's exact test was applied to assess the extent of TD in 629,958 SNPs across the autosomes. Based on the empirical distribution of P(Fisher) and further permutation tests, we identified 1,205 outlier loci and 224 candidate genes with TD. Using the PANTHER gene ontology database, we found 19 categories of biological processes with an enrichment of candidate genes. In particular, the "protein phosphorylation" category contained the largest number of candidates in both HapMap samples. Further analysis uncovered an intriguing non-synonymous change in PPP1R12B, a gene related to protein phosphorylation, which appears to influence the allele transmission from male parents in the YRI (Yoruba from Ibadan, Nigeria) population. Our findings also indicate an ethnicity-related property of TD signatures in HapMap samples and provide new clues for our understanding of TD in humans.

  15. Chromosomal abnormalities and autism

    Directory of Open Access Journals (Sweden)

    Farida El-Baz

    2016-01-01

    Conclusion: Chromosomal abnormalities were not detected in the studied autistic children, and so the relation between the genetics and autism still needs further work up with different study methods and techniques.

  16. [Sex chromosomes and meiosis].

    Science.gov (United States)

    Guichaoua, M-R; Geoffroy-Siraudin, C; Tassistro, V; Ghalamoun-Slaimi, R; Perrin, J; Metzler-Guillemain, C

    2009-01-01

    Sex chromosome behaviour fundamentally differs between male and female meiosis. In oocyte, X chromosomes synapse giving a XX bivalent which is not recognizable in their morphology and behaviour from autosomal bivalents. In human male, X and Y chromosomes differ from one another in their morphology and their genetic content, leading to a limited pairing and preventing genetic recombination, excepted in homologous region PAR1. During pachytene stage of the first meiotic prophase, X and Y chromosomes undergo a progressive condensation and form a transcriptionally silenced peripheral XY body. The condensation of the XY bivalent during pachytene stage led us to describe four pachytene substages and to localize the pachytene checkpoint between substages 2 and 3. We also defined the pachytene index (PI=P1+P2/P1+P2+P3+P4) which is always less than 0.50 in normal meiosis. XY body undergoes decondensation at diplotene stage, but transcriptional inactivation of the two sex chromosomes or Meiotic Sex Chromosome Inactivation (MSCI) persists through to the end of spermatogenesis. Sex chromosome inactivation involves several proteins, some of them were now identified. Two isoforms of the HP1 protein, HP1beta and HP1gamma, are involved in the facultative heterochromatinization of the XY body, but the initiation of this process involves the phosphorylation of the protein H2AX by the kinase ATR whose recruitment depends on BRCA1. Extensive researches on the inactivation of the sex chromosomes during male meiosis will allow to a better understanding of some male infertilities.

  17. Chromosome doubling method

    Science.gov (United States)

    Kato, Akio

    2006-11-14

    The invention provides methods for chromosome doubling in plants. The technique overcomes the low yields of doubled progeny associated with the use of prior techniques for doubling chromosomes in plants such as grasses. The technique can be used in large scale applications and has been demonstrated to be highly effective in maize. Following treatment in accordance with the invention, plants remain amenable to self fertilization, thereby allowing the efficient isolation of doubled progeny plants.

  18. Activation of X Chromosome Inactivation

    NARCIS (Netherlands)

    C.M. Maduro (Cheryl)

    2016-01-01

    markdownabstractIn mammals, males are the heterogametic sex having an X chromosome and a Y chromosome whereas females have two X chromosomes. Despite originating from an ancient homologous autosomal pair, the X and Y chromosome now differ greatly in size and gene content after ~180 MY of evolution.

  19. Identification of novel RA susceptibility loci at chromosomes 10p15, 12q13 and 22q13

    Science.gov (United States)

    Barton, Anne; Thomson, Wendy; Ke, Xiayi; Eyre, Steve; Hinks, Anne; Bowes, John; Plant, Darren; Gibbons, Laura J; Wilson, Anthony G; Bax, Deborah E; Morgan, Ann W; Emery, Paul; Steer, Sophia; Hocking, Lynne; Reid, David M; Wordsworth, Paul; Harrison, Pille; Worthington, Jane

    2009-01-01

    The WTCCC study identified 49 single nucleotide polymorphisms (SNPs) putatively associated with RA at p=1×10-4-1×10-5 (Tier 3). Here, we show that 3 of these SNPs, mapping to chromosome 10p15 (rs4750316), 12q13 (rs1678542) and 22q13 (rs3218253), are also associated (trend p = 4×10-5, p=4×10-4 and p=4×10-4, respectively) in a validation study of 4,106 RA cases and an expanded reference group of 11,238 subjects, confirming them as true susceptibility loci in Caucasians. PMID:18794857

  20. Vibrio chromosomes share common history

    Directory of Open Access Journals (Sweden)

    Gevers Dirk

    2010-05-01

    Full Text Available Abstract Background While most gamma proteobacteria have a single circular chromosome, Vibrionales have two circular chromosomes. Horizontal gene transfer is common among Vibrios, and in light of this genetic mobility, it is an open question to what extent the two chromosomes themselves share a common history since their formation. Results Single copy genes from each chromosome (142 genes from chromosome I and 42 genes from chromosome II were identified from 19 sequenced Vibrionales genomes and their phylogenetic comparison suggests consistent phylogenies for each chromosome. Additionally, study of the gene organization and phylogeny of the respective origins of replication confirmed the shared history. Conclusions Thus, while elements within the chromosomes may have experienced significant genetic mobility, the backbones share a common history. This allows conclusions based on multilocus sequence analysis (MLSA for one chromosome to be applied equally to both chromosomes.

  1. Identification and analysis of Single Nucleotide Polymorphisms (SNPs in the mosquito Anopheles funestus, malaria vector

    Directory of Open Access Journals (Sweden)

    Hemingway Janet

    2007-01-01

    Full Text Available Abstract Background Single nucleotide polymorphisms (SNPs are the most common source of genetic variation in eukaryotic species and have become an important marker for genetic studies. The mosquito Anopheles funestus is one of the major malaria vectors in Africa and yet, prior to this study, no SNPs have been described for this species. Here we report a genome-wide set of SNP markers for use in genetic studies on this important human disease vector. Results DNA fragments from 50 genes were amplified and sequenced from 21 specimens of An. funestus. A third of specimens were field collected in Malawi, a third from a colony of Mozambican origin and a third form a colony of Angolan origin. A total of 494 SNPs including 303 within the coding regions of genes and 5 indels were identified. The physical positions of these SNPs in the genome are known. There were on average 7 SNPs per kilobase similar to that observed in An. gambiae and Drosophila melanogaster. Transitions outnumbered transversions, at a ratio of 2:1. The increased frequency of transition substitutions in coding regions is likely due to the structure of the genetic code and selective constraints. Synonymous sites within coding regions showed a higher polymorphism rate than non-coding introns or 3' and 5'flanking DNA with most of the substitutions in coding regions being observed at the 3rd codon position. A positive correlation in the level of polymorphism was observed between coding and non-coding regions within a gene. By genotyping a subset of 30 SNPs, we confirmed the validity of the SNPs identified during this study. Conclusion This set of SNP markers represents a useful tool for genetic studies in An. funestus, and will be useful in identifying candidate genes that affect diverse ranges of phenotypes that impact on vector control, such as resistance insecticide, mosquito behavior and vector competence.

  2. Tyramide-FISH mapping of single genes for development of an integrated recombination and cytogenetic map of chromosome 5 of Allium cepa

    Science.gov (United States)

    Chromosome 5 of onion carries major quantitative trait loci (QTL) of interest to breeders that control dry-matter content, pungency and storability of bulbs, amounts and types of epicuticular waxes, and resistances to abiotic factors. SNPs, SSRs and RFLPs in expressed regions of the onion genome hav...

  3. Introduction of an single nucleodite polymorphism-based "Major Y-chromosome haplogroup typing kit" suitable for predicting the geographical origin of male lineages

    DEFF Research Database (Denmark)

    Brión, María; Sanchez, Juan J; Balogh, Kinga;

    2005-01-01

    The European Consortium "High-throughput analysis of single nucleotide polymorphisms for the forensic identification of persons--SNPforID", has performed a selection of candidate Y-chromosome single nucleotide polymorphisms (SNPs) for making inferences on the geographic origin of an unknown sampl...

  4. Mining the 30UTR of Autism-implicated Genes for SNPs Perturbing MicroRNA Regulation

    Institute of Scientific and Technical Information of China (English)

    Varadharajan Vaishnavi; Mayakannan Manikandan; Arasambattu Kannan Munirajan

    2014-01-01

    Autism spectrum disorder (ASD) refers to a group of childhood neurodevelopmental dis-orders with polygenic etiology. The expression of many genes implicated in ASD is tightly regulated by various factors including microRNAs (miRNAs), a class of noncoding RNAs 22 nucleotides in length that function to suppress translation by pairing with‘miRNA recognition elements’ (MREs) present in the 30untranslated region (30UTR) of target mRNAs. This emphasizes the role played by miRNAs in regulating neurogenesis, brain development and differentiation and hence any perturba-tions in this regulatory mechanism might affect these processes as well. Recently, single nucleotide polymorphisms (SNPs) present within 30UTRs of mRNAs have been shown to modulate existing MREs or even create new MREs. Therefore, we hypothesized that SNPs perturbing miRNA-medi-ated gene regulation might lead to aberrant expression of autism-implicated genes, thus resulting in disease predisposition or pathogenesis in at least a subpopulation of ASD individuals. We developed a systematic computational pipeline that integrates data from well-established databases. By following a stringent selection criterion, we identified 9 MRE-modulating SNPs and another 12 MRE-creating SNPs in the 30UTR of autism-implicated genes. These high-confidence candidate SNPs may play roles in ASD and hence would be valuable for further functional validation.

  5. Single nucleotide polymorphisms (SNPs) in key cytokines may modulate food allergy phenotypes

    Science.gov (United States)

    Brown, Paula; Nair, Bindukumar; Sykes, Donald E.; Rich, Gary; Reynolds, Jessica L.; Aalinkeel, Ravikumar; Wheeler, John; Schwartz, Stanley A.

    2012-01-01

    Single nucleotide polymorphisms (SNPs) can play a direct or indirect role in phenotypic expression in food allergy pathogenesis. Our goal was to quantitate the expression of SNPs in relevant cytokines that were expressed in food allergic patients. SNPs in cytokine genes IL-4 and IL-10 are known to be important in IgE generation and regulation. We examined IL-4 (C-590T), IL-4Rα (1652A/G) and IL-10 (C-627A) SNPs using real-time PCR followed by restriction fragment length polymorphism (RFLP) analysis. Our results show that the AA, AG and GG genotypes for IL-4Rα (1652A/G) polymorphisms were statistically different in radioallergosorbent test (RAST) positive versus negative patients, and although no statistically significant differences were observed between genotypes in the IL-4 (C-590T) and IL-10 (C-627A) SNPs, we observed a significant decrease in IL-4 (C-590T) gene expression and increase in IL-4Rα (1652A/G) and IL-10 (C-627A) gene expression between RAST+ versus RAST− patients, respectively. We also observed significant modulation in the protein expression of IL-4 and IL-10 in the serum samples of the RAST+ patients as compared to the RAST− patients indicating that changes in SNP expression resulted in altered phenotypic response in these patients. PMID:23230389

  6. Studies on interaction of colloidal silver nanoparticles (SNPs) with five different bacterial species.

    Science.gov (United States)

    Khan, S Sudheer; Mukherjee, Amitava; Chandrasekaran, N

    2011-10-01

    Silver nanoparticles (SNPs) are being increasingly used in many consumer products like textile fabrics, cosmetics, washing machines, food and drug products owing to its excellent antimicrobial properties. Here we have studied the adsorption and toxicity of SNPs on bacterial species such as Pseudomonas aeruginosa, Micrococcus luteus, Bacillus subtilis, Bacillus barbaricus and Klebsiella pneumoniae. The influence of zeta potential on the adsorption of SNPs on bacterial cell surface was investigated at acidic, neutral and alkaline pH and with varying salt (NaCl) concentrations (0.05, 0.1, 0.5, 1 and 1.5 M). The survival rate of bacterial species decreased with increase in adsorption of SNPs. Maximum adsorption and toxicity was observed at pH 5, and NaCl concentration of 0.5 M, there by resulting in less toxicity. The zeta potential study suggests that, the adsorption of SNPs on the cell surface was related to electrostatic force of attraction. The equilibrium and kinetics of the adsorption process were also studied. The adsorption equilibrium isotherms fitted well to the Langmuir model. The kinetics of adsorption fitted best to pseudo-first-order. These findings form a basis for interpreting the interaction of nanoparticles with environmental bacterial species.

  7. Association analysis identifies Melampsora ×columbiana poplar leaf rust resistance SNPs.

    Directory of Open Access Journals (Sweden)

    Jonathan La Mantia

    Full Text Available Populus species are currently being domesticated through intensive time- and resource-dependent programs for utilization in phytoremediation, wood and paper products, and conversion to biofuels. Poplar leaf rust disease can greatly reduce wood volume. Genetic resistance is effective in reducing economic losses but major resistance loci have been race-specific and can be readily defeated by the pathogen. Developing durable disease resistance requires the identification of non-race-specific loci. In the presented study, area under the disease progress curve was calculated from natural infection of Melampsora ×columbiana in three consecutive years. Association analysis was performed using 412 P. trichocarpa clones genotyped with 29,355 SNPs covering 3,543 genes. We found 40 SNPs within 26 unique genes significantly associated (permutated P<0.05 with poplar rust severity. Moreover, two SNPs were repeated in all three years suggesting non-race-specificity and three additional SNPs were differentially expressed in other poplar rust interactions. These five SNPs were found in genes that have orthologs in Arabidopsis with functionality in pathogen induced transcriptome reprogramming, Ca²⁺/calmodulin and salicylic acid signaling, and tolerance to reactive oxygen species. The additive effect of non-R gene functional variants may constitute high levels of durable poplar leaf rust resistance. Therefore, these findings are of significance for speeding the genetic improvement of this long-lived, economically important organism.

  8. Partition dataset according to amino acid type improves the prediction of deleterious non-synonymous SNPs

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Jing; Li, Yuan-Yuan [School of Biotechnology, East China University of Science and Technology, Shanghai 200237 (China); Shanghai Center for Bioinformation Technology, Shanghai 200235 (China); Li, Yi-Xue, E-mail: yxli@sibs.ac.cn [School of Biotechnology, East China University of Science and Technology, Shanghai 200237 (China); Shanghai Center for Bioinformation Technology, Shanghai 200235 (China); Ye, Zhi-Qiang, E-mail: yezq@pkusz.edu.cn [Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055 (China); Key Laboratory of Systems Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China)

    2012-03-02

    Highlights: Black-Right-Pointing-Pointer Proper dataset partition can improve the prediction of deleterious nsSNPs. Black-Right-Pointing-Pointer Partition according to original residue type at nsSNP is a good criterion. Black-Right-Pointing-Pointer Similar strategy is supposed promising in other machine learning problems. -- Abstract: Many non-synonymous SNPs (nsSNPs) are associated with diseases, and numerous machine learning methods have been applied to train classifiers for sorting disease-associated nsSNPs from neutral ones. The continuously accumulated nsSNP data allows us to further explore better prediction approaches. In this work, we partitioned the training data into 20 subsets according to either original or substituted amino acid type at the nsSNP site. Using support vector machine (SVM), training classification models on each subset resulted in an overall accuracy of 76.3% or 74.9% depending on the two different partition criteria, while training on the whole dataset obtained an accuracy of only 72.6%. Moreover, the dataset was also randomly divided into 20 subsets, but the corresponding accuracy was only 73.2%. Our results demonstrated that partitioning the whole training dataset into subsets properly, i.e., according to the residue type at the nsSNP site, will improve the performance of the trained classifiers significantly, which should be valuable in developing better tools for predicting the disease-association of nsSNPs.

  9. Single Nucleotide Polymorphisms (SNPs) Discovery and Linkage Disequilibrium (LD) in Forest Trees

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    With completion of the Populus genome sequencing project and the availability of many expressed sequence tags (ESTs) databases in forest trees, attention is now rapidly shifting towards the study of individual genetic variation in natural populations. The most abundant form of genetic variation in many eukaryotic species is represented by single nucleotide polymorphisms (SNPs), which can account for heritable inter-individual differences in complex phenotypes. Unlike humans, the linkage disequilibrium (LD) rapidly decays within candidate genes in forest trees. Thus, SNPs-based candidate gene association studies are considered to be a most effective approach to dissect the complex quantitative traits in forest trees. The present study demonstrates that LD mapping can be used to identify alleles associated with quantitative traits and suggests that this new approach could be particularly useful for performing breeding programs in forest trees. In this review, we will describe the fundamentals, patterns of SNPs distribution and frequency, summarize recent advances in SNPs discovery and LD and comment on the application of LD in the dissection of complex quantitative traits in forest tress. We also put forward the outlook for future SNPs-based association analysis of quantitative traits in forest trees.

  10. Multistudy fine mapping of chromosome 2q identifies XRCC5 as a chronic obstructive pulmonary disease susceptibility gene

    DEFF Research Database (Denmark)

    Hersh, Craig P; Pillai, Sreekumar G; Zhu, Guohua;

    2010-01-01

    RATIONALE: Several family-based studies have identified genetic linkage for lung function and airflow obstruction to chromosome 2q. OBJECTIVES: We hypothesized that merging results of high-resolution single nucleotide polymorphism (SNP) mapping in four separate populations would lead to the ident......RATIONALE: Several family-based studies have identified genetic linkage for lung function and airflow obstruction to chromosome 2q. OBJECTIVES: We hypothesized that merging results of high-resolution single nucleotide polymorphism (SNP) mapping in four separate populations would lead...... to the identification of chronic obstructive pulmonary disease (COPD) susceptibility genes on chromosome 2q. METHODS: Within the chromosome 2q linkage region, 2,843 SNPs were genotyped in 806 COPD cases and 779 control subjects from Norway, and 2,484 SNPs were genotyped in 309 patients with severe COPD from...... XRCC5, was replicated in the Boston Early-Onset COPD Study, with a combined P = 2.51 x 10(-5) across the four studies, which remains significant when adjusted for multiple testing (P = 0.02). Genotype imputation confirmed the association with SNPs in XRCC5. CONCLUSIONS: By combining data from COPD...

  11. A Comprehensive In Silico Analysis of the Functional and Structural Impact of SNPs in the IGF1R Gene

    Directory of Open Access Journals (Sweden)

    S. A. de Alencar

    2010-01-01

    Full Text Available Insulin-like growth factor 1 receptor (IGF1R acts as a critical mediator of cell proliferation and survival. Many single nucleotide polymorphisms (SNPs found in the IGF1R gene have been associated with various diseases, including both breast and prostate cancer. The genetics of these diseases could be better understood by knowing the functions of these SNPs. In this study, we performed a comprehensive analysis of the functional and structural impact of all known SNPs in this gene using publicly available computational prediction tools. Out of a total of 2412 SNPs in IGF1R retrieved from dbSNP, we found 32 nsSNPs, 58 sSNPs, 83 mRNA 3′ UTR SNPs, and 2225 intronic SNPs. Among the nsSNPs, a total of six missense nsSNPs were found to be damaging by both a sequence homology-based tool (SIFT and a structural homology-based method (PolyPhen, and one nonsense nsSNP was found. Further, we modeled mutant proteins and compared the total energy values with the native IGF1R protein, and showed that a mutation from arginine to cysteine at position 1216 (rs61740868 on the surface of the protein caused the greatest impact on stability. Also, the FASTSNP tool suggested that 31 sSNPs and 3 intronic SNPs might affect splicing regulation. Based on our investigation, we report potential candidate SNPs for future studies on IGF1R mutations.

  12. Silica nanoparticles induce multinucleation through activation of PI3K/Akt/GSK-3β pathway and downregulation of chromosomal passenger proteins in L-02 cells

    Science.gov (United States)

    Geng, Weijia; Li, Yang; Yu, Yongbo; Yu, Yang; Duan, Junchao; Jiang, Lizhen; Li, Qiuling; Sun, Zhiwei

    2016-04-01

    Silica nanoparticles (SNPs) are applicable in various fields due to their unique physicochemical characteristics. However, concerns over their potential adverse effects have been raised. In our previous studies, we reported that SNPs could induce abnormal high incidence of multinucleation. The aim of this study is to further investigate the mechanisms of multinucleation induced by SNPs (68 nm) in human normal liver L-02 cells (L-02 cells). In order to determine the cytotoxicity of SNPs, MTT assay was performed, and the cell viability was decreased in a dose-dependent manner. The intracellular reactive oxygen species (ROS) detected by flow cytometry and multinucleation observed by Giemsa stain showed that ROS generation and rate of multinucleated cells increased after SNPs exposure. N-acetyl-cysteine (NAC), a glutathione precursor against SNP-induced toxicity, was used as a ROS inhibitor to elucidate the relationship between ROS and multinucleation. The presence of NAC resulted in inhibition of both ROS generation and rate of multinucleation. Moreover, Western blot analysis showed that the protein levels of Cdc20, Aurora B, and Survivin were down-regulated, and the PI3K/Akt/GSK-3β pathway was activated by SNPs. In conclusion, our findings strongly suggested that multinucleation induced by SNPs was related to PI3K/Akt/GSK-3β signal pathway activation and downregulation of G2/M phase-related protein and chromosomal passenger proteins.

  13. "Chromosome": a knowledge-based system for the chromosome classification.

    Science.gov (United States)

    Ramstein, G; Bernadet, M

    1993-01-01

    Chromosome, a knowledge-based analysis system has been designed for the classification of human chromosomes. Its aim is to perform an optimal classification by driving a tool box containing the procedures of image processing, pattern recognition and classification. This paper presents the general architecture of Chromosome, based on a multiagent system generator. The image processing tool box is described from the met aphasic enhancement to the fine classification. Emphasis is then put on the knowledge base intended for the chromosome recognition. The global classification process is also presented, showing how Chromosome proceeds to classify a given chromosome. Finally, we discuss further extensions of the system for the karyotype building.

  14. Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS.

    Science.gov (United States)

    DeJesus-Hernandez, Mariely; Mackenzie, Ian R; Boeve, Bradley F; Boxer, Adam L; Baker, Matt; Rutherford, Nicola J; Nicholson, Alexandra M; Finch, NiCole A; Flynn, Heather; Adamson, Jennifer; Kouri, Naomi; Wojtas, Aleksandra; Sengdy, Pheth; Hsiung, Ging-Yuek R; Karydas, Anna; Seeley, William W; Josephs, Keith A; Coppola, Giovanni; Geschwind, Daniel H; Wszolek, Zbigniew K; Feldman, Howard; Knopman, David S; Petersen, Ronald C; Miller, Bruce L; Dickson, Dennis W; Boylan, Kevin B; Graff-Radford, Neill R; Rademakers, Rosa

    2011-10-20

    Several families have been reported with autosomal-dominant frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), genetically linked to chromosome 9p21. Here, we report an expansion of a noncoding GGGGCC hexanucleotide repeat in the gene C9ORF72 that is strongly associated with disease in a large FTD/ALS kindred, previously reported to be conclusively linked to chromosome 9p. This same repeat expansion was identified in the majority of our families with a combined FTD/ALS phenotype and TDP-43-based pathology. Analysis of extended clinical series found the C9ORF72 repeat expansion to be the most common genetic abnormality in both familial FTD (11.7%) and familial ALS (23.5%). The repeat expansion leads to the loss of one alternatively spliced C9ORF72 transcript and to formation of nuclear RNA foci, suggesting multiple disease mechanisms. Our findings indicate that repeat expansion in C9ORF72 is a major cause of both FTD and ALS.

  15. Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants.

    Science.gov (United States)

    Burton, Paul R; Clayton, David G; Cardon, Lon R; Craddock, Nick; Deloukas, Panos; Duncanson, Audrey; Kwiatkowski, Dominic P; McCarthy, Mark I; Ouwehand, Willem H; Samani, Nilesh J; Todd, John A; Donnelly, Peter; Barrett, Jeffrey C; Davison, Dan; Easton, Doug; Evans, David M; Leung, Hin-Tak; Marchini, Jonathan L; Morris, Andrew P; Spencer, Chris C A; Tobin, Martin D; Attwood, Antony P; Boorman, James P; Cant, Barbara; Everson, Ursula; Hussey, Judith M; Jolley, Jennifer D; Knight, Alexandra S; Koch, Kerstin; Meech, Elizabeth; Nutland, Sarah; Prowse, Christopher V; Stevens, Helen E; Taylor, Niall C; Walters, Graham R; Walker, Neil M; Watkins, Nicholas A; Winzer, Thilo; Jones, Richard W; McArdle, Wendy L; Ring, Susan M; Strachan, David P; Pembrey, Marcus; Breen, Gerome; St Clair, David; Caesar, Sian; Gordon-Smith, Katharine; Jones, Lisa; Fraser, Christine; Green, Elaine K; Grozeva, Detelina; Hamshere, Marian L; Holmans, Peter A; Jones, Ian R; Kirov, George; Moskivina, Valentina; Nikolov, Ivan; O'Donovan, Michael C; Owen, Michael J; Collier, David A; Elkin, Amanda; Farmer, Anne; Williamson, Richard; McGuffin, Peter; Young, Allan H; Ferrier, I Nicol; Ball, Stephen G; Balmforth, Anthony J; Barrett, Jennifer H; Bishop, Timothy D; Iles, Mark M; Maqbool, Azhar; Yuldasheva, Nadira; Hall, Alistair S; Braund, Peter S; Dixon, Richard J; Mangino, Massimo; Stevens, Suzanne; Thompson, John R; Bredin, Francesca; Tremelling, Mark; Parkes, Miles; Drummond, Hazel; Lees, Charles W; Nimmo, Elaine R; Satsangi, Jack; Fisher, Sheila A; Forbes, Alastair; Lewis, Cathryn M; Onnie, Clive M; Prescott, Natalie J; Sanderson, Jeremy; Matthew, Christopher G; Barbour, Jamie; Mohiuddin, M Khalid; Todhunter, Catherine E; Mansfield, John C; Ahmad, Tariq; Cummings, Fraser R; Jewell, Derek P; Webster, John; Brown, Morris J; Lathrop, Mark G; Connell, John; Dominiczak, Anna; Marcano, Carolina A Braga; Burke, Beverley; Dobson, Richard; Gungadoo, Johannie; Lee, Kate L; Munroe, Patricia B; Newhouse, Stephen J; Onipinla, Abiodun; Wallace, Chris; Xue, Mingzhan; Caulfield, Mark; Farrall, Martin; Barton, Anne; Bruce, Ian N; Donovan, Hannah; Eyre, Steve; Gilbert, Paul D; Hilder, Samantha L; Hinks, Anne M; John, Sally L; Potter, Catherine; Silman, Alan J; Symmons, Deborah P M; Thomson, Wendy; Worthington, Jane; Dunger, David B; Widmer, Barry; Frayling, Timothy M; Freathy, Rachel M; Lango, Hana; Perry, John R B; Shields, Beverley M; Weedon, Michael N; Hattersley, Andrew T; Hitman, Graham A; Walker, Mark; Elliott, Kate S; Groves, Christopher J; Lindgren, Cecilia M; Rayner, Nigel W; Timpson, Nicolas J; Zeggini, Eleftheria; Newport, Melanie; Sirugo, Giorgio; Lyons, Emily; Vannberg, Fredrik; Hill, Adrian V S; Bradbury, Linda A; Farrar, Claire; Pointon, Jennifer J; Wordsworth, Paul; Brown, Matthew A; Franklyn, Jayne A; Heward, Joanne M; Simmonds, Matthew J; Gough, Stephen C L; Seal, Sheila; Stratton, Michael R; Rahman, Nazneen; Ban, Maria; Goris, An; Sawcer, Stephen J; Compston, Alastair; Conway, David; Jallow, Muminatou; Newport, Melanie; Sirugo, Giorgio; Rockett, Kirk A; Bumpstead, Suzannah J; Chaney, Amy; Downes, Kate; Ghori, Mohammed J R; Gwilliam, Rhian; Hunt, Sarah E; Inouye, Michael; Keniry, Andrew; King, Emma; McGinnis, Ralph; Potter, Simon; Ravindrarajah, Rathi; Whittaker, Pamela; Widden, Claire; Withers, David; Cardin, Niall J; Davison, Dan; Ferreira, Teresa; Pereira-Gale, Joanne; Hallgrimsdo'ttir, Ingeleif B; Howie, Bryan N; Su, Zhan; Teo, Yik Ying; Vukcevic, Damjan; Bentley, David; Brown, Matthew A; Compston, Alastair; Farrall, Martin; Hall, Alistair S; Hattersley, Andrew T; Hill, Adrian V S; Parkes, Miles; Pembrey, Marcus; Stratton, Michael R; Mitchell, Sarah L; Newby, Paul R; Brand, Oliver J; Carr-Smith, Jackie; Pearce, Simon H S; McGinnis, R; Keniry, A; Deloukas, P; Reveille, John D; Zhou, Xiaodong; Sims, Anne-Marie; Dowling, Alison; Taylor, Jacqueline; Doan, Tracy; Davis, John C; Savage, Laurie; Ward, Michael M; Learch, Thomas L; Weisman, Michael H; Brown, Mathew

    2007-11-01

    We have genotyped 14,436 nonsynonymous SNPs (nsSNPs) and 897 major histocompatibility complex (MHC) tag SNPs from 1,000 independent cases of ankylosing spondylitis (AS), autoimmune thyroid disease (AITD), multiple sclerosis (MS) and breast cancer (BC). Comparing these data against a common control dataset derived from 1,500 randomly selected healthy British individuals, we report initial association and independent replication in a North American sample of two new loci related to ankylosing spondylitis, ARTS1 and IL23R, and confirmation of the previously reported association of AITD with TSHR and FCRL3. These findings, enabled in part by increased statistical power resulting from the expansion of the control reference group to include individuals from the other disease groups, highlight notable new possibilities for autoimmune regulation and suggest that IL23R may be a common susceptibility factor for the major 'seronegative' diseases.

  16. A Bayesian Hierarchical Model for Relating Multiple SNPs within Multiple Genes to Disease Risk

    Directory of Open Access Journals (Sweden)

    Lewei Duan

    2013-01-01

    Full Text Available A variety of methods have been proposed for studying the association of multiple genes thought to be involved in a common pathway for a particular disease. Here, we present an extension of a Bayesian hierarchical modeling strategy that allows for multiple SNPs within each gene, with external prior information at either the SNP or gene level. The model involves variable selection at the SNP level through latent indicator variables and Bayesian shrinkage at the gene level towards a prior mean vector and covariance matrix that depend on external information. The entire model is fitted using Markov chain Monte Carlo methods. Simulation studies show that the approach is capable of recovering many of the truly causal SNPs and genes, depending upon their frequency and size of their effects. The method is applied to data on 504 SNPs in 38 candidate genes involved in DNA damage response in the WECARE study of second breast cancers in relation to radiotherapy exposure.

  17. Estimating the proportion of variation in susceptibility to multiple sclerosis captured by common SNPs

    Science.gov (United States)

    Watson, Corey T.; Disanto, Giulio; Breden, Felix; Giovannoni, Gavin; Ramagopalan, Sreeram V.

    2012-10-01

    Multiple sclerosis (MS) is a complex disease with underlying genetic and environmental factors. Although the contribution of alleles within the major histocompatibility complex (MHC) are known to exert strong effects on MS risk, much remains to be learned about the contributions of loci with more modest effects identified by genome-wide association studies (GWASs), as well as loci that remain undiscovered. We use a recently developed method to estimate the proportion of variance in disease liability explained by 475,806 single nucleotide polymorphisms (SNPs) genotyped in 1,854 MS cases and 5,164 controls. We reveal that ~30% of MS genetic liability is explained by SNPs in this dataset, the majority of which is accounted for by common variants. These results suggest that the unaccounted for proportion could be explained by variants that are in imperfect linkage disequilibrium with common GWAS SNPs, highlighting the potential importance of rare variants in the susceptibility to MS.

  18. A robust linkage map of the porcine autosome based on gene-associated SNPs

    DEFF Research Database (Denmark)

    Vingborg, Rikke K K; Gregersen, Vivi R; Zhan, Bujie;

    2009-01-01

    Background Genetic linkage maps are necessary for mapping of mendelian traits and quantitative trait loci (QTLs). To identify the actual genes, which control these traits, a map based on gene-associated single nucleotide polymorphism (SNP) markers is highly valuable. In this study, the SNPs were...... genotyped in a large family material comprising more than 5,000 piglets derived from 12 Duroc boars crossed with 236 Danish Landrace/Danish Large White sows. The SNPs were identified in sequence alignments of 4,600 different amplicons obtained from the 12 boars and containing coding regions of genes derived...... from expressed sequence tags (ESTs) and genomic shotgun sequences. Results Linkage maps of all 18 porcine autosomes were constructed based on 456 gene-associated and six porcine EST-based SNPs. The total length of the averaged-sex whole porcine autosome was estimated to 1,711.8 cM resulting...

  19. Chromosome numbers in Bromeliaceae

    Directory of Open Access Journals (Sweden)

    Cotias-de-Oliveira Ana Lúcia Pires

    2000-01-01

    Full Text Available The present study reports chromosome numbers of 17 species of Bromeliaceae, belonging to the genera Encholirium, Bromelia, Orthophytum, Hohenbergia, Billbergia, Neoglaziovia, Aechmea, Cryptanthus and Ananas. Most species present 2n = 50, however, Bromelia laciniosa, Orthophytum burle-marxii and O. maracasense are polyploids with 2n = 150, 2n = 100 and 2n = 150, respectively, while for Cryptanthus bahianus, 2n = 34 + 1-4B. B chromosomes were observed in Bromelia plumieri and Hohenbergia aff. utriculosa. The chromosome number of all species was determined for the first time, except for Billbergia chlorosticta and Cryptanthus bahianus. Our data supports the hypothesis of a basic number of x = 25 for the Bromeliaceae family and decreasing aneuploidy in the genus Cryptanthus.

  20. Those amazing dinoflagellate chromosomes

    Institute of Scientific and Technical Information of China (English)

    PETER J RIZZO

    2003-01-01

    Dinoflagellates are a very large and diverse group of eukaryotic algae that play a major role in aquatic food webs of both fresh water and marine habitats. Moreover, the toxic members of this group pose a health threat in the form of red tides. Finally, dinoflagellates are of great evolutionary importance,because of their taxonomic position, and their unusual chromosome structure and composition. While the cytoplasm of dinoflagellates is typically eukaryotic, the nucleus is unique when compared to the nucleus of other eukaryotes. More specifically, while the chromosomes of all other eukaryotes contain histones,dinoflagellate chromosomes lack histones completely. There are no known exceptions to this observation: all dinoflagellates lack histones, and all other eukaryotes contain histones. Nevertheless, dinoflagellates remain a relatively unstudied group of eukaryotes.

  1. SNPs in stress-responsive rice genes: validation, genotyping, functional relevance and population structure

    Directory of Open Access Journals (Sweden)

    Parida Swarup K

    2012-08-01

    Full Text Available Abstract Background Single nucleotide polymorphism (SNP validation and large-scale genotyping are required to maximize the use of DNA sequence variation and determine the functional relevance of candidate genes for complex stress tolerance traits through genetic association in rice. We used the bead array platform-based Illumina GoldenGate assay to validate and genotype SNPs in a select set of stress-responsive genes to understand their functional relevance and study the population structure in rice. Results Of the 384 putative SNPs assayed, we successfully validated and genotyped 362 (94.3%. Of these 325 (84.6% showed polymorphism among the 91 rice genotypes examined. Physical distribution, degree of allele sharing, admixtures and introgression, and amino acid replacement of SNPs in 263 abiotic and 62 biotic stress-responsive genes provided clues for identification and targeted mapping of trait-associated genomic regions. We assessed the functional and adaptive significance of validated SNPs in a set of contrasting drought tolerant upland and sensitive lowland rice genotypes by correlating their allelic variation with amino acid sequence alterations in catalytic domains and three-dimensional secondary protein structure encoded by stress-responsive genes. We found a strong genetic association among SNPs in the nine stress-responsive genes with upland and lowland ecological adaptation. Higher nucleotide diversity was observed in indica accessions compared with other rice sub-populations based on different population genetic parameters. The inferred ancestry of 16% among rice genotypes was derived from admixed populations with the maximum between upland aus and wild Oryza species. Conclusions SNPs validated in biotic and abiotic stress-responsive rice genes can be used in association analyses to identify candidate genes and develop functional markers for stress tolerance in rice.

  2. Typing of 24 mtDNA SNPs in a Chinese Population Using SNaPshot Minisequencing

    Institute of Scientific and Technical Information of China (English)

    黄代新; 桂程; 易少华; 杨庆恩; 杨荣芝; 梅焜

    2010-01-01

    Three SNaPshot multiplex assays were developed to test 23 coding region single nucleotide polymorphisms(SNPs) and one control region SNP outside hypervariable regions(HVR)Ⅰand Ⅱ,which was aimed at increasing the discrimination power of the mitochondrial DNA(mtDNA) typing in forensic casework,and confirming haplogroup assignments of mtDNA profiles in both human population studies and medical research.The selected SNPs targeted the East Asian phylogeny.These multiplex assays were validated by comparing with t...

  3. Computation of haplotypes on SNPs subsets: advantage of the "global method"

    Directory of Open Access Journals (Sweden)

    Do Hervé

    2006-10-01

    Full Text Available Abstract Background Genetic association studies aim at finding correlations between a disease state and genetic variations such as SNPs or combinations of SNPs, termed haplotypes. Some haplotypes have a particular biological meaning such as the ones derived from SNPs located in the promoters, or the ones derived from non synonymous SNPs. All these haplotypes are "subhaplotypes" because they refer only to a part of the SNPs found in the gene. Until now, subhaplotypes were directly computed from the very SNPs chosen to constitute them, without taking into account the rest of the information corresponding to the other SNPs located in the gene. In the present work, we describe an alternative approach, called the "global method", which takes into account all the SNPs known in the region and compare the efficacy of the two "direct" and "global" methods. Results We used empirical haplotypes data sets from the GH1 promoter and the APOE gene, and 10 simulated datasets, and randomly introduced in them missing information (from 0% up to 20% to compare the 2 methods. For each method, we used the PHASE haplotyping software since it was described to be the best. We showed that the use of the "global method" for subhaplotyping leads always to a better error rate than the classical direct haplotyping. The advantage provided by this alternative method increases with the percentage of missing genotyping data (diminution of the average error rate from 25% to less than 10%. We applied the global method software on the GRIV cohort for AIDS genetic associations and some associations previously identified through direct subhaplotyping were found to be erroneous. Conclusion The global method for subhaplotyping can reduce, sometimes dramatically, the error rate on patient resolutions and haplotypes frequencies. One should thus use this method in order to minimise the risk of a false interpretation in genetic studies involving subhaplotypes. In practice the global method

  4. Targeted Metabolic Engineering Guided by Computational Analysis of Single-Nucleotide Polymorphisms (SNPs)

    DEFF Research Database (Denmark)

    Udatha, D B R K Gupta; Rasmussen, Simon; Sicheritz-Pontén, Thomas

    2013-01-01

    The non-synonymous SNPs, the so-called non-silent SNPs, which are single-nucleotide variations in the coding regions that give "birth" to amino acid mutations, are often involved in the modulation of protein function. Understanding the effect of individual amino acid mutations on a protein....../enzyme function or stability is useful for altering its properties for a wide variety of engineering studies. Since measuring the effects of amino acid mutations experimentally is a laborious process, a variety of computational methods have been discussed here that aid to extract direct genotype to phenotype...

  5. Chromosomal rearrangements in cattle and pigs revealed by chromosome microdissection and chromosome painting

    Directory of Open Access Journals (Sweden)

    Yerle Martine

    2003-11-01

    Full Text Available Abstract A pericentric inversion of chromosome 4 in a boar, as well as a case of (2q-;5p+ translocation mosaicism in a bull were analysed by chromosome painting using probes generated by conventional microdissection. For the porcine inversion, probes specific for p arms and q arms were produced and hybridised simultaneously on metaphases of a heterozygote carrier. In the case of the bovine translocation, two whole chromosome probes (chromosome 5, and derived chromosome 5 were elaborated and hybridised independently on chromosomal preparations of the bull who was a carrier of the mosaic translocation. The impossibility of differentiating chromosomes 2 and der(2 from other chromosomes of the metaphases did not allow the production of painting probes for these chromosomes. For all experiments, the quality of painting was comparable to that usually observed with probes obtained from flow-sorted chromosomes. The results obtained allowed confirmation of the interpretations proposed with G-banding karyotype analyses. In the bovine case, however, the reciprocity of the translocation could not be proven. The results presented in this paper show the usefulness of the microdissection technique for characterising chromosomal rearrangements in species for which commercial probes are not available. They also confirmed that the main limiting factor of the technique is the quality of the chromosomal preparations, which does not allow the identification of target chromosomes or chromosome fragments in all cases.

  6. Identifying Liver Cancer-Related Enhancer SNPs by Integrating GWAS and Histone Modification ChIP-seq Data

    OpenAIRE

    Zhang, Tianjiao; Hu, Yang; Wu, Xiaoliang; Ma, Rui; Jiang, Qinghua; Wang, Yadong

    2016-01-01

    Many disease-related single nucleotide polymorphisms (SNPs) have been inferred from genome-wide association studies (GWAS) in recent years. Numerous studies have shown that some SNPs located in protein-coding regions are associated with numerous diseases by affecting gene expression. However, in noncoding regions, the mechanism of how SNPs contribute to disease susceptibility remains unclear. Enhancer elements are functional segments of DNA located in noncoding regions that play an important ...

  7. Chromosomal rearrangement interferes with meiotic X chromosome inactivation

    OpenAIRE

    Homolka, David; Ivanek, Robert; Capkova, Jana; Jansa, Petr; Forejt, Jiri

    2007-01-01

    Heterozygosity for certain mouse and human chromosomal rearrangements is characterized by the incomplete meiotic synapsis of rearranged chromosomes, by their colocalization with the XY body in primary spermatocytes, and by male-limited sterility. Previously, we argued that such X–autosomal associations could interfere with meiotic sex chromosome inactivation. Recently, supporting evidence has reported modifications of histones in rearranged chromosomes by a process called the meiotic silencin...

  8. Genetic variants in urinary bladder cancer: collective power of the "wimp SNPs".

    Science.gov (United States)

    Golka, Klaus; Selinski, Silvia; Lehmann, Marie-Louise; Blaszkewicz, Meinolf; Marchan, Rosemarie; Ickstadt, Katja; Schwender, Holger; Bolt, Hermann M; Hengstler, Jan G

    2011-06-01

    In recent years, genome-wide association studies (GWAS) have identified more than 300 validated associations between genetic variants and risk of approximately 70 common diseases. A small number of rare variants with a frequency of usually less than 1% are associated with a strongly enhanced risk, such as genetic variants of TP53, RB1, BRCA1, and BRCA2. Only a very small number of SNPs (with a frequency of more that 1% of the rare allele) have effects of a factor of two or higher. Examples include APOE4 in Alzheimer's disease, LOXL1 in exfoliative glaucoma, and CFH in age-related macular degeneration. However, the majority of all identified SNPs have odds ratios between 1.1 and 1.5. In the case of urinary bladder cancer, all known SNPs that have been validated in sufficiently large populations are associated with odds ratios smaller than 1.5. These SNPs are located next to the following genes: MYC, TP63, PSCA, the TERT-CLPTM1L locus, FGFR3, TACC3, NAT2, CBX6, APOBEC3A, CCNE1, and UGT1A. It is likely that these moderate risk or "wimp SNPs" interact, and because of their high number, collectively have a strong influence on whether an individual will develop cancer or not. It should be considered that variants identified so far explain only approximately 5-10% of the overall inherited risk. Possibly, the remaining variance is due to an even higher number of SNPs with odds ratios smaller than 1.1. Recent studies have provided the following information: (1) The functions of genes identified as relevant for bladder cancer focus on detoxification of carcinogens, control of the cell cycle and apoptosis, as well as maintenance of DNA integrity. (2) Many novel SNPs are far away from the protein coding regions, suggesting that these SNPs are located on distant-acting transcriptional enhancers. (3) The low odds ratio of each individual bladder cancer-associated SNP is too low to justify reasonable preventive measures. However, if the recently identified SNPs interact, they may

  9. Genomic and expression profiling of human spermatocytic seminomas: primary spermatocyte as tumorigenic precursor and DMRT1 as candidate chromosome 9 gene.

    Science.gov (United States)

    Looijenga, Leendert H J; Hersmus, Remko; Gillis, Ad J M; Pfundt, Rolph; Stoop, Hans J; van Gurp, Ruud J H L M; Veltman, Joris; Beverloo, H Berna; van Drunen, Ellen; van Kessel, Ad Geurts; Pera, Renee Reijo; Schneider, Dominik T; Summersgill, Brenda; Shipley, Janet; McIntyre, Alan; van der Spek, Peter; Schoenmakers, Eric; Oosterhuis, J Wolter

    2006-01-01

    Spermatocytic seminomas are solid tumors found solely in the testis of predominantly elderly individuals. We investigated these tumors using a genome-wide analysis for structural and numerical chromosomal changes through conventional karyotyping, spectral karyotyping, and array comparative genomic hybridization using a 32 K genomic tiling-path resolution BAC platform (confirmed by in situ hybridization). Our panel of five spermatocytic seminomas showed a specific pattern of chromosomal imbalances, mainly numerical in nature (range, 3-24 per tumor). Gain of chromosome 9 was the only consistent anomaly, which in one case also involved amplification of the 9p21.3-pter region. Parallel chromosome level expression profiling as well as microarray expression analyses (Affymetrix U133 plus 2.0) was also done. Unsupervised cluster analysis showed that a profile containing transcriptional data on 373 genes (difference of > or = 3.0-fold) is suitable for distinguishing these tumors from seminomas/dysgerminomas. The diagnostic markers SSX2-4 and POU5F1 (OCT3/OCT4), previously identified by us, were among the top discriminatory genes, thereby validating the experimental set-up. In addition, novel discriminatory markers suitable for diagnostic purposes were identified, including Deleted in Azospermia (DAZ). Although the seminomas/dysgerminomas were characterized by expression of stem cell-specific genes (e.g., POU5F1, PROM1/CD133, and ZFP42), spermatocytic seminomas expressed multiple cancer testis antigens, including TSP50 and CTCFL (BORIS), as well as genes known to be expressed specifically during prophase meiosis I (TCFL5, CLGN, and LDHc). This is consistent with different cells of origin, the primordial germ cell and primary spermatocyte, respectively. Based on the region of amplification defined on 9p and the associated expression plus confirmatory immunohistochemistry, DMRT1 (a male-specific transcriptional regulator) was identified as a likely candidate gene for

  10. Electochemical detection of chromosome translocation

    DEFF Research Database (Denmark)

    Kwasny, Dorota; Dimaki, Maria; Silahtaroglu, Asli;

    2014-01-01

    Cytogenetics is a study of the cell structure with a main focus on chromosomes content and their structure. Chromosome abnormalities, such as translocations may cause various genetic disorders and heametological malignancies. Chromosome translocations are structural rearrangements of two...... chromosomes that results in formation of derivative chromosomes with a mixed DNA sequence. The method currently used for their detection is Fluorescent In Situ Hybridization, which requires a use of expensive, fluorescently labeled probes that target the derivative chromosomes. We present here a double...... hybridization approach developed for label-free detection of the chromosome translocations. For specific translocation detection it is necessary to determine that the two DNA sequences forming a derivative chromosome are connected, which is achieved by two subsequent hybridization steps. The electrochemical...

  11. Chromosome Variations And Human Behavior

    Science.gov (United States)

    Soudek, D.

    1974-01-01

    Article focused on the science of cytogenetics, which studied the transmission of the units of heredity called chromosomes, and considered the advantage of proper diagnosis of genetic diseases, treated on the chromosomal level. (Author/RK)

  12. The distal end of porcine chromosome 6p is involved in the regulation of skatole levels in boars

    Directory of Open Access Journals (Sweden)

    Crooijmans Richard PMA

    2011-04-01

    Full Text Available Abstract Background Boar taint is an unpleasant condition of pork, mainly due to the accumulation of androstenone and skatole in male pigs at onset of puberty. This condition is the cause of considerable economic losses in the pig industry and the most common practice to control it is to castrate male piglets. Because of the economic and animal welfare concerns there is interest in developing genetic markers that could be used in selection schemes to decrease the incidence of boar taint. The Porcine 60 K SNP Beadchip was used to genotype 891 pigs from a composite Duroc sire line, for which skatole levels in fat had been collected. Results The genome-wide association study revealed that 16 SNPs (single nucleotide polymorphisms located on the proximal region of chromosome 6 were significantly associated with skatole levels. These SNPs are grouped in three separate clusters located in the initial 6 Mb region of chromosome 6. The differences observed between the homozygote genotypes for SNPs in the three clusters were substantial, including a difference of 102.8 ng/g skatole in melted fat between the homozygotes for the ALGA0107039 marker. Single SNPs explain up to 22% of the phenotypic variance. No obvious candidate genes could be pinpointed in the region, which may be due to the need of further annotation of the pig genome. Conclusions This study demonstrated new SNP markers significantly associated with skatole levels in the distal region of chromosome 6p. These markers defined three independent clusters in the region, which contain a low number of protein-coding genes. The considerable differences observed between the homozygous genotypes for several SNPs may be used in future selection schemes to reduce skatole levels in pigs

  13. Ring chromosome 13

    DEFF Research Database (Denmark)

    Brandt, C A; Hertz, Jens Michael; Petersen, M B;

    1992-01-01

    A stillborn male child with anencephaly and multiple malformations was found to have the karyotype 46,XY,r(13) (p11q21.1). The breakpoint at 13q21.1, determined by high resolution banding, is the most proximal breakpoint ever reported in patients with ring chromosome 13. In situ hybridisation...

  14. Chromosomes, cancer and radiosensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Samouhos, E.

    1983-08-01

    Some specific chromosomal abnormalities are associated with certain cancers. The earliest description of such a specific association is the one of the Philadelphia chromosome and myelogenous leukemia (1960). Other congenital karyotype abnormalities are associated with specific cancers. Examples of these are Down's syndrome with leukemia and Klinefelter's syndrome with male breast cancer. Genetic diseases of increased chromosome breakage, or of defective chromosome repair, are associated with greatly increased cancer incidence. Three such diseases have been recognized: 1) Fanconi's anemia, associated with leukemias and lymphomas, 2) Bloom's syndrome, associated with acute leukemias and lymphosarcoma, and 3) ataxia telangiectasia, associated with Hodgkin's disease, leukemia, and lymphosarcomas. Ten percent of individuals with ataxia telangiectasia will develop one of these neoplasms. Individuals with certain of these syndromes display an unusually high radiosensitivity. Radiation therapy for cancers has been fatal in patients who received as low as 3000 rad. This remarkable radiosensitivity has been quantitated in cell cultures from such cases. Evidence suggests that the apparent sensitivity may reflect subnormal ability to repair radiation damage. The rapid proliferation of information in this field stems from the interdigitation of many disciplines and specialties, including cytogenetics, cell biology, molecular biology, epidemiology, radiobiology, and several others. This paper is intended for clinicians; it presents a structured analytic scheme for correlating and classifying this multidisciplinary information as it becomes available.

  15. The Y Chromosome

    Science.gov (United States)

    Offner, Susan

    2010-01-01

    The Y chromosome is of great interest to students and can be used to teach about many important biological concepts in addition to sex determination. This paper discusses mutation, recombination, mammalian sex determination, sex determination in general, and the evolution of sex determination in mammals. It includes a student activity that…

  16. Why Chromosome Palindromes?

    Directory of Open Access Journals (Sweden)

    Esther Betrán

    2012-01-01

    Full Text Available We look at sex-limited chromosome (Y or W evolution with particular emphasis on the importance of palindromes. Y chromosome palindromes consist of inverted duplicates that allow for local recombination in an otherwise nonrecombining chromosome. Since palindromes enable intrachromosomal gene conversion that can help eliminate deleterious mutations, they are often highlighted as mechanisms to protect against Y degeneration. However, the adaptive significance of recombination resides in its ability to decouple the evolutionary fates of linked mutations, leading to both a decrease in degeneration rate and an increase in adaptation rate. Our paper emphasizes the latter, that palindromes may exist to accelerate adaptation by increasing the potential targets and fixation rates of incoming beneficial mutations. This hypothesis helps reconcile two enigmatic features of the “palindromes as protectors” view: (1 genes that are not located in palindromes have been retained under purifying selection for tens of millions of years, and (2 under models that only consider deleterious mutations, gene conversion benefits duplicate gene maintenance but not initial fixation. We conclude by looking at ways to test the hypothesis that palindromes enhance the rate of adaptive evolution of Y-linked genes and whether this effect can be extended to palindromes on other chromosomes.

  17. Telomere dysfunction and chromosome instability

    Energy Technology Data Exchange (ETDEWEB)

    Murnane, John P., E-mail: jmurnane@radonc.ucsf.edu [Department of Radiation Oncology, University of California San Francisco, 2340 Sutter Street, San Francisco, CA 94143-1331 (United States)

    2012-02-01

    The ends of chromosomes are composed of a short repeat sequence and associated proteins that together form a cap, called a telomere, that keeps the ends from appearing as double-strand breaks (DSBs) and prevents chromosome fusion. The loss of telomeric repeat sequences or deficiencies in telomeric proteins can result in chromosome fusion and lead to chromosome instability. The similarity between chromosome rearrangements resulting from telomere loss and those found in cancer cells implicates telomere loss as an important mechanism for the chromosome instability contributing to human cancer. Telomere loss in cancer cells can occur through gradual shortening due to insufficient telomerase, the protein that maintains telomeres. However, cancer cells often have a high rate of spontaneous telomere loss despite the expression of telomerase, which has been proposed to result from a combination of oncogene-mediated replication stress and a deficiency in DSB repair in telomeric regions. Chromosome fusion in mammalian cells primarily involves nonhomologous end joining (NHEJ), which is the major form of DSB repair. Chromosome fusion initiates chromosome instability involving breakage-fusion-bridge (B/F/B) cycles, in which dicentric chromosomes form bridges and break as the cell attempts to divide, repeating the process in subsequent cell cycles. Fusion between sister chromatids results in large inverted repeats on the end of the chromosome, which amplify further following additional B/F/B cycles. B/F/B cycles continue until the chromosome acquires a new telomere, most often by translocation of the end of another chromosome. The instability is not confined to a chromosome that loses its telomere, because the instability is transferred to the chromosome donating a translocation. Moreover, the amplified regions are unstable and form extrachromosomal DNA that can reintegrate at new locations. Knowledge concerning the factors promoting telomere loss and its consequences is

  18. [Dicentric Y chromosome].

    Science.gov (United States)

    Abdelmoula, N Bouayed; Amouri, A

    2005-01-01

    Dicentric Y chromosomes are the most common Y structural abnormalities and their influence on gonadal and somatic development is extremely variable. Here, we report the third comprehensive review of the literature concerning dicentric Y chromosomes reported since 1994. We find 78 new cases for which molecular studies (PCR or FISH) have been widely applied to investigate SRY (68% of cases), GBY, ZFY, RFS4Y, GCY and different genes at AZF region. For dic(Yq), all cases (n = 20) were mosaic for 45,X and 4 of them were also mosaic for a 46,XY cell line. When breakpoints were available (15/20 cases), they were in Yp11. 50% of cases were phenotypic female and 20% phenotypic male while 20% of cases were reported with gonadal dysgenesis. Gonadal histology was defined in 8 cases but only in one case, gonadal tissu was genetically investigated because of gonadoblastoma. For dic(Yp) (n = 55), mosaicism concerned only 45,X cell line and was found in 50 cases while the remainder five cases were homogeneous. When breakpoints were available, it was at Yq11 in 50 cases and at Yq12 in two cases. 54% of cases were phenotypic female, 26% were phenotypic male and 18% were associated with genitalia ambiguous. SRY was analyzed in 33 cases, sequenced in 9 cases and was muted in only one case. Gonads were histologically explored in 34 cases and genetically investigated in 8 cases. Gonadoblastoma was found in only two cases. Through this review, it seems that phenotype-genotype correlations are still not possible and that homogeneous studies of dic(Y) in more patients using molecular tools for structural characterization of the rearranged Y chromosome and assessment of mosaicism in many organs are necessary to clarify the basis of the phenotypic heterogeneity of dicentric Y chromosomes and then to help phenotypic prediction of such chromosome rearrangement.

  19. Biomarker Detection in Association Studies: Modeling SNPs Simultaneously via Logistic ANOVA

    KAUST Repository

    Jung, Yoonsuh

    2014-10-02

    In genome-wide association studies, the primary task is to detect biomarkers in the form of Single Nucleotide Polymorphisms (SNPs) that have nontrivial associations with a disease phenotype and some other important clinical/environmental factors. However, the extremely large number of SNPs comparing to the sample size inhibits application of classical methods such as the multiple logistic regression. Currently the most commonly used approach is still to analyze one SNP at a time. In this paper, we propose to consider the genotypes of the SNPs simultaneously via a logistic analysis of variance (ANOVA) model, which expresses the logit transformed mean of SNP genotypes as the summation of the SNP effects, effects of the disease phenotype and/or other clinical variables, and the interaction effects. We use a reduced-rank representation of the interaction-effect matrix for dimensionality reduction, and employ the L 1-penalty in a penalized likelihood framework to filter out the SNPs that have no associations. We develop a Majorization-Minimization algorithm for computational implementation. In addition, we propose a modified BIC criterion to select the penalty parameters and determine the rank number. The proposed method is applied to a Multiple Sclerosis data set and simulated data sets and shows promise in biomarker detection.

  20. Association study of FOXO3A SNPs and aging phenotypes in Danish oldest-old individuals

    DEFF Research Database (Denmark)

    Soerensen, Mette; Nygaard, Marianne; Dato, Serena

    2015-01-01

    FOXO3A variation has repeatedly been reported to associate with human longevity, yet only few studies have investigated whether FOXO3A variation also associates with aging-related traits. Here, we investigate the association of 15 FOXO3A tagging single nucleotide polymorphisms (SNPs) in 1088 olde...

  1. Typing of 49 autosomal SNPs by single base extension and capillary electrophoresis for forensic genetic testing

    DEFF Research Database (Denmark)

    Børsting, Claus; Tomas Mas, Carmen; Morling, Niels

    2012-01-01

    of the amplicons range from 65 to 115 bp. The high sensitivity and the short amplicon sizes make the assay very suitable for typing of degraded DNA samples, and the low mutation rate of SNPs makes the assay very useful for relationship testing. Combined, these advantages make the assay well suited for disaster...

  2. Application of SNPs for population genetics of nonmodel organisms: new opportunities and challenges

    DEFF Research Database (Denmark)

    Helyar, S.J.; Hansen, Jakob Hemmer; Bekkevold, Dorte;

    2011-01-01

    challenging. Here, we discuss common issues when employing SNP markers, including the high numbers of markers typically employed, the effects of ascertainment bias and the inclusion of nonneutral loci in a marker panel. We provide a critique of considerations specifically associated with the application...... and population genetic analysis of SNPs in nonmodel taxa, focusing specifically on some of the most commonly applied methods....

  3. Cross-amplification and validation of SNPs conserved over 44 million years between seals and dogs.

    Directory of Open Access Journals (Sweden)

    Joseph I Hoffman

    Full Text Available High-density SNP arrays developed for humans and their companion species provide a rapid and convenient tool for generating SNP data in closely-related non-model organisms, but have not yet been widely applied to phylogenetically divergent taxa. Consequently, we used the CanineHD BeadChip to genotype 24 Antarctic fur seal (Arctocephalus gazella individuals. Despite seals and dogs having diverged around 44 million years ago, 33,324 out of 173,662 loci (19.2% could be genotyped, of which 173 were polymorphic and clearly interpretable. Two SNPs were validated using KASP genotyping assays, with the resulting genotypes being 100% concordant with those obtained from the high-density array. Two loci were also confirmed through in silico visualisation after mapping them to the fur seal transcriptome. Polymorphic SNPs were distributed broadly throughout the dog genome and did not differ significantly in proximity to genes from either monomorphic SNPs or those that failed to cross-amplify in seals. However, the nearest genes to polymorphic SNPs were significantly enriched for functional annotations relating to energy metabolism, suggesting a possible bias towards conserved regions of the genome.

  4. SNP2TFBS – a database of regulatory SNPs affecting predicted transcription factor binding site affinity

    Science.gov (United States)

    Kumar, Sunil; Ambrosini, Giovanna; Bucher, Philipp

    2017-01-01

    SNP2TFBS is a computational resource intended to support researchers investigating the molecular mechanisms underlying regulatory variation in the human genome. The database essentially consists of a collection of text files providing specific annotations for human single nucleotide polymorphisms (SNPs), namely whether they are predicted to abolish, create or change the affinity of one or several transcription factor (TF) binding sites. A SNP's effect on TF binding is estimated based on a position weight matrix (PWM) model for the binding specificity of the corresponding factor. These data files are regenerated at regular intervals by an automatic procedure that takes as input a reference genome, a comprehensive SNP catalogue and a collection of PWMs. SNP2TFBS is also accessible over a web interface, enabling users to view the information provided for an individual SNP, to extract SNPs based on various search criteria, to annotate uploaded sets of SNPs or to display statistics about the frequencies of binding sites affected by selected SNPs. Homepage: http://ccg.vital-it.ch/snp2tfbs/. PMID:27899579

  5. Typing of 49 autosomal SNPs by SNaPshot in the Slovenian population

    DEFF Research Database (Denmark)

    Drobnic, Katja; Børsting, Claus; Rockenbauer, Eszter;

    2010-01-01

    A total of 157 unrelated individuals residing in Slovenia were typed for 49 of the autosomal single nucleotide polymorphisms (SNPs) in the SNPforID 52plex with the SNaPshot assay. We obtained full SNP profiles in all but one individual and perfect concordance was obtained in duplicated analyses. ...

  6. Identification of pummelo cultivars by using a panel of 25 selected SNPs and 12 DNA segments.

    Directory of Open Access Journals (Sweden)

    Bo Wu

    Full Text Available Pummelo cultivars are usually difficult to identify morphologically, especially when fruits are unavailable. The problem was addressed in this study with the use of two methods: high resolution melting analysis of SNPs and sequencing of DNA segments. In the first method, a set of 25 SNPs with high polymorphic information content were selected from SNPs predicted by analyzing ESTs and sequenced DNA segments. High resolution melting analysis was then used to genotype 260 accessions including 55 from Myanmar, and 178 different genotypes were thus identified. A total of 99 cultivars were assigned to 86 different genotypes since the known somatic mutants were identical to their original genotypes at the analyzed SNP loci. The Myanmar samples were genotypically different from each other and from all other samples, indicating they were derived from sexual propagation. Statistical analysis showed that the set of SNPs was powerful enough for identifying at least 1000 pummelo genotypes, though the discrimination power varied in different pummelo groups and populations. In the second method, 12 genomic DNA segments of 24 representative pummelo accessions were sequenced. Analysis of the sequences revealed the existence of a high haplotype polymorphism in pummelo, and statistical analysis showed that the segments could be used as genetic barcodes that should be informative enough to allow reliable identification of 1200 pummelo cultivars. The high level of haplotype diversity and an apparent population structure shown by DNA segments and by SNP genotypes, respectively, were discussed in relation to the origin and domestication of the pummelo species.

  7. Known susceptibility SNPs for sporadic prostate cancer show a similar association with "hereditary" prostate cancer

    NARCIS (Netherlands)

    Cremers, R.G.H.M.; Galesloot, T.E.; Aben, K.K.H.; Oort, I.M. van; Vasen, H.F.A.; Vermeulen, S.; Kiemeney, L.A.L.M.

    2015-01-01

    BACKGROUND: More than 70 single nucleotide polymorphisms (SNPs) have been reported to be associated with prostate cancer (PC) risk; these were mainly identified in the general population with predominantly sporadic PC (SPC). Previous studies have suggested similar associations between a selection of

  8. Association of ESR1 gene tagging SNPs with breast cancer risk

    DEFF Research Database (Denmark)

    Dunning, Alison M; Healey, Catherine S; Baynes, Caroline

    2009-01-01

    We have conducted a three-stage, comprehensive single nucleotide polymorphism (SNP)-tagging association study of ESR1 gene variants (SNPs) in more than 55,000 breast cancer cases and controls from studies within the Breast Cancer Association Consortium (BCAC). No large risks or highly significant...

  9. SNPsnap: a Web-based tool for identification and annotation of matched SNPs

    DEFF Research Database (Denmark)

    Pers, Tune Hannes; Timshel, Pascal; Hirschhorn, Joel N.

    2015-01-01

    Summary : An important computational step following genome-wide association studies (GWAS) is to assess whether disease or trait-associated single-nucleotide polymorphisms (SNPs) enrich for particular biological annotations. SNP-based enrichment analysis needs to account for biases such as co......@broadinstitute.org Supplementary information : Supplementary data are available at Bioinformatics online....

  10. Angiogenic, neurotrophic, and inflammatory system SNPs moderate the association between birth weight and ADHD symptom severity.

    Science.gov (United States)

    Smith, Taylor F; Anastopoulos, Arthur D; Garrett, Melanie E; Arias-Vasquez, Alejandro; Franke, Barbara; Oades, Robert D; Sonuga-Barke, Edmund; Asherson, Philip; Gill, Michael; Buitelaar, Jan K; Sergeant, Joseph A; Kollins, Scott H; Faraone, Stephen V; Ashley-Koch, Allison

    2014-12-01

    Low birth weight is associated with increased risk for Attention-Deficit/Hyperactivity Disorder (ADHD); however, the etiological underpinnings of this relationship remain unclear. This study investigated if genetic variants in angiogenic, dopaminergic, neurotrophic, kynurenine, and cytokine-related biological pathways moderate the relationship between birth weight and ADHD symptom severity. A total of 398 youth from two multi-site, family-based studies of ADHD were included in the analysis. The sample consisted of 360 ADHD probands, 21 affected siblings, and 17 unaffected siblings. A set of 164 SNPs from 31 candidate genes, representing five biological pathways, were included in our analyses. Birth weight and gestational age data were collected from a state birth registry, medical records, and parent report. Generalized Estimating Equations tested for main effects and interactions between individual SNPs and birth weight centile in predicting ADHD symptom severity. SNPs within neurotrophic (NTRK3) and cytokine genes (CNTFR) were associated with ADHD inattentive symptom severity. There was no main effect of birth weight centile on ADHD symptom severity. SNPs within angiogenic (NRP1 & NRP2), neurotrophic (NTRK1 & NTRK3), cytokine (IL16 & S100B), and kynurenine (CCBL1 & CCBL2) genes moderate the association between birth weight centile and ADHD symptom severity. The SNP main effects and SNP × birth weight centile interactions remained significant after adjusting for multiple testing. Genetic variability in angiogenic, neurotrophic, and inflammatory systems may moderate the association between restricted prenatal growth, a proxy for an adverse prenatal environment, and risk to develop ADHD.

  11. RNAsnp: efficient detection of local RNA secondary structure changes induced by SNPs

    DEFF Research Database (Denmark)

    Radhakrishnan, Sabarinathan; Tafer, Hakim; Seemann, Ernst Stefan

    2013-01-01

    precomputed tables of the distribution of SNP effects as function of length and GC content. RNAsnp thus achieves both a noise reduction and speed-up of several orders of magnitude over shuffling-based approaches. On a data set comprising 501 SNPs associated with human-inherited diseases, we predict 54 to have...

  12. Hansa: an automated method for discriminating disease and neutral human nsSNPs.

    Science.gov (United States)

    Acharya, Vishal; Nagarajaram, Hampapathalu A

    2012-02-01

    Variations are mostly due to nonsynonymous single nucleotide polymorphisms (nsSNPs), some of which are associated with certain diseases. Phenotypic effects of a large number of nsSNPs have not been characterized. Although several methods have been developed to predict the effects of nsSNPs as "disease" or "neutral," there is still a need for development of methods with improved prediction accuracies. We, therefore, developed a support vector machine (SVM) based method named Hansa which uses a novel set of discriminatory features to classify nsSNPs into disease (pathogenic) and benign (neutral) types. Validation studies on a benchmark dataset and further on an independent dataset of well-characterized known disease and neutral mutations show that Hansa outperforms the other known methods. For example, fivefold cross-validation studies using the benchmark HumVar dataset reveal that at the false positive rate (FPR) of 20% Hansa yields a true positive rate (TPR) of 82% that is about 10% higher than the best-known method. Hansa is available in the form of a web server at http://hansa.cdfd.org.in:8080.

  13. SNPs at 3'-UTR of the bovine CDIPT gene associated with Qinchuan cattle meat quality traits.

    Science.gov (United States)

    Fu, C Z; Wang, H; Mei, C G; Wang, J L; Jiang, B J; Ma, X H; Wang, H B; Cheng, G; Zan, L S

    2013-03-13

    The CDIPT is crucial to the fatty acid metabolic pathway, intracellular signal transduction and energy metabolism in eukaryotic cells. We detected three SNPs at 3'-untranslated regions (UTR), named 3'-UTR_108 A > G, 3'-UTR_448 G > A and 3'-UTR_477 C > G, of the CDIPT gene in 618 Qinchuan cattle using PCR-RFLP and DNA sequencing methods. At each of the three SNPs, we found three genotypes named as follows: AA, AB, BB (3'-UTR_108 A > G), CC, CD, DD (3'-UTR_448 G > A) and EE, EF, FF (3'-UTR_477 C > G.). Based on association analysis of these SNPs with ultrasound measurement traits, individuals of genotype BB had a significantly larger loin muscle area than genotype AA. Individuals of genotype CC had significantly thicker back fat than individuals of genotype DD. Individuals of genotype EE also had significantly thicker back fat than did individuals of genotype FF. We conclude that these SNPs of the CDIPT gene could be used as molecular markers for selecting and breeding beef cattle with superior body traits, depending on breeding goals.

  14. Comprehensive survey of SNPs in the Affymetrix exon array using the 1000 Genomes dataset.

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    Eric R Gamazon

    Full Text Available Microarray gene expression data has been used in genome-wide association studies to allow researchers to study gene regulation as well as other complex phenotypes including disease risks and drug response. To reach scientifically sound conclusions from these studies, however, it is necessary to get reliable summarization of gene expression intensities. Among various factors that could affect expression profiling using a microarray platform, single nucleotide polymorphisms (SNPs in target mRNA may lead to reduced signal intensity measurements and result in spurious results. The recently released 1000 Genomes Project dataset provides an opportunity to evaluate the distribution of both known and novel SNPs in the International HapMap Project lymphoblastoid cell lines (LCLs. We mapped the 1000 Genomes Project genotypic data to the Affymetrix GeneChip Human Exon 1.0ST array (exon array, which had been used in our previous studies and for which gene expression data had been made publicly available. We also evaluated the potential impact of these SNPs on the differentially spliced probesets we had identified previously. Though the 1000 Genomes Project data allowed a comprehensive survey of the SNPs in this particular array, the same approach can certainly be applied to other microarray platforms. Furthermore, we present a detailed catalogue of SNP-containing probesets (exon-level and transcript clusters (gene-level, which can be considered in evaluating findings using the exon array as well as benefit the design of follow-up experiments and data re-analysis.

  15. LD-Spline: Mapping SNPs on genotyping platforms to genomic regions using patterns of linkage disequilibrium

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    Bush William S

    2009-12-01

    Full Text Available Abstract Background Gene-centric analysis tools for genome-wide association study data are being developed both to annotate single locus statistics and to prioritize or group single nucleotide polymorphisms (SNPs prior to analysis. These approaches require knowledge about the relationships between SNPs on a genotyping platform and genes in the human genome. SNPs in the genome can represent broader genomic regions via linkage disequilibrium (LD, and population-specific patterns of LD can be exploited to generate a data-driven map of SNPs to genes. Methods In this study, we implemented LD-Spline, a database routine that defines the genomic boundaries a particular SNP represents using linkage disequilibrium statistics from the International HapMap Project. We compared the LD-Spline haplotype block partitioning approach to that of the four gamete rule and the Gabriel et al. approach using simulated data; in addition, we processed two commonly used genome-wide association study platforms. Results We illustrate that LD-Spline performs comparably to the four-gamete rule and the Gabriel et al. approach; however as a SNP-centric approach LD-Spline has the added benefit of systematically identifying a genomic boundary for each SNP, where the global block partitioning approaches may falter due to sampling variation in LD statistics. Conclusion LD-Spline is an integrated database routine that quickly and effectively defines the genomic region marked by a SNP using linkage disequilibrium, with a SNP-centric block definition algorithm.

  16. Dynamics of X Chromosome Inactivation

    NARCIS (Netherlands)

    F. Loos (Friedemann)

    2015-01-01

    markdownabstract__Abstract__ Dosage compensation evolved to account for the difference in expression of sex chromosome-linked genes. In mammals dosage compensation is achieved by inactivation of one X chromosome during early female embryogenesis in a process called X chromosome inactivation (XCI).

  17. Parent-of-origin effects in autism identified through genome-wide linkage analysis of 16,000 SNPs.

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    Delphine Fradin

    Full Text Available BACKGROUND: Autism is a common heritable neurodevelopmental disorder with complex etiology. Several genome-wide linkage and association scans have been carried out to identify regions harboring genes related to autism or autism spectrum disorders, with mixed results. Given the overlap in autism features with genetic abnormalities known to be associated with imprinting, one possible reason for lack of consistency would be the influence of parent-of-origin effects that may mask the ability to detect linkage and association. METHODS AND FINDINGS: We have performed a genome-wide linkage scan that accounts for potential parent-of-origin effects using 16,311 SNPs among families from the Autism Genetic Resource Exchange (AGRE and the National Institute of Mental Health (NIMH autism repository. We report parametric (GH, Genehunter and allele-sharing linkage (Aspex results using a broad spectrum disorder case definition. Paternal-origin genome-wide statistically significant linkage was observed on chromosomes 4 (LOD(GH = 3.79, empirical p<0.005 and LOD(Aspex = 2.96, p = 0.008, 15 (LOD(GH = 3.09, empirical p<0.005 and LOD(Aspex = 3.62, empirical p = 0.003 and 20 (LOD(GH = 3.36, empirical p<0.005 and LOD(Aspex = 3.38, empirical p = 0.006. CONCLUSIONS: These regions may harbor imprinted sites associated with the development of autism and offer fruitful domains for molecular investigation into the role of epigenetic mechanisms in autism.

  18. Chromosomal breakpoints characterization of two supernumerary ring chromosomes 20.

    Science.gov (United States)

    Guediche, N; Brisset, S; Benichou, J-J; Guérin, N; Mabboux, P; Maurin, M-L; Bas, C; Laroudie, M; Picone, O; Goldszmidt, D; Prévot, S; Labrune, P; Tachdjian, G

    2010-02-01

    The occurrence of an additional ring chromosome 20 is a rare chromosome abnormality, and no common phenotype has been yet described. We report on two new patients presenting with a supernumerary ring chromosome 20 both prenatally diagnosed. The first presented with intrauterine growth retardation and some craniofacial dysmorphism, and the second case had a normal phenotype except for obesity. Conventional cytogenetic studies showed for each patient a small supernumerary marker chromosome (SMC). Using fluorescence in situ hybridization, these SMCs corresponded to ring chromosomes 20 including a part of short and long arms of chromosome 20. Detailed molecular cytogenetic characterization showed different breakpoints (20p11.23 and 20q11.23 for Patient 1 and 20p11.21 and 20q11.21 for Patient 2) and sizes of the two ring chromosomes 20 (13.6 Mb for case 1 and 4.8 Mb for case 2). Review of the 13 case reports of an extra r(20) ascertained postnatally (8 cases) and prenatally (5 cases) showed varying degrees of phenotypic abnormalities. We document a detailed molecular cytogenetic chromosomal breakpoints characterization of two cases of supernumerary ring chromosomes 20. These results emphasize the need to characterize precisely chromosomal breakpoints of supernumerary ring chromosomes 20 in order to establish genotype-phenotype correlation. This report may be helpful for prediction of natural history and outcome, particularly in prenatal diagnosis.

  19. Familial complex chromosomal rearrangement resulting in a recombinant chromosome.

    Science.gov (United States)

    Berend, Sue Ann; Bodamer, Olaf A F; Shapira, Stuart K; Shaffer, Lisa G; Bacino, Carlos A

    2002-05-15

    Familial complex chromosomal rearrangements (CCRs) are rare and tend to involve fewer breakpoints and fewer chromosomes than CCRs that are de novo in origin. We report on a CCR identified in a child with congenital heart disease and dysmorphic features. Initially, the child's karyotype was thought to involve a straightforward three-way translocation between chromosomes 3, 8, and 16. However, after analyzing the mother's chromosomes, the mother was found to have a more complex rearrangement that resulted in a recombinant chromosome in the child. The mother's karyotype included an inverted chromosome 2 and multiple translocations involving chromosomes 3, 5, 8, and 16. No evidence of deletion or duplication that could account for the clinical findings in the child was identified.

  20. Identification of Type 2 Diabetes-associated combination of SNPs using Support Vector Machine

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    Park Keun-Joon

    2010-04-01

    Full Text Available Abstract Background Type 2 diabetes mellitus (T2D, a metabolic disorder characterized by insulin resistance and relative insulin deficiency, is a complex disease of major public health importance. Its incidence is rapidly increasing in the developed countries. Complex diseases are caused by interactions between multiple genes and environmental factors. Most association studies aim to identify individual susceptibility single markers using a simple disease model. Recent studies are trying to estimate the effects of multiple genes and multi-locus in genome-wide association. However, estimating the effects of association is very difficult. We aim to assess the rules for classifying diseased and normal subjects by evaluating potential gene-gene interactions in the same or distinct biological pathways. Results We analyzed the importance of gene-gene interactions in T2D susceptibility by investigating 408 single nucleotide polymorphisms (SNPs in 87 genes involved in major T2D-related pathways in 462 T2D patients and 456 healthy controls from the Korean cohort studies. We evaluated the support vector machine (SVM method to differentiate between cases and controls using SNP information in a 10-fold cross-validation test. We achieved a 65.3% prediction rate with a combination of 14 SNPs in 12 genes by using the radial basis function (RBF-kernel SVM. Similarly, we investigated subpopulation data sets of men and women and identified different SNP combinations with the prediction rates of 70.9% and 70.6%, respectively. As the high-throughput technology for genome-wide SNPs improves, it is likely that a much higher prediction rate with biologically more interesting combination of SNPs can be acquired by using this method. Conclusions Support Vector Machine based feature selection method in this research found novel association between combinations of SNPs and T2D in a Korean population.

  1. Predicting deleterious nsSNPs: an analysis of sequence and structural attributes

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    Saqi Mansoor AS

    2006-04-01

    Full Text Available Abstract Background There has been an explosion in the number of single nucleotide polymorphisms (SNPs within public databases. In this study we focused on non-synonymous protein coding single nucleotide polymorphisms (nsSNPs, some associated with disease and others which are thought to be neutral. We describe the distribution of both types of nsSNPs using structural and sequence based features and assess the relative value of these attributes as predictors of function using machine learning methods. We also address the common problem of balance within machine learning methods and show the effect of imbalance on nsSNP function prediction. We show that nsSNP function prediction can be significantly improved by 100% undersampling of the majority class. The learnt rules were then applied to make predictions of function on all nsSNPs within Ensembl. Results The measure of prediction success is greatly affected by the level of imbalance in the training dataset. We found the balanced dataset that included all attributes produced the best prediction. The performance as measured by the Matthews correlation coefficient (MCC varied between 0.49 and 0.25 depending on the imbalance. As previously observed, the degree of sequence conservation at the nsSNP position is the single most useful attribute. In addition to conservation, structural predictions made using a balanced dataset can be of value. Conclusion The predictions for all nsSNPs within Ensembl, based on a balanced dataset using all attributes, are available as a DAS annotation. Instructions for adding the track to Ensembl are at http://www.brightstudy.ac.uk/das_help.html

  2. Identification of polymorphisms and transcriptional activity of the proto-oncogene KIT located on both autosomal and B chromosomes of the Chinese raccoon dog.

    Science.gov (United States)

    Li, Y M; Zhang, Y; Zhu, W J; Yan, S Q; Sun, J H

    2016-02-05

    B chromosomes are dispensable and co-exist with autosomal and sex chromosomes. The karyotype of the Chinese raccoon dog (Nyctereutes procyonoides procyonoides) comprises 0-4 B chromosomes. The proto-oncogene KIT is found on all B chromosomes of the Chinese raccoon dog. In the present study, partial DNA and mRNA sequences of KIT were amplified and sequenced from four individuals containing B chromosomes. Sequence analyses revealed that polymorphisms including single nucleotide polymorphisms (SNPs) and inserts/deletions were rich in the KIT gene of Chinese raccoon dog at the genomic level. However, no polymorphism was detected at the mRNA level. A comparison of mRNA sequences from Chinese raccoon dogs with the corresponding sequences derived from arctic fox and dog, which do not contain B chromosomes, revealed the mRNA sequences of the 10 SNPs to be identical between these three species. Therefore, these findings suggest that KIT located on the B chromosomes in Chinese raccoon dog lacks transcriptional activity.

  3. A selective sweep of >8 Mb on chromosome 26 in the Boxer genome

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    Altet Laura

    2011-07-01

    Full Text Available Abstract Background Modern dog breeds display traits that are either breed-specific or shared by a few breeds as a result of genetic bottlenecks during the breed creation process and artificial selection for breed standards. Selective sweeps in the genome result from strong selection and can be detected as a reduction or elimination of polymorphism in a given region of the genome. Results Extended regions of homozygosity, indicative of selective sweeps, were identified in a genome-wide scan dataset of 25 Boxers from the United Kingdom genotyped at ~20,000 single-nucleotide polymorphisms (SNPs. These regions were further examined in a second dataset of Boxers collected from a different geographical location and genotyped using higher density SNP arrays (~170,000 SNPs. A selective sweep previously associated with canine brachycephaly was detected on chromosome 1. A novel selective sweep of over 8 Mb was observed on chromosome 26 in Boxer and for a shorter region in English and French bulldogs. It was absent in 171 samples from eight other dog breeds and 7 Iberian wolf samples. A region of extended increased heterozygosity on chromosome 9 overlapped with a previously reported copy number variant (CNV which was polymorphic in multiple dog breeds. Conclusion A selective sweep of more than 8 Mb on chromosome 26 was identified in the Boxer genome. This sweep is likely caused by strong artificial selection for a trait of interest and could have inadvertently led to undesired health implications for this breed. Furthermore, we provide supporting evidence for two previously described regions: a selective sweep on chromosome 1 associated with canine brachycephaly and a CNV on chromosome 9 polymorphic in multiple dog breeds.

  4. Association between single nucleotide polymorphisms on chromosome 17q and the risk of prostate cancer in a Chinese population

    Institute of Scientific and Technical Information of China (English)

    Chang-Hu Zhou; Dong Wei; Ze Yang; Jian-Ye Wang; Su-Yan Cao; Xiao-Hong Shi; Yao-Guang Zhang; Ming Liu; Xin Wang; Jin Huang; Yi-Ge Yang

    2011-01-01

    In European populations,7 single nucleotide polymorphisms(SNPs) on chromosome 17q,3 SNPs on 17812,and 4 SNPs on 17824.3 were recently identified to be closely related to the risk of prostate cancer by a genome-wide association study.In Japanese populations,the correlation between 2 SNPs on 17q and the risk of prostate cancer and tumor aggressiveness was also confirmed by a large-scale experiment.However,whether 17q is associated with prostate cancer and its clinical manifestations in Chinese populations is still unknown.Therefore,we conducted a case-control study in a northern Chinese population and tested 2 SNPs,rs4430796 and rs1859962,on 17q in 124 prostate cancer patients and 111 controls using polymerase chain reaction-high resolution melting curve (PCR-HRM) combined with sequencing.We analyzed the association of the 2 SNPs with the risk of prostate cancer as well as patients'lifestyles,onset ages,Gleason scores,PSA levels,and pathologic stages.We found a significant difference in the G allele of SNP rs1859962(P=0.035,OR=1.51,95% CI=1.03-2.21) but not in the rs4430796 genotype frequency or allele frequency distribution between prostate cancer patients and the controls(P>0.05).Neither of the SNPs was significantly associated with the onset age,Gleason score,PSA level,pathologic stage,or other clinical indicators of patients with prostate cancer(P>0.05).Our results show that polymorphism of the G allele of SNP rs1859962 is associated with the risk of prostate cancer in a Chinese population.

  5. Chromosome 19 International Workshop

    Energy Technology Data Exchange (ETDEWEB)

    Pericak-Vance, M.A. (Duke Univ., Durham, NC (United States). Medical Center); Ropers, H.H. (Univ. Hospital Nijmegen, (The Netherlands). Dept. of Human Genetics); Carrano, A.J. (Lawrence Livermore National Lab., CA (United States))

    1993-01-04

    The Second International Workshop on Human Chromosome 19 was hosted on January 25 and 26, 1992, by the Department of Human Genetics, University Hospital Nijmegen, The Netherlands, at the 'Meerdal Conference Center'. The workshop was supported by a grant from the European Community obtained through HUGO, the Dutch Research Organization (NWO) and the Muscular Dystrophy Association (MDA). Travel support for American participants was provided by the Department of Energy. The goals of this workshop were to produce genetic, physical and integrated maps of chromosome 19, to identify inconsistencies and gaps, and to discuss and exchange resources and techniques available for the completion of these maps. The second day of the meeting was largely devoted to region or disease specific efforts. In particular, the meeting served as a platform for assessing and discussing the recent progress made into the molecular elucidation of myotonic dystrophy.

  6. A follow-up study for left ventricular mass on chromosome 12p11 identifies potential candidate genes

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    Slifer Susan

    2011-07-01

    Full Text Available Abstract Background Left ventricular mass (LVM is an important risk factor for cardiovascular disease. Previously we found evidence for linkage to chromosome 12p11 in Dominican families, with a significant increase in a subset of families with high average waist circumference (WC. In the present study, we use association analysis to further study the genetic effect on LVM. Methods Association analysis with LVM was done in the one LOD critical region of the linkage peak in an independent sample of 897 Caribbean Hispanics. Genotype data were available on 7085 SNPs from 23 to 53 MB on chromosome 12p11. Adjustment was made for vascular risk factors and population substructure using an additive genetic model. Subset analysis by WC was performed to test for a difference in genetic effects between the high and low WC subsets. Results In the overall analysis, the most significant association was found to rs10743465, downstream of the SOX5 gene (p = 1.27E-05. Also, 19 additional SNPs had nominal p TMTC1. Twelve additional SNPs in or near 6 genes had p Conclusions The current study supports previously identified evidence by linkage for a genetic effect on LVM on chromosome 12p11 using association analysis in population-based Caribbean Hispanic cohort. SOX5 may play an important role in the regulation of LVM. An interaction of TMTC1 with abdominal obesity may contribute to phenotypic variation of LVM.

  7. Quick, “Imputation-free” meta-analysis with proxy-SNPs

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    Meesters Christian

    2012-09-01

    Full Text Available Abstract Background Meta-analysis (MA is widely used to pool genome-wide association studies (GWASes in order to a increase the power to detect strong or weak genotype effects or b as a result verification method. As a consequence of differing SNP panels among genotyping chips, imputation is the method of choice within GWAS consortia to avoid losing too many SNPs in a MA. YAMAS (Yet Another Meta Analysis Software, however, enables cross-GWAS conclusions prior to finished and polished imputation runs, which eventually are time-consuming. Results Here we present a fast method to avoid forfeiting SNPs present in only a subset of studies, without relying on imputation. This is accomplished by using reference linkage disequilibrium data from 1,000 Genomes/HapMap projects to find proxy-SNPs together with in-phase alleles for SNPs missing in at least one study. MA is conducted by combining association effect estimates of a SNP and those of its proxy-SNPs. Our algorithm is implemented in the MA software YAMAS. Association results from GWAS analysis applications can be used as input files for MA, tremendously speeding up MA compared to the conventional imputation approach. We show that our proxy algorithm is well-powered and yields valuable ad hoc results, possibly providing an incentive for follow-up studies. We propose our method as a quick screening step prior to imputation-based MA, as well as an additional main approach for studies without available reference data matching the ethnicities of study participants. As a proof of principle, we analyzed six dbGaP Type II Diabetes GWAS and found that the proxy algorithm clearly outperforms naïve MA on the p-value level: for 17 out of 23 we observe an improvement on the p-value level by a factor of more than two, and a maximum improvement by a factor of 2127. Conclusions YAMAS is an efficient and fast meta-analysis program which offers various methods, including conventional MA as well as inserting proxy-SNPs

  8. Schizophrenia susceptibility genes on chromosome 13q32

    Institute of Scientific and Technical Information of China (English)

    胡颖; 许琪; 鞠桂芝; 刘树铮; 史杰萍; 于雅琴; 尉军

    2004-01-01

    @@Schizophrenia is a complex mental disorder affecting approximately 1% of the general population worldwide.1 It has a high incidence in the general population, a poor prognosis and a poor outcome, in that it has become a major social problem. Family, twin, and adoption studies have clearly shown that a genetic component is quite likely to play an important role in determining susceptibility to schizophrenia. The genome-wide scan indicates that several chromosomal regions are linked to schizophrenia, some of which have been replicated independently including 6p21-24, 8p21-22, 13q14-33 and 22q11-12.2,3 This study was designed to detect two single nucleotide polymorphisms (SNPs) located in the 13q14-33 region, rs188608 at the STK24 locus and rs2892679 at the GPC6 locus, among Chinese population.

  9. Seq4SNPs: new software for retrieval of multiple, accurately annotated DNA sequences, ready formatted for SNP assay design

    Directory of Open Access Journals (Sweden)

    Dunning Alison M

    2009-06-01

    Full Text Available Abstract Background In moderate-throughput SNP genotyping there was a gap in the workflow, between choosing a set of SNPs and submitting their sequences to proprietary assay design software, which was not met by existing software. Retrieval and formatting of sequences flanking each SNP, prior to assay design, becomes rate-limiting for more than about ten SNPs, especially if annotated for repetitive regions and adjacent variations. We routinely process up to 50 SNPs at once. Implementation We created Seq4SNPs, a web-based, walk-away software that can process one to several hundred SNPs given rs numbers as input. It outputs a file of fully annotated sequences formatted for one of three proprietary design softwares: TaqMan's Primer-By-Design FileBuilder, Sequenom's iPLEX or SNPstream's Autoprimer, as well as unannotated fasta sequences. We found genotyping assays to be inhibited by repetitive sequences or the presence of additional variations flanking the SNP under test, and in multiplexes, repetitive sequence flanking one SNP adversely affects multiple assays. Assay design software programs avoid such regions if the input sequences are appropriately annotated, so we used Seq4SNPs to provide suitably annotated input sequences, and improved our genotyping success rate. Adjacent SNPs can also be avoided, by annotating sequences used as input for primer design. Conclusion The accuracy of annotation by Seq4SNPs is significantly better than manual annotation (P Using Seq4SNPs to incorporate all annotation for additional SNPs and repetitive elements into sequences, for genotyping assay designer software, minimizes assay failure at the design stage, reducing the cost of genotyping. Seq4SNPs provides a rapid route for replacement of poor test SNP sequences. We routinely use this software for assay sequence preparation. Seq4SNPs is available as a service at http://moya.srl.cam.ac.uk/oncology/bio/s4shome.html and http://moya.srl

  10. Coding SNPs as intrinsic markers for sample tracking in large-scale transcriptome studies.

    Science.gov (United States)

    Xu, Weihong; Gao, Hong; Seok, Junhee; Wilhelmy, Julie; Mindrinos, Michael N; Davis, Ronald W; Xiao, Wenzhong

    2012-06-01

    Large-scale transcriptome profiling in clinical studies often involves assaying multiple samples of a patient to monitor disease progression, treatment effect, and host response in multiple tissues. Such profiling is prone to human error, which often results in mislabeled samples. Here, we present a method to detect mislabeled sample outliers using coding single nucleotide polymorphisms (cSNPs) specifically designed on the microarray and demonstrate that the mislabeled samples can be efficiently identified by either simple clustering of allele-specific expression scores or Mahalanobis distance-based outlier detection method. Based on our results, we recommend the incorporation of cSNPs into future transcriptome array designs as intrinsic markers for sample tracking.

  11. Low enzymatic activity haplotypes of the human catechol-O-methyltransferase gene: enrichment for marker SNPs.

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    Andrea G Nackley

    Full Text Available Catechol-O-methyltransferase (COMT is an enzyme that plays a key role in the modulation of catechol-dependent functions such as cognition, cardiovascular function, and pain processing. Three common haplotypes of the human COMT gene, divergent in two synonymous and one nonsynonymous (val(158met position, designated as low (LPS, average (APS, and high pain sensitive (HPS, are associated with experimental pain sensitivity and risk of developing chronic musculoskeletal pain conditions. APS and HPS haplotypes produce significant functional effects, coding for 3- and 20-fold reductions in COMT enzymatic activity, respectively. In the present study, we investigated whether additional minor single nucleotide polymorphisms (SNPs, accruing in 1 to 5% of the population, situated in the COMT transcript region contribute to haplotype-dependent enzymatic activity. Computer analysis of COMT ESTs showed that one synonymous minor SNP (rs769224 is linked to the APS haplotype and three minor SNPs (two synonymous: rs6267, rs740602 and one nonsynonymous: rs8192488 are linked to the HPS haplotype. Results from in silico and in vitro experiments revealed that inclusion of allelic variants of these minor SNPs in APS or HPS haplotypes did not modify COMT function at the level of mRNA folding, RNA transcription, protein translation, or enzymatic activity. These data suggest that neutral variants are carried with APS and HPS haplotypes, while the high activity LPS haplotype displays less linked variation. Thus, both minor synonymous and nonsynonymous SNPs in the coding region are markers of functional APS and HPS haplotypes rather than independent contributors to COMT activity.

  12. Genetic variation and recent positive selection in worldwide human populations: evidence from nearly 1 million SNPs.

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    David López Herráez

    Full Text Available BACKGROUND: Genome-wide scans of hundreds of thousands of single-nucleotide polymorphisms (SNPs have resulted in the identification of new susceptibility variants to common diseases and are providing new insights into the genetic structure and relationships of human populations. Moreover, genome-wide data can be used to search for signals of recent positive selection, thereby providing new insights into the genetic adaptations that occurred as modern humans spread out of Africa and around the world. METHODOLOGY: We genotyped approximately 500,000 SNPs in 255 individuals (5 individuals from each of 51 worldwide populations from the Human Genome Diversity Panel (HGDP-CEPH. When merged with non-overlapping SNPs typed previously in 250 of these same individuals, the resulting data consist of over 950,000 SNPs. We then analyzed the genetic relationships and ancestry of individuals without assigning them to populations, and we also identified candidate regions of recent positive selection at both the population and regional (continental level. CONCLUSIONS: Our analyses both confirm and extend previous studies; in particular, we highlight the impact of various dispersals, and the role of substructure in Africa, on human genetic diversity. We also identified several novel candidate regions for recent positive selection, and a gene ontology (GO analysis identified several GO groups that were significantly enriched for such candidate genes, including immunity and defense related genes, sensory perception genes, membrane proteins, signal receptors, lipid binding/metabolism genes, and genes involved in the nervous system. Among the novel candidate genes identified are two genes involved in the thyroid hormone pathway that show signals of selection in African Pygmies that may be related to their short stature.

  13. Investigation on the role of nsSNPs in HNPCC genes – a bioinformatics approach

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    Sethumadhavan Rao

    2009-04-01

    Full Text Available Abstract Background A central focus of cancer genetics is the study of mutations that are causally implicated in tumorigenesis. The identification of such causal mutations not only provides insight into cancer biology but also presents anticancer therapeutic targets and diagnostic markers. Missense mutations are nucleotide substitutions that change an amino acid in a protein, the deleterious effects of these mutations are commonly attributed to their impact on primary amino acid sequence and protein structure. Methods The method to identify functional SNPs from a pool, containing both functional and neutral SNPs is challenging by experimental protocols. To explore possible relationships between genetic mutation and phenotypic variation, we employed different bioinformatics algorithms like Sorting Intolerant from Tolerant (SIFT, Polymorphism Phenotyping (PolyPhen, and PupaSuite to predict the impact of these amino acid substitutions on protein activity of mismatch repair (MMR genes causing hereditary nonpolyposis colorectal cancer (HNPCC. Results SIFT classified 22 of 125 variants (18% as 'Intolerant." PolyPhen classified 40 of 125 amino acid substitutions (32% as "Probably or possibly damaging". The PupaSuite predicted the phenotypic effect of SNPs on the structure and function of the affected protein. Based on the PolyPhen scores and availability of three-dimensional structures, structure analysis was carried out with the major mutations that occurred in the native protein coded by MSH2 and MSH6 genes. The amino acid residues in the native and mutant model protein were further analyzed for solvent accessibility and secondary structure to check the stability of the proteins. Conclusion Based on this approach, we have shown that four nsSNPs, which were predicted to have functional consequences (MSH2-Y43C, MSH6-Y538S, MSH6-S580L, and MSH6-K854M, were already found to be associated with cancer risk. Our study demonstrates the presence of other

  14. Endothelial nitric oxide synthase tagSNPs influence the effects of enalapril in essential hypertension.

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    Oliveira-Paula, Gustavo H; Lacchini, Riccardo; Luizon, Marcelo R; Fontana, Vanessa; Silva, Pamela S; Biagi, Celso; Tanus-Santos, Jose E

    2016-05-01

    The antihypertensive effects of angiotensin-converting enzyme inhibitors (ACEi) are associated with up-regulation of endothelial nitric oxide synthase (NOS3) activity. This mechanism may explain how polymorphisms in NOS3 gene affect the antihypertensive responses to ACEi. While clinically relevant NOS3 polymorphisms were previously shown to affect the antihypertensive responses to enalapril, no study has tested the hypothesis that NOS3 tagSNPs influence the antihypertensive effects of this drug. We examined whether the NOS3 tagSNPs rs3918226, rs3918188, and rs743506, and their haplotypes, affect the antihypertensive responses to enalapril in 101 patients with essential hypertension. Subjects were prospectively treated only with enalapril for 8 weeks. Genotypes were determined by Taqman(®) allele discrimination assay and real-time polymerase chain reaction (PCR) and haplotype frequencies were estimated. We compared the effects of NOS3 tagSNPs on changes in blood pressure after enalapril treatment. To confirm our findings, multiple linear regression analysis was performed adjusting for age, gender, ethnicity, and alcohol consumption. We found that hypertensive patients carrying the AA genotype for the tagSNP rs3918188 showed lower decreases in blood pressure in response to enalapril. Moreover, the TCA haplotype was associated with improved decreases in blood pressure in response to enalapril compared with the CAG haplotype. Adjustment for covariates in multiple linear regression analysis did not change these effects. In addition, when patients were stratified according to the dose of enalapril used, we found that the carries of the T allele for the functional tagSNP rs3918226 showed more intense decreases in blood pressure in response to enalapril 20 mg/day. Our findings suggest that NOS3 tagSNPs influence the effects of enalapril in essential hypertension.

  15. Pedigree with frontotemporal lobar degeneration – motor neuron disease and Tar DNA binding protein-43 positive neuropathology: genetic linkage to chromosome 9

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    Loy Clement T

    2008-08-01

    Full Text Available Abstract Background Frontotemporal lobar degeneration (FTLD represents a clinically, pathologically and genetically heterogenous neurodegenerative disorder, often complicated by neurological signs such as motor neuron-related limb weakness, spasticity and paralysis, parkinsonism and gait disturbances. Linkage to chromosome 9p had been reported for pedigrees with the neurodegenerative disorder, frontotemporal lobar degeneration (FTLD and motor neuron disease (MND. The objective in this study is to identify the genetic locus in a multi-generational Australian family with FTLD-MND. Methods Clinical review and standard neuropathological analysis of brain sections from affected pedigree members. Genome-wide scan using microsatellite markers and single nucleotide polymorphism fine mapping. Examination of candidate genes by direct DNA sequencing. Results Neuropathological examination revealed cytoplasmic deposition of the TDP-43 protein in three affected individuals. Moreover, we identify a family member with clinical Alzheimer's disease, and FTLD-Ubiquitin neuropathology. Genetic linkage and haplotype analyses, defined a critical region between markers D9S169 and D9S1845 on chromosome 9p21. Screening of all candidate genes within this region did not reveal any novel genetic alterations that co-segregate with disease haplotype, suggesting that one individual carrying a meiotic recombination may represent a phenocopy. Re-analysis of linkage data using the new affection status revealed a maximal two-point LOD score of 3.24 and a multipoint LOD score of 3.41 at marker D9S1817. This provides the highest reported LOD scores from a single FTLD-MND pedigree. Conclusion Our reported increase in the minimal disease region should inform other researchers that the chromosome 9 locus may be more telomeric than predicted by published recombination boundaries. Moreover, the existence of a family member with clinical Alzheimer's disease, and who shares the disease

  16. Genetic association of SNPs in the FTO gene and predisposition to obesity in Malaysian Malays

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    Y.D. Apalasamy

    2012-12-01

    Full Text Available The common variants in the fat mass- and obesity-associated (FTO gene have been previously found to be associated with obesity in various adult populations. The objective of the present study was to investigate whether the single nucleotide polymorphisms (SNPs and linkage disequilibrium (LD blocks in various regions of the FTO gene are associated with predisposition to obesity in Malaysian Malays. Thirty-one FTO SNPs were genotyped in 587 (158 obese and 429 non-obese Malaysian Malay subjects. Obesity traits and lipid profiles were measured and single-marker association testing, LD testing, and haplotype association analysis were performed. LD analysis of the FTO SNPs revealed the presence of 57 regions with complete LD (D’ = 1.0. In addition, we detected the association of rs17817288 with low-density lipoprotein cholesterol. The FTO gene may therefore be involved in lipid metabolism in Malaysian Malays. Two haplotype blocks were present in this region of the FTO gene, but no particular haplotype was found to be significantly associated with an increased risk of obesity in Malaysian Malays.

  17. SNPs of melanocortin 4 receptor (MC4R) associated with body weight in Beagle dogs.

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    Zeng, Ruixia; Zhang, Yibo; Du, Peng

    2014-01-01

    Melanocortin 4 receptor (MC4R), which is associated with inherited human obesity, is involoved in food intake and body weight of mammals. To study the relationships between MC4R gene polymorphism and body weight in Beagle dogs, we detected and compared the nucleotide sequence of the whole coding region and 3'- and 5'- flanking regions of the dog MC4R gene (1214 bp). In 120 Beagle dogs, two SNPs (A420C, C895T) were identified and their relation with body weight was analyzed with RFLP-PCR method. The results showed that the SNP at A420C was significantly associated with canine body weight trait when it changed amino acid 101 of the MC4R protein from asparagine to threonine, while canine body weight variations were significant in female dogs when MC4R nonsense mutation at C895T. It suggested that the two SNPs might affect the MC4R gene's function which was relative to body weight in Beagle dogs. Therefore, MC4R was a candidate gene for selecting different size dogs with the MC4R SNPs (A420C, C895T) being potentially valuable as a genetic marker.

  18. Enrichment of risk SNPs in regulatory regions implicate diverse tissues in Parkinson's disease etiology.

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    Coetzee, Simon G; Pierce, Steven; Brundin, Patrik; Brundin, Lena; Hazelett, Dennis J; Coetzee, Gerhard A

    2016-07-27

    Recent genome-wide association studies (GWAS) of Parkinson's disease (PD) revealed at least 26 risk loci, with associated single nucleotide polymorphisms (SNPs) located in non-coding DNA having unknown functions in risk. In order to explore in which cell types these SNPs (and their correlated surrogates at r(2) ≥ 0.8) could alter cellular function, we assessed their location overlap with histone modification regions that indicate transcription regulation in 77 diverse cell types. We found statistically significant enrichment of risk SNPs at 12 loci in active enhancers or promoters. We investigated 4 risk loci in depth that were most significantly enriched (-logeP > 14) and contained 8 putative enhancers in the different cell types. These enriched loci, along with eQTL associations, were unexpectedly present in non-neuronal cell types. These included lymphocytes, mesendoderm, liver- and fat-cells, indicating that cell types outside the brain are involved in the genetic predisposition to PD. Annotating regulatory risk regions within specific cell types may unravel new putative risk mechanisms and molecular pathways that contribute to PD development.

  19. Concordant gene expression in leukemia cells and normal leukocytes is associated with germline cis-SNPs.

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    Deborah French

    Full Text Available The degree to which gene expression covaries between different primary tissues within an individual is not well defined. We hypothesized that expression that is concordant across tissues is more likely influenced by genetic variability than gene expression which is discordant between tissues. We quantified expression of 11,873 genes in paired samples of primary leukemia cells and normal leukocytes from 92 patients with acute lymphoblastic leukemia (ALL. Genetic variation at >500,000 single nucleotide polymorphisms (SNPs was also assessed. The expression of only 176/11,783 (1.5% genes was correlated (p<0.008, FDR = 25% in the two tissue types, but expression of a high proportion (20 of these 176 genes was significantly related to cis-SNP genotypes (adjusted p<0.05. In an independent set of 134 patients with ALL, 14 of these 20 genes were validated as having expression related to cis-SNPs, as were 9 of 20 genes in a second validation set of HapMap cell lines. Genes whose expression was concordant among tissue types were more likely to be associated with germline cis-SNPs than genes with discordant expression in these tissues; genes affected were involved in housekeeping functions (GSTM2, GAPDH and NCOR1 and purine metabolism.

  20. Genetic association of SNPs in the FTO gene and predisposition to obesity in Malaysian Malays

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    Apalasamy, Y.D. [Pharmacogenomics Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur (Malaysia); Ming, M.F.; Rampal, S.; Bulgiba, A. [Julius Centre University of Malaya, Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur (Malaysia); Mohamed, Z. [Pharmacogenomics Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur (Malaysia)

    2012-08-24

    The common variants in the fat mass- and obesity-associated (FTO) gene have been previously found to be associated with obesity in various adult populations. The objective of the present study was to investigate whether the single nucleotide polymorphisms (SNPs) and linkage disequilibrium (LD) blocks in various regions of the FTO gene are associated with predisposition to obesity in Malaysian Malays. Thirty-one FTO SNPs were genotyped in 587 (158 obese and 429 non-obese) Malaysian Malay subjects. Obesity traits and lipid profiles were measured and single-marker association testing, LD testing, and haplotype association analysis were performed. LD analysis of the FTO SNPs revealed the presence of 57 regions with complete LD (D' = 1.0). In addition, we detected the association of rs17817288 with low-density lipoprotein cholesterol. The FTO gene may therefore be involved in lipid metabolism in Malaysian Malays. Two haplotype blocks were present in this region of the FTO gene, but no particular haplotype was found to be significantly associated with an increased risk of obesity in Malaysian Malays.

  1. Impact of Single Nucleotide Polymorphisms (SNPs) on Immunosuppressive Therapy in Lung Transplantation

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    Ruiz, Jesus; Herrero, María José; Bosó, Virginia; Megías, Juan Eduardo; Hervás, David; Poveda, Jose Luis; Escrivá, Juan; Pastor, Amparo; Solé, Amparo; Aliño, Salvador Francisco

    2015-01-01

    Lung transplant patients present important variability in immunosuppressant blood concentrations during the first months after transplantation. Pharmacogenetics could explain part of this interindividual variability. We evaluated SNPs in genes that have previously shown correlations in other kinds of solid organ transplantation, namely ABCB1 and CYP3A5 genes with tacrolimus (Tac) and ABCC2, UGT1A9 and SLCO1B1 genes with mycophenolic acid (MPA), during the first six months after lung transplantation (51 patients). The genotype was correlated to the trough blood drug concentrations corrected for dose and body weight (C0/Dc). The ABCB1 variant in rs1045642 was associated with significantly higher Tac concentration, at six months post-transplantation (CT vs. CC). In the MPA analysis, CT patients in ABCC2 rs3740066 presented significantly lower blood concentrations than CC or TT, three months after transplantation. Other tendencies, confirming previously expected results, were found associated with the rest of studied SNPs. An interesting trend was recorded for the incidence of acute rejection according to NOD2/CARD15 rs2066844 (CT: 27.9%; CC: 12.5%). Relevant SNPs related to Tac and MPA in other solid organ transplants also seem to be related to the efficacy and safety of treatment in the complex setting of lung transplantation. PMID:26307985

  2. Impact of Single Nucleotide Polymorphisms (SNPs on Immunosuppressive Therapy in Lung Transplantation

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    Jesus Ruiz

    2015-08-01

    Full Text Available Lung transplant patients present important variability in immunosuppressant blood concentrations during the first months after transplantation. Pharmacogenetics could explain part of this interindividual variability. We evaluated SNPs in genes that have previously shown correlations in other kinds of solid organ transplantation, namely ABCB1 and CYP3A5 genes with tacrolimus (Tac and ABCC2, UGT1A9 and SLCO1B1 genes with mycophenolic acid (MPA, during the first six months after lung transplantation (51 patients. The genotype was correlated to the trough blood drug concentrations corrected for dose and body weight (C0/Dc. The ABCB1 variant in rs1045642 was associated with significantly higher Tac concentration, at six months post-transplantation (CT vs. CC. In the MPA analysis, CT patients in ABCC2 rs3740066 presented significantly lower blood concentrations than CC or TT, three months after transplantation. Other tendencies, confirming previously expected results, were found associated with the rest of studied SNPs. An interesting trend was recorded for the incidence of acute rejection according to NOD2/CARD15 rs2066844 (CT: 27.9%; CC: 12.5%. Relevant SNPs related to Tac and MPA in other solid organ transplants also seem to be related to the efficacy and safety of treatment in the complex setting of lung transplantation.

  3. Identification of SNPs in the promoter of β-lactoglobulin gene in three Sicilian goat breeds

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    Baldassare Portolano

    2010-01-01

    Full Text Available The aim of this work was to sequence the full-length promoter region of the caprine β-lactoglobulin (β-lg gene in three Sicilian goat breeds (Girgentana, Maltese, and Derivata di Siria, in order to identify polymorphisms, to search for transcription factors (TFs sites, and to check if polymorphisms found lay within TFs binding sites. The promoter region of β-lg gene in Sicilian goat breeds showed high level of polymorphism due to the presence of 31 SNPs. Binding sites for several TFs were found within the goat β-lg promoter and within regions conserved between ovine and caprine species. Two SNPs were detected within TFs binding sites, such as MPBF and NF-I. Further studies are in progress to confirm polymorphic sites, to evaluate the possible effect of these mutations on binding affinity of TFs, their relationship with β-lg gene expression, and the functional role of SNPs within the TFs sites of the promoter region on milk traits.

  4. HapMap SNP Scanner: an online program to mine SNPs responsible for cell phenotype.

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    Yamamura, T; Hikita, J; Bleakley, M; Hirosawa, T; Sato-Otsubo, A; Torikai, H; Hamajima, T; Nannya, Y; Demachi-Okamura, A; Maruya, E; Saji, H; Yamamoto, Y; Takahashi, T; Emi, N; Morishima, Y; Kodera, Y; Kuzushima, K; Riddell, S R; Ogawa, S; Akatsuka, Y

    2012-08-01

    Minor histocompatibility (H) antigens are targets of graft-vs-host disease and graft-vs-tumor responses after human leukocyte antigen matched allogeneic hematopoietic stem cell transplantation. Recently, we reported a strategy for genetic mapping of linkage disequilibrium blocks that encoded novel minor H antigens using the large dataset from the International HapMap Project combined with conventional immunologic assays to assess recognition of HapMap B-lymphoid cell line by minor H antigen-specific T cells. In this study, we have constructed and provide an online interactive program and demonstrate its utility for searching for single-nucleotide polymorphisms (SNPs) responsible for minor H antigen generation. The website is available as 'HapMap SNP Scanner', and can incorporate T-cell recognition and other data with genotyping datasets from CEU, JPT, CHB, and YRI to provide a list of candidate SNPs that correlate with observed phenotypes. This method should substantially facilitate discovery of novel SNPs responsible for minor H antigens and be applicable for assaying of other specific cell phenotypes (e.g. drug sensitivity) to identify individuals who may benefit from SNP-based customized therapies.

  5. Comparison of ENCODE region SNPs between Cebu Filipino and Asian HapMap samples.

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    Marvelle, Amanda F; Lange, Leslie A; Qin, Li; Wang, Yunfei; Lange, Ethan M; Adair, Linda S; Mohlke, Karen L

    2007-01-01

    Patterns of linkage disequilibrium (LD) act as the framework for designing efficient association studies; these patterns are being studied and catalogued by The International HapMap Project. The current study assessed the transferability of tag SNPs chosen from HapMap panels to a cohort of 80 individuals from metro Cebu, Philippines, who participated in the Cebu Longitudinal Health and Nutrition Survey (CLHNS). The analyses focused on 627 single nucleotide polymorphisms (SNPs) in the central 40 kb within each of the 10 HapMap ENCODE regions. The similarity between the genetic variants in Cebu Filipino samples and HapMap panels was examined using allele frequency estimates, measures of pairwise linkage disequilibrium (LD), and haplotype frequency estimates. For these measures, strong correlations were observed between the Cebu Filipino samples and the Asian panels from HapMap, with the strongest correlations observed with the Han Chinese from Beijing (CHB) panel. Tag SNPs selected using the HapMap CHB panel were particularly effective at representing the genetic variation in Cebu Filipino samples. These results suggest that the HapMap data will be an effective resource for future studies in Cebu Filipino samples.

  6. Intraspecific chromosome variability

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    N Dubinin

    2010-12-01

    Full Text Available (Editorial preface. The publication is presented in order to remind us of one of dramatic pages of the history of genetics. It re-opens for the contemporary reader a comprehensive work marking the priority change from plant cytogenetics to animal cytogenetics led by wide population studies which were conducted on Drosophila polytene chromosomes. The year of the publication (1937 became the point of irretrievable branching between the directions of Old World and New World genetics connected with the problems of chromosome variability and its significance for the evolution of the species. The famous book of T. Dobzhansky (1937 was published by Columbia University in the US under the title “Genetics and the origin of species”, and in the shadow of this American ‘skybuilding’ all other works grew dim. It is remarkable that both Dobzhansky and Dubinin come to similar conclusions about the role of chromosomes in speciation. This is not surprising given that they both might be considered as representatives of the Russian genetic school, by their birth and education. Interestingly, Dobzhansky had never referred to the full paper of Dubinin et al. (1937, though a previous short communication in Nature (1936 was included together with all former papers on the related subject. In full, the volume of the original publication printed in the Biological Journal in Moscow comprised 47 pages, in that number 41 pages of the Russian text accompanied by 16 Figs, a table and reference list, and, above all, 6 pages of the English summary. This final part in English is now reproduced in the authors’ version with the only addition being the reference list in the originally printed form.

  7. Chromosome assortment in Saccharum.

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    Al-Janabi, S M; Honeycutt, R J; Sobral, B W

    1994-12-01

    Recent work has revealed random chromosome pairing and assortment in Saccharum spontaneum L., the most widely distributed, and morphologically and cytologically variable of the species of Saccharum. This conclusion was based on the analysis of a segregating population from across between S. spontaneum 'SES 208' and a spontaneously-doubled haploid of itself, derived from anther culture. To determine whether polysomic inheritance is common in Saccharum and whether it is observed in a typical biparental cross, we studied chromosome pairing and assortment in 44 progeny of a cross between euploid, meiotically regular, 2n=80 forms of Saccharum officinarum 'LA Purple' and Saccharum robustum ' Mol 5829'. Papuan 2n=80 forms of S. robustum have been suggested as the immediate progenitor species for cultivated sugarcane (S. officinarum). A total of 738 loci in LA Purple and 720 loci in Mol 5829 were amplified and typed in the progeny by arbitrarily primed PCR using 45 primers. Fifty and 33 single-dose polymorphisms were identified in the S. officinarum and S. robustum genomes, respectively (χ 2 at 98%). Linkage analysis of single-dose polymorphisms in both genomes revealed linkages in repulsion and coupling phases. In the S. officinarum genome, a map hypothesis gave 7 linkage groups with 17 linked and 33 unlinked markers. Four of 13 pairwise linkages were in repulsion phase and 9 were in coupling phase. In the S. robustum genome, a map hypothesis gave 5 linkage groups, defined by 12 markers, with 21 markers unlinked, and 2 of 9 pairwise linkages were in repulsion phase. Therefore, complete polysomic inheritance was not observed in either species, suggesting that chromosomal behavior is different from that observed by linkage analysis of over 500 markers in the S. spontaneum map. Implications of this finding for evolution and breeding are discussed.

  8. Comparing genetic variants detected in the 1000 genomes project with SNPs determined by the International HapMap Consortium.

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    Zhang, Wenqian; Ng, Hui Wen; Shu, Mao; Luo, Heng; Su, ZhenQiang; Ge, Weigong; Perkins, Roger; Tong, Weida; Hong, Huixiao

    2015-12-01

    Single-nucleotide polymorphisms (SNPs) determined based on SNP arrays from the international HapMap consortium (HapMap) and the genetic variants detected in the 1000 genomes project (1KGP) can serve as two references for genomewide association studies (GWAS). We conducted comparative analyses to provide a means for assessing concerns regarding SNP array-based GWAS findings as well as for realistically bounding expectations for next generation sequencing (NGS)-based GWAS. We calculated and compared base composition, transitions to transversions ratio, minor allele frequency and heterozygous rate for SNPs from HapMap and 1KGP for the 622 common individuals. We analysed the genotype discordance between HapMap and 1KGP to assess consistency in the SNPs from the two references. In 1KGP, 90.58% of 36,817,799 SNPs detected were not measured in HapMap. More SNPs with minor allele frequencies less than 0.01 were found in 1KGP than HapMap. The two references have low disc ordance (generally smaller than 0.02) in genotypes of common SNPs, with most discordance from heterozygous SNPs. Our study demonstrated that SNP array-based GWAS findings were reliable and useful, although only a small portion of genetic variances were explained. NGS can detect not only common but also rare variants, supporting the expectation that NGS-based GWAS will be able to incorporate a much larger portion of genetic variance than SNP arrays-based GWAS.

  9. Variation in conserved non-coding sequences on chromosome 5q andsusceptibility to asthma and atopy

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    Donfack, Joseph; Schneider, Daniel H.; Tan, Zheng; Kurz,Thorsten; Dubchak, Inna; Frazer, Kelly A.; Ober, Carole

    2005-09-10

    Background: Evolutionarily conserved sequences likely havebiological function. Methods: To determine whether variation in conservedsequences in non-coding DNA contributes to risk for human disease, westudied six conserved non-coding elements in the Th2 cytokine cluster onhuman chromosome 5q31 in a large Hutterite pedigree and in samples ofoutbred European American and African American asthma cases and controls.Results: Among six conserved non-coding elements (>100 bp,>70percent identity; human-mouse comparison), we identified one singlenucleotide polymorphism (SNP) in each of two conserved elements and sixSNPs in the flanking regions of three conserved elements. We genotypedour samples for four of these SNPs and an additional three SNPs each inthe IL13 and IL4 genes. While there was only modest evidence forassociation with single SNPs in the Hutterite and European Americansamples (P<0.05), there were highly significant associations inEuropean Americans between asthma and haplotypes comprised of SNPs in theIL4 gene (P<0.001), including a SNP in a conserved non-codingelement. Furthermore, variation in the IL13 gene was strongly associatedwith total IgE (P = 0.00022) and allergic sensitization to mold allergens(P = 0.00076) in the Hutterites, and more modestly associated withsensitization to molds in the European Americans and African Americans (P<0.01). Conclusion: These results indicate that there is overalllittle variation in the conserved non-coding elements on 5q31, butvariation in IL4 and IL13, including possibly one SNP in a conservedelement, influence asthma and atopic phenotypes in diversepopulations.

  10. A set of EST-SNPs for map saturation and cultivar identification in melon

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    Monforte Antonio J

    2009-07-01

    Full Text Available Abstract Background There are few genomic tools available in melon (Cucumis melo L., a member of the Cucurbitaceae, despite its importance as a crop. Among these tools, genetic maps have been constructed mainly using marker types such as simple sequence repeats (SSR, restriction fragment length polymorphisms (RFLP and amplified fragment length polymorphisms (AFLP in different mapping populations. There is a growing need for saturating the genetic map with single nucleotide polymorphisms (SNP, more amenable for high throughput analysis, especially if these markers are located in gene coding regions, to provide functional markers. Expressed sequence tags (ESTs from melon are available in public databases, and resequencing ESTs or validating SNPs detected in silico are excellent ways to discover SNPs. Results EST-based SNPs were discovered after resequencing ESTs between the parental lines of the PI 161375 (SC × 'Piel de sapo' (PS genetic map or using in silico SNP information from EST databases. In total 200 EST-based SNPs were mapped in the melon genetic map using a bin-mapping strategy, increasing the map density to 2.35 cM/marker. A subset of 45 SNPs was used to study variation in a panel of 48 melon accessions covering a wide range of the genetic diversity of the species. SNP analysis correctly reflected the genetic relationships compared with other marker systems, being able to distinguish all the accessions and cultivars. Conclusion This is the first example of a genetic map in a cucurbit species that includes a major set of SNP markers discovered using ESTs. The PI 161375 × 'Piel de sapo' melon genetic map has around 700 markers, of which more than 500 are gene-based markers (SNP, RFLP and SSR. This genetic map will be a central tool for the construction of the melon physical map, the step prior to sequencing the complete genome. Using the set of SNP markers, it was possible to define the genetic relationships within a collection of forty

  11. 118 SNPs of folate-related genes and risks of spina bifida and conotruncal heart defects

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    Shaw Gary M

    2009-06-01

    Full Text Available Abstract Background Folic acid taken in early pregnancy reduces risks for delivering offspring with several congenital anomalies. The mechanism by which folic acid reduces risk is unknown. Investigations into genetic variation that influences transport and metabolism of folate will help fill this data gap. We focused on 118 SNPs involved in folate transport and metabolism. Methods Using data from a California population-based registry, we investigated whether risks of spina bifida or conotruncal heart defects were influenced by 118 single nucleotide polymorphisms (SNPs associated with the complex folate pathway. This case-control study included 259 infants with spina bifida and a random sample of 359 nonmalformed control infants born during 1983–86 or 1994–95. It also included 214 infants with conotruncal heart defects born during 1983–86. Infant genotyping was performed blinded to case or control status using a designed SNPlex assay. We examined single SNP effects for each of the 118 SNPs, as well as haplotypes, for each of the two outcomes. Results Few odds ratios (ORs revealed sizable departures from 1.0. With respect to spina bifida, we observed ORs with 95% confidence intervals that did not include 1.0 for the following SNPs (heterozygous or homozygous relative to the reference genotype: BHMT (rs3733890 OR = 1.8 (1.1–3.1, CBS (rs2851391 OR = 2.0 (1.2–3.1; CBS (rs234713 OR = 2.9 (1.3–6.7; MTHFD1 (rs2236224 OR = 1.7 (1.1–2.7; MTHFD1 (hcv11462908 OR = 0.2 (0–0.9; MTHFD2 (rs702465 OR = 0.6 (0.4–0.9; MTHFD2 (rs7571842 OR = 0.6 (0.4–0.9; MTHFR (rs1801133 OR = 2.0 (1.2–3.1; MTRR (rs162036 OR = 3.0 (1.5–5.9; MTRR (rs10380 OR = 3.4 (1.6–7.1; MTRR (rs1801394 OR = 0.7 (0.5–0.9; MTRR (rs9332 OR = 2.7 (1.3–5.3; TYMS (rs2847149 OR = 2.2 (1.4–3.5; TYMS (rs1001761 OR = 2.4 (1.5–3.8; and TYMS (rs502396 OR = 2.1 (1.3–3.3. However, multiple SNPs observed for a given gene showed evidence of linkage disequilibrium indicating

  12. Chromosome Connections: Compelling Clues to Common Ancestry

    Science.gov (United States)

    Flammer, Larry

    2013-01-01

    Students compare banding patterns on hominid chromosomes and see striking evidence of their common ancestry. To test this, human chromosome no. 2 is matched with two shorter chimpanzee chromosomes, leading to the hypothesis that human chromosome 2 resulted from the fusion of the two shorter chromosomes. Students test that hypothesis by looking for…

  13. Chromosomal rearrangement interferes with meiotic X chromosome inactivation.

    Science.gov (United States)

    Homolka, David; Ivanek, Robert; Capkova, Jana; Jansa, Petr; Forejt, Jiri

    2007-10-01

    Heterozygosity for certain mouse and human chromosomal rearrangements is characterized by the incomplete meiotic synapsis of rearranged chromosomes, by their colocalization with the XY body in primary spermatocytes, and by male-limited sterility. Previously, we argued that such X-autosomal associations could interfere with meiotic sex chromosome inactivation. Recently, supporting evidence has reported modifications of histones in rearranged chromosomes by a process called the meiotic silencing of unsynapsed chromatin (MSUC). Here, we report on the transcriptional down-regulation of genes within the unsynapsed region of the rearranged mouse chromosome 17, and on the subsequent disturbance of X chromosome inactivation. The partial transcriptional suppression of genes in the unsynapsed chromatin was most prominent prior to the mid-pachytene stage of primary spermatocytes. Later, during the mid-late pachytene, the rearranged autosomes colocalized with the XY body, and the X chromosome failed to undergo proper transcriptional silencing. Our findings provide direct evidence on the MSUC acting at the mRNA level, and implicate that autosomal asynapsis in meiosis may cause male sterility by interfering with meiotic sex chromosome inactivation.

  14. SNPs analysis of ABCA4 gene in Han Chinese in Beijing%中国北京汉族人群 ABCA4基因的 SNPs 研究

    Institute of Scientific and Technical Information of China (English)

    张小龙; 王红

    2015-01-01

    Objective:To provide the basis of single nucleotide polymorphism(SNPs)for identification and analysis of ABCA4 gene related etiologic studies in Han Chinese in Beijing(CHB).Methods:SNPs of ABCA4 gene were analyzed for minor allele frequencies (MAFs),haplotype frequencies,linkage disequilibrium patterns,and tag SNPs by Haploview program using the HapMap data.Re-sults:129(37.6%)of 343 SNPs were monotonic.95 tagging SNPs were identified in 214 eligible SNPs with 3 haplotype blocks identi-fied.The frequencies of the top 2 haplotypes among each of the 3 haplotype blocks were between 91.1% and 94.0%.Conclusion:SNPs in ABCA4 gene were analyzed by Haploview program.The analysis provides clues for future studies involving this gene.%目的:研究北京汉族人群中 ABCA4基因单核苷酸多态性,为病因学研究提供依据。方法:选取国际人类基因组单体型图计划(HapMap)公布的北京汉族人群(Han Chinese in Beijing,China,CHB)ABCA4基因 SNPs 基因型数据,利用 Haploview 4.2软件对其进行分析。结果:Hapmap 提供的343个 ABCA4基因的 SNPs 中,有129个(37.6%)纯合基因型 SNPs 和214个(62.39%)合格 SNPs。本研究共确定95个标签 SNPs,构建了 3个单体域,各单体域均以前2种单体型为主,累计频率在91.1%~94.0%之间。结论:通过分析北京汉族人群 ABCA4基因 SNPs 数据,得到了标签 SNPs、单体域和主要单体型,为进一步的病因学研究打下了基础。

  15. Cohesin in determining chromosome architecture

    Energy Technology Data Exchange (ETDEWEB)

    Haering, Christian H., E-mail: christian.haering@embl.de [Cell Biology and Biophysics Unit, European Molecular Biology Laboratory (EMBL), Heidelberg (Germany); Jessberger, Rolf, E-mail: rolf.jessberger@tu-dresden.de [Institute of Physiological Chemistry, Dresden University of Technology, Dresden (Germany)

    2012-07-15

    Cells use ring-like structured protein complexes for various tasks in DNA dynamics. The tripartite cohesin ring is particularly suited to determine chromosome architecture, for it is large and dynamic, may acquire different forms, and is involved in several distinct nuclear processes. This review focuses on cohesin's role in structuring chromosomes during mitotic and meiotic cell divisions and during interphase.

  16. Exploration of the Applicable Conditions of x2 Test Combined with False Discovery Rate for Screening Pathogenic SNPs%探讨x2检验结合FDR筛选致病SNPs位点的适用条件

    Institute of Scientific and Technical Information of China (English)

    郑娟娟; 孙远洁; 李昂; 温琪; 佟海龙; 刘艳; 赵晓雯

    2012-01-01

    Objective To explore the applicable conditions of ^2 test combined with false discovery rate (FDR) for screening single nucleotide polymorphisms (SNPs) locus by investigating the different simulation conditions in the SNPs data. Methods According to the data of the first 5,000 SNPs in chromosome 22 of Utah residents with Northern and Western European ancestry from the CEPH collection released in HapMap III in February 2009, case ?control data were simulated by HAP-GEN2, and Tag SNPs were screened by Haploview4.2. The correct rates of different simulation conditions in screening pathogenic SNPs were compared. Results The methods of obtaining the relative risk (RR) were not significantly different. Three genetic models all showed that the correct rate increased with the rising RR. For the same RR, the additive model had the highest correct rate, the dominant model had the second, and the recessive model had the lowest. For the additive model with RR > 2.2, the dominant model with RR >4 and the recessive model with RR >5, the correct rate was over 60% . Conclusions Combination of x2 test with FDR has the best application in the additive model. In the actual scientific research, the feasibility of x2 test combined with FDR should be considered on the basis of the concrete conditions of the target disease.%目的 在单核苷酸多态性(SNPs)数据中探讨不同模拟条件x2检验结合错误发现率(FDR)筛选SNPs位点的适用条件.方法 依据2009年2月发布HapMapⅢ期美国犹他州北欧和西欧后裔人群22号染色体前5000个SNPs数据,采用HAPGEN2模拟病例对照数据,运用Haploview4.2筛选标签SNPs(TagSNPs),比较不同模拟条件筛选致病SNPs的正确率.结果 相对危险度(RR)获取方式无显著差异;3种遗传模型均表现正确率随RR值增大而增高,RR相同时,加性模型正确率最高,显性模型次之,隐性模型最低;加性模型RR>2.2、显性模型RR>4和隐性模型RR>5时,正确率超过60

  17. Diagnostic SNPs for inferring population structure in American mink (Neovison vison) identified through RAD sequencing

    DEFF Research Database (Denmark)

    2015-01-01

    Data from: "Diagnostic SNPs for inferring population structure in American mink (Neovison vison) identified through RAD sequencing" in Genomic Resources Notes accepted 1 October 2014 to 30 November 2014....

  18. Genetics Home Reference: Y chromosome infertility

    Science.gov (United States)

    ... Home Health Conditions Y chromosome infertility Y chromosome infertility Enable Javascript to view the expand/collapse boxes. ... PDF Open All Close All Description Y chromosome infertility is a condition that affects the production of ...

  19. Higher order structure of chromosomes.

    Science.gov (United States)

    Okada, T A; Comings, D E

    1979-04-01

    Isolated Chinese hamster metaphase chromosomes were resuspended in 4 M ammonium acetate and spread on a surface of distilled water or 0.15 to 0.5 M ammonium acetate. The DNA was released in the form of a regular series of rosettes connected by interrossette DNA. The mean length of the rosette DNA was 14 micron, similar to the mean length of 10 micron for chromomere DNA of Drosophila polytene chromosomes. The mean interrosette DNA was 4.2 micron. SDS gel electrophoresis of the chromosomal nonhistone proteins showed them to be very similar to nuclear nonhistone proteins except for the presence of more actin and tubulin. Nuclear matrix proteins were present in the chromosomes and may play a role in forming the rosettes. Evidence that the rosette pattern is artifactual versus the possibility that it represents a real organizational substructure of the chromosomes is reviewed.

  20. Bacterial chromosome organization and segregation.

    Science.gov (United States)

    Badrinarayanan, Anjana; Le, Tung B K; Laub, Michael T

    2015-01-01

    If fully stretched out, a typical bacterial chromosome would be nearly 1 mm long, approximately 1,000 times the length of a cell. Not only must cells massively compact their genetic material, but they must also organize their DNA in a manner that is compatible with a range of cellular processes, including DNA replication, DNA repair, homologous recombination, and horizontal gene transfer. Recent work, driven in part by technological advances, has begun to reveal the general principles of chromosome organization in bacteria. Here, drawing on studies of many different organisms, we review the emerging picture of how bacterial chromosomes are structured at multiple length scales, highlighting the functions of various DNA-binding proteins and the impact of physical forces. Additionally, we discuss the spatial dynamics of chromosomes, particularly during their segregation to daughter cells. Although there has been tremendous progress, we also highlight gaps that remain in understanding chromosome organization and segregation.

  1. Chromosome choreography: the meiotic ballet.

    Science.gov (United States)

    Page, Scott L; Hawley, R Scott

    2003-08-08

    The separation of homologous chromosomes during meiosis in eukaryotes is the physical basis of Mendelian inheritance. The core of the meiotic process is a specialized nuclear division (meiosis I) in which homologs pair with each other, recombine, and then segregate from each other. The processes of chromosome alignment and pairing allow for homolog recognition. Reciprocal meiotic recombination ensures meiotic chromosome segregation by converting sister chromatid cohesion into mechanisms that hold homologous chromosomes together. Finally, the ability of sister kinetochores to orient to a single pole at metaphase I allows the separation of homologs to two different daughter cells. Failures to properly accomplish this elegant chromosome dance result in aneuploidy, a major cause of miscarriage and birth defects in human beings.

  2. Powerful identification of cis-regulatory SNPs in human primary monocytes using allele-specific gene expression.

    Directory of Open Access Journals (Sweden)

    Jonas Carlsson Almlöf

    Full Text Available A large number of genome-wide association studies have been performed during the past five years to identify associations between SNPs and human complex diseases and traits. The assignment of a functional role for the identified disease-associated SNP is not straight-forward. Genome-wide expression quantitative trait locus (eQTL analysis is frequently used as the initial step to define a function while allele-specific gene expression (ASE analysis has not yet gained a wide-spread use in disease mapping studies. We compared the power to identify cis-acting regulatory SNPs (cis-rSNPs by genome-wide allele-specific gene expression (ASE analysis with that of traditional expression quantitative trait locus (eQTL mapping. Our study included 395 healthy blood donors for whom global gene expression profiles in circulating monocytes were determined by Illumina BeadArrays. ASE was assessed in a subset of these monocytes from 188 donors by quantitative genotyping of mRNA using a genome-wide panel of SNP markers. The performance of the two methods for detecting cis-rSNPs was evaluated by comparing associations between SNP genotypes and gene expression levels in sample sets of varying size. We found that up to 8-fold more samples are required for eQTL mapping to reach the same statistical power as that obtained by ASE analysis for the same rSNPs. The performance of ASE is insensitive to SNPs with low minor allele frequencies and detects a larger number of significantly associated rSNPs using the same sample size as eQTL mapping. An unequivocal conclusion from our comparison is that ASE analysis is more sensitive for detecting cis-rSNPs than standard eQTL mapping. Our study shows the potential of ASE mapping in tissue samples and primary cells which are difficult to obtain in large numbers.

  3. Schizophrenia and chromosomal deletions

    Energy Technology Data Exchange (ETDEWEB)

    Lindsay, E.A.; Baldini, A. [Baylor College of Medicine, Houston, TX (United States); Morris, M. A. [Univ. of Geneva School of Medicine, NY (United States)] [and others

    1995-06-01

    Recent genetic linkage analysis studies have suggested the presence of a schizophrenia locus on the chromosomal region 22q11-q13. Schizophrenia has also been frequently observed in patients affected with velo-cardio-facial syndrome (VCFS), a disorder frequently associated with deletions within 22q11.1. It has been hypothesized that psychosis in VCFS may be due to deletion of the catechol-o-methyl transferase gene. Prompted by these observations, we screened for 22q11 deletions in a population of 100 schizophrenics selected from the Maryland Epidemiological Sample. Our results show that there are schizophrenic patients carrying a deletion of 22q11.1 and a mild VCFS phenotype that might remain unrecognized. These findings should encourage a search for a schizophrenia-susceptibility gene within the deleted region and alert those in clinical practice to the possible presence of a mild VCFS phenotype associated with schizophrenia. 9 refs.

  4. A genome-wide association study of heat stress-associated SNPs in catfish.

    Science.gov (United States)

    Jin, Y; Zhou, T; Geng, X; Liu, S; Chen, A; Yao, J; Jiang, C; Tan, S; Su, B; Liu, Z

    2017-04-01

    Heat tolerance is a complex and economically important trait for catfish genetic breeding programs. With global climate change, it is becoming an increasingly important trait. To better understand the molecular basis of heat stress, a genome-wide association study (GWAS) was carried out using the 250 K catfish SNP array with interspecific backcross progenies, which derived from crossing female channel catfish with male F1 hybrid catfish (female channel catfish × male blue catfish). Three significant associated SNPs were detected by performing an EMMAX approach for GWAS. The SNP located on linkage group 14 explained 12.1% of phenotypical variation. The other two SNPs, located on linkage group 16, explained 11.3 and 11.5% of phenotypical variation respectively. A total of 14 genes with heat stress related functions were detected within the significant associated regions. Among them, five genes-TRAF2, FBXW5, ANAPC2, UBR1 and KLHL29- have known functions in the protein degradation process through the ubiquitination pathway. Other genes related to heat stress include genes involved in protein biosynthesis (PRPF4 and SYNCRIP), protein folding (DNAJC25), molecule and iron transport (SLC25A46 and CLIC5), cytoskeletal reorganization (COL12A1) and energy metabolism (COX7A2, PLCB1 and PLCB4) processes. The results provide fundamental information about genes and pathways that is useful for further investigation into the molecular mechanisms of heat stress. The associated SNPs could be promising candidates for selecting heat-tolerant catfish lines after validating their effects on larger and various catfish populations.

  5. VnD: a structure-centric database of disease-related SNPs and drugs.

    Science.gov (United States)

    Yang, Jin Ok; Oh, Sangho; Ko, Gunhwan; Park, Seong-Jin; Kim, Woo-Yeon; Lee, Byungwook; Lee, Sanghyuk

    2011-01-01

    Numerous genetic variations have been found to be related to human diseases. Significant portion of those affect the drug response as well by changing the protein structure and function. Therefore, it is crucial to understand the trilateral relationship among genomic variations, diseases and drugs. We present the variations and drugs (VnD), a consolidated database containing information on diseases, related genes and genetic variations, protein structures and drug information. VnD was built in three steps. First, we integrated various resources systematically to deduce catalogs of disease-related genes, single nucleotide polymorphisms (SNPs), protein mutations and relevant drugs. VnD contains 137,195 disease-related gene records (13,940 distinct genes) and 16,586 genetic variation records (1790 distinct variations). Next, we carried out structure modeling and docking simulation for wild-type and mutant proteins to examine the structural and functional consequences of non-synonymous SNPs in the drug-related genes. Conformational changes in 590 wild-type and 4437 mutant proteins from drug-related genes were included in our database. Finally, we investigated the structural and biochemical properties relevant to drug binding such as the distribution of SNPs in proximal protein pockets, thermo-chemical stability, interactions with drugs and physico-chemical properties. The VnD database, available at http://vnd.kobic.re.kr:8080/VnD/ or vandd.org, would be a useful platform for researchers studying the underlying mechanism for association among genetic variations, diseases and drugs.

  6. Differences in allele frequencies of autosomal dominant hypercholesterolemia SNPs in the Malaysian population.

    Science.gov (United States)

    Alex, Livy; Chahil, Jagdish Kaur; Lye, Say Hean; Bagali, Pramod; Ler, Lian Wee

    2012-06-01

    Hypercholesterolemia is caused by different interactions of lifestyle and genetic determinants. At the genetic level, it can be attributed to the interactions of multiple polymorphisms, or as in the example of familial hypercholesterolemia (FH), it can be the result of a single mutation. A large number of genetic markers, mostly single nucleotide polymorphisms (SNP) or mutations in three genes, implicated in autosomal dominant hypercholesterolemia (ADH), viz APOB (apolipoprotein B), LDLR (low density lipoprotein receptor) and PCSK9 (proprotein convertase subtilisin/kexin type-9), have been identified and characterized. However, such studies have been insufficiently undertaken specifically in Malaysia and Southeast Asia in general. The main objective of this study was to identify ADH variants, specifically ADH-causing mutations and hypercholesterolemia-associated polymorphisms in multiethnic Malaysian population. We aimed to evaluate published SNPs in ADH causing genes, in this population and to report any unusual trends. We examined a large number of selected SNPs from previous studies of APOB, LDLR, PCSK9 and other genes, in clinically diagnosed ADH patients (n=141) and healthy control subjects (n=111). Selection of SNPs was initiated by searching within genes reported to be associated with ADH from known databases. The important finding was 137 mono-allelic markers (44.1%) and 173 polymorphic markers (55.8%) in both subject groups. By comparing to publicly available data, out of the 137 mono-allelic markers, 23 markers showed significant differences in allele frequency among Malaysians, European Whites, Han Chinese, Yoruba and Gujarati Indians. Our data can serve as reference for others in related fields of study during the planning of their experiments.

  7. Use of SNPs to determine the breakpoints of complex deficiencies, facilitating gene mapping in Caenorhabditis elegans

    Directory of Open Access Journals (Sweden)

    Hoffmann Melissa

    2005-05-01

    Full Text Available Abstract Background Genetic deletions or deficiencies have been used for gene mapping and discovery in various organisms, ranging from the nematode Caenorhabditis elegans all the way to humans. One problem with large deletions is the determination of the location of their breakpoints. This is exacerbated in the case of complex deficiencies that delete a region of the genome, while retaining some of the intervening sequence. Previous methods, using genetic complementation or cytology were hampered by low marker density and were consequently not very precise at positioning the breakpoints of complex deficiencies. The identification of increasing numbers of Single Nucleotide Polymorphisms (SNPs has resulted in the use of these as genetic markers, and consequently in their utilization for defining the breakpoints of deletions using molecular biology methods. Results Here, we show that SNPs can be used to help position the breakpoints of a complex deficiency in C. elegans. The technique uses a combination of genetic crosses and molecular biology to generate robust and highly reproducible results with strong internal controls when trying to determine the breakpoints of deficiencies. The combined use of this technique and standard genetic mapping allowed us to rapidly narrow down the region of interest in our attempts to clone a gene. Conclusion Unlike previous methods used to locate deficiency breakpoints, our technique has the advantage of not being limited by the amount of starting material. It also incorporates internal controls to eliminate false positives and negatives. The technique can also easily be adapted for use in other organisms in which both genetic deficiencies and SNPs are available, thereby aiding gene discovery in these other models.

  8. Simultaneous analysis of all SNPs in genome-wide and re-sequencing association studies.

    Directory of Open Access Journals (Sweden)

    Clive J Hoggart

    2008-07-01

    Full Text Available Testing one SNP at a time does not fully realise the potential of genome-wide association studies to identify multiple causal variants, which is a plausible scenario for many complex diseases. We show that simultaneous analysis of the entire set of SNPs from a genome-wide study to identify the subset that best predicts disease outcome is now feasible, thanks to developments in stochastic search methods. We used a Bayesian-inspired penalised maximum likelihood approach in which every SNP can be considered for additive, dominant, and recessive contributions to disease risk. Posterior mode estimates were obtained for regression coefficients that were each assigned a prior with a sharp mode at zero. A non-zero coefficient estimate was interpreted as corresponding to a significant SNP. We investigated two prior distributions and show that the normal-exponential-gamma prior leads to improved SNP selection in comparison with single-SNP tests. We also derived an explicit approximation for type-I error that avoids the need to use permutation procedures. As well as genome-wide analyses, our method is well-suited to fine mapping with very dense SNP sets obtained from re-sequencing and/or imputation. It can accommodate quantitative as well as case-control phenotypes, covariate adjustment, and can be extended to search for interactions. Here, we demonstrate the power and empirical type-I error of our approach using simulated case-control data sets of up to 500 K SNPs, a real genome-wide data set of 300 K SNPs, and a sequence-based dataset, each of which can be analysed in a few hours on a desktop workstation.

  9. Association study of FOXO3A SNPs and aging phenotypes in Danish oldest-old individuals.

    Science.gov (United States)

    Soerensen, Mette; Nygaard, Marianne; Dato, Serena; Stevnsner, Tinna; Bohr, Vilhelm A; Christensen, Kaare; Christiansen, Lene

    2015-02-01

    FOXO3A variation has repeatedly been reported to associate with human longevity, yet only few studies have investigated whether FOXO3A variation also associates with aging-related traits. Here, we investigate the association of 15 FOXO3A tagging single nucleotide polymorphisms (SNPs) in 1088 oldest-old Danes (age 92-93) with 4 phenotypes known to predict their survival: cognitive function, hand grip strength, activity of daily living (ADL), and self-rated health. Based on previous studies in humans and foxo animal models, we also explore self-reported diabetes, cancer, cardiovascular disease, osteoporosis, and bone (femur/spine/hip/wrist) fracture. Gene-based testing revealed significant associations of FOXO3A variation with ADL (P = 0.044) and bone fracture (P = 0.006). The single-SNP statistics behind the gene-based analysis indicated increased ADL (decreased disability) and reduced bone fracture risk for carriers of the minor alleles of 8 and 10 SNPs, respectively. These positive directions of effects are in agreement with the positive effects on longevity previously reported for these SNPs. However, when correcting for the test of 9 phenotypes by Bonferroni correction, bone fracture showed borderline significance (P = 0.054), while ADL did not (P = 0.396). Although the single-SNP associations did not formally replicate in another study population of oldest-old Danes (n = 1279, age 94-100), the estimates were of similar direction of effect as observed in the Discovery sample. A pooled analysis of both study populations displayed similar or decreased sized P-values for most associations, hereby supporting the initial findings. Nevertheless, confirmation in additional study populations is needed.

  10. Discovering Genome-Wide Tag SNPs Based on the Mutual Information of the Variants

    Science.gov (United States)

    Elmas, Abdulkadir; Ou Yang, Tai-Hsien; Wang, Xiaodong

    2016-01-01

    Exploring linkage disequilibrium (LD) patterns among the single nucleotide polymorphism (SNP) sites can improve the accuracy and cost-effectiveness of genomic association studies, whereby representative (tag) SNPs are identified to sufficiently represent the genomic diversity in populations. There has been considerable amount of effort in developing efficient algorithms to select tag SNPs from the growing large-scale data sets. Methods using the classical pairwise-LD and multi-locus LD measures have been proposed that aim to reduce the computational complexity and to increase the accuracy, respectively. The present work solves the tag SNP selection problem by efficiently balancing the computational complexity and accuracy, and improves the coverage in genomic diversity in a cost-effective manner. The employed algorithm makes use of mutual information to explore the multi-locus association between SNPs and can handle different data types and conditions. Experiments with benchmark HapMap data sets show comparable or better performance against the state-of-the-art algorithms. In particular, as a novel application, the genome-wide SNP tagging is performed in the 1000 Genomes Project data sets, and produced a well-annotated database of tagging variants that capture the common genotype diversity in 2,504 samples from 26 human populations. Compared to conventional methods, the algorithm requires as input only the genotype (or haplotype) sequences, can scale up to genome-wide analyses, and produces accurate solutions with more information-rich output, providing an improved platform for researchers towards the subsequent association studies. PMID:27992465

  11. Association of Genome-Wide Association Study (GWAS) Identified SNPs and Risk of Breast Cancer in an Indian Population

    Science.gov (United States)

    Nagrani, Rajini; Mhatre, Sharayu; Rajaraman, Preetha; Chatterjee, Nilanjan; Akbari, Mohammad R.; Boffetta, Paolo; Brennan, Paul; Badwe, Rajendra; Gupta, Sudeep; Dikshit, Rajesh

    2017-01-01

    To date, no studies have investigated the association of the GWAS-identified SNPs with BC risk in Indian population. We investigated the association of 30 previously reported and replicated BC susceptibility SNPs in 1,204 cases and 1,212 controls from a hospital based case-control study conducted at the Tata Memorial Hospital, Mumbai. As a measure of total susceptibility burden, the polygenic risk score (PRS) for each individual was defined by the weighted sum of genotypes from 21 independent SNPs with weights derived from previously published estimates of association odds-ratios. Logistic regression models were used to assess risk associated with individual SNPs and overall PRS, and stratified by menopausal and receptor status. A total of 11 SNPs from eight genomic regions (FGFR2, 9q31.2, MAP3K, CCND1, ZM1Z1, RAD51L11, ESR1 and UST) showed statistically significant (p-value ≤ 0.05) evidence of association, either overall or when stratified by menopausal status or hormone receptor status. BC SNPs previously identified in Caucasian population showed evidence of replication in the Indian population mainly with respect to risk of postmenopausal and hormone receptor positive BC. PMID:28098224

  12. Phosphorylation states of cell cycle and DNA repair proteins can be altered by the nsSNPs

    Directory of Open Access Journals (Sweden)

    Savas Sevtap

    2005-08-01

    Full Text Available Abstract Background Phosphorylation is a reversible post-translational modification that affects the intrinsic properties of proteins, such as structure and function. Non-synonymous single nucleotide polymorphisms (nsSNPs result in the substitution of the encoded amino acids and thus are likely to alter the phosphorylation motifs in the proteins. Methods In this study, we used the web-based NetPhos tool to predict candidate nsSNPs that either introduce or remove putative phosphorylation sites in proteins that act in DNA repair and cell cycle pathways. Results Our results demonstrated that a total of 15 nsSNPs (16.9% were likely to alter the putative phosphorylation patterns of 14 proteins. Three of these SNPs (CDKN1A-S31R, OGG1-S326C, and XRCC3-T241M have already found to be associated with altered cancer risk. We believe that this set of nsSNPs constitutes an excellent resource for further molecular and genetic analyses. Conclusion The novel systematic approach used in this study will accelerate the understanding of how naturally occurring human SNPs may alter protein function through the modification of phosphorylation mechanisms and contribute to disease susceptibility.

  13. Analysis of 49 autosomal SNPs in three ethnic groups from Iran

    DEFF Research Database (Denmark)

    Sharafi Farzad, M; Tomas Mas, Carmen; Børsting, C

    2013-01-01

    A total number of 149 individuals from Iran (Persians, Lurs and Kurds) were analyzed for 49 autosomal SNPs using PCR, SBE and capillary electrophoresis. No deviation from Hardy-Weinberg expectations was observed. One SNP pair (rs1015250-rs251934) showed significant linkage disequilibrium in Kurds....... However, this was most likely due to chance. High intrapopulation variability and no significant population structure were observed among the three ethnic groups from Iran. Pairwise FST values obtained from the mean numbers of pairwise differences between SNP profiles were calculated for Persians, Lurs...

  14. Rapid multiplex high resolution melting method to analyze inflammatory related SNPs in preterm birth

    Directory of Open Access Journals (Sweden)

    Pereyra Silvana

    2012-01-01

    Full Text Available Abstract Background Complex traits like cancer, diabetes, obesity or schizophrenia arise from an intricate interaction between genetic and environmental factors. Complex disorders often cluster in families without a clear-cut pattern of inheritance. Genomic wide association studies focus on the detection of tens or hundreds individual markers contributing to complex diseases. In order to test if a subset of single nucleotide polymorphisms (SNPs from candidate genes are associated to a condition of interest in a particular individual or group of people, new techniques are needed. High-resolution melting (HRM analysis is a new method in which polymerase chain reaction (PCR and mutations scanning are carried out simultaneously in a closed tube, making the procedure fast, inexpensive and easy. Preterm birth (PTB is considered a complex disease, where genetic and environmental factors interact to carry out the delivery of a newborn before 37 weeks of gestation. It is accepted that inflammation plays an important role in pregnancy and PTB. Methods Here, we used real time-PCR followed by HRM analysis to simultaneously identify several gene variations involved in inflammatory pathways on preterm labor. SNPs from TLR4, IL6, IL1 beta and IL12RB genes were analyzed in a case-control study. The results were confirmed either by sequencing or by PCR followed by restriction fragment length polymorphism. Results We were able to simultaneously recognize the variations of four genes with similar accuracy than other methods. In order to obtain non-overlapping melting temperatures, the key step in this strategy was primer design. Genotypic frequencies found for each SNP are in concordance with those previously described in similar populations. None of the studied SNPs were associated with PTB. Conclusions Several gene variations related to the same inflammatory pathway were screened through a new flexible, fast and non expensive method with the purpose of analyzing

  15. Chromatid Painting for Chromosomal Inversion Detection Project

    Data.gov (United States)

    National Aeronautics and Space Administration — We propose the continued development of a novel approach to the detection of chromosomal inversions. Transmissible chromosome aberrations (translocations and...

  16. CHROMOSOMAL MAPPING IN STRAINS OF STAPHYLOCOCCUS AUREUS,

    Science.gov (United States)

    STAPHYLOCOCCUS AUREUS , CHROMOSOMES), (*CHROMOSOMES, MAPPING), NITROSO COMPOUNDS, GUANIDINES, GENETICS, MUTATIONS, DRUGS, TOLERANCES(PHYSIOLOGY), TEST METHODS, DEOXYRIBONUCLEIC ACIDS, INHIBITION, RESISTANCE(BIOLOGY).

  17. Chromatid Painting for Chromosomal Inversion Detection Project

    Data.gov (United States)

    National Aeronautics and Space Administration — We propose a novel approach to the detection of chromosomal inversions. Transmissible chromosome aberrations (translocations and inversions) have profound genetic...

  18. Mitotic chromosome condensation in vertebrates

    Energy Technology Data Exchange (ETDEWEB)

    Vagnarelli, Paola, E-mail: P.Vagnarelli@ed.ac.uk

    2012-07-15

    Work from several laboratories over the past 10-15 years has revealed that, within the interphase nucleus, chromosomes are organized into spatially distinct territories [T. Cremer, C. Cremer, Chromosome territories, nuclear architecture and gene regulation in mammalian cells, Nat. Rev. Genet. 2 (2001) 292-301 and T. Cremer, M. Cremer, S. Dietzel, S. Muller, I. Solovei, S. Fakan, Chromosome territories-a functional nuclear landscape, Curr. Opin. Cell Biol. 18 (2006) 307-316]. The overall compaction level and intranuclear location varies as a function of gene density for both entire chromosomes [J.A. Croft, J.M. Bridger, S. Boyle, P. Perry, P. Teague,W.A. Bickmore, Differences in the localization and morphology of chromosomes in the human nucleus, J. Cell Biol. 145 (1999) 1119-1131] and specific chromosomal regions [N.L. Mahy, P.E. Perry, S. Gilchrist, R.A. Baldock, W.A. Bickmore, Spatial organization of active and inactive genes and noncoding DNA within chromosome territories, J. Cell Biol. 157 (2002) 579-589] (Fig. 1A, A'). In prophase, when cyclin B activity reaches a high threshold, chromosome condensation occurs followed by Nuclear Envelope Breakdown (NEB) [1]. At this point vertebrate chromosomes appear as compact structures harboring an attachment point for the spindle microtubules physically recognizable as a primary constriction where the two sister chromatids are held together. The transition from an unshaped interphase chromosome to the highly structured mitotic chromosome (compare Figs. 1A and B) has fascinated researchers for several decades now; however a definite picture of how this process is achieved and regulated is not yet in our hands and it will require more investigation to comprehend the complete process. From a biochemical point of view a vertebrate mitotic chromosomes is composed of DNA, histone proteins (60%) and non-histone proteins (40%) [6]. I will discuss below what is known to date on the contribution of these two different classes

  19. Genetic population study of Y-chromosome markers in Benin and Ivory Coast ethnic groups.

    Science.gov (United States)

    Fortes-Lima, Cesar; Brucato, Nicolas; Croze, Myriam; Bellis, Gil; Schiavinato, Stephanie; Massougbodji, Achille; Migot-Nabias, Florence; Dugoujon, Jean-Michel

    2015-11-01

    Ninety-six single nucleotide polymorphisms (SNPs) and seventeen short tandem repeat (STRs) were investigated on the Y-chromosome of 288 unrelated healthy individuals from populations in Benin (Bariba, Yoruba, and Fon) and the Ivory Coast (Ahizi and Yacouba). We performed a multidimensional scaling analysis based on FST and RST genetic distances using a large extensive database of sub-Saharan African populations. There is more genetic homogeneity in Ivory Coast populations compared with populations from Benin. Notably, the Beninese Yoruba are significantly differentiated from neighbouring groups, but also from the Yoruba from Nigeria (FST>0.05; P<0.01). The Y-chromosome dataset presented here provides new valuable data to understand the complex genetic diversity and human male demographic events in West Africa.

  20. Identification of susceptibility genes for bipolar affective disorder and schizophrenia on chromosome 22q13

    DEFF Research Database (Denmark)

    Severinsen, Jacob Eg

    2006-01-01

    Linkage analyses suggest that chromosome 22q12-13 may harbor one or more shared susceptibility loci for bipolar affective disorder (BPD) and schizophrenia (SZ). In a study of distantly related cases and control individuals from the Faeroe Islands our group has previously reported that chromosome 22......q13 may harbor two shared susceptibility loci for BPD and SZ. The aim of the Ph.D. project was to identify and characterize susceptibility genes for BPD and SZ located in these two loci on 22q13, primarily by association analyses of selected positional candidate genes in a number of population...... samples (total of 1,751 individuals), and by bioinformatic and expression analyses of a subset of disease associated genes and gene variants. In total 67 single nucleotide polymorphisms (SNPs) located in 18 positional candidate genes, and 4 microsattelite markers were investigated, using a Scottish case...

  1. Y-chromosome haplotype distribution in Han Chinese populations and modern human origin in East Asians

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    We investigated the distribution of Y-chromosome haplotype using 19 Y-SNPs in Han Chinese populations from 22 provinces of China. Our data indicate distinctive patterns of Y chromosome between southern and northern Han Chinese populations. The southern populations are much more polymorphic than northern populations. The latter has only a subset of the southern haplotypes. This result confirms the genetic difference observed between southern and northern ethnic populations in East Asia. It supports the hypothesis that the first settlement of modern hu-mans of African origin occurred in the southern part of East Asia during the last Ice Age, and a northward migration led to the peopling of northern China.

  2. Identification of a linkage disequilibrium block in chromosome 1q associated with BMD in premenopausal white women.

    Science.gov (United States)

    Ichikawa, Shoji; Koller, Daniel L; Curry, Leah R; Lai, Dongbing; Xuei, Xiaoling; Pugh, Elizabeth W; Tsai, Ya-Yu; Doheny, Kimberly F; Edenberg, Howard J; Hui, Siu L; Foroud, Tatiana; Peacock, Munro; Econs, Michael J

    2008-10-01

    Osteoporosis is a complex disease with both genetic and environmental risk factors. A major determinant of osteoporotic fractures is peak BMD obtained during young adulthood. We previously reported linkage of chromosome 1q (LOD = 4.3) with variation in spinal areal BMD in healthy premenopausal white women. In this study, we used a two-stage genotyping approach to identify genes in the linked region that contributed to the variation of femoral neck and lumbar spine areal BMD. In the first stage, 654 SNPs across the linked region were genotyped in a sample of 1309 premenopausal white women. The most significant evidence of association for lumbar spine (p = 1.3 x 10(-6)) was found with rs1127091 in the GATAD2B gene. In the second stage, 52 SNPs around this candidate gene were genotyped in an expanded sample of 1692 white women. Significant evidence of association with spinal BMD (p 2.5% of the variation in spinal BMD in these women. The 230-kb LD block contains 11 genes, but because of the extensive LD, the specific gene(s) contributing to the variation in BMD could not be determined. In conclusion, the significant association between spinal BMD and SNPs in the 230-kb LD block in chromosome 1q indicates that genetic factor(s) in this block plays an important role in peak spinal BMD in healthy premenopausal white women.

  3. Variation in conserved non-coding sequences on chromosome 5q and susceptibility to asthma and atopy

    Directory of Open Access Journals (Sweden)

    Dubchak Inna

    2005-12-01

    Full Text Available Abstract Background Evolutionarily conserved sequences likely have biological function. Methods To determine whether variation in conserved sequences in non-coding DNA contributes to risk for human disease, we studied six conserved non-coding elements in the Th2 cytokine cluster on human chromosome 5q31 in a large Hutterite pedigree and in samples of outbred European American and African American asthma cases and controls. Results Among six conserved non-coding elements (>100 bp, >70% identity; human-mouse comparison, we identified one single nucleotide polymorphism (SNP in each of two conserved elements and six SNPs in the flanking regions of three conserved elements. We genotyped our samples for four of these SNPs and an additional three SNPs each in the IL13 and IL4 genes. While there was only modest evidence for association with single SNPs in the Hutterite and European American samples (P IL4 gene (P IL13 gene was strongly associated with total IgE (P = 0.00022 and allergic sensitization to mold allergens (P = 0.00076 in the Hutterites, and more modestly associated with sensitization to molds in the European Americans and African Americans (P Conclusion These results indicate that there is overall little variation in the conserved non-coding elements on 5q31, but variation in IL4 and IL13, including possibly one SNP in a conserved element, influence asthma and atopic phenotypes in diverse populations.

  4. Gametocidal chromosomes enhancing chromosome aberration in common wheat induced by 5-azacytidine.

    Science.gov (United States)

    Su, W-Y; Cong, W-W; Shu, Y-J; Wang, D; Xu, G-H; Guo, C-H

    2013-07-08

    The gametocidal (Gc) chromosome from Aegilops spp induces chromosome mutation, which is introduced into common wheat as a tool of chromosome manipulation for genetic improvement. The Gc chromosome functions similar to a restriction-modification system in bacteria, in which DNA methylation is an important regulator. We treated root tips of wheat carrying Gc chromosomes with the hypomethylation agent 5-azacytidine; chromosome breakage and micronuclei were observed in these root tips. The frequency of aberrations differed in wheat containing different Gc chromosomes, suggesting different functions inducing chromosome breakage. Gc chromosome 3C caused the greatest degree of chromosome aberration, while Gc chromosome 3C(SAT) and 2C caused only slight chromosome aberration. Gc chromosome 3C induced different degrees of chromosome aberration in wheat varieties Triticum aestivum var. Chinese Spring and Norin 26, demonstrating an inhibition function in common wheat.

  5. Evaluation of random forest regression for prediction of breeding value from genomewide SNPs

    Indian Academy of Sciences (India)

    Rupam Kumar Sarkar; A. R. Rao; Prabina Kumar Meher; T. Nepolean; T. Mohapatra

    2015-06-01

    Genomic prediction is meant for estimating the breeding value using molecular marker data which has turned out to be a powerful tool for efficient utilization of germplasm resources and rapid improvement of cultivars. Model-based techniques have been widely used for prediction of breeding values of genotypes from genomewide association studies. However, application of the random forest (RF), a model-free ensemble learning method, is not widely used for prediction. In this study, the optimum values of tuning parameters of RF have been identified and applied to predict the breeding value of genotypes based on genomewide single-nucleotide polymorphisms (SNPs), where the number of SNPs ($P$ variables) is much higher than the number of genotypes ($n$ observations) ($P >> n$). Further, a comparison was made with the model-based genomic prediction methods, namely, least absolute shrinkage and selection operator (LASSO), ridge regression (RR) and elastic net (EN) under $P >> n$. It was found that the correlations between the predicted and observed trait response were 0.591, 0.539, 0.431 and 0.587 for RF, LASSO, RR and EN, respectively, which implies superiority of the RF over the model-based techniques in genomic prediction. Hence, we suggest that the RF methodology can be used as an alternative to the model-based techniques for the prediction of breeding value at genome level with higher accuracy.

  6. LD2SNPing: linkage disequilibrium plotter and RFLP enzyme mining for tag SNPs

    Directory of Open Access Journals (Sweden)

    Cheng Yu-Huei

    2009-06-01

    Full Text Available Abstract Background Linkage disequilibrium (LD mapping is commonly used to evaluate markers for genome-wide association studies. Most types of LD software focus strictly on LD analysis and visualization, but lack supporting services for genotyping. Results We developed a freeware called LD2SNPing, which provides a complete package of mining tools for genotyping and LD analysis environments. The software provides SNP ID- and gene-centric online retrievals for SNP information and tag SNP selection from dbSNP/NCBI and HapMap, respectively. Restriction fragment length polymorphism (RFLP enzyme information for SNP genotype is available to all SNP IDs and tag SNPs. Single and multiple SNP inputs are possible in order to perform LD analysis by online retrieval from HapMap and NCBI. An LD statistics section provides D, D', r2, δQ, ρ, and the P values of the Hardy-Weinberg Equilibrium for each SNP marker, and Chi-square and likelihood-ratio tests for the pair-wise association of two SNPs in LD calculation. Finally, 2D and 3D plots, as well as plain-text output of the results, can be selected. Conclusion LD2SNPing thus provides a novel visualization environment for multiple SNP input, which facilitates SNP association studies. The software, user manual, and tutorial are freely available at http://bio.kuas.edu.tw/LD2NPing.

  7. The evolutionary history of Afrocanarian blue tits inferred from genomewide SNPs.

    Science.gov (United States)

    Gohli, Jostein; Leder, Erica H; Garcia-Del-Rey, Eduardo; Johannessen, Lars Erik; Johnsen, Arild; Laskemoen, Terje; Popp, Magnus; Lifjeld, Jan T

    2015-01-01

    A common challenge in phylogenetic reconstruction is to find enough suitable genomic markers to reliably trace splitting events with short internodes. Here, we present phylogenetic analyses based on genomewide single-nucleotide polymorphisms (SNPs) of an enigmatic avian radiation, the subspecies complex of Afrocanarian blue tits (Cyanistes teneriffae). The two sister species, the Eurasian blue tit (Cyanistes caeruleus) and the azure tit (Cyanistes cyanus), constituted the out-group. We generated a large data set of SNPs for analysis of population structure and phylogeny. We also adapted our protocol to utilize degraded DNA from old museum skins from Libya. We found strong population structuring that largely confirmed subspecies monophyly and constructed a coalescent-based phylogeny with full support at all major nodes. The results are consistent with a recent hypothesis that La Palma and Libya are relic populations of an ancient Afrocanarian blue tit, although a small data set for Libya could not resolve its position relative to La Palma. The birds on the eastern islands of Fuerteventura and Lanzarote are similar to those in Morocco. Together they constitute the sister group to the clade containing the other Canary Islands (except La Palma), in which El Hierro is sister to the three central islands. Hence, extant Canary Islands populations seem to originate from multiple independent colonization events. We also found population divergences in a key reproductive trait, viz. sperm length, which may constitute reproductive barriers between certain populations. We recommend a taxonomic revision of this polytypic species, where several subspecies should qualify for species rank.

  8. VEGF-A and VEGFR1 SNPs associate with preeclampsia in a Philippine population.

    Science.gov (United States)

    Amosco, Melissa D; Villar, Van Anthony M; Naniong, Justin Michael A; David-Bustamante, Lara Marie G; Jose, Pedro A; Palmes-Saloma, Cynthia P

    The vascular endothelial growth factor (VEGF) family is important for establishing normal pregnancy, and related single nucleotide polymorphisms (SNPs) are implicated in abnormal placentation and preeclampsia. We evaluated the association between preeclampsia and several VEGF SNPs among Filipinos, an ethnically distinct group with high prevalence of preeclampsia. The genotypes and allelic variants were determined in a case-control study (191 controls and 165 preeclampsia patients) through SNP analysis of VEGF-A (rs2010963, rs3025039) and VEGF-C (rs7664413) and their corresponding receptors VEGFR1 (rs722503, rs12584067, rs7335588) and VEGFR3 (rs307826) from venous blood DNA. VEGF-A rs3025039 C allele has been shown to associate with preeclampsia (odds ratio of 1.648 (1.03-2.62)), while the T allele bestowed an additive effect for the maintenance of normal, uncomplicated pregnancy and against the development of preeclampsia (odds ratio of 0.62 (0.39-0.98)). VEGFR1 rs722503 is associated with preeclampsia occurring at or after the age of 40 years. The results showed that genetic variability of VEGF-A and VEGFR1 are important in the etiology of preeclampsia among Filipinos.

  9. Analysis of Case-Control Association Studies: SNPs, Imputation and Haplotypes

    KAUST Repository

    Chatterjee, Nilanjan

    2009-11-01

    Although prospective logistic regression is the standard method of analysis for case-control data, it has been recently noted that in genetic epidemiologic studies one can use the "retrospective" likelihood to gain major power by incorporating various population genetics model assumptions such as Hardy-Weinberg-Equilibrium (HWE), gene-gene and gene-environment independence. In this article we review these modern methods and contrast them with the more classical approaches through two types of applications (i) association tests for typed and untyped single nucleotide polymorphisms (SNPs) and (ii) estimation of haplotype effects and haplotype-environment interactions in the presence of haplotype-phase ambiguity. We provide novel insights to existing methods by construction of various score-tests and pseudo-likelihoods. In addition, we describe a novel two-stage method for analysis of untyped SNPs that can use any flexible external algorithm for genotype imputation followed by a powerful association test based on the retrospective likelihood. We illustrate applications of the methods using simulated and real data. © Institute of Mathematical Statistics, 2009.

  10. Optimization of heteroduplex analysis for the detection of BRCA mutations and SNPs

    Directory of Open Access Journals (Sweden)

    Lucian Negura

    2011-02-01

    Full Text Available BRCA1 and BRCA2 are tumour suppressor genes whose mutant phenotypes predispose to breast and ovarian cancer. Screening for mutations in these genes is now standard practice for hereditary breast and ovarian cancer (HBOC cases in Europe, and permits medical follow-up and genetic counselling adapted to the needs of individuals in such families. Currently, most laboratories performing diagnostic analysis of the BRCA genes use PCR of exons and intron-exon boundaries coupled to a pre-screening step to identify anomalous amplicons. The techniques employed for the detection of mutations and SNPs have evolved over time and vary in sensitivity, specificity and cost-effectiveness. As a variant for pre-screening techniques, we chose the recently developed Surveyor® heteroduplex cleavage method as a sensitive and specific technique to reveal anomalous amplicons of the BRCA genes, using only basic laboratory equipment and agarose gel electrophoresis. Here we present the detection of either mutations or SNPs within the BRCA1 exon 7, using heteroduplex analysis (HA by mismatch-specific endonuclease, confirmed by dideoxy sequencing.

  11. Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs.

    Science.gov (United States)

    Lee, S Hong; Ripke, Stephan; Neale, Benjamin M; Faraone, Stephen V; Purcell, Shaun M; Perlis, Roy H; Mowry, Bryan J; Thapar, Anita; Goddard, Michael E; Witte, John S; Absher, Devin; Agartz, Ingrid; Akil, Huda; Amin, Farooq; Andreassen, Ole A; Anjorin, Adebayo; Anney, Richard; Anttila, Verneri; Arking, Dan E; Asherson, Philip; Azevedo, Maria H; Backlund, Lena; Badner, Judith A; Bailey, Anthony J; Banaschewski, Tobias; Barchas, Jack D; Barnes, Michael R; Barrett, Thomas B; Bass, Nicholas; Battaglia, Agatino; Bauer, Michael; Bayés, Mònica; Bellivier, Frank; Bergen, Sarah E; Berrettini, Wade; Betancur, Catalina; Bettecken, Thomas; Biederman, Joseph; Binder, Elisabeth B; Black, Donald W; Blackwood, Douglas H R; Bloss, Cinnamon S; Boehnke, Michael; Boomsma, Dorret I; Breen, Gerome; Breuer, René; Bruggeman, Richard; Cormican, Paul; Buccola, Nancy G; Buitelaar, Jan K; Bunney, William E; Buxbaum, Joseph D; Byerley, William F; Byrne, Enda M; Caesar, Sian; Cahn, Wiepke; Cantor, Rita M; Casas, Miguel; Chakravarti, Aravinda; Chambert, Kimberly; Choudhury, Khalid; Cichon, Sven; Cloninger, C Robert; Collier, David A; Cook, Edwin H; Coon, Hilary; Cormand, Bru; Corvin, Aiden; Coryell, William H; Craig, David W; Craig, Ian W; Crosbie, Jennifer; Cuccaro, Michael L; Curtis, David; Czamara, Darina; Datta, Susmita; Dawson, Geraldine; Day, Richard; De Geus, Eco J; Degenhardt, Franziska; Djurovic, Srdjan; Donohoe, Gary J; Doyle, Alysa E; Duan, Jubao; Dudbridge, Frank; Duketis, Eftichia; Ebstein, Richard P; Edenberg, Howard J; Elia, Josephine; Ennis, Sean; Etain, Bruno; Fanous, Ayman; Farmer, Anne E; Ferrier, I Nicol; Flickinger, Matthew; Fombonne, Eric; Foroud, Tatiana; Frank, Josef; Franke, Barbara; Fraser, Christine; Freedman, Robert; Freimer, Nelson B; Freitag, Christine M; Friedl, Marion; Frisén, Louise; Gallagher, Louise; Gejman, Pablo V; Georgieva, Lyudmila; Gershon, Elliot S; Geschwind, Daniel H; Giegling, Ina; Gill, Michael; Gordon, Scott D; Gordon-Smith, Katherine; Green, Elaine K; Greenwood, Tiffany A; Grice, Dorothy E; Gross, Magdalena; Grozeva, Detelina; Guan, Weihua; Gurling, Hugh; De Haan, Lieuwe; Haines, Jonathan L; Hakonarson, Hakon; Hallmayer, Joachim; Hamilton, Steven P; Hamshere, Marian L; Hansen, Thomas F; Hartmann, Annette M; Hautzinger, Martin; Heath, Andrew C; Henders, Anjali K; Herms, Stefan; Hickie, Ian B; Hipolito, Maria; Hoefels, Susanne; Holmans, Peter A; Holsboer, Florian; Hoogendijk, Witte J; Hottenga, Jouke-Jan; Hultman, Christina M; Hus, Vanessa; Ingason, Andrés; Ising, Marcus; Jamain, Stéphane; Jones, Edward G; Jones, Ian; Jones, Lisa; Tzeng, Jung-Ying; Kähler, Anna K; Kahn, René S; Kandaswamy, Radhika; Keller, Matthew C; Kennedy, James L; Kenny, Elaine; Kent, Lindsey; Kim, Yunjung; Kirov, George K; Klauck, Sabine M; Klei, Lambertus; Knowles, James A; Kohli, Martin A; Koller, Daniel L; Konte, Bettina; Korszun, Ania; Krabbendam, Lydia; Krasucki, Robert; Kuntsi, Jonna; Kwan, Phoenix; Landén, Mikael; Långström, Niklas; Lathrop, Mark; Lawrence, Jacob; Lawson, William B; Leboyer, Marion; Ledbetter, David H; Lee, Phil H; Lencz, Todd; Lesch, Klaus-Peter; Levinson, Douglas F; Lewis, Cathryn M; Li, Jun; Lichtenstein, Paul; Lieberman, Jeffrey A; Lin, Dan-Yu; Linszen, Don H; Liu, Chunyu; Lohoff, Falk W; Loo, Sandra K; Lord, Catherine; Lowe, Jennifer K; Lucae, Susanne; MacIntyre, Donald J; Madden, Pamela A F; Maestrini, Elena; Magnusson, Patrik K E; Mahon, Pamela B; Maier, Wolfgang; Malhotra, Anil K; Mane, Shrikant M; Martin, Christa L; Martin, Nicholas G; Mattheisen, Manuel; Matthews, Keith; Mattingsdal, Morten; McCarroll, Steven A; McGhee, Kevin A; McGough, James J; McGrath, Patrick J; McGuffin, Peter; McInnis, Melvin G; McIntosh, Andrew; McKinney, Rebecca; McLean, Alan W; McMahon, Francis J; McMahon, William M; McQuillin, Andrew; Medeiros, Helena; Medland, Sarah E; Meier, Sandra; Melle, Ingrid; Meng, Fan; Meyer, Jobst; Middeldorp, Christel M; Middleton, Lefkos; Milanova, Vihra; Miranda, Ana; Monaco, Anthony P; Montgomery, Grant W; Moran, Jennifer L; Moreno-De-Luca, Daniel; Morken, Gunnar; Morris, Derek W; Morrow, Eric M; Moskvina, Valentina; Muglia, Pierandrea; Mühleisen, Thomas W; Muir, Walter J; Müller-Myhsok, Bertram; Murtha, Michael; Myers, Richard M; Myin-Germeys, Inez; Neale, Michael C; Nelson, Stan F; Nievergelt, Caroline M; Nikolov, Ivan; Nimgaonkar, Vishwajit; Nolen, Willem A; Nöthen, Markus M; Nurnberger, John I; Nwulia, Evaristus A; Nyholt, Dale R; O'Dushlaine, Colm; Oades, Robert D; Olincy, Ann; Oliveira, Guiomar; Olsen, Line; Ophoff, Roel A; Osby, Urban; Owen, Michael J; Palotie, Aarno; Parr, Jeremy R; Paterson, Andrew D; Pato, Carlos N; Pato, Michele T; Penninx, Brenda W; Pergadia, Michele L; Pericak-Vance, Margaret A; Pickard, Benjamin S; Pimm, Jonathan; Piven, Joseph; Posthuma, Danielle; Potash, James B; Poustka, Fritz; Propping, Peter; Puri, Vinay; Quested, Digby J; Quinn, Emma M; Ramos-Quiroga, Josep Antoni; Rasmussen, Henrik B; Raychaudhuri, Soumya; Rehnström, Karola; Reif, Andreas; Ribasés, Marta; Rice, John P; Rietschel, Marcella; Roeder, Kathryn; Roeyers, Herbert; Rossin, Lizzy; Rothenberger, Aribert; Rouleau, Guy; Ruderfer, Douglas; Rujescu, Dan; Sanders, Alan R; Sanders, Stephan J; Santangelo, Susan L; Sergeant, Joseph A; Schachar, Russell; Schalling, Martin; Schatzberg, Alan F; Scheftner, William A; Schellenberg, Gerard D; Scherer, Stephen W; Schork, Nicholas J; Schulze, Thomas G; Schumacher, Johannes; Schwarz, Markus; Scolnick, Edward; Scott, Laura J; Shi, Jianxin; Shilling, Paul D; Shyn, Stanley I; Silverman, Jeremy M; Slager, Susan L; Smalley, Susan L; Smit, Johannes H; Smith, Erin N; Sonuga-Barke, Edmund J S; St Clair, David; State, Matthew; Steffens, Michael; Steinhausen, Hans-Christoph; Strauss, John S; Strohmaier, Jana; Stroup, T Scott; Sutcliffe, James S; Szatmari, Peter; Szelinger, Szabocls; Thirumalai, Srinivasa; Thompson, Robert C; Todorov, Alexandre A; Tozzi, Federica; Treutlein, Jens; Uhr, Manfred; van den Oord, Edwin J C G; Van Grootheest, Gerard; Van Os, Jim; Vicente, Astrid M; Vieland, Veronica J; Vincent, John B; Visscher, Peter M; Walsh, Christopher A; Wassink, Thomas H; Watson, Stanley J; Weissman, Myrna M; Werge, Thomas; Wienker, Thomas F; Wijsman, Ellen M; Willemsen, Gonneke; Williams, Nigel; Willsey, A Jeremy; Witt, Stephanie H; Xu, Wei; Young, Allan H; Yu, Timothy W; Zammit, Stanley; Zandi, Peter P; Zhang, Peng; Zitman, Frans G; Zöllner, Sebastian; Devlin, Bernie; Kelsoe, John R; Sklar, Pamela; Daly, Mark J; O'Donovan, Michael C; Craddock, Nicholas; Sullivan, Patrick F; Smoller, Jordan W; Kendler, Kenneth S; Wray, Naomi R

    2013-09-01

    Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17-29% of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 ± 0.04 s.e.), moderate between schizophrenia and major depressive disorder (0.43 ± 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 ± 0.06 s.e.), and ADHD and major depressive disorder (0.32 ± 0.07 s.e.), low between schizophrenia and ASD (0.16 ± 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohn's disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.

  12. Chromosome segregation in Vibrio cholerae.

    Science.gov (United States)

    Ramachandran, Revathy; Jha, Jyoti; Chattoraj, Dhruba K

    2014-01-01

    The study of chromosome segregation is currently one of the most exciting research frontiers in cell biology. In this review, we discuss our current knowledge of the chromosome segregation process in Vibrio cholerae, based primarily on findings from fluorescence microscopy experiments. This bacterium is of special interest because of its eukaryotic feature of having a divided genome, a feature shared with 10% of known bacteria. We also discuss how the segregation mechanisms of V. cholerae compare with those in other bacteria, and highlight some of the remaining questions regarding the process of bacterial chromosome segregation.

  13. Numerous transitions of sex chromosomes in Diptera.

    Science.gov (United States)

    Vicoso, Beatriz; Bachtrog, Doris

    2015-04-01

    Many species groups, including mammals and many insects, determine sex using heteromorphic sex chromosomes. Diptera flies, which include the model Drosophila melanogaster, generally have XY sex chromosomes and a conserved karyotype consisting of six chromosomal arms (five large rods and a small dot), but superficially similar karyotypes may conceal the true extent of sex chromosome variation. Here, we use whole-genome analysis in 37 fly species belonging to 22 different families of Diptera and uncover tremendous hidden diversity in sex chromosome karyotypes among flies. We identify over a dozen different sex chromosome configurations, and the small dot chromosome is repeatedly used as the sex chromosome, which presumably reflects the ancestral karyotype of higher Diptera. However, we identify species with undifferentiated sex chromosomes, others in which a different chromosome replaced the dot as a sex chromosome or in which up to three chromosomal elements became incorporated into the sex chromosomes, and others yet with female heterogamety (ZW sex chromosomes). Transcriptome analysis shows that dosage compensation has evolved multiple times in flies, consistently through up-regulation of the single X in males. However, X chromosomes generally show a deficiency of genes with male-biased expression, possibly reflecting sex-specific selective pressures. These species thus provide a rich resource to study sex chromosome biology in a comparative manner and show that similar selective forces have shaped the unique evolution of sex chromosomes in diverse fly taxa.

  14. Association between SNPs in defined functional pathways and risk of early or late toxicity as well as individual radiosensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Reuther, Sebastian; Raabe, Annette; Borgmann, Kerstin; Dikomey, Ekkehard [University Medical Center Hamburg-Eppendorf, Laboratory of Radiobiology and Experimental Radiooncology, Department of Radiotherapy and Radiooncology, Hamburg (Germany); Szymczak, Silke [University at Luebeck, Institute of Medical Biometry and Statistics, University Medical Center Schleswig-Holstein (Germany); Christian-Albrechts-University Kiel, Institute of Clinical Molecular Biology, Kiel (Germany); Ziegler, Andreas [University at Luebeck, Institute of Medical Biometry and Statistics, University Medical Center Schleswig-Holstein (Germany); University of Luebeck, Center for Clinical Trials, Luebeck (Germany); Petersen, Cordula [University Medical Center Hamburg-Eppendorf, Clinic of Radiotherapy and Radiooncology, Hamburg (Germany); Hoeller, Ulrike [Charite Universitaetsmedizin Berlin, Department of Radiotherapy, Berlin (Germany)

    2014-08-26

    The aim of this study was to determine the impact of functional single nucleotide polymorphism (SNP) pathways involved in the ROS pathway, DNA repair, or TGFB1 signaling on acute or late normal toxicity as well as individual radiosensitivity. Patients receiving breast-conserving surgery and radiotherapy were examined either for erythema (n = 83), fibrosis (n = 123), or individual radiosensitivity (n = 123). The 17 SNPs analyzed are involved in the ROS pathway (GSTP1, SOD2, NQO1, NOS3, XDH), DNA repair (XRCC1, XRCC3, XRCC6, ERCC2, LIG4, ATM) or TGFB signaling (SKIL, EP300, APC, AXIN1, TGFB1). Associations with biological and clinical endpoints were studied for single SNPs but especially for combinations of SNPs assuming that a SNP is either beneficial or deleterious and needs to be weighted. With one exception, no significant association was seen between a single SNP and the three endpoints studied. No significant associations were also observed when applying a multi-SNP model assuming that each SNP was deleterious. In contrast, significant associations were obtained when SNPs were suggested to be either beneficial or deleterious. These associations increased, when each SNP was weighted individually. Detailed analysis revealed that both erythema and individual radiosensitivity especially depend on SNPs affecting DNA repair and TGFB1 signaling, while SNPs in ROS pathway were of minor importance. Functional pathways of SNPs may be used to form a risk score allowing to predict acute and late radiation-induced toxicity but also to unravel the underlying biological mechanisms. (orig.) [German] Fuer ein SNP-Netzwerk (''single nucleotide polymorphism'', Einzelnukleotidpolymorphismus), welches im ROS-Signalweg, an der DNA-Reparatur und im TGFB1-Signalweg involviert ist, sollen die Bedeutung fuer die akute und spaete Toxizitaet sowie die individuelle Strahlenempfindlichkeit bestimmt werden. Nach Strahlentherapie wurden Brustkrebspatientinnen entweder

  15. An integrated approach of comparative genomics and heritability analysis of pig and human on obesity trait: evidence for candidate genes on human chromosome 2

    Science.gov (United States)

    2012-01-01

    Background Traditional candidate gene approach has been widely used for the study of complex diseases including obesity. However, this approach is largely limited by its dependence on existing knowledge of presumed biology of the phenotype under investigation. Our combined strategy of comparative genomics and chromosomal heritability estimate analysis of obesity traits, subscapular skinfold thickness and back-fat thickness in Korean cohorts and pig (Sus scrofa), may overcome the limitations of candidate gene analysis and allow us to better understand genetic predisposition to human obesity. Results We found common genes including FTO, the fat mass and obesity associated gene, identified from significant SNPs by association studies of each trait. These common genes were related to blood pressure and arterial stiffness (P = 1.65E-05) and type 2 diabetes (P = 0.00578). Through the estimation of variance of genetic component (heritability) for each chromosome by SNPs, we observed a significant positive correlation (r = 0.479) between genetic contributions of human and pig to obesity traits. Furthermore, we noted that human chromosome 2 (syntenic to pig chromosomes 3 and 15) was most important in explaining the phenotypic variance for obesity. Conclusions Obesity genetics still awaits further discovery. Navigating syntenic regions suggests obesity candidate genes on chromosome 2 that are previously known to be associated with obesity-related diseases: MRPL33, PARD3B, ERBB4, STK39, and ZNF385B. PMID:23253381

  16. An integrated approach of comparative genomics and heritability analysis of pig and human on obesity trait: evidence for candidate genes on human chromosome 2

    Directory of Open Access Journals (Sweden)

    Kim Jaemin

    2012-12-01

    Full Text Available Abstract Background Traditional candidate gene approach has been widely used for the study of complex diseases including obesity. However, this approach is largely limited by its dependence on existing knowledge of presumed biology of the phenotype under investigation. Our combined strategy of comparative genomics and chromosomal heritability estimate analysis of obesity traits, subscapular skinfold thickness and back-fat thickness in Korean cohorts and pig (Sus scrofa, may overcome the limitations of candidate gene analysis and allow us to better understand genetic predisposition to human obesity. Results We found common genes including FTO, the fat mass and obesity associated gene, identified from significant SNPs by association studies of each trait. These common genes were related to blood pressure and arterial stiffness (P = 1.65E-05 and type 2 diabetes (P = 0.00578. Through the estimation of variance of genetic component (heritability for each chromosome by SNPs, we observed a significant positive correlation (r = 0.479 between genetic contributions of human and pig to obesity traits. Furthermore, we noted that human chromosome 2 (syntenic to pig chromosomes 3 and 15 was most important in explaining the phenotypic variance for obesity. Conclusions Obesity genetics still awaits further discovery. Navigating syntenic regions suggests obesity candidate genes on chromosome 2 that are previously known to be associated with obesity-related diseases: MRPL33, PARD3B, ERBB4, STK39, and ZNF385B.

  17. Microsatellite and single nucleotide polymorphisms in the β-globin locus control region-hypersensitive Site 2: SPECIFICITY of Tunisian βs chromosomes.

    Science.gov (United States)

    Ben Mustapha, Maha; Moumni, Imen; Zorai, Amine; Douzi, Kaïs; Ghanem, Abderraouf; Abbes, Salem

    2012-01-01

    The diversity of sickle cell disease severity is attributed to several cis acting factors, among them the single nucleotide polymorphisms (SNPs) and (AT) rich region in the β-locus control region (β-LCR). This contains five DNase I hypersensitive sites (HS) located 6 to 22 kb upstream to the ϵ gene. The most important of these is the HS2 (5' β-LCR-HS2), characterized by the presence of three different SNPs and a microsatellite region known to be in association with β(S) chromosomes in various populations. The aim of this study was to present the molecular investigation of the 5' β-LCR-HS2 site in normal and sickle cell disease individuals in order to determine if there is any correlation or specificity between these molecular markers, the β(S) Tunisian chromosomes and phenotypical expression of sickle cell disease. One hundred and twenty-four chromosomes from Tunisian individuals (49 β(S) carriers and 13 normal individuals) were screened by polymerase chain reaction (PCR) and sequencing for the polymorphic short tandem microsatellite repeats (AT)(X)N(12)(AT)(Y) and the three SNPs (rs7119428, rs9736333 and rs60240093) of the 5' β-LCR-HS2. Twelve configurations of the microsatellite motif were found with an ancestral configuration elaborated by ClustalW software. Normal and mutated alleles were observed at the homozygous and heterozygous states for the three SNPs. Correlation between microsatellites and SNPs suggests that mutant SNP alleles were mainly associated, in the homozygous sickle cell disease phenotype, with the (AT)(8)N(12)GT(AT)(7) configuration, whereas, normal SNP alleles were associated with the (AT)(X)N(12)(AT)(11) configurations in normal β(A) chromosomes. The correlation of these various configurations with Hb F expression was also investigated. The principal component analysis (PCA) showed the correlation between the homozygous sickle cell disease phenotype, mutated SNP alleles and the Benin microsatellite configuration (AT)(8)N(12)GT

  18. Analysis of genotype polymorphism of tumor-related genes harbored in chromosome arm lp and 8p in hepatocellular carcinoma patients by cSNP chip

    Institute of Scientific and Technical Information of China (English)

    Juan WANG; Wenqin SONG

    2009-01-01

    The majority of single nucleotide polymorphisms (SNPs) found in the coding region (cSNPs) are single base substitutions that may or may not lead to amino acid substitutions,most of which are related to diseases.Some cSNPs may prove useful for their potential links to functional cSNPs via linkage disequilibrium mapping.We have selected 48 cSNPs located in the coding regions of 25 genes to construct the cSNP chip.These genes are harbored in the high frequency loss regions of the chromosome 1p and 8p and related with apoptosis,cell cycles,signal transduction,oncogene,tumor suppressor genes and so on.All of the cSNPs can lead to amino acid substitutions except TP73 (rs1801174).The PCR products amplified from 31 hepatocellular carcinoma (HCC) specimens were labeled with Dig-dUTP and then hybridized with the cSNP chips.The results showed that there was no hybridization signal when there was more than one site of mutation in the amplification sequence,indicating that the cSNP chip had a high sensitivity.The statistic data of the SNP (MT,homozygous and HT,heterozygous) in the HCC patients with different phenotypes (HBV +/-,differentiation stage,family history positive or negative,tumor size) indicated that the number of MT was distinctly different between patients with positive HBV and negative HBV.The MT and HT numbers of all the 48 cSNPs were significantly different between low differentiation and high differentiation HCC patients.The numbers of MT and HT were not different between positived and negative family history groups and between tumor size>3 cm and≤3 cm groups.The study results provided useful information for understanding the molecular mechanisms of HCC development.

  19. Natural functional SNPs in miR-155 alter its expression level, blood cell counts and immune responses

    Directory of Open Access Journals (Sweden)

    Congcong Li

    2016-08-01

    Full Text Available miR-155 has been confirmed to be a key factor in immune responses in humans and other mammals. Therefore, investigation of variations in miR-155 could be useful for understanding the differences in immunity between individuals. In this study, four SNPs in miR-155 were identified in mice (Mus musculus and humans (Homo sapiens. In mice, the four SNPs were closely linked and formed two miR-155 haplotypes (A and B. Ten distinct types of blood parameters were associated with miR-155 expression under normal conditions. Additionally, 4 and 14 blood parameters were significantly different between these two genotypes under normal and lipopolysaccharide (LPS stimulation conditions, respectively. Moreover, the expression levels of miR-155, the inflammatory response to LPS stimulation and the lethal ratio following Salmonella typhimurium infection were significantly increased in mice harboring the AA genotype. Further, two SNPs, one in the loop region and the other near the 3' terminal of pre-miR-155, were confirmed to be responsible for the differential expression of miR-155 in mice. Interestingly, two additional SNPs, one in the loop region and the other in the middle of miR-155*, modulated the function of miR-155 in humans. Predictions of secondary RNA structure using RNAfold showed that these SNPs affected the structure of miR-155 in both mice and humans. Our results provide novel evidence of the natural functional SNPs of miR-155 in both mice and humans, which may affect the expression levels of mature miR-155 by modulating its secondary structure. The SNPs of human miR-155 may be considered as causal mutations for some immune-related diseases in the clinic. The two genotypes of mice could be used as natural models for studying the mechanisms of immune diseases caused by abnormal expression of miR-155 in humans.

  20. Sex without sex chromosomes: genetic architecture of multiple loci independently segregating to determine sex ratios in the copepod Tigriopus californicus.

    Science.gov (United States)

    Alexander, H J; Richardson, J M L; Edmands, S; Anholt, B R

    2015-12-01

    Sex-determining systems are remarkably diverse and may evolve rapidly. Polygenic sex-determination systems are predicted to be transient and evolutionarily unstable, yet examples have been reported across a range of taxa. Here, we provide the first direct evidence of polygenic sex determination in Tigriopus californicus, a harpacticoid copepod with no heteromorphic sex chromosomes. Using genetically distinct inbred lines selected for male- and female-biased clutches, we generated a genetic map with 39 SNPs across 12 chromosomes. Quantitative trait locus mapping of sex ratio phenotype (the proportion of male offspring produced by an F2 female) in four F2 families revealed six independently segregating quantitative trait loci on five separate chromosomes, explaining 19% of the variation in sex ratios. The sex ratio phenotype varied among loci across chromosomes in both direction and magnitude, with the strongest phenotypic effects on chromosome 10 moderated to some degree by loci on four other chromosomes. For a given locus, sex ratio phenotype varied in magnitude for individuals derived from different dam lines. These data, together with the environmental factors known to contribute to sex determination, characterize the underlying complexity and potential lability of sex determination, and confirm the polygenic architecture of sex determination in T. californicus.

  1. Towards a consensus Y-chromosomal phylogeny and Y-SNP set in forensics in the next-generation sequencing era.

    Science.gov (United States)

    Larmuseau, Maarten H D; Van Geystelen, Anneleen; Kayser, Manfred; van Oven, Mannis; Decorte, Ronny

    2015-03-01

    Currently, several different Y-chromosomal phylogenies and haplogroup nomenclatures are presented in scientific literature and at conferences demonstrating the present diversity in Y-chromosomal phylogenetic trees and Y-SNP sets used within forensic and anthropological research. This situation can be ascribed to the exponential growth of the number of Y-SNPs discovered due to mostly next-generation sequencing (NGS) studies. As Y-SNPs and their respective phylogenetic positions are important in forensics, such as for male lineage characterization and paternal bio-geographic ancestry inference, there is a need for forensic geneticists to know how to deal with these newly identified Y-SNPs and phylogenies, especially since these phylogenies are often created with other aims than to carry out forensic genetic research. Therefore, we give here an overview of four categories of currently used Y-chromosomal phylogenies and the associated Y-SNP sets in scientific research in the current NGS era. We compare these categories based on the construction method, their advantages and disadvantages, the disciplines wherein the phylogenetic tree can be used, and their specific relevance for forensic geneticists. Based on this overview, it is clear that an up-to-date reduced tree with a consensus Y-SNP set and a stable nomenclature will be the most appropriate reference resource for forensic research. Initiatives to reach such an international consensus are therefore highly recommended.

  2. The contribution of the functional IL6R polymorphism rs2228145, eQTLs and other genome-wide SNPs to the heritability of plasma sIL-6R levels.

    Science.gov (United States)

    van Dongen, Jenny; Jansen, Rick; Smit, Dirk; Hottenga, Jouke-Jan; Mbarek, Hamdi; Willemsen, Gonneke; Kluft, Cornelis; Penninx, Brenda W J; Ferreira, Manuel A; Boomsma, Dorret I; de Geus, Eco J C

    2014-07-01

    The non-synonymous SNP rs2228145 in the IL6R gene on chromosome 1q21.3 is associated with a wide range of common diseases, including asthma, rheumatoid arthritis, type 1 diabetes and coronary heart disease. We examined the contribution of this functional IL6R gene polymorphism rs2228145 versus other genome-wide SNPs to the variance of sIL-6R levels in blood plasma in a large population-based sample (N ~5,000), and conducted an expression QTL analysis to identify SNPs associated with IL6R gene expression. Based on data from 2,360 twin families, the broad heritability of sIL-6R was estimated at 72 and 51% of the total variance was explained by the functional SNP rs2228145. Converging findings from GWAS, linkage, and GCTA analyses indicate that additional variance of sIL-6R levels can be explained by other variants in the IL6R region, including variants at the 3'-end of IL6R tagged by rs60760897 that are associated with IL6R RNA expression.

  3. Chromosome fragility in Freemartin cattle

    Directory of Open Access Journals (Sweden)

    V. Barbieri

    2010-04-01

    Full Text Available The aim of the present study was to verify chromosome fragility in freemartin cattle using chromosome aberration (CA and sister chromatid exchange (SCE tests. A total of eighteen co-twins were investigated. Fourteen animals were identified as cytogenetically chimeric (2n=60, XX/XY while 4 were classified as normal. Freemartin cattle showed a higher percentage of aneuploid cells (18.64% and highly significant statistical differences (P < 0.001 in mean values of gaps (4.53 ± 2.05, chromatid breaks (0.26 ± 0.51, and significant statistical differences (P < 0.005 in mean values of chromosome breaks (0.12 ± 0.43 when compared to 10 control animals from single births (aneuploid cells, 11.20%; gaps, 2.01 ± 1.42; chromatid breaks, 0.05 ± 0.22; chromosome breaks, 0.02 ± 0.14.

  4. Chromosome Segregation in Vibrio cholerae

    OpenAIRE

    Ramachandran, R.; Jha, J.; Chattoraj, DK

    2014-01-01

    The study of chromosome segregation is currently one of the most exciting research frontiers in cell biology. In this review, we discuss our current knowledge of the chromosome segregation process in Vibrio cholerae, based primarily on findings from fluorescence microscopy experiments. This bacterium is of special interest because of its eukaryotic feature of having a divided genome, a feature shared with 10% of known bacteria. We also discuss how the segregation mechanisms of V. cholerae com...

  5. B chromosomes and sex in animals.

    Science.gov (United States)

    Camacho, J P M; Schmid, M; Cabrero, J

    2011-01-01

    Supernumerary (B) chromosomes are dispensable elements found in many eukaryote genomes in addition to standard (A) chromosomes. In many respects, B chromosomes resemble sex chromosomes, so that a common ancestry for them has frequently been suggested. For instance, B chromosomes in grasshoppers, and other insects, show a pycnotic cycle of condensation-decondensation during meiosis remarkably similar to that of the X chromosome. In some cases, B chromosome size is even very similar to that of the X chromosome. These resemblances have led to suggest the X as the B ancestor in many cases. In addition, sex chromosome origin from B chromosomes has also been suggested. In this article, we review the existing evidence for both evolutionary pathways, as well as sex differences for B frequency at adult and embryo progeny levels, B chromosome effects or B chromosome transmission. In addition, we review cases found in the literature showing sex-ratio distortion associated with B chromosome presence, the most extreme case being the paternal sex ratio (PSR) chromosomes in some Hymenoptera. We finally analyse the possibility of B chromosome regularisation within the host genome and, as a consequence of it, whether B chromosomes can become regular members of the host genome.

  6. Origin and domestication of papaya Yh chromosome

    Science.gov (United States)

    Sex in papaya is controlled by a pair of nascent sex chromosomes. Females are XX, and two slightly different Y chromosomes distinguish males (XY) and hermaphrodites (XYh). The hermaphrodite-specific region of the Yh chromosome (HSY) and its X chromosome counterpart were sequenced and analyzed previo...

  7. Numerically abnormal chromosome constitutions in humans

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1993-12-31

    Chapter 24, discusses numerically abnormal chromosome constitutions in humans. This involves abnormalities of human chromosome number, including polyploidy (when the number of sets of chromosomes increases) and aneuploidy (when the number of individual normal chromosomes changes). Chapter sections discuss the following chromosomal abnormalities: human triploids, imprinting and uniparental disomy, human tetraploids, hydatidiform moles, anomalies caused by chromosomal imbalance, 13 trisomy (D{sub 1} trisomy, Patau syndrome), 21 trisomy (Down syndrome), 18 trisomy syndrome (Edwards syndrome), other autosomal aneuploidy syndromes, and spontaneous abortions. The chapter concludes with remarks on the nonrandom participation of chromosomes in trisomy. 69 refs., 3 figs., 4 tabs.

  8. Mining the 3′UTR of Autism-implicated Genes for SNPs Perturbing MicroRNA Regulation

    Directory of Open Access Journals (Sweden)

    Varadharajan Vaishnavi

    2014-04-01

    Full Text Available Autism spectrum disorder (ASD refers to a group of childhood neurodevelopmental disorders with polygenic etiology. The expression of many genes implicated in ASD is tightly regulated by various factors including microRNAs (miRNAs, a class of noncoding RNAs ∼22 nucleotides in length that function to suppress translation by pairing with ‘miRNA recognition elements’ (MREs present in the 3′untranslated region (3′UTR of target mRNAs. This emphasizes the role played by miRNAs in regulating neurogenesis, brain development and differentiation and hence any perturbations in this regulatory mechanism might affect these processes as well. Recently, single nucleotide polymorphisms (SNPs present within 3′UTRs of mRNAs have been shown to modulate existing MREs or even create new MREs. Therefore, we hypothesized that SNPs perturbing miRNA-mediated gene regulation might lead to aberrant expression of autism-implicated genes, thus resulting in disease predisposition or pathogenesis in at least a subpopulation of ASD individuals. We developed a systematic computational pipeline that integrates data from well-established databases. By following a stringent selection criterion, we identified 9 MRE-modulating SNPs and another 12 MRE-creating SNPs in the 3′UTR of autism-implicated genes. These high-confidence candidate SNPs may play roles in ASD and hence would be valuable for further functional validation.

  9. Breast cancer risk-associated SNPs modulate the affinity of chromatin for FOXA1 and alter gene expression

    Science.gov (United States)

    Cowper-Sal·lari, Richard; Zhang, Xiaoyang; Wright, Jason B.; Bailey, Swneke D.; Cole, Michael D.; Eeckhoute, Jerome; Moore, Jason H.; Lupien, Mathieu

    2012-01-01

    Genome-wide association studies (GWASs) have identified thousands of single nucleotide polymorphisms (SNPs) associated with human traits and diseases. But because the vast majority of these SNPs are located in the noncoding regions of the genome their risk promoting mechanisms are elusive. Employing a new methodology combining cistromics, epigenomics and genotype imputation we annotate the noncoding regions of the genome in breast cancer cells and systematically identify the functional nature of SNPs associated with breast cancer risk. Our results demonstrate that breast cancer risk-associated SNPs are enriched in the cistromes of FOXA1 and ESR1 and the epigenome of H3K4me1 in a cancer and cell-type-specific manner. Furthermore, the majority of these risk-associated SNPs modulate the affinity of chromatin for FOXA1 at distal regulatory elements, which results in allele-specific gene expression, exemplified by the effect of the rs4784227 SNP on the TOX3 gene found within the 16q12.1 risk locus. PMID:23001124

  10. A Mismatch EndoNuclease Array-Based Methodology (MENA for Identifying Known SNPs or Novel Point Mutations

    Directory of Open Access Journals (Sweden)

    Josep M. Comeron

    2016-04-01

    Full Text Available Accurate and rapid identification or confirmation of single nucleotide polymorphisms (SNPs, point mutations and other human genomic variation facilitates understanding the genetic basis of disease. We have developed a new methodology (called MENA (Mismatch EndoNuclease Array pairing DNA mismatch endonuclease enzymology with tiling microarray hybridization in order to genotype both known point mutations (such as SNPs as well as identify previously undiscovered point mutations and small indels. We show that our assay can rapidly genotype known SNPs in a human genomic DNA sample with 99% accuracy, in addition to identifying novel point mutations and small indels with a false discovery rate as low as 10%. Our technology provides a platform for a variety of applications, including: (1 genotyping known SNPs as well as confirming newly discovered SNPs from whole genome sequencing analyses; (2 identifying novel point mutations and indels in any genomic region from any organism for which genome sequence information is available; and (3 screening panels of genes associated with particular diseases and disorders in patient samples to identify causative mutations. As a proof of principle for using MENA to discover novel mutations, we report identification of a novel allele of the beethoven (btv gene in Drosophila, which encodes a ciliary cytoplasmic dynein motor protein important for auditory mechanosensation.

  11. A Mismatch EndoNuclease Array-Based Methodology (MENA) for Identifying Known SNPs or Novel Point Mutations

    Science.gov (United States)

    Comeron, Josep M.; Reed, Jordan; Christie, Matthew; Jacobs, Julia S.; Dierdorff, Jason; Eberl, Daniel F.; Manak, J. Robert

    2016-01-01

    Accurate and rapid identification or confirmation of single nucleotide polymorphisms (SNPs), point mutations and other human genomic variation facilitates understanding the genetic basis of disease. We have developed a new methodology (called MENA (Mismatch EndoNuclease Array)) pairing DNA mismatch endonuclease enzymology with tiling microarray hybridization in order to genotype both known point mutations (such as SNPs) as well as identify previously undiscovered point mutations and small indels. We show that our assay can rapidly genotype known SNPs in a human genomic DNA sample with 99% accuracy, in addition to identifying novel point mutations and small indels with a false discovery rate as low as 10%. Our technology provides a platform for a variety of applications, including: (1) genotyping known SNPs as well as confirming newly discovered SNPs from whole genome sequencing analyses; (2) identifying novel point mutations and indels in any genomic region from any organism for which genome sequence information is available; and (3) screening panels of genes associated with particular diseases and disorders in patient samples to identify causative mutations. As a proof of principle for using MENA to discover novel mutations, we report identification of a novel allele of the beethoven (btv) gene in Drosophila, which encodes a ciliary cytoplasmic dynein motor protein important for auditory mechanosensation. PMID:27600073

  12. Theodore E. Woodward Award: lactase persistence SNPs in African populations regulate promoter activity in intestinal cell culture.

    Science.gov (United States)

    Sibley, Eric; Ahn, Jong Kun

    2011-01-01

    Lactase-phlorizin hydrolase, lactase, is the intestinal enzyme responsible for the digestion of the milk sugar lactose. The majority of the world's human population experiences a decline in expression of the lactase gene by late childhood (lactase non-persistence). Individuals with lactase persistence, however, continue to express high levels of the lactase gene throughout adulthood. Lactase persistence is a heritable autosomal dominant condition and has been strongly correlated with several single nucleotide polymorphisms (SNPs) located ∼14 kb upstream of the lactase gene in different ethnic populations: -13910*T in Europeans and -13907*G, -13915*G, and -14010*C in several African populations. The coincidence of the four SNPs clustering within 100 bp strongly suggests that this region mediates the lactase non-persistence/persistence phenotype. Having previously characterized the European SNP, we aimed to determine whether the African SNPs similarly mediate a functional role in regulating the lactase promoter. Human intestinal Caco-2 cells were transfected with lactase SNP/promoter-reporter constructs and assayed for promoter activity. The -13907*G and -13915*G SNPs result in a significant enhancement of lactase promoter activity relative to the ancestral lactase non-persistence genotype. Such differential regulation by the SNPs is consistent with a causative role in the mechanism specifying the lactase persistence phenotype.

  13. Association of Five SNPs at the PARK16 locus as a Susceptibility Locus with Parkinson's Disease for Forensic Application

    Institute of Scientific and Technical Information of China (English)

    CUI Hong-gang; TIAN Xiao-fei; LUO Xiao-guang; LI Feng-rui; ZHU Lan-hui; ZHOU Yi-shu; REN Yan

    2013-01-01

    To investigate the association of five SNPs (rs823083,rs708723,rs4951261,rs823076 and rs16856110) at the PARK16 locus with Parkinson's disease (PD),and to potentiate its forensic application.The genomic DNAs of 215 PD patients and 212 matched controls from the northern Han Chinese population were amplified in two independent PCR systems and subsequently genotyped by digestion with the three endonucleases (Hinf Ⅰ,Nco Ⅰ and Msp Ⅰ).The genetic parameters and association studies were carried out with SPSS 13.0,Haploview version 4.2 and PLINK 1.07 sofiwares.We detected accurately all genotypes in the five SNPs with multiplex PCR-RFLP and mismatched multiplex PCR-RFLP techniques.The genotypes of four SNPs,except for rs823083,were in Hardy-Weinberg equilibrium.The four SNPs,rs16856110,rs4951261,rs708723 and rs823076,which were in linkage equilibrium,should not be associated with PD (P-values ranging from 0.077 to 0.544).The SNPs investigated at the PARK16 locus were not found to be involved in PD-associated blocks in the northern Han Chinese population.The allele distributions of rs708723,rs4951261,rs823076 and rs16856110 in the northern Han Chinese population can be highly polymorphic,which can be applied to genetic analvsis and forensic practices.

  14. Flow karyotyping and sorting of human chromosomes

    Energy Technology Data Exchange (ETDEWEB)

    Gray, J.W.; Lucas, J.; Peters, D.; Pinkel, D.; Trask, B.; van den Engh, G.; Van Dilla, M.A.

    1986-07-16

    Flow cytometry and sorting are becoming increasingly useful as tools for chromosome classfication and for the detection of numerical and structural chromosome aberrations. Chromosomes of a single type can be purified with these tools to facilitate gene mapping or production of chromosome specific recombinant DNA libraries. For analysis of chromosomes with flow cytometry, the chromosomes are extracted from mitotic cells, stained with one or more fluorescent dyes and classified one-by-one according to their dye content(s). Thus, the flow approach is fundamentally different than conventional karyotyping where chromosomes are classified within the context of a metaphase spread. Flow sorting allows purification of chromosomes that can be distinguished flow cytometrically. The authors describe the basic principles of flow cytometric chromosome classification i.e. flow karyotyping, and chromosome sorting and describe several applications. 30 refs., 8 figs.

  15. Machine-learning approaches for classifying haplogroup from Y chromosome STR data.

    Directory of Open Access Journals (Sweden)

    Joseph Schlecht

    2008-06-01

    Full Text Available Genetic variation on the non-recombining portion of the Y chromosome contains information about the ancestry of male lineages. Because of their low rate of mutation, single nucleotide polymorphisms (SNPs are the markers of choice for unambiguously classifying Y chromosomes into related sets of lineages known as haplogroups, which tend to show geographic structure in many parts of the world. However, performing the large number of SNP genotyping tests needed to properly infer haplogroup status is expensive and time consuming. A novel alternative for assigning a sampled Y chromosome to a haplogroup is presented here. We show that by applying modern machine-learning algorithms we can infer with high accuracy the proper Y chromosome haplogroup of a sample by scoring a relatively small number of Y-linked short tandem repeats (STRs. Learning is based on a diverse ground-truth data set comprising pairs of SNP test results (haplogroup and corresponding STR scores. We apply several independent machine-learning methods in tandem to learn formal classification functions. The result is an integrated high-throughput analysis system that automatically classifies large numbers of samples into haplogroups in a cost-effective and accurate manner.

  16. Characterization of the OmyY1 Region on the Rainbow Trout Y Chromosome

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    Ruth B. Phillips

    2013-01-01

    Full Text Available We characterized the male-specific region on the Y chromosome of rainbow trout, which contains both sdY (the sex-determining gene and the male-specific genetic marker, OmyY1. Several clones containing the OmyY1 marker were screened from a BAC library from a YY clonal line and found to be part of an 800 kb BAC contig. Using fluorescence in situ hybridization (FISH, these clones were localized to the end of the short arm of the Y chromosome in rainbow trout, with an additional signal on the end of the X chromosome in many cells. We sequenced a minimum tiling path of these clones using Illumina and 454 pyrosequencing. The region is rich in transposons and rDNA, but also appears to contain several single-copy protein-coding genes. Most of these genes are also found on the X chromosome; and in several cases sex-specific SNPs in these genes were identified between the male (YY and female (XX homozygous clonal lines. Additional genes were identified by hybridization of the BACs to the cGRASP salmonid 4x44K oligo microarray. By BLASTn evaluations using hypothetical transcripts of OmyY1-linked candidate genes as query against several EST databases, we conclude at least 12 of these candidate genes are likely functional, and expressed.

  17. Characterization of the OmyY1 region on the rainbow trout Y chromosome

    Science.gov (United States)

    Phillips, Ruth B.; DeKoning, Jenefer J.; Brunelli, Joseph P.; Faber-Hammond, Joshua J.; Hansen, John D.; Christensen, Kris A.; Renn, Suzy C.P.; Thorgaard, Gary H.

    2013-01-01

    We characterized the male-specific region on the Y chromosome of rainbow trout, which contains both sdY (the sex-determining gene) and the male-specific genetic marker, OmyY1. Several clones containing the OmyY1 marker were screened from a BAC library from a YY clonal line and found to be part of an 800 kb BAC contig. Using fluorescence in situ hybridization (FISH), these clones were localized to the end of the short arm of the Y chromosome in rainbow trout, with an additional signal on the end of the X chromosome in many cells. We sequenced a minimum tiling path of these clones using Illumina and 454 pyrosequencing. The region is rich in transposons and rDNA, but also appears to contain several single-copy protein-coding genes. Most of these genes are also found on the X chromosome; and in several cases sex-specific SNPs in these genes were identified between the male (YY) and female (XX) homozygous clonal lines. Additional genes were identified by hybridization of the BACs to the cGRASP salmonid 4x44K oligo microarray. By BLASTn evaluations using hypothetical transcripts of OmyY1-linked candidate genes as query against several EST databases, we conclude at least 12 of these candidate genes are likely functional, and expressed.

  18. Identification of a short region on chromosome 6 affecting direct calving ease in Piedmontese cattle breed.

    Directory of Open Access Journals (Sweden)

    Silvia Bongiorni

    Full Text Available Calving in cattle is affected by calf morphology and by dam characteristics. It is described by two different traits: maternal calving ease, which is the ability to generate dams with good physiological predisposition to calving, and direct calving ease, which is the ability to generate calves that are easily born. The aim of this study was to identify regions of cattle genome harboring genes possibly affecting direct calving ease in the Piedmontese cattle breed. A population of 323 bulls scored for direct calving ease (EBV was analyzed by a medium-density SNP marker panel (54,001 SNPs to perform a genome-wide scan. The strongest signal was detected on chromosome 6 between 37.8 and 38.7 Mb where 13 SNPs associated to direct calving ease were found. Three genes are located in this region: LAP3, encoding for a leucine aminopeptidase involved in the oxytocin hydrolysis; NCAPG, encoding for a non-SMC condensin I complex, which has been associated in cattle with fetal growth and carcass size; and LCORL, which has been associated to height in humans and cattle. To further confirm the results of the genome-wide scan we genotyped additional SNPs within these genes and analyzed their association with direct calving ease. The results of this additional analysis fully confirmed the findings of the GWAS and particularly indicated LAP3 as the most probable gene involved. Linkage Disequilibrium (LD analysis showed high correlation between SNPs located within LAP3 and LCORL indicating a possible selection signature due either to increased fitness or breeders' selection for the trait.

  19. The association of XRCC1 haplotypes and chromosomal damage levels in peripheral blood lymphocyte among coke-oven workers

    Energy Technology Data Exchange (ETDEWEB)

    Shuguang Leng; Juan Cheng; Linyuan Zhang; Yong Niu; Yufei Dai; Zufei Pan; Bin Li; Fengsheng He; Yuxin Zheng [Chinese Center for Disease Control and Prevention, Beijing (China). National Institute of Occupational Health and Poison Control

    2005-05-15

    Theoretically, a haplotype has a higher level of heterozygosity than individual single nucleotide polymorphism (SNP) and the association study based on the haplotype may have an increased power for detecting disease associations compared with SNP-based analysis. In this study, we investigated the effects of four haplotype-tagging SNPs (htSNP) and the inferred haplotype pairs of the X-ray cross-complementing group 1 (XRCC1) gene on chromosome damage detected by the cytokinesis-block micronucleus assay. The study included 141 coke-oven workers with exposure to a high level of polycyclic aromatic hydrocarbons and 66 nonexposed controls. The frequencies of total MN and MNed cells were borderline associated with the Arg{sup 194}Trp polymorphism (P = 0.053 and P = 0.050, respectively) but not associated with the Arg{sup 280}His, Arg{sup 399}Gln and Gln{sup 632}Gln polymorphisms among coke-oven workers. Five haplotypes, including CGGG, TGGG, CAGG, CGAG, and CGGA, were inferred based on the four htSNPs of XRCC1 gene. The haplotype CGGG was associated with the decreased frequencies of total MN and MNed cells, and the haplotypes TGGG and CGAG were associated with the increased frequencies of total MN and MNed cells with adjustment for covariates among coke-oven workers. This study showed that the haplotypes derived from htSNPs in the XRCC1 gene were more likely than single SNPs to correlate with the polycyclic aromatic hydrocarbon-induced chromosome damage among coke-oven workers.

  20. Analysis of 49 autosomal SNPs in three ethnic groups from Iran

    DEFF Research Database (Denmark)

    Sharafi Farzad, M; Tomas Mas, Carmen; Børsting, C;

    2013-01-01

    A total number of 149 individuals from Iran (Persians, Lurs and Kurds) were analyzed for 49 autosomal SNPs using PCR, SBE and capillary electrophoresis. No deviation from Hardy-Weinberg expectations was observed. One SNP pair (rs1015250-rs251934) showed significant linkage disequilibrium in Kurds....... However, this was most likely due to chance. High intrapopulation variability and no significant population structure were observed among the three ethnic groups from Iran. Pairwise FST values obtained from the mean numbers of pairwise differences between SNP profiles were calculated for Persians, Lurs......, Kurds and eighteen other worldwide populations. For each of the three Iranian ethnic groups, the lowest FST values calculated between an Iranian and non-Iranian populations were observed between Iranians and populations in Iraq and Turkey. The three Iranian ethnic groups grouped together with other West...

  1. Polymorphic L1 retrotransposons are frequently in strong linkage disequilibrium with neighboring SNPs.

    Science.gov (United States)

    Higashino, Saneyuki; Ohno, Tomoyuki; Ishiguro, Koichi; Aizawa, Yasunori

    2014-05-10

    L1 retrotransposons have been the major driver of structural variation of the human genome. L1 insertion polymorphism (LIP)-mediated genomic variation can alter the transcriptome and contribute to the divergence of human phenotypes. To assess this possibility, a genome-wide association study (GWAS) including LIPs is required. Toward this ultimate goal, the present study examined linkage disequilibrium between six LIPs and their neighboring single nucleotide polymorphisms (SNPs). Genomic PCR and sequencing of L1-plus and -minus alleles from different donors revealed that all six LIPs were in strong linkage disequilibrium with at least one SNP. In addition, comparison of syntenic regions containing the identified SNP nucleotides was performed among modern humans (L1-plus and -minus alleles), archaic humans and non-human primates, revealing two different evolutionary schemes that might have resulted in the observed strong SNP-LIP linkage disequilibria. This study provides an experimental framework and guidance for a future SNP-LIP integrative GWAS.

  2. Prediction of HLA class II alleles using SNPs in an African population.

    Directory of Open Access Journals (Sweden)

    Fasil Tekola Ayele

    Full Text Available Despite the importance of the human leukocyte antigen (HLA gene locus in research and clinical practice, direct HLA typing is laborious and expensive. Furthermore, the analysis requires specialized software and expertise which are unavailable in most developing country settings. Recently, in silico methods have been developed for predicting HLA alleles using single nucleotide polymorphisms (SNPs. However, the utility of these methods in African populations has not been systematically evaluated.In the present study, we investigate prediction of HLA class II (HLA-DRB1 and HLA-DQB1 alleles using SNPs in the Wolaita population, southern Ethiopia. The subjects comprised 297 Ethiopians with genome-wide SNP data, of whom 188 had also been HLA typed and were used for training and testing the model. The 109 subjects with SNP data alone were used for empirical prediction using the multi-allelic gene prediction method. We evaluated accuracy of the prediction, agreement between predicted and HLA typed alleles, and discriminative ability of the prediction probability supplied by the model. We found that the model predicted intermediate (two-digit resolution for HLA-DRB1 and HLA-DQB1 alleles at accuracy levels of 96% and 87%, respectively. All measures of performance showed high accuracy and reliability for prediction. The distribution of the majority of HLA alleles in the study was similar to that previously reported for the Oromo and Amhara ethnic groups from Ethiopia.We demonstrate that HLA class II alleles can be predicted from SNP genotype data with a high level of accuracy at intermediate (two-digit resolution in an African population. This finding offers new opportunities for HLA studies of disease epidemiology and population genetics in developing countries.

  3. Linkage disequilibrium blocks, haplotype structure, and htSNPs of human CYP7A1 gene

    Directory of Open Access Journals (Sweden)

    Wan Yu-Jui

    2006-05-01

    Full Text Available Abstract Background Cholesterol 7-alpha-hydroxylase (CYP7A1 is the rate limiting enzyme for converting cholesterol into bile acids. Genetic variations in the CYP7A1 gene have been associated with metabolic disorders of cholesterol and bile acids, including hypercholesterolemia, hypertriglyceridemia, arteriosclerosis, and gallstone disease. Current genetic studies are focused mainly on analysis of a single nucleotide polymorphism (SNP at A-278C in the promoter region of the CYP7A1 gene. Here we report a genetic approach for an extensive analysis on linkage disequilibrium (LD blocks and haplotype structures of the entire CYP7A1 gene and its surrounding sequences in Africans, Caucasians, Asians, Mexican-Americans, and African-Americans. Result The LD patterns and haplotype blocks of CYP7A1 gene were defined in Africans, Caucasians, and Asians using genotyping data downloaded from the HapMap database to select a set of haplotype-tagging SNPs (htSNP. A low cost, microarray-based platform on thin-film biosensor chips was then developed for high-throughput genotyping to study transferability of the HapMap htSNPs to Mexican-American and African-American populations. Comparative LD patterns and haplotype block structure was defined across all test populations. Conclusion A constant genetic structure in CYP7A1 gene and its surrounding sequences was found that may lead to a better design for association studies of genetic variations in CYP7A1 gene with cholesterol and bile acid metabolism.

  4. IL12B and IL23R gene SNPs in Japanese psoriasis.

    Science.gov (United States)

    Oka, Akira; Mabuchi, Tomotaka; Ikeda, Shigaku; Terui, Tadashi; Haida, Yuko; Ozawa, Akira; Yatsu, Keisuke; Kulski, Jerzy K; Inoko, Hidetoshi

    2013-11-01

    Psoriasis is a common human skin disease whereby abnormal production of inflammatory mediators is believed to play an important role in its pathogenesis. The IL12B gene, which encodes the shared IL-12p40 subunit in two cytokines, IL-12 and IL-23, and the IL23R gene, which encodes a subunit of the receptor for IL-23, were identified as psoriasis-susceptibility genetic factors in recent candidate gene and genome-wide association studies of Chinese and Europeans. Since there are significant differences in the incidence of psoriasis between Europeans and Japanese suggesting a genetic ethnic effect, we examined the association of IL12B and IL23R gene polymorphisms with psoriasis in a cohort of Japanese. In this study, we genotyped two SNPs (rs3212227 and rs6887695) in the IL12B gene and one SNP (rs11209026) in the IL23R gene using 560 Japanese psoriasis cases and 560 controls and compared our results with those previously published for Europeans and Asians. Our study showed significant associations between psoriasis and both IL12B gene SNPs, rs3212227 (odds ratio (OR) = 1.35, P = 4.94E-04) and rs6887695 (OR = 1.32, P = 2.00E-03), but no significant association between psoriasis and the IL23R SNP, rs11209026. Furthermore, a significant haplotype association was found for the IL12B gene protective haplotype C-C (OR = 0.71, P = 1.84E-04) in Japanese, as previously elucidated in the studies of European ancestry.

  5. FEPI-MB: identifying SNPs-disease association using a Markov Blanket-based approach

    Directory of Open Access Journals (Sweden)

    Han Bing

    2011-11-01

    Full Text Available Abstract Background The interactions among genetic factors related to diseases are called epistasis. With the availability of genotyped data from genome-wide association studies, it is now possible to computationally unravel epistasis related to the susceptibility to common complex human diseases such as asthma, diabetes, and hypertension. However, the difficulties of detecting epistatic interaction arose from the large number of genetic factors and the enormous size of possible combinations of genetic factors. Most computational methods to detect epistatic interactions are predictor-based methods and can not find true causal factor elements. Moreover, they are both time-consuming and sample-consuming. Results We propose a new and fast Markov Blanket-based method, FEPI-MB (Fast EPistatic Interactions detection using Markov Blanket, for epistatic interactions detection. The Markov Blanket is a minimal set of variables that can completely shield the target variable from all other variables. Learning of Markov blankets can be used to detect epistatic interactions by a heuristic search for a minimal set of SNPs, which may cause the disease. Experimental results on both simulated data sets and a real data set demonstrate that FEPI-MB significantly outperforms other existing methods and is capable of finding SNPs that have a strong association with common diseases. Conclusions FEPI-MB algorithm outperforms other computational methods for detection of epistatic interactions in terms of both the power and sample-efficiency. Moreover, compared to other Markov Blanket learning methods, FEPI-MB is more time-efficient and achieves a better performance.

  6. Association of CAPN10 SNPs and haplotypes with polycystic ovary syndrome among South Indian Women.

    Directory of Open Access Journals (Sweden)

    Shilpi Dasgupta

    Full Text Available Polycystic Ovary Syndrome (PCOS is known to be characterized by metabolic disorder in which hyperinsulinemia and peripheral insulin resistance are central features. Given the physiological overlap between PCOS and type-2 diabetes (T2DM, and calpain 10 gene (CAPN10 being a strong candidate for T2DM, a number of studies have analyzed CAPN10 SNPs among PCOS women yielding contradictory results. Our study is first of its kind to investigate the association pattern of CAPN10 polymorphisms (UCSNP-44, 43, 56, 19 and 63 with PCOS among Indian women. 250 PCOS cases and 299 controls from Southern India were recruited for this study. Allele and genotype frequencies of the SNPs were determined and compared between the cases and controls. Results show significant association of UCSNP-44 genotype CC with PCOS (p = 0.007 with highly significant odds ratio when compared to TC (OR = 2.51, p = 0.003, 95% CI = 1.37-4.61 as well as TT (OR = 1.94, p = 0.016, 95% CI = 1.13-3.34. While the haplotype carrying the SNP-44 and SNP-19 variants (21121 exhibited a 2 fold increase in the risk for PCOS (OR = 2.37, p = 0.03, the haplotype containing SNP-56 and SNP-19 variants (11221 seems to have a protective role against PCOS (OR = 0.20, p = 0.004. Our results support the earlier evidence for a possible role of UCSNP-44 of the CAPN10 gene in the manifestation of PCOS.

  7. Replication study of 34 common SNPs associated with prostate cancer in the Romanian population.

    Science.gov (United States)

    Jinga, Viorel; Csiki, Irma Eva; Manolescu, Andrei; Iordache, Paul; Mates, Ioan Nicolae; Radavoi, Daniel; Rascu, Stefan; Badescu, Daniel; Badea, Paula; Mates, Dana

    2016-04-01

    Prostate cancer is the third-most common form of cancer in men in Romania. The Romanian unscreened population represents a good sample to study common genetic risk variants. However, a comprehensive analysis has not been conducted yet. Here, we report our replication efforts in a Romanian population of 979 cases and 1027 controls, for potential association of 34 literature-reported single nucleotide polymorphisms (SNPs) with prostate cancer. We also examined whether any SNP was differentially associated with tumour grade or stage at diagnosis, with disease aggressiveness, and with the levels of PSA (prostate specific antigen). In the allelic analysis, we replicated the previously reported risk for 19 loci on 4q24, 6q25.3, 7p15.2, 8q24.21, 10q11.23, 10q26.13, 11p15.5, 11q13.2, 11q13.3. Statistically significant associations were replicated for other six SNPs only with a particular disease phenotype: low-grade tumour and low PSA levels (rs1512268), high PSA levels (rs401681 and rs11649743), less aggressive cancers (rs1465618, rs721048, rs17021918). The strongest association of our tested SNP's with PSA in controls was for rs2735839, with 29% increase for each copy of the major allele G, consistent with previous results. Our results suggest that rs4962416, previously associated only with prostate cancer, is also associated with PSA levels, with 12% increase for each copy of the minor allele C. The study enabled the replication of the effect for the majority of previously reported genetic variants in a set of clinically relevant prostate cancers. This is the first replication study on these loci, known to associate with prostate cancer, in a Romanian population.

  8. Identification of SNPs in barley(Hordeum vulgare L.)by deep sequencing of six reduced representation libraries

    Institute of Scientific and Technical Information of China (English)

    Ganggang; Guo; Dawa; Dondup; Lisha; Zhang; Sha; Hu; Xingmiao; Yuan; Jing; Zhang

    2014-01-01

    High-density genetic markers are required for genotyping and linkage mapping in identifying genes from crops with complex genomes, such as barley. As the most common variation, single nucleotide polymorphisms(SNPs) are suitable for accurate genotyping by using the next-generation sequencing(NGS) technology. Reduced representation libraries(RRLs) of five barley accessions and one mutant were sequenced using NGS technology for SNP discovery. Twenty million short reads were generated and the proportion of repetitive sequences was reduced by more than 56%. A total of 6061 SNPs were identified, and 451 were mapped to the draft sequence of the barley genome with pairing reads. Eleven SNPs were validated using length polymorphic allele-specific PCR markers.

  9. Chromosome therapy. Correction of large chromosomal aberrations by inducing ring chromosomes in induced pluripotent stem cells (iPSCs).

    Science.gov (United States)

    Kim, Taehyun; Bershteyn, Marina; Wynshaw-Boris, Anthony

    2014-01-01

    The fusion of the short (p) and long (q) arms of a chromosome is referred to as a "ring chromosome." Ring chromosome disorders occur in approximately 1 in 50,000-100,000 patients. Ring chromosomes can result in birth defects, mental disabilities, and growth retardation if additional genes are deleted during the formation of the ring. Due to the severity of these large-scale aberrations affecting multiple contiguous genes, no possible therapeutic strategies for ring chromosome disorders have so far been proposed. Our recent study (Bershteyn et al.) using patient-derived fibroblast lines containing ring chromosomes, found that cellular reprogramming of these fibroblasts into induced pluripotent stem cells (iPSCs) resulted in the cell-autonomous correction of the ring chromosomal aberration via compensatory uniparental disomy (UPD). These observations have important implications for studying the mechanism of chromosomal number control and may lead to the development of effective therapies for other, more common, chromosomal aberrations.

  10. Nucleotide diversity maps reveal variation in diversity among wheat genomes and chromosomes

    Directory of Open Access Journals (Sweden)

    McGuire Patrick E

    2010-12-01

    Full Text Available Abstract Background A genome-wide assessment of nucleotide diversity in a polyploid species must minimize the inclusion of homoeologous sequences into diversity estimates and reliably allocate individual haplotypes into their respective genomes. The same requirements complicate the development and deployment of single nucleotide polymorphism (SNP markers in polyploid species. We report here a strategy that satisfies these requirements and deploy it in the sequencing of genes in cultivated hexaploid wheat (Triticum aestivum, genomes AABBDD and wild tetraploid wheat (Triticum turgidum ssp. dicoccoides, genomes AABB from the putative site of wheat domestication in Turkey. Data are used to assess the distribution of diversity among and within wheat genomes and to develop a panel of SNP markers for polyploid wheat. Results Nucleotide diversity was estimated in 2114 wheat genes and was similar between the A and B genomes and reduced in the D genome. Within a genome, diversity was diminished on some chromosomes. Low diversity was always accompanied by an excess of rare alleles. A total of 5,471 SNPs was discovered in 1791 wheat genes. Totals of 1,271, 1,218, and 2,203 SNPs were discovered in 488, 463, and 641 genes of wheat putative diploid ancestors, T. urartu, Aegilops speltoides, and Ae. tauschii, respectively. A public database containing genome-specific primers, SNPs, and other information was constructed. A total of 987 genes with nucleotide diversity estimated in one or more of the wheat genomes was placed on an Ae. tauschii genetic map, and the map was superimposed on wheat deletion-bin maps. The agreement between the maps was assessed. Conclusions In a young polyploid, exemplified by T. aestivum, ancestral species are the primary source of genetic diversity. Low effective recombination due to self-pollination and a genetic mechanism precluding homoeologous chromosome pairing during polyploid meiosis can lead to the loss of diversity from large

  11. Complex-disease networks of trait-associated single-nucleotide polymorphisms (SNPs) unveiled by information theory

    Science.gov (United States)

    Li, Haiquan; Lee, Younghee; Chen, James L; Rebman, Ellen; Li, Jianrong

    2012-01-01

    Objective Thousands of complex-disease single-nucleotide polymorphisms (SNPs) have been discovered in genome-wide association studies (GWAS). However, these intragenic SNPs have not been collectively mined to unveil the genetic architecture between complex clinical traits. The authors hypothesize that biological annotations of host genes of trait-associated SNPs may reveal the biomolecular modularity across complex-disease traits and offer insights for drug repositioning. Methods Trait-to-polymorphism (SNPs) associations confirmed in GWAS were used. A novel method to quantify trait–trait similarity anchored in Gene Ontology annotations of human proteins and information theory was developed. The results were then validated with the shortest paths of physical protein interactions between biologically similar traits. Results A network was constructed consisting of 280 significant intertrait similarities among 177 disease traits, which covered 1438 well-validated disease-associated SNPs. Thirty-nine percent of intertrait connections were confirmed by curators, and the following additional studies demonstrated the validity of a proportion of the remainder. On a phenotypic trait level, higher Gene Ontology similarity between proteins correlated with smaller ‘shortest distance’ in protein interaction networks of complexly inherited diseases (Spearman p<2.2×10−16). Further, ‘cancer traits’ were similar to one another, as were ‘metabolic syndrome traits’ (Fisher's exact test p=0.001 and 3.5×10−7, respectively). Conclusion An imputed disease network by information-anchored functional similarity from GWAS trait-associated SNPs is reported. It is also demonstrated that small shortest paths of protein interactions correlate with complex-disease function. Taken together, these findings provide the framework for investigating drug targets with unbiased functional biomolecular networks rather than worn-out single-gene and subjective canonical pathway approaches

  12. Y染色体SNPs及其在法医学中的应用%Y-chromosomal SNPs and its application in forensic science

    Institute of Scientific and Technical Information of China (English)

    张爱平; 刘超; 刘长晖

    2009-01-01

    Y-SNPs综合了Y染色体和SNPs的特点,具有男性特异性,突变率低,日益引起法医学工作者的关注.本文综合介绍了Y-SNPs的特性、单体群的命名规范及在法医学中的应用价值.

  13. Inherited unbalanced structural chromosome abnormalities at prenatal chromosome analysis are rarely ascertained through recurrent miscarriage

    NARCIS (Netherlands)

    Franssen, M. T. M.; Korevaar, J. C.; Tjoa, W. M.; Leschot, N. J.; Bossuyt, P. M. M.; Knegt, A. C.; Suykerbuyk, R. F.; Hochstenbach, R.; van der Veen, F.; Goddijn, M.

    2008-01-01

    Objective To determine the mode of ascertainment of inherited unbalanced structural chromosome abnormalities detected at prenatal chromosome analysis. Methods From the databases of three centres for clinical genetics in the Netherlands, all cases of inherited unbalanced structural chromosome abnorma

  14. APCR, factor V gene known and novel SNPs and adverse pregnancy outcomes in an Irish cohort of pregnant women

    LENUS (Irish Health Repository)

    Sedano-Balbas, Sara

    2010-03-10

    Abstract Background Activated Protein C Resistance (APCR), a poor anticoagulant response of APC in haemostasis, is the commonest heritable thrombophilia. Adverse outcomes during pregnancy have been linked to APCR. This study determined the frequency of APCR, factor V gene known and novel SNPs and adverse outcomes in a group of pregnant women. Methods Blood samples collected from 907 pregnant women were tested using the Coatest® Classic and Modified functional haematological tests to establish the frequency of APCR. PCR-Restriction Enzyme Analysis (PCR-REA), PCR-DNA probe hybridisation analysis and DNA sequencing were used for molecular screening of known mutations in the factor V gene in subjects determined to have APCR based on the Coatest® Classic and\\/or Modified functional haematological tests. Glycosylase Mediated Polymorphism Detection (GMPD), a SNP screening technique and DNA sequencing, were used to identify SNPs in the factor V gene of 5 APCR subjects. Results Sixteen percent of the study group had an APCR phenotype. Factor V Leiden (FVL), FV Cambridge, and haplotype (H) R2 alleles were identified in this group. Thirty-three SNPs; 9 silent SNPs and 24 missense SNPs, of which 20 SNPs were novel, were identified in the 5 APCR subjects. Adverse pregnancy outcomes were found at a frequency of 35% in the group with APCR based on Classic Coatest® test only and at 45% in the group with APCR based on the Modified Coatest® test. Forty-eight percent of subjects with FVL had adverse outcomes while in the group of subjects with no FVL, adverse outcomes occurred at a frequency of 37%. Conclusions Known mutations and novel SNPs in the factor V gene were identified in the study cohort determined to have APCR in pregnancy. Further studies are required to investigate the contribution of these novel SNPs to the APCR phenotype. Adverse outcomes including early pregnancy loss (EPL), preeclampsia (PET) and intrauterine growth restriction (IGUR) were not significantly more

  15. Mutations and/or close relatives? Six case work examples where 49 autosomal SNPs were used as supplementary markers

    DEFF Research Database (Denmark)

    Børsting, Claus; Morling, Niels

    2011-01-01

    Six case work examples are presented, where the individuals were typed for 15 autosomal short tandem repeats (STRs) and 49 autosomal single nucleotide polymorphisms (SNPs). The 15 STRs were typed with the AmpFlSTR Identifiler PCR Amplification Kit and the 49 SNPs were typed with the SNPfor...... father would have been falsely included based on the STR results, while the SNP results showed that the alleged father was not the true parent. These case work examples underline the importance of performing supplementary investigations in selected cases and demonstrate the usefulness of the SNPfor...

  16. Cost-effective multiplexing before capture allows screening of 25 000 clinically relevant SNPs in childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Wesolowska, Agata; Dalgaard, M. D.; Borst, L.;

    2011-01-01

    a model disease for exploring the impact of genetic variation due to well-characterized cytogenetics, drug response pathways and precise monitoring of minimal residual disease. Here, we have selected clinically relevant genes and SNPs through literature screening, and on the basis of associations with key...... designed a cost-effective, high-throughput capture assay of â¼25â000 clinically relevant SNPs, and demonstrated that multiple samples can be tagged and pooled before genome capture in targeted enrichment with a sufficient sequencing depth for genotyping. This multiplexed, targeted sequencing method allows...

  17. A large-scale rheumatoid arthritis genetic study identifies association at chromosome 9q33.2.

    Directory of Open Access Journals (Sweden)

    Monica Chang

    2008-06-01

    Full Text Available Rheumatoid arthritis (RA is a chronic, systemic autoimmune disease affecting both joints and extra-articular tissues. Although some genetic risk factors for RA are well-established, most notably HLA-DRB1 and PTPN22, these markers do not fully account for the observed heritability. To identify additional susceptibility loci, we carried out a multi-tiered, case-control association study, genotyping 25,966 putative functional SNPs in 475 white North American RA patients and 475 matched controls. Significant markers were genotyped in two additional, independent, white case-control sample sets (661 cases/1322 controls from North America and 596 cases/705 controls from The Netherlands identifying a SNP, rs1953126, on chromosome 9q33.2 that was significantly associated with RA (OR(common = 1.28, trend P(comb = 1.45E-06. Through a comprehensive fine-scale-mapping SNP-selection procedure, 137 additional SNPs in a 668 kb region from MEGF9 to STOM on 9q33.2 were chosen for follow-up genotyping in a staged-approach. Significant single marker results (P(comb 5.41E-09. The observed association patterns for these SNPs had heightened statistical significance and a higher degree of consistency across sample sets. In addition, the allele frequencies for these SNPs displayed reduced variability between control groups when compared to other SNPs. Lastly, in combination with the other two known genetic risk factors, HLA-DRB1 and PTPN22, the variants reported here generate more than a 45-fold RA-risk differential.

  18. Dean flow fractionation of chromosomes

    Science.gov (United States)

    Hockin, Matt; Sant, Himanshu J.; Capecchi, Mario; Gale, Bruce K.

    2016-03-01

    Efforts to transfer intact mammalian chromosomes between cells have been attempted for more than 50 years with the consistent result being transfer of sub unit length pieces regardless of method. Inertial microfluidics is a new field that has shown much promise in addressing the fractionation of particles in the 2-20 μm size range (with unknown limits) and separations are based upon particles being carried by curving confined flows (within a spiral shaped, often rectangular flow chamber) and migrating to stable "equilibrium" positions of varying distance from a chamber wall depending on the balance of dean and lift forces. We fabricated spiral channels for inertial microfluidic separations using a standard soft lithography process. The concentration of chromosomes, small contaminant DNA and large cell debris in each outlets were evaluated using microscope (60X) and a flow cytometer. Using Dean Flow Fractionation, we were able to focus 4.5 times more chromosomes in outlet 2 compared to outlet 4 where most of the large debris is found. We recover 16% of the chromosomes in outlet #1- 50% in 2, 23% in 3 and 11% in 4. It should be noted that these estimates of recovery do not capture one piece of information- it actually may be that the chromosomes at each outlet are physically different and work needs to be done to verify this potential.

  19. Chromosome segregation in plant meiosis

    Directory of Open Access Journals (Sweden)

    Linda eZamariola

    2014-06-01

    Full Text Available Faithful chromosome segregation in meiosis is essential for ploidy stability over sexual life cycles. In plants, defective chromosome segregation caused by gene mutations or other factors leads to the formation of unbalanced or unreduced gametes creating aneuploid or polyploid progeny, respectively. Accurate segregation requires the coordinated execution of conserved processes occurring throughout the two meiotic cell divisions. Synapsis and recombination ensure the establishment of chiasmata that hold homologous chromosomes together allowing their correct segregation in the first meiotic division, which is also tightly regulated by cell-cycle dependent release of cohesin and monopolar attachment of sister kinetochores to microtubules. In meiosis II, bi-orientation of sister kinetochores and proper spindle orientation correctly segregate chromosomes in four haploid cells. Checkpoint mechanisms acting at kinetochores control the accuracy of kinetochore-microtubule attachment, thus ensuring the completion of segregation. Here we review the current knowledge on the processes taking place during chromosome segregation in plant meiosis, focusing on the characterization of the molecular factors involved.

  20. The Reduction of Chromosome Number in Meiosis Is Determined by Properties Built into the Chromosomes

    OpenAIRE

    Paliulis, Leocadia V.; Nicklas, R. Bruce

    2000-01-01

    In meiosis I, two chromatids move to each spindle pole. Then, in meiosis II, the two are distributed, one to each future gamete. This requires that meiosis I chromosomes attach to the spindle differently than meiosis II chromosomes and that they regulate chromosome cohesion differently. We investigated whether the information that dictates the division type of the chromosome comes from the whole cell, the spindle, or the chromosome itself. Also, we determined when chromosomes can switch from ...

  1. Association, characterisation and meta-analysis of SNPs linked to general reading ability in a German dyslexia case-control cohort

    Science.gov (United States)

    Müller, Bent; Wilcke, Arndt; Czepezauer, Ivonne; Ahnert, Peter; Boltze, Johannes; Kirsten, Holger; Friederici, Angela D.; Emmrich, Frank; Brauer, Jens; Wilcke, Arndt; Neef, Nicole; Boltze, Johannes; Skeide, Michael; Kirsten, Holger; Schaadt, Gesa; Müller, Bent; Kraft, Indra; Czepezauer, Ivonne; Dörr, Liane

    2016-01-01

    Dyslexia is a severe disorder in the acquisition of reading and writing. Several studies investigated the role of genetics for reading, writing and spelling ability in the general population. However, many of the identified SNPs were not analysed in case-control cohorts. Here, we investigated SNPs previously linked to reading or spelling ability in the general population in a German case-control cohort. Furthermore, we characterised these SNPs for functional relevance with in silico methods and meta-analysed them with previous studies. A total of 16 SNPs within five genes were included. The total number of risk alleles was higher in cases than in controls. Three SNPs were nominally associated with dyslexia: rs7765678 within DCDC2, and rs2038137 and rs6935076 within KIAA0319. The relevance of rs2038137 and rs6935076 was further supported by the meta-analysis. Functional profiling included analysis of tissue-specific expression, annotations for regulatory elements and effects on gene expression levels (eQTLs). Thereby, we found molecular mechanistical implications for 13 of all 16 included SNPs. SNPs associated in our cohort showed stronger gene-specific eQTL effects than non-associated SNPs. In summary, our results validate SNPs previously linked to reading and spelling in the general population in dyslexics and provide insights into their putative molecular pathomechanisms. PMID:27312598

  2. Confirmation of Y haplogroup tree topologies with newly suggested Y-SNPs for the C2, O2b and O3a subhaplogroups.

    Science.gov (United States)

    Kwon, So Yeun; Lee, Hwan Young; Lee, Eun Young; Yang, Woo Ick; Shin, Kyoung-Jin

    2015-11-01

    Y chromosome single nucleotide polymorphisms (Y-SNPs) are useful markers for reconstructing male lineages through hierarchically arranged allelic sets known as haplogroups, and are thereby widely used in the fields such as human evolution, anthropology and forensic genetics. The Y haplogroup tree was recently revised with newly suggested Y-SNP markers for designation of several subgroups of haplogroups C2, O2b and O3a, which are predominant in Koreans. Therefore, herein we analyzed these newly suggested Y-SNPs in 545 unrelated Korean males who belong to the haplogroups C2, O2b or O3a, and investigated the reconstructed topology of the Y haplogroup tree. We were able to confirm that markers L1373, Z1338/JST002613-27, Z1300, CTS2657, Z8440 and F845 define the C2 subhaplogroups, C2b, C2e, C2e1, C2e1a, C2e1b and C2e2, respectively, and that markers F3356, L682, F11, F238/F449 and F444 define the O subhaplogroups O2b1, O2b1b, O3a1c1, O3a1c2 and O3a2c1c, respectively. Among six C2 subhaplogroups (C2b, C2e, C2e1*, C2e1a, C2e1b and C2e2), the C2e haplogroup and its subhaplogroups were found to be predominant, and among the four O2b subhaplogroups (O2b*, O2b1*, O2b1a and O2b1b), O2b1b was most frequently observed. Among the O3a subhaplogroups, O3a2c1 was predominant and it was further divided into the subhaplogroups O3a2c1a and O3a2c1c with a newly suggested marker. However, the JST002613-27 marker, which had been known to define the haplogroup C2f, was found to be an ancestral marker of the C2e haplogroup, as is the Z1338 marker. Also, the M312 marker for the O2b1 haplogroup designation was replaced by F3356, because all of the O2b1 haplotypes showed a nucleotide change at F3356, but not at M312. In addition, the F238 marker was always observed to be phylogenetically equivalent to F449, while both of the markers were assigned to the O3a1c2 haplogroup. The confirmed phylogenetic tree of this study with the newly suggested Y-SNPs could be valuable for anthropological and

  3. Genetic loci on chromosome 5 are associated with circulating levels of interleukin-5 and eosinophil count in a European population with high risk for cardiovascular disease.

    Science.gov (United States)

    McLeod, Olga; Silveira, Angela; Valdes-Marquez, Elsa; Björkbacka, Harry; Almgren, Peter; Gertow, Karl; Gådin, Jesper R; Bäcklund, Alexandra; Sennblad, Bengt; Baldassarre, Damiano; Veglia, Fabrizio; Humphries, Steve E; Tremoli, Elena; de Faire, Ulf; Nilsson, Jan; Melander, Olle; Hopewell, Jemma C; Clarke, Robert; Björck, Hanna M; Hamsten, Anders; Öhrvik, John; Strawbridge, Rona J

    2016-05-01

    IL-5 is a Th2 cytokine which activates eosinophils and is suggested to have an atheroprotective role. Genetic variants in the IL5 locus have been associated with increased risk of CAD and ischemic stroke. In this study we aimed to identify genetic variants associated with IL-5 concentrations and apply a Mendelian randomisation approach to assess IL-5 levels for causal effect on intima-media thickness in a European population at high risk of coronary artery disease. We analysed SNPs within robustly associated candidate loci for immune, inflammatory, metabolic and cardiovascular traits. We identified 2 genetic loci for IL-5 levels (chromosome 5, rs56183820, BETA=0.11, P=6.73E(-5) and chromosome 14, rs4902762, BETA=0.12, P=5.76E(-6)) and one for eosinophil count (rs72797327, BETA=-0.10, P=1.41E(-6)). Both chromosome 5 loci were in the vicinity of the IL5 gene, however the association with IL-5 levels failed to replicate in a meta-analysis of 2 independent cohorts (rs56183820, BETA=0.04, P=0.2763, I(2)=24, I(2)-P=0.2516). No significant associations were observed between SNPs associated with IL-5 levels or eosinophil count and IMT measures. Expression quantitative trait analyses indicate effects of the IL-5 and eosinophil-associated SNPs on RAD50 mRNA expression levels (rs12652920 (r2=0.93 with rs56183820) BETA=-0.10, P=8.64E(-6) and rs11739623 (r2=0.96 with rs72797327) BETA=-0.23, P=1.74E(-29), respectively). Our data do not support a role for IL-5 levels and eosinophil count in intima-media thickness, however SNPs associated with IL-5 and eosinophils might influence stability of the atherosclerotic plaque via modulation of RAD50 levels.

  4. 基于贝叶斯网潜类模型的高维SNPs分析%Analysis of High-dimensional SNPs data Based on Latent class Model of Bayesian Network

    Institute of Scientific and Technical Information of China (English)

    马靖; 张韶凯; 张岩波

    2012-01-01

    采用贝叶斯(Bayesian)网的潜类模型对GAW17高维SNPs数据进行分析,为复杂性状疾病遗传以及基因定位等方面的研究提供新的方法支持.本研究从GAW17提供的包含697个个体22条常染色体的上万个SNP中,随机挑选出1号染色体上12个基因的29个SNPs作为研究对象.按照累计信息贡献率达到95%的原则,应用贝叶斯网潜变量模型选出C1S11408,C1S3201,CIS1786等15个与X0互信息量大的SNPs位点来对研究人群进行分类与解释.结果表明697个个体总的被分为2个潜在类别,各类别的概率分别为0.68和0.32.对两类人群的疾病分布状况进行分析,结果表明二者不一致,第二个类别人群患病率(38.64%)明显高于第一个类别人群(25.99%)(x2=11.46,P =0.001).由此可见,两类人群疾病患病率的差别正是由选出的15个SN Ps造成的,从而有理由认为这些SNPs为可疑致病位点,为进一步的研究提供明确的思路.%To analyze high -dimension SNPs data of GAW17 by latent class model based on Bayesian network ,and to provide a new method for the study of heredity and gene location of complex diseases. The data provided by GAW17 consists of a collection of 697 individuals and include tens of thousands of SNPs on 22 euchromosome. This research randomly chooses 29 SNPs located 12 gene on chromosome 1 as research object. According to the principle that accumulative contribution rate of information should reach to 95% , the model selects 15 SNPs which contain a-bundance mutual information with XO, including C1S11408, C1S3201, C1S1786 and so on, classifies the study population, and explains the meaning. The population including 697 individuals is divided into 2 latent classes , the probability of the two classes are 0. 68 and 0.32, respectively. To analyze the disease situation of the 2 classes, and the results show that they are not accordance. The prevalence of the second class (38.64% ) is higher than the first class(25. 99

  5. Y chromosome haplotype distribution of brown bears (Ursus arctos) in Northern Europe provides insight into population history and recovery.

    Science.gov (United States)

    Schregel, Julia; Eiken, Hans Geir; Grøndahl, Finn Audun; Hailer, Frank; Aspi, Jouni; Kojola, Ilpo; Tirronen, Konstantin; Danilov, Piotr; Rykov, Alexander; Poroshin, Eugene; Janke, Axel; Swenson, Jon E; Hagen, Snorre B

    2015-12-01

    High-resolution, male-inherited Y-chromosomal markers are a useful tool for population genetic analyses of wildlife species, but to date have only been applied in this context to relatively few species besides humans. Using nine Y-chromosomal STRs and three Y-chromosomal single nucleotide polymorphism markers (Y-SNPs), we studied whether male gene flow was important for the recent recovery of the brown bear (Ursus arctos) in Northern Europe, where the species declined dramatically in numbers and geographical distribution during the last centuries but is expanding now. We found 36 haplotypes in 443 male extant brown bears from Sweden, Norway, Finland and northwestern Russia. In 14 individuals from southern Norway from 1780 to 1920, we found two Y chromosome haplotypes present in the extant population as well as four Y chromosome haplotypes not present among the modern samples. Our results suggested major differences in genetic connectivity, diversity and structure between the eastern and the western populations in Northern Europe. In the west, our results indicated that the recovered population originated from only four male lineages, displaying pronounced spatial structuring suggestive of large-scale population size increase under limited male gene flow within the western subpopulation. In the east, we found a contrasting pattern, with high haplotype diversity and admixture. This first population genetic analysis of male brown bears shows conclusively that male gene flow was not the main force of population recovery.

  6. Genome-wide screening for highly discriminative SNPs for personal identification and their assessment in world populations.

    Science.gov (United States)

    Li, Liming; Wang, Yi; Yang, Shuping; Xia, Mingying; Yang, Yajun; Wang, Jiucun; Lu, Daru; Pan, Xingwei; Ma, Teng; Jiang, Pei; Yu, Ge; Zhao, Ziqin; Ping, Yuan; Zhou, Huaigu; Zhao, Xueying; Sun, Hui; Liu, Bing; Jia, Dongtao; Li, Chengtao; Hu, Rile; Lu, Hongzhou; Liu, Xiaoyang; Chen, Wenqing; Mi, Qin; Xue, Fuzhong; Su, Yongdong; Jin, Li; Li, Shilin

    2017-05-01

    The applications of DNA profiling aim to identify perpetrators, missing family members and disaster victims in forensic investigations. Single nucleotide polymorphisms (SNPs) based forensic applications are emerging rapidly with a potential to replace short tandem repeats (STRs) based panels which are now being used widely, and there is a need for a well-designed SNP panel to meet such challenge for this transition. Here we present a panel of 175 SNP markers (referred to as Fudan ID Panel or FID), selected from ∼3.6 million SNPs, for the application of personal identification. We optimized and validated FID panel using 729 Chinese individuals using a next generation sequencing (NGS) technology. We showed that the SNPs in the panel possess very high heterozygosity as well as low within- and among-continent differentiations, enabling FID panel exhibit discrimination power in both regional and worldwide populations, with the average match probabilities ranging from 4.77×10(-71) to 1.06×10(-64) across 54 world populations. With the advent of biomedical research, the SNPs connecting physical anthropological, physiological, behavioral and phenotypic traits will be eventually added to the forensic panels that will revolutionize criminal investigation.

  7. Characterization of genome-wide SNPs for the water flea Daphnia pulicaria generated by genotyping-by-sequencing (GBS)

    DEFF Research Database (Denmark)

    Muñoz, Joaquín; Chaturvedi, Anurag; De Meester, Luc;

    2016-01-01

    populations. We report a unique resource of novel Single Nucleotide Polymorphic (SNP) markers for Daphnia pulicaria using the reduction in genomic complexity with the restriction enzymes approach, genotyping-by-sequencing. Using the genome of D. pulex as a reference, SNPs were scored for 53 clones from five...

  8. Identification of candidate genes for prostate cancer-risk SNPs utilizing a normal prostate tissue eQTL data set

    Science.gov (United States)

    Thibodeau, S. N.; French, A. J.; McDonnell, S. K.; Cheville, J.; Middha, S.; Tillmans, L.; Riska, S.; Baheti, S.; Larson, M. C.; Fogarty, Z.; Zhang, Y.; Larson, N.; Nair, A.; O'Brien, D.; Wang, L.; Schaid, D J.

    2015-01-01

    Multiple studies have identified loci associated with the risk of developing prostate cancer but the associated genes are not well studied. Here we create a normal prostate tissue-specific eQTL data set and apply this data set to previously identified prostate cancer (PrCa)-risk SNPs in an effort to identify candidate target genes. The eQTL data set is constructed by the genotyping and RNA sequencing of 471 samples. We focus on 146 PrCa-risk SNPs, including all SNPs in linkage disequilibrium with each risk SNP, resulting in 100 unique risk intervals. We analyse cis-acting associations where the transcript is located within 2 Mb (±1 Mb) of the risk SNP interval. Of all SNP–gene combinations tested, 41.7% of SNPs demonstrate a significant eQTL signal after adjustment for sample histology and 14 expression principal component covariates. Of the 100 PrCa-risk intervals, 51 have a significant eQTL signal and these are associated with 88 genes. This study provides a rich resource to study biological mechanisms underlying genetic risk to PrCa. PMID:26611117

  9. Evidences of SNPs in the variable region of hemocyanin Ig-like domain in shrimp Litopenaeus vannamei.

    Science.gov (United States)

    Guo, Lingling; Zhao, Xianliang; Zhang, Yueling; Wang, Zehuan; Zhong, Mingqi; Li, Shengkang; Lun, Jingsheng

    2013-11-01

    Single nucleotide polymorphisms (SNPs) are the commonest mode of genetic variation in invertebrate immune-related genes. Hemocyanin presents in the hemolymph of both mollusks and arthropods and functions as an important antigen non-specific immune protein. But people know very little about its gene polymorphism so far. In current study, bioinformatics, molecular biology and environmental challenge approaches were used to identify the SNPs within hemocyanin Ig-like domain in shrimp Litopenaeus vannamei. A total of 11 SNPs were found in a variable region of Ig-like domain from L. vannamei hemocyanin large subunit (1258-1460 bp, HcLV1), 5 of which (1272, 1315, 1380, 1410 and 1450) were confirmed present in both genomic DNA and cDNA by clone sequencing. Furthermore, HcLV1 showed 3, 5 and 5 SSCP bands, respectively, in 16, 25 and 30 °C-treated shrimps, suggesting that the SSCP pattern of HcLV1 could be modulated by environmental stress. In addition, HcLV1 displayed two extra bands with different mobility when shrimps treated with Vibrio parahaemolyticus for 6-24 h, which was not observed in the control group. In conclusion, our data suggest that shrimp L. vannamei hemocyanin Ig-like domain possesses SNPs, which may be associated with environmental stress or pathogenic challenge.

  10. Prediction of Disease Causing Non-Synonymous SNPs by the Artificial Neural Network Predictor NetDiseaseSNP

    DEFF Research Database (Denmark)

    Johansen, Morten Bo; Gonzalez-Izarzugaza, Jose Maria; Brunak, Søren

    2013-01-01

    We have developed a sequence conservation-based artificial neural network predictor called NetDiseaseSNP which classifies nsSNPs as disease-causing or neutral. Our method uses the excellent alignment generation algorithm of SIFT to identify related sequences and a combination of 31 features...

  11. Analysis of artificially degraded DNA using STRs and SNPs--results of a collaborative European (EDNAP) exercise

    DEFF Research Database (Denmark)

    Dixon, L A; Dobbins, A E; Pulker, H K;

    2005-01-01

    the discriminating power of the current techniques. A collaborative study between nine European and US laboratories was organised under the auspices of EDNAP. Each laboratory was supplied with a SNP multiplex kit (Foren-SNPs) provided by the Forensic Science Service, two mini-STR kits provided by the National...

  12. Association of three SNPs in TOX3 and breast cancer risk: Evidence from 97275 cases and 128686 controls.

    Science.gov (United States)

    Zhang, Li; Long, Xinghua

    2015-01-01

    The associations of SNPs in TOX3 gene with breast cancer risk were investigated by some Genome-wide association studies and epidemiological studies, but the study results were contradictory. To derive a more precise estimate of the associations, we conducted a meta-analysis. ORs with 95% CI were used to assess the strength of association between TOX3 polymorphisms and breast cancer risk in fixed or random effect model. A total of 37 publications with 97275 cases and 128686 controls were identified. We observed that the rs3803662 C > T, rs12443621 A > G and rs8051542 C > T were all correlated with increased risk of breast cancer. In the stratified analyses by ethnicity, significantly elevated risk was detected for all genetic models of the three SNPs in Caucasians. In Asian populations, there were significant associations of rs3803662 and rs8051542 with breast cancer risk. Whereas there was no evidence for statistical significant association between the three SNPs and breast cancer risk in Africans. Additionally, we observed different associations of rs3803662 with breast cancer risk based on different ER subtype and BRCA1/BRCA2 mutation carriers. In conclusion, the meta-analysis suggested that three SNPs in TOX3 were significantly associated with breast cancer risk in different populations.

  13. Role of DISC1 interacting proteins in schizophrenia risk from genome-wide analysis of missense SNPs.

    Science.gov (United States)

    Costas, Javier; Suárez-Rama, Jose Javier; Carrera, Noa; Paz, Eduardo; Páramo, Mario; Agra, Santiago; Brenlla, Julio; Ramos-Ríos, Ramón; Arrojo, Manuel

    2013-11-01

    A balanced translocation affecting DISC1 cosegregates with several psychiatric disorders, including schizophrenia, in a Scottish family. DISC1 is a hub protein of a network of protein-protein interactions involved in multiple developmental pathways within the brain. Gene set-based analysis has been proposed as an alternative to individual analysis of single nucleotide polymorphisms (SNPs) to get information from genome-wide association studies. In this work, we tested for an overrepresentation of the DISC1 interacting proteins within the top results of our ranked list of genes based on our previous genome-wide association study of missense SNPs in schizophrenia. Our data set consisted of 5100 common missense SNPs genotyped in 476 schizophrenic patients and 447 control subjects from Galicia, NW Spain. We used a modification of the Gene Set Enrichment Analysis adapted for SNPs, as implemented in the GenGen software. The analysis detected an overrepresentation of the DISC1 interacting proteins (permuted P-value=0.0158), indicative of the role of this gene set in schizophrenia risk. We identified seven leading-edge genes, MACF1, UTRN, DST, DISC1, KIF3A, SYNE1, and AKAP9, responsible for the overrepresentation. These genes are involved in neuronal cytoskeleton organization and intracellular transport through the microtubule cytoskeleton, suggesting that these processes may be impaired in schizophrenia.

  14. Adiponectin gene ADIPOQ SNP associations with serum adiponectin in two female populations and effects of SNPs on promoter activity

    NARCIS (Netherlands)

    Kyriakou, Theodosios; Collins, Laura J.; Spencer-Jones, Nicola J.; Malcolm, Claire; Wang, Xiaoling; Snieder, Harold; Swaminathan, Ramasamyiyer; Burling, Keith A.; Hart, Deborah J.; Spector, Tim D.; O'Dell, Sandra D.

    2008-01-01

    Adiponectin is an insulin sensitiser in muscle and liver, and low serum levels characterise obesity and insulin resistance. Eight tagging single nucleotide polymorphisms (tSNPs) in the ADIPOQ gene and promoter were selected, and association with serum adiponectin was tested, in two independent sampl

  15. Chromosome-specific families in Vibrio genomes

    Directory of Open Access Journals (Sweden)

    Oksana eLukjancenko

    2014-03-01

    Full Text Available We have compared chromosome-specific genes in a set of 18 finished Vibrio genomes, and, in addition, also calculated the pan- and core-genomes from a data set of more than 250 draft Vibrio genome sequences. These genomes come from 9 known species and 2 unknown species. Within the finished chromosomes, we find a core set of 1269 encoded protein families for chromosome 1, and a core of 252 encoded protein families for chromosome 2. Many of these core proteins are also found in the draft genomes (although which chromosome they are located on is unknown. Of the chromosome specific core protein families, 1169 and 153 are uniquely found in chromosomes 1 and 2, respectively. Gene ontology (GO terms for each of the protein families were determined, and the different sets for each chromosome were compared. A total of 363 different `Molecular Function` GO categories were found for chromosome 1 specific protein families, and these include several broad activities: pyridoxine 5' phosphate synthetase, glucosylceramidase, heme transport, DNA ligase, amino acid binding, and ribosomal components; in contrast, chromosome 2 specific protein families have only 66 Molecular Function GO terms and include many membrane-associated activities, such as ion channels, transmembrane transporters, and electron transport chain proteins. Thus, it appears that whilst there are many 'housekeeping systems' encoded in chromosome 1, there are far fewer core functions found in chromosome 2. However, the presence of many membrane-associated encoded proteins in chromosome 2 is surprising.

  16. In silico analysis of single nucleotide polymorphism (SNPs in human β-globin gene.

    Directory of Open Access Journals (Sweden)

    Mohammed Alanazi

    Full Text Available Single amino acid substitutions in the globin chain are the most common forms of genetic variations that produce hemoglobinopathies--the most widespread inherited disorders worldwide. Several hemoglobinopathies result from homozygosity or compound heterozygosity to beta-globin (HBB gene mutations, such as that producing sickle cell hemoglobin (HbS, HbC, HbD and HbE. Several of these mutations are deleterious and result in moderate to severe hemolytic anemia, with associated complications, requiring lifelong care and management. Even though many hemoglobinopathies result from single amino acid changes producing similar structural abnormalities, there are functional differences in the generated variants. Using in silico methods, we examined the genetic variations that can alter the expression and function of the HBB gene. Using a sequence homology-based Sorting Intolerant from Tolerant (SIFT server we have searched for the SNPs, which showed that 200 (80% non-synonymous polymorphism were found to be deleterious. The structure-based method via PolyPhen server indicated that 135 (40% non-synonymous polymorphism may modify protein function and structure. The Pupa Suite software showed that the SNPs will have a phenotypic consequence on the structure and function of the altered protein. Structure analysis was performed on the key mutations that occur in the native protein coded by the HBB gene that causes hemoglobinopathies such as: HbC (E→K, HbD (E→Q, HbE (E→K and HbS (E→V. Atomic Non-Local Environment Assessment (ANOLEA, Yet Another Scientific Artificial Reality Application (YASARA, CHARMM-GUI webserver for macromolecular dynamics and mechanics, and Normal Mode Analysis, Deformation and Refinement (NOMAD-Ref of Gromacs server were used to perform molecular dynamics simulations and energy minimization calculations on β-Chain residue of the HBB gene before and after mutation. Furthermore, in the native and altered protein models, amino acid

  17. Transcriptome characterization and high throughput SSRs and SNPs discovery in Cucurbita pepo (Cucurbitaceae

    Directory of Open Access Journals (Sweden)

    Nuez Fernando

    2011-02-01

    Full Text Available Abstract Background Cucurbita pepo belongs to the Cucurbitaceae family. The "Zucchini" types rank among the highest-valued vegetables worldwide, and other C. pepo and related Cucurbita spp., are food staples and rich sources of fat and vitamins. A broad range of genomic tools are today available for other cucurbits that have become models for the study of different metabolic processes. However, these tools are still lacking in the Cucurbita genus, thus limiting gene discovery and the process of breeding. Results We report the generation of a total of 512,751 C. pepo EST sequences, using 454 GS FLX Titanium technology. ESTs were obtained from normalized cDNA libraries (root, leaves, and flower tissue prepared using two varieties with contrasting phenotypes for plant, flowering and fruit traits, representing the two C. pepo subspecies: subsp. pepo cv. Zucchini and subsp. ovifera cv Scallop. De novo assembling was performed to generate a collection of 49,610 Cucurbita unigenes (average length of 626 bp that represent the first transcriptome of the species. Over 60% of the unigenes were functionally annotated and assigned to one or more Gene Ontology terms. The distributions of Cucurbita unigenes followed similar tendencies than that reported for Arabidopsis or melon, suggesting that the dataset may represent the whole Cucurbita transcriptome. About 34% unigenes were detected to have known orthologs of Arabidopsis or melon, including genes potentially involved in disease resistance, flowering and fruit quality. Furthermore, a set of 1,882 unigenes with SSR motifs and 9,043 high confidence SNPs between Zucchini and Scallop were identified, of which 3,538 SNPs met criteria for use with high throughput genotyping platforms, and 144 could be detected as CAPS. A set of markers were validated, being 80% of them polymorphic in a set of variable C. pepo and C. moschata accessions. Conclusion We present the first broad survey of gene sequences and allelic

  18. A Markov blanket-based method for detecting causal SNPs in GWAS

    Directory of Open Access Journals (Sweden)

    Han Bing

    2010-04-01

    Full Text Available Abstract Background Detecting epistatic interactions associated with complex and common diseases can help to improve prevention, diagnosis and treatment of these diseases. With the development of genome-wide association studies (GWAS, designing powerful and robust computational method for identifying epistatic interactions associated with common diseases becomes a great challenge to bioinformatics society, because the study of epistatic interactions often deals with the large size of the genotyped data and the huge amount of combinations of all the possible genetic factors. Most existing computational detection methods are based on the classification capacity of SNP sets, which may fail to identify SNP sets that are strongly associated with the diseases and introduce a lot of false positives. In addition, most methods are not suitable for genome-wide scale studies due to their computational complexity. Results We propose a new Markov Blanket-based method, DASSO-MB (Detection of ASSOciations using Markov Blanket to detect epistatic interactions in case-control GWAS. Markov blanket of a target variable T can completely shield T from all other variables. Thus, we can guarantee that the SNP set detected by DASSO-MB has a strong association with diseases and contains fewest false positives. Furthermore, DASSO-MB uses a heuristic search strategy by calculating the association between variables to avoid the time-consuming training process as in other machine-learning methods. We apply our algorithm to simulated datasets and a real case-control dataset. We compare DASSO-MB to other commonly-used methods and show that our method significantly outperforms other methods and is capable of finding SNPs strongly associated with diseases. Conclusions Our study shows that DASSO-MB can identify a minimal set of causal SNPs associated with diseases, which contains less false positives compared to other existing methods. Given the huge size of genomic dataset

  19. WASP: a Web-based Allele-Specific PCR assay designing tool for detecting SNPs and mutations

    Directory of Open Access Journals (Sweden)

    Assawamakin Anunchai

    2007-08-01

    Full Text Available Abstract Background Allele-specific (AS Polymerase Chain Reaction is a convenient and inexpensive method for genotyping Single Nucleotide Polymorphisms (SNPs and mutations. It is applied in many recent studies including population genetics, molecular genetics and pharmacogenomics. Using known AS primer design tools to create primers leads to cumbersome process to inexperience users since information about SNP/mutation must be acquired from public databases prior to the design. Furthermore, most of these tools do not offer the mismatch enhancement to designed primers. The available web applications do not provide user-friendly graphical input interface and intuitive visualization of their primer results. Results This work presents a web-based AS primer design application called WASP. This tool can efficiently design AS primers for human SNPs as well as mutations. To assist scientists with collecting necessary information about target polymorphisms, this tool provides a local SNP database containing over 10 million SNPs of various populations from public domain databases, namely NCBI dbSNP, HapMap and JSNP respectively. This database is tightly integrated with the tool so that users can perform the design for existing SNPs without going off the site. To guarantee specificity of AS primers, the proposed system incorporates a primer specificity enhancement technique widely used in experiment protocol. In particular, WASP makes use of different destabilizing effects by introducing one deliberate 'mismatch' at the penultimate (second to last of the 3'-end base of AS primers to improve the resulting AS primers. Furthermore, WASP offers graphical user interface through scalable vector graphic (SVG draw that allow users to select SNPs and graphically visualize designed primers and their conditions. Conclusion WASP offers a tool for designing AS primers for both SNPs and mutations. By integrating the database for known SNPs (using gene ID or rs number

  20. In silico analysis of functional nsSNPs in human TRPC6 gene associated with steroid resistant nephrotic syndrome.

    Science.gov (United States)

    Joshi, Bhoomi B; Koringa, Prakash G; Mistry, Kinnari N; Patel, Amrut K; Gang, Sishir; Joshi, Chaitanya G

    2015-11-01

    The aim of the present study is to identify functional non-synonymous SNPs of TRPC6 gene using various in silico approaches. These SNPs are believed to have a direct impact on protein stability through conformation changes. Transient receptor potential cation channel-6 (TRPC6) is one of the proteins that plays a key role causing focal segmental glomerulosclerosis (FSGS) associated with the steroid-resistant nephritic syndrome (SRNS). Data of TRPC6 was collected from dbSNP and further used to investigate a damaging effect using SIFT, PolyPhen, PROVEAN, and PANTHER. The comparative analysis predicted that two functional SNPs "rs35857503 at position N157T and rs36111323 at position A404V" showed a damaging effect (score of 0.096-1.00).We modeled the 3D structure of TRPC6 using a SWISS-MODEL workspace and validated it via PROCHECK to get a Ramachandran plot (83.0% residues in the most favored region, 12.7% in additionally allowed regions, 2.3% in a generously allowed region and 2.0% were in a disallowed region). QMEAN (0.311) and MUSTER (10.06) scores were under acceptable limits. Putative functional SNPs that may possibly undergo post-translation modifications were also identified in TRPC6 protein. It was found that mutation at N157T can lead to alteration in glycation whereas mutation at A404V was present at a ligand binding site. Additionally, I-Mutant showed a decrease in stability for these nsSNPs upon mutation, thus suggesting that the N157T and A404V variants of TRPC6 could directly or indirectly destabilize the amino acid interactions causing functional deviations of protein to some extent.

  1. Sex chromosome rearrangements in Polyphaga beetles.

    Science.gov (United States)

    Dutrillaux, A M; Dutrillaux, B

    2009-01-01

    The presence of a parachute sex chromosome bivalent (Xyp) at metaphase I of male meiosis is a well-known characteristic of Coleoptera, present in almost all families of this order and assumed to represent their ancestral sex chromosome formula. Sex chromosomes appear to be manifold more frequently involved in inter-chromosomal rearrangements than the average of the nine autosomal pairs usually forming their karyotype. This leads to various formulae such as neo-sex, multiple sex and perhaps unique sex chromosomes. These rearrangements alter the intimate association between sex chromosomes and nucleolar proteins, which are usual components of the Xyp. Different situations, selected in a series of 125 mitotic and meiotic cytogenetic studies of Polyphaga beetle species, are reported and discussed, with the aim to improve our knowledge on the mechanisms of sex chromosome rearrangements, the relationships with nucleoli and the consequences on dosage compensation and chromosome segregation.

  2. Vibrio chromosome-specific families

    DEFF Research Database (Denmark)

    Lukjancenko, Oksana; Ussery, David

    2014-01-01

    We have compared chromosome-specific genes in a set of 18 finished Vibrio genomes, and, in addition, also calculated the pan- and core-genomes from a data set of more than 250 draft Vibrio genome sequences. These genomes come from 9 known species and 2 unknown species. Within the finished...

  3. Chromosome Territory Modeller and Viewer.

    Science.gov (United States)

    Tkacz, Magdalena A; Chromiński, Kornel; Idziak-Helmcke, Dominika; Robaszkiewicz, Ewa; Hasterok, Robert

    2016-01-01

    This paper presents ChroTeMo, a tool for chromosome territory modelling, accompanied by ChroTeVi-a chromosome territory visualisation software that uses the data obtained by ChroTeMo. These tools have been developed in order to complement the molecular cytogenetic research of interphase nucleus structure in a model grass Brachypodium distachyon. Although the modelling tool has been initially created for one particular species, it has universal application. The proposed version of ChroTeMo allows for generating a model of chromosome territory distribution in any given plant or animal species after setting the initial, species-specific parameters. ChroTeMo has been developed as a fully probabilistic modeller. Due to this feature, the comparison between the experimental data on the structure of a nucleus and the results obtained from ChroTeMo can indicate whether the distribution of chromosomes inside a nucleus is also fully probabilistic or is subjected to certain non-random patterns. The presented tools have been written in Python, so they are multiplatform, portable and easy to read. Moreover, if necessary they can be further developed by users writing their portions of code. The source code, documentation, and wiki, as well as the issue tracker and the list of related articles that use ChroTeMo and ChroTeVi, are accessible in a public repository at Github under GPL 3.0 license.

  4. CHROMOSOMAL MULTIPLICITY IN BURKHOLDERIA CEPACIA

    Science.gov (United States)

    We have used CHEF gel electrophoresis to screen preparations of large DNA from different Burkholderia cepacia isolates for the presence of DNA species corresponding to the linearized forms of the three chromosomes of 3.4,2.5, and 0.9 Mb identified in B. cepacia strain 17616. DNA ...

  5. Chromosome synteny in cucumis species

    Science.gov (United States)

    Cucumber, Cucumis sativus L. (2n = 2x = 14) and melon, C. melo L. (2n = 2x = 24) are two important vegetable species in the genus Cucumis (family Cucurbitaceae). Two inter-fertile botanical varieties with 14 chromosomes, the cultivated C. sativus var. sativus L. and the wild C. sativus var. hardwick...

  6. Chromosomal disorders and male infertility

    Institute of Scientific and Technical Information of China (English)

    Gary L Harton; Helen G Tempest

    2012-01-01

    infertility in humans is surprisingly common occurring in approximately 15% of the population wishing to start a family.Despite this,the molecular and genetic factors underlying the cause of infertility remain largely undiscovered.Nevertheless,more and more genetic factors associated with infertility are being identified.This review will focus on our current understanding of the chromosomal basis of male infertility specifically:chromosomal aneuploidy,structural and numerical karyotype abnormalities and Y chromosomal microdeletions.Chromosomal aneuploidy is the leading cause of pregnancy loss and developmental disabilities in humans.Aneuploidy is predominantly maternal in origin,but concerns have been raised regarding the safety of intracytoplasmic sperm injection as infertile men have significantly higher levels of sperm aneuploidy compared to their fertile counterparts.Males with numerical or structural karyotype abnormalities are also at an increased risk of producing aneuploid sperm.Our current understanding of how sperm aneuploidy translates to embryo aneuploidy will be reviewed,as well as the application of preimplantation genetic diagnosis (PGD) in such cases.Clinical recommendations where possible will be made,as well as discussion of the use of emerging array technology in PGD and its potential applications in male infertility.

  7. Au-nanoprobes for detection of SNPs associated with antibiotic resistance in Mycobacterium tuberculosis

    Science.gov (United States)

    Veigas, Bruno; Machado, Diana; Perdigão, João; Portugal, Isabel; Couto, Isabel; Viveiros, Miguel; Baptista, Pedro V.

    2010-10-01

    Tuberculosis (TB) is one of the leading causes of infection in humans, causing high morbility and mortality all over the world. The rate of new cases of multidrug resistant tuberculosis (MDRTB) continues to increase, and since these infections are very difficult to manage, they constitute a serious health problem. In most cases, drug resistance in Mycobacterium tuberculosis has been related to mutations in several loci within the pathogen's genome. The development of fast, cheap and simple screening methodologies would be of paramount relevance for the early detection of these mutations, essential for the timely and effective diagnosis and management of MDRTB patients. The use of gold nanoparticles derivatized with thiol-modified oligonucleotides (Au-nanoprobes) has led to new approaches in molecular diagnostics. Based on the differential non-cross-linking aggregation of Au-nanoprobes, we were able to develop a colorimetric method for the detection of specific sequences and to apply this approach to pathogen identification and single base mutations/single nucleotide polymorphisms (SNP) discrimination. Here we report on the development of Au-nanoprobes for the specific identification of SNPs within the beta subunit of the RNA polymerase (rpoB locus), responsible for resistance to rifampicin in over 95% of rifampicin resistant M. tuberculosis strains.

  8. A new ALF from Litopenaeus vannamei and its SNPs related to WSSV resistance

    Science.gov (United States)

    Liu, Jingwen; Yu, Yang; Li, Fuhua; Zhang, Xiaojun; Xiang, Jianhai

    2014-11-01

    Anti-lipopolysaccharide factors (ALFs) are basic components of the crustacean immune system that defend against a range of pathogens. The cDNA sequence of a new ALF, designated nLvALF2, with an open reading frame encoding 132 amino acids was cloned. Its deduced amino acid sequence contained the conserved functional domain of ALFs, the LPS binding domain (LBD). Its genomic sequence consisted of three exons and four introns. nLvALF2 was mainly expressed in the Oka organ and gills of shrimps. The transcriptional level of nLvALF2 increased significantly after white spot syndrome virus (WSSV) infection, suggesting its important roles in protecting shrimps from WSSV. Single nucleotide polymorphisms (SNPs) were found in the genomic sequence of nLvALF2, of which 38 were analyzed for associations with the susceptibility/resistance of shrimps to WSSV. The loci g.2422 A>G, g.2466 T>C, and g.2529 G>A were significantly associated with the resistance to WSSV ( PLitopenaeus vannamei.

  9. Association of ESR1 gene tagging SNPs with breast cancer risk

    Science.gov (United States)

    Dunning, Alison M.; Healey, Catherine S.; Baynes, Caroline; Maia, Ana-Teresa; Scollen, Serena; Vega, Ana; Rodríguez, Raquel; Barbosa-Morais, Nuno L.; Ponder, Bruce A.J.; Low, Yen-Ling; Bingham, Sheila; Haiman, Christopher A.; Le Marchand, Loic; Broeks, Annegien; Schmidt, Marjanka K.; Hopper, John; Southey, Melissa; Beckmann, Matthias W.; Fasching, Peter A.; Peto, Julian; Johnson, Nichola; Bojesen, Stig E.; Nordestgaard, Børge; Milne, Roger L.; Benitez, Javier; Hamann, Ute; Ko, Yon; Schmutzler, Rita K.; Burwinkel, Barbara; Schürmann, Peter; Dörk, Thilo; Heikkinen, Tuomas; Nevanlinna, Heli; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kosma, Veli-Matti; Chen, Xiaoqing; Spurdle, Amanda; Change-Claude, Jenny; Flesch-Janys, Dieter; Couch, Fergus J.; Olson, Janet E.; Severi, Gianluca; Baglietto, Laura; Børresen-Dale, Anne-Lise; Kristensen, Vessela; Hunter, David J.; Hankinson, Susan E.; Devilee, Peter; Vreeswijk, Maaike; Lissowska, Jolanta; Brinton, Louise; Liu, Jianjun; Hall, Per; Kang, Daehee; Yoo, Keun-Young; Shen, Chen-Yang; Yu, Jyh-Cherng; Anton-Culver, Hoda; Ziogoas, Argyrios; Sigurdson, Alice; Struewing, Jeff; Easton, Douglas F.; Garcia-Closas, Montserrat; Humphreys, Manjeet K.; Morrison, Jonathan; Pharoah, Paul D.P.; Pooley, Karen A.; Chenevix-Trench, Georgia

    2009-01-01

    We have conducted a three-stage, comprehensive single nucleotide polymorphism (SNP)-tagging association study of ESR1 gene variants (SNPs) in more than 55 000 breast cancer cases and controls from studies within the Breast Cancer Association Consortium (BCAC). No large risks or highly significant associations were revealed. SNP rs3020314, tagging a region of ESR1 intron 4, is associated with an increase in breast cancer susceptibility with a dominant mode of action in European populations. Carriers of the c-allele have an odds ratio (OR) of 1.05 [95% Confidence Intervals (CI) 1.02–1.09] relative to t-allele homozygotes, P = 0.004. There is significant heterogeneity between studies, P = 0.002. The increased risk appears largely confined to oestrogen receptor-positive tumour risk. The region tagged by SNP rs3020314 contains sequence that is more highly conserved across mammalian species than the rest of intron 4, and it may subtly alter the ratio of two mRNA splice forms. PMID:19126777

  10. Molecular diagnostic testing for Klinefelter syndrome and other male sex chromosome aneuploidies

    Directory of Open Access Journals (Sweden)

    Hager Karl

    2012-04-01

    Full Text Available Abstract Background Male sex chromosome aneuploidies are underdiagnosed despite concomitant physical and behavioral manifestations. Objective To develop a non-invasive, rapid and high-throughput molecular diagnostic assay for detection of male sex chromosome aneuploidies, including 47,XXY (Klinefelter, 47,XYY, 48,XXYY and 48,XXXY syndromes. Methods The assay utilizes three XYM and four XA markers to interrogate Y:X and X:autosome ratios, respectively. The seven markers were PCR amplified using genomic DNA isolated from a cohort of 323 males with aneuploid (n = 117 and 46,XY (n = 206 karyotypes. The resulting PCR products were subjected to Pyrosequencing, a quantitative DNA sequencing method. Results Receiver operator characteristic (ROC curves were used to establish thresholds for the discrimination of aneuploid from normal samples. The XYM markers permitted the identification of 47,XXY, 48,XXXY and 47,XYY syndromes with 100% sensitivity and specificity in both purified DNA and buccal swab samples. The 48,XXYY karyotype was delineated by XA marker data from 46,XY; an X allele threshold of 43% also permitted detection of 48,XXYY with 100% sensitivity and specificity. Analysis of X chromosome-specific biallelic SNPs demonstrated that 43 of 45 individuals (96% with 48,XXYY karyotype had two distinct X chromosomes, while 2 (4% had a duplicate X, providing evidence that 48,XXYY may result from nondisjunction during early mitotic divisions of a 46,XY embryo. Conclusions Quantitative Pyrosequencing, with high-throughput potential, can detect male sex chromosome aneuploidies with 100% sensitivity.

  11. A Plain English Map of the Human Chromosomes.

    Science.gov (United States)

    Offner, Susan

    1992-01-01

    Presents a chromosome map for 19 known chromosomes in human genetics. Describes the characteristics attributed to the genetic codes for each of the chromosomes and discusses the teaching applications of the chromosome map. (MDH)

  12. Porcine UCHL1: genomic organization, chromosome localization and expression analysis

    DEFF Research Database (Denmark)

    Larsen, Knud; Madsen, Lone Bruhn; Bendixen, Christian

    2012-01-01

    to and protection from Parkinson’s disease. Here we report cloning, characterization, expression analysis and mapping of porcine UCHL1. The UCHL1 cDNA was amplified by reverse transcriptase polymerase chain reaction (RT-PCR) using oligonucleotide primers derived from in silico sequences. The porcine cDNA codes...... for a protein of 223 amino acids which shows a very high similarity to human (98%) and to mouse (97%) UCHL1. In addition, the genomic organization of the porcine UCHL1 gene was determined. The porcine UCHL1 gene was mapped to chromosome 8(½p21)–p23. Three SNPs were found in the porcine UCHL1 sequence....... Expression analysis by quantitative real time RT-PCR demonstrated that porcine UCHL1 mRNA is differentially expressed in various organs and tissues and similar to its human counterpart. UCHL1 transcript is most abundant in brain tissues and in the spinal cord. The UCHL1 mRNA expression was also investigated...

  13. Familial transmission of a ring chromosome 21

    DEFF Research Database (Denmark)

    Hertz, Jens Michael

    1987-01-01

    A ring chromosome 21 was found in a phenotypically normal mother and her son. The clinical findings in the son were bilateral retention of the testes and a slightly delayed puberty onset. Consequences of a ring formation of a chromosome 21 in phenotypically normal patients are presented...... and discussed, and the previously reported cases of familially transmitted G-group ring chromosomes are reviewed....

  14. Female meiotic sex chromosome inactivation in chicken

    NARCIS (Netherlands)

    S. Schoenmakers (Sam); E. Wassenaar (Evelyne); J.W. Hoogerbrugge (Jos); J.S.E. Laven (Joop); J.A. Grootegoed (Anton); W.M. Baarends (Willy)

    2009-01-01

    textabstractDuring meiotic prophase in male mammals, the heterologous X and Y chromosomes remain largely unsynapsed, and meiotic sex chromosome inactivation (MSCI) leads to formation of the transcriptionally silenced XY body. In birds, the heterogametic sex is female, carrying Z and W chromosomes (Z

  15. Association study of candidate genes for susceptibility to schizophrenia and bipolar disorder on chromosome 22Q13

    DEFF Research Database (Denmark)

    Severinsen, Jacob; Binderup, Helle; Mors, Ole

    Chromosome 22q is suspected to harbor risk genes for schizophrenia as well as bipolar affective disorder. This is evidenced through genetic mapping studies, investigations of cytogenetic abnormalities, and direct examination of candidate genes. In a recent study of distantly related patients from...... the Faroe Islands we have obtained evidence suggesting two regions on chromosome 22q13 to potentially harbor susceptibility genes for both schizophrenia and bipolar affective disorder. We have selected a number of candidate genes from these two regions for further analysis, including the neuro-gene WKL1...... and unrelated controls, and in a Scottish case-control sample comprising 200 schizophrenics, 200 bipolar patients and 200 controls. None of the investigated SNPs have so far showed strong evidence of association to either bipolar disorder or schizophrenia....

  16. Genome-wide divergence, haplotype distribution and population demographic histories for Gossypium hirsutum and Gossypium barbadense as revealed by genome-anchored SNPs

    Science.gov (United States)

    Use of 10,129 singleton SNPs of known genomic location in tetraploid cotton provided unique opportunities to characterize genome-wide diversity among 440 Gossypium hirsutum and 219 G. barbadense cultivars and landrace accessions of widespread origin. Using the SNPs distributed genome-wide, we exami...

  17. Design of a High Density SNP Genotyping Assay in the Pig Using SNPs Identified and Characterized by Next Generation Sequencing Technology

    DEFF Research Database (Denmark)

    Ramos, Antonio M; Crooijmans, Richard P M A; Nabeel, Nabeel A;

    2009-01-01

    Background The dissection of complex traits of economic importance to the pig industry requires the availability of a significant number of genetic markers, such as single nucleotide polymorphisms (SNPs). This study was conducted to discover several hundreds of thousands of porcine SNPs using nex...

  18. An X chromosome association scan of the Norfolk Island genetic isolate provides evidence for a novel migraine susceptibility locus at Xq12.

    Directory of Open Access Journals (Sweden)

    Bridget H Maher

    Full Text Available Migraine is a common and debilitating neurovascular disorder with a complex envirogenomic aetiology. Numerous studies have demonstrated a preponderance of women affected with migraine and previous pedigree linkage studies in our laboratory have identified susceptibility loci on chromosome Xq24-Xq28. In this study we have used the genetic isolate of Norfolk Island to further analyse the X chromosome for migraine susceptibility loci.An association approach was employed to analyse 14,124 SNPs spanning the entire X chromosome. Genotype data from 288 individuals comprising a large core-pedigree, of which 76 were affected with migraine, were analysed. Although no SNP reached chromosome-wide significance (empirical α = 1 × 10(-5 ranking by P-value revealed two primary clusters of SNPs in the top 25. A 10 SNP cluster represents a novel migraine susceptibility locus at Xq12 whilst a 11 SNP cluster represents a previously identified migraine susceptibility locus at Xq27. The strongest association at Xq12 was seen for rs599958 (OR = 1.75, P = 8.92 × 10(-4, whilst at Xq27 the strongest association was for rs6525667 (OR = 1.53, P = 1.65 × 10(-4. Further analysis of SNPs at these loci was performed in 5,122 migraineurs from the Women's Genome Health Study and provided additional evidence for association at the novel Xq12 locus (P<0.05.Overall, this study provides evidence for a novel migraine susceptibility locus on Xq12. The strongest effect SNP (rs102834, joint P = 1.63 × 10(-5 is located within the 5'UTR of the HEPH gene, which is involved in iron homeostasis in the brain and may represent a novel pathway for involvement in migraine pathogenesis.

  19. X-chromosome SNP analyses in 11 human Mediterranean populations show a high overall genetic homogeneity except in North-west Africans (Moroccans

    Directory of Open Access Journals (Sweden)

    Ben Dhiab Mohamed

    2008-02-01

    Full Text Available Abstract Background Due to its history, with a high number of migration events, the Mediterranean basin represents a challenging area for population genetic studies. A large number of genetic studies have been carried out in the Mediterranean area using different markers but no consensus has been reached on the genetic landscape of the Mediterranean populations. In order to further investigate the genetics of the human Mediterranean populations, we typed 894 individuals from 11 Mediterranean populations with 25 single-nucleotide polymorphisms (SNPs located on the X-chromosome. Results A high overall homogeneity was found among the Mediterranean populations except for the population from Morocco, which seemed to differ genetically from the rest of the populations in the Mediterranean area. A very low genetic distance was found between populations in the Middle East and most of the western part of the Mediterranean Sea. A higher migration rate in females versus males was observed by comparing data from X-chromosome, mt-DNA and Y-chromosome SNPs both in the Mediterranean and a wider geographic area. Multilocus association was observed among the 25 SNPs on the X-chromosome in the populations from Ibiza and Cosenza. Conclusion Our results support both the hypothesis of (1 a reduced impact of the Neolithic Wave and more recent migration movements in NW-Africa, and (2 the importance of the Strait of Gibraltar as a geographic barrier. In contrast, the high genetic homogeneity observed in the Mediterranean area could be interpreted as the result of the Neolithic wave caused by a large demic diffusion and/or more recent migration events. A differentiated contribution of males and females to the genetic landscape of the Mediterranean area was observed with a higher migration rate in females than in males. A certain level of background linkage disequilibrium in populations in Ibiza and Cosenza could be attributed to their demographic background.

  20. Analysis and visualization of chromosomal abnormalities in SNP data with SNPscan

    Directory of Open Access Journals (Sweden)

    Thomas George H

    2006-01-01

    Full Text Available Abstract Background A variety of diseases are caused by chromosomal abnormalities such as aneuploidies (having an abnormal number of chromosomes, microdeletions, microduplications, and uniparental disomy. High density single nucleotide polymorphism (SNP microarrays provide information on chromosomal copy number changes, as well as genotype (heterozygosity and homozygosity. SNP array studies generate multiple types of data for each SNP site, some with more than 100,000 SNPs represented on each array. The identification of different classes of anomalies within SNP data has been challenging. Results We have developed SNPscan, a web-accessible tool to analyze and visualize high density SNP data. It enables researchers (1 to visually and quantitatively assess the quality of user-generated SNP data relative to a benchmark data set derived from a control population, (2 to display SNP intensity and allelic call data in order to detect chromosomal copy number anomalies (duplications and deletions, (3 to display uniparental isodisomy based on loss of heterozygosity (LOH across genomic regions, (4 to compare paired samples (e.g. tumor and normal, and (5 to generate a file type for viewing SNP data in the University of California, Santa Cruz (UCSC Human Genome Browser. SNPscan accepts data exported from Affymetrix Copy Number Analysis Tool as its input. We validated SNPscan using data generated from patients with known deletions, duplications, and uniparental disomy. We also inspected previously generated SNP data from 90 apparently normal individuals from the Centre d'Étude du Polymorphisme Humain (CEPH collection, and identified three cases of uniparental isodisomy, four females having an apparently mosaic X chromosome, two mislabelled SNP data sets, and one microdeletion on chromosome 2 with mosaicism from an apparently normal female. These previously unrecognized abnormalities were all detected using SNPscan. The microdeletion was independently

  1. A genome-wide association study reveals a quantitative trait locus for days open on chromosome 2 in Japanese Black cattle.

    Science.gov (United States)

    Sasaki, Shinji; Ibi, Takayuki; Kojima, Takatoshi; Sugimoto, Yoshikazu

    2016-02-01

    Days open (DO), which is the interval from calving to conception, is an important trait related to reproductive performance in cattle. To identify quantitative trait loci for DO in Japanese Black cattle, we conducted a genome-wide association study with 33,303 single nucleotide polymorphisms (SNPs) using 459 animals with extreme DO values selected from a larger group of 15,488 animals. We identified a SNP on bovine chromosome 2 (BTA2) that was associated with DO. After imputation using phased haplotype data inferred from 586 812 SNPs of 1041 Japanese Black cattle, six SNPs associated with DO were located in an 8.5-kb region of high linkage disequilibrium on BTA2. These SNPs were located on the telomeric side at a distance of 177 kb from the parathyroid hormone 2 receptor (PTH2R) gene. The association was replicated in a sample of 1778 animals. In the replicated population, the frequency of the reduced-DO allele (Q) was 0.63, and it accounted for 1.72% of the total genetic variance. The effect of a Q-to-q allele substitution on DO was a decrease of 3.74 days. The results suggest that the Q allele could serve as a marker in Japanese Black cattle to select animals with superior DO performance.

  2. The origin of human chromosome 2 analyzed by comparative chromosome mapping with a DNA microlibrary

    OpenAIRE

    Wienberg, Johannes; Jauch, Anna; Lüdecke, H J; Senger, G.; Horsthemke, B; Claussen, U.; Cremer, Thomas; Arnold, N; Lengauer, Christoph

    1994-01-01

    Fluorescencein situ hybridization (FISH) of microlibraries established from distinct chromosome subregions can test the evolutionary conservation of chromosome bands as well as chromosomal rearrangements that occurred during primate evolution and will help to clarify phylogenetic relationships. We used a DNA library established by microdissection and microcloning from the entire long arm of human chromosome 2 for fluorescencein situ hybridization and comparative mapping of the chromosomes of ...

  3. Chromosomal instability in Streptomyces avermitilis: major deletion in the central region and stable circularized chromosome

    Directory of Open Access Journals (Sweden)

    Wen Ying

    2010-07-01

    Full Text Available Abstract Background The chromosome of Streptomyces has been shown to be unstable, frequently undergoing gross chromosomal rearrangements. However, the mechanisms underlying this phenomenon remain unclear, with previous studies focused on two chromosomal ends as targets for rearrangements. Here we investigated chromosomal instability of Streptomyces avermitilis, an important producer of avermectins, and characterized four gross chromosomal rearrangement events, including a major deletion in the central region. The present findings provide a valuable contribution to the mechanistic study of genetic instability in Streptomyces. Results Thirty randomly-selected "bald" mutants derived from the wild-type strain all contained gross chromosomal rearrangements of various types. One of the bald mutants, SA1-8, had the same linear chromosomal structure as the high avermectin-producing mutant 76-9. Chromosomes of both strains displayed at least three independent chromosomal rearrangements, including chromosomal arm replacement to form new 88-kb terminal inverted repeats (TIRs, and two major deletions. One of the deletions eliminated the 36-kb central region of the chromosome, but surprisingly did not affect viability of the cells. The other deletion (74-kb was internal to the right chromosomal arm. The chromosome of another bald mutant, SA1-6, was circularized with deletions at both ends. No obvious homology was found in all fusion sequences. Generational stability analysis showed that the chromosomal structure of SA1-8 and SA1-6 was stable. Conclusions Various chromosomal rearrangements, including chromosomal arm replacement, interstitial deletions and chromosomal circularization, occurred in S. avermitilis by non-homologous recombination. The finding of an inner deletion involving in the central region of S. avermitilis chromosome suggests that the entire Streptomyces chromosome may be the target for rearrangements, which are not limited, as previously

  4. Y-chromosome polymorphism: Possible largest Y chromosome in man?

    Energy Technology Data Exchange (ETDEWEB)

    Murthy, D.S.K.; Al-Awadi, S.A.; Bastaki, L. [Kuwait Medical Genetics Centre, Sulaibikat (Kuwait)] [and others

    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.

  5. Determining effects of non-synonymous SNPs on protein-protein interactions using supervised and semi-supervised learning.

    Directory of Open Access Journals (Sweden)

    Nan Zhao

    2014-05-01

    Full Text Available Single nucleotide polymorphisms (SNPs are among the most common types of genetic variation in complex genetic disorders. A growing number of studies link the functional role of SNPs with the networks and pathways mediated by the disease-associated genes. For example, many non-synonymous missense SNPs (nsSNPs have been found near or inside the protein-protein interaction (PPI interfaces. Determining whether such nsSNP will disrupt or preserve a PPI is a challenging task to address, both experimentally and computationally. Here, we present this task as three related classification problems, and develop a new computational method, called the SNP-IN tool (non-synonymous SNP INteraction effect predictor. Our method predicts the effects of nsSNPs on PPIs, given the interaction's structure. It leverages supervised and semi-supervised feature-based classifiers, including our new Random Forest self-learning protocol. The classifiers are trained based on a dataset of comprehensive mutagenesis studies for 151 PPI complexes, with experimentally determined binding affinities of the mutant and wild-type interactions. Three classification problems were considered: (1 a 2-class problem (strengthening/weakening PPI mutations, (2 another 2-class problem (mutations that disrupt/preserve a PPI, and (3 a 3-class classification (detrimental/neutral/beneficial mutation effects. In total, 11 different supervised and semi-supervised classifiers were trained and assessed resulting in a promising performance, with the weighted f-measure ranging from 0.87 for Problem 1 to 0.70 for the most challenging Problem 3. By integrating prediction results of the 2-class classifiers into the 3-class classifier, we further improved its performance for Problem 3. To demonstrate the utility of SNP-IN tool, it was applied to study the nsSNP-induced rewiring of two disease-centered networks. The accurate and balanced performance of SNP-IN tool makes it readily available to study the

  6. SNPs in the coding region of the metastasis-inducing gene MACC1 and clinical outcome in colorectal cancer

    Directory of Open Access Journals (Sweden)

    Schmid Felicitas

    2012-07-01

    Full Text Available Abstract Background Colorectal cancer is one of the main cancers in the Western world. About 90% of the deaths arise from formation of distant metastasis. The expression of the newly identified gene metastasis associated in colon cancer 1 (MACC1 is a prognostic indicator for colon cancer metastasis. Here, we analyzed for the first time the impact of single nucleotide polymorphisms (SNPs in the coding region of MACC1 for clinical outcome of colorectal cancer patients. Additionally, we screened met proto-oncogene (Met, the transcriptional target gene of MACC1, for mutations. Methods We sequenced the coding exons of MACC1 in 154 colorectal tumors (stages I, II and III and the crucial exons of Met in 60 colorectal tumors (stages I, II and III. We analyzed the association of MACC1 polymorphisms with clinical data, including metachronous metastasis, UICC stages, tumor invasion, lymph node metastasis and patients’ survival (n = 154, stages I, II and III. Furthermore, we performed biological assays in order to evaluate the functional impact of MACC1 SNPs on the motility of colorectal cancer cells. Results We genotyped three MACC1 SNPs in the coding region. Thirteen % of the tumors had the genotype cg (rs4721888, L31V, 48% a ct genotype (rs975263, S515L and 84% a gc or cc genotype (rs3735615, R804T. We found no association of these SNPs with clinicopathological parameters or with patients’ survival, when analyzing the entire patients’ cohort. An increased risk for a shorter metastasis-free survival of patients with a ct genotype (rs975263 was observed in younger colon cancer patients with stage I or II (P = 0.041, n = 18. In cell culture, MACC1 SNPs did not affect MACC1-induced cell motility and proliferation. Conclusion In summary, the identification of coding MACC1 SNPs in primary colorectal tumors does not improve the prediction for metastasis formation or for patients’ survival compared to MACC1 expression analysis alone. The ct genotype (rs

  7. Construction of the High-Density Genetic Linkage Map and Chromosome Map of Large Yellow Croaker (Larimichthys crocea

    Directory of Open Access Journals (Sweden)

    Jingqun Ao

    2015-11-01

    Full Text Available High-density genetic maps are essential for genome assembly, comparative genomic analysis and fine mapping of complex traits. In this study, 31,191 single nucleotide polymorphisms (SNPs evenly distributed across the large yellow croaker (Larimichthys crocea genome were identified using restriction-site associated DNA sequencing (RAD-seq. Among them, 10,150 high-confidence SNPs were assigned to 24 consensus linkage groups (LGs. The total length of the genetic linkage map was 5451.3 cM with an average distance of 0.54 cM between loci. This represents the densest genetic map currently reported for large yellow croaker. Using 2889 SNPs to target specific scaffolds, we assigned 533 scaffolds, comprising 421.44 Mb (62.04% of the large yellow croaker assembled sequence, to the 24 linkage groups. The mapped assembly scaffolds in large yellow croaker were used for genome synteny analyses against the stickleback (Gasterosteus aculeatus and medaka (Oryzias latipes. Greater synteny was observed between large yellow croaker and stickleback. This supports the hypothesis that large yellow croaker is more closely related to stickleback than to medaka. Moreover, 1274 immunity-related genes and 195 hypoxia-related genes were mapped to the 24 chromosomes of large yellow croaker. The integration of the high-resolution genetic map and the assembled sequence provides a valuable resource for fine mapping and positional cloning of quantitative trait loci associated with economically important traits in large yellow croaker.

  8. Chromosome congression explained by nanoscale electrostatics.

    Science.gov (United States)

    Gagliardi, L John; Shain, Daniel H

    2014-02-24

    Nanoscale electrostatic microtubule disassembly forces between positively charged molecules in kinetochores and negative charges on plus ends of microtubules have been implicated in poleward chromosome motions and may also contribute to antipoleward chromosome movements. We propose that chromosome congression can be understood in terms of antipoleward nanoscale electrostatic microtubule assembly forces between negatively charged microtubule plus ends and like-charged chromosome arms, acting in conjunction with poleward microtubule disassembly forces. Several other aspects of post-attachment prometaphase chromosome motions, as well as metaphase oscillations, are consistently explained within this framework.

  9. The Chromosomes of Birds during Meiosis.

    Science.gov (United States)

    Pigozzi, María I

    2016-01-01

    The cytological analysis of meiotic chromosomes is an exceptional tool to approach complex processes such as synapsis and recombination during the division. Chromosome studies of meiosis have been especially valuable in birds, where naturally occurring mutants or experimental knock-out animals are not available to fully investigate the basic mechanisms of major meiotic events. This review highlights the main contributions of synaptonemal complex and lampbrush chromosome research to the current knowledge of avian meiosis, with special emphasis on the organization of chromosomes during prophase I, the impact of chromosome rearrangements during meiosis, and distinctive features of the ZW pair.

  10. Polymer models of chromosome (re)organization

    Science.gov (United States)

    Mirny, Leonid

    Chromosome Conformation Capture technique (Hi-C) provides comprehensive information about frequencies of spatial interactions between genomic loci. Inferring 3D organization of chromosomes from these data is a challenging biophysical problem. We develop a top-down approach to biophysical modeling of chromosomes. Starting with a minimal set of biologically motivated interactions we build ensembles of polymer conformations that can reproduce major features observed in Hi-C experiments. I will present our work on modeling organization of human metaphase and interphase chromosomes. Our works suggests that active processes of loop extrusion can be a universal mechanism responsible for formation of domains in interphase and chromosome compaction in metaphase.

  11. Chromosome painting of Z and W sex chromosomes in Characidium (Characiformes, Crenuchidae).

    Science.gov (United States)

    Pazian, Marlon F; Shimabukuro-Dias, Cristiane Kioko; Pansonato-Alves, José Carlos; Oliveira, Claudio; Foresti, Fausto

    2013-03-01

    Some species of the genus Characidium have heteromorphic ZZ/ZW sex chromosomes with a totally heterochromatic W chromosome. Methods for chromosome microdissection associated with chromosome painting have become important tools for cytogenetic studies in Neotropical fish. In Characidium cf. fasciatum, the Z chromosome contains a pericentromeric heterochromatin block, whereas the W chromosome is completely heterochromatic. Therefore, a probe was produced from the W chromosome through microdissection and degenerate oligonucleotide-primed polymerase chain reaction amplification. FISH was performed using the W probe on the chromosomes of specimens of this species. This revealed expressive marks in the pericentromeric region of the Z chromosome as well as a completely painted W chromosome. When applying the same probe on chromosome preparations of C. cf. gomesi and Characidium sp., a pattern similar to C. cf. fasciatum was found, while C. cf. zebra, C. cf. lagosantense and Crenuchus spilurus species showed no hybridization signals. Structural changes in the chromosomes of an ancestral sexual system in the group that includes the species C. cf. gomesi, C. cf. fasciatum and Characidium sp., could have contributed to the process of speciation and could represent a causal mechanism of chromosomal diversification in this group. The heterochromatinization process possibly began in homomorphic and homologous chromosomes of an ancestral form, and this process could have given rise to the current patterns found in the species with sex chromosome heteromorphism.

  12. ASSOCIATIONS BETWEEN SNPs IN BOVINE ESTROGEN RECEPTOR GENE AND PRODUCTION TRAITS IN HOLSTEIN CATTLE

    Directory of Open Access Journals (Sweden)

    Nina Moravčíková

    2015-02-01

    Full Text Available aim of this study was to determine allelic and genotypic frequency of two SNPs in ERα gene and evaluate the associations between ERα genetic variants and milk production traits in Holstein cattle. Analysis of the molecular mechanisms involved in the regulation of reproduction in connection with milk production and followed genotyping of the individuals with optimal genetic potential may facilitate the animal selection in dairy cattle farms. Genomic DNA was obtained in total from 150 hair root samples of Holstein cows. Two polymorphic sites in 5´region on ERα gene (BTA6 were analysed. Genotyping of animals was carried out by PCR-RFLP method using SnaBI and BglI restriction endonucleases. After restriction analyses was detected in population the presence of two ERα/SnaBI (GG, AG, and three ERα/BglI genotypes (GG, AG, AA. The highest proportion was found for individuals with ERα/SnaBI GG (85% and ERα/BglI AA (83% genotypes. The missing of ERα/SnaBI AA genotype was reflected to the higher distribution of G allele (0.92± 0.02. For the ERα/BglI polymorphism was observed the higher frequency of A allele (0.91±0.02. The differences between observed and expected genotype frequencies caused the deviations from HWE in locus ERα/SnaBI. The statistical analyses of ERα genotypes effect on milk production traits was performed with linear models (GLM procedure. Based on the selected effect we were able to estimate the variability of analyzed traits on 80%. The ERα/SnaBI and ERα/BglI genotypes affected the variability of milk, protein and fat yield only non-significant (P > 0.05.

  13. In vitro human keratinocyte migration rates are associated with SNPs in the KRT1 interval.

    Directory of Open Access Journals (Sweden)

    Heng Tao

    Full Text Available Efforts to develop effective therapeutic treatments for promoting fast wound healing after injury to the epidermis are hindered by a lack of understanding of the factors involved. Re-epithelialization is an essential step of wound healing involving the migration of epidermal keratinocytes over the wound site. Here, we examine genetic variants in the keratin-1 (KRT1 locus for association with migration rates of human epidermal keratinocytes (HEK isolated from different individuals. Although the role of intermediate filament genes, including KRT1, in wound activated keratinocytes is well established, this is the first study to examine if genetic variants in humans contribute to differences in the migration rates of these cells. Using an in vitro scratch wound assay we observe quantifiable variation in HEK migration rates in two independent sets of samples; 24 samples in the first set and 17 samples in the second set. We analyze genetic variants in the KRT1 interval and identify SNPs significantly associated with HEK migration rates in both samples sets. Additionally, we show in the first set of samples that the average migration rate of HEK cells homozygous for one common haplotype pattern in the KRT1 interval is significantly faster than that of HEK cells homozygous for a second common haplotype pattern. Our study demonstrates that genetic variants in the KRT1 interval contribute to quantifiable differences in the migration rates of keratinocytes isolated from different individuals. Furthermore we show that in vitro cell assays can successfully be used to deconstruct complex traits into simple biological model systems for genetic association studies.

  14. Temperature Switch PCR (TSP: Robust assay design for reliable amplification and genotyping of SNPs

    Directory of Open Access Journals (Sweden)

    Mather Diane E

    2009-12-01

    Full Text Available Abstract Background Many research and diagnostic applications rely upon the assay of individual single nucleotide polymorphisms (SNPs. Thus, methods to improve the speed and efficiency for single-marker SNP genotyping are highly desirable. Here, we describe the method of temperature-switch PCR (TSP, a biphasic four-primer PCR system with a universal primer design that permits amplification of the target locus in the first phase of thermal cycling before switching to the detection of the alleles. TSP can simplify assay design for a range of commonly used single-marker SNP genotyping methods, and reduce the requirement for individual assay optimization and operator expertise in the deployment of SNP assays. Results We demonstrate the utility of TSP for the rapid construction of robust and convenient endpoint SNP genotyping assays based on allele-specific PCR and high resolution melt analysis by generating a total of 11,232 data points. The TSP assays were performed under standardised reaction conditions, requiring minimal optimization of individual assays. High genotyping accuracy was verified by 100% concordance of TSP genotypes in a blinded study with an independent genotyping method. Conclusion Theoretically, TSP can be directly incorporated into the design of assays for most current single-marker SNP genotyping methods. TSP provides several technological advances for single-marker SNP genotyping including simplified assay design and development, increased assay specificity and genotyping accuracy, and opportunities for assay automation. By reducing the requirement for operator expertise, TSP provides opportunities to deploy a wider range of single-marker SNP genotyping methods in the laboratory. TSP has broad applications and can be deployed in any animal and plant species.

  15. Chromosomal patterns in human malignant astrocytomas.

    Science.gov (United States)

    Rey, J A; Bello, M J; de Campos, J M; Kusak, M E; Ramos, C; Benitez, J

    1987-12-01

    Cytogenetic analysis by direct and/or in vitro preparations was performed on 34 malignant astrocytomas. Thirty tumors showed near-diploid chromosome numbers, whereas, tritetraploid chromosome complements were present in four tumors. The most frequent chromosomal changes implied numerical deviations by a gain of chromosomes #7, #19, and #20, and by losses of #10, #22, and Y. Structural rearrangements were present in stem- or side lines of 24 tumors. Although no common chromosomal rearrangement seems to exist among those tumors, chromosomes #1, #6, #7, and #9 were predominantly involved. Polysomy and structural rearrangements of chromosome #7 could be related to the overexpression of epidermal growth factor gene, previously observed in some malignant gliomas.

  16. Entropy as the driver of chromosome segregation.

    Science.gov (United States)

    Jun, Suckjoon; Wright, Andrew

    2010-08-01

    We present a new physical biology approach to understanding the relationship between the organization and segregation of bacterial chromosomes. We posit that replicated Escherichia coli daughter strands will spontaneously demix as a result of entropic forces, despite their strong confinement within the cell; in other words, we propose that entropy can act as a primordial physical force which drives chromosome segregation under the right physical conditions. Furthermore, proteins implicated in the regulation of chromosome structure and segregation may in fact function primarily in supporting such an entropy-driven segregation mechanism by regulating the physical state of chromosomes. We conclude that bacterial chromosome segregation is best understood in terms of spontaneous demixing of daughter strands. Our concept may also have important implications for chromosome segregation in eukaryotes, in which spindle-dependent chromosome movement follows an extended period of sister chromatid demixing and compaction.

  17. Flow cytometric detection of aberrant chromosomes

    Energy Technology Data Exchange (ETDEWEB)

    Gray, J.W.; Lucas, J.; Yu, L.C.; Langlois, R.

    1983-05-11

    This report describes the quantification of chromosomal aberrations by flow cytometry. Both homogeneously and heterogeneously occurring chromosome aberrations were studied. Homogeneously occurring aberrations were noted in chromosomes isolated from human colon carcinoma (LoVo) cells, stained with Hoechst 33258 and chromomycin A3 and analyzed using dual beam flow cytometry. The resulting bivariate flow karyotype showed a homogeneously occurring marker chromosome of intermediate size. Heterogeneously occurring aberrations were quantified by slit-scan flow cytometry in chromosomes isolated from control and irradiated Chinese hamster cells and stained with propidium iodide. Heterogeneously occurring dicentric chromosomes were detected by their shapes (two centrometers). The frequencies of such chromosomes estimated by slit-scan flow cytometry correlated well with the frequencies determined by visual microscopy.

  18. Chromosome X aneuploidy in Brazilian schizophrenic patients.

    Science.gov (United States)

    de Moraes, Leopoldo Silva; Khayat, André Salim; de Lima, Patrícia Danielle Lima; Lima, Eleonidas Moura; Pinto, Giovanny Rebouças; Leal, Mariana Ferreira; de Arruda Cardoso Smith, Marília; Burbano, Rommel Rodríguez

    2010-01-01

    The identification of cytogenetic abnormalities in schizophrenic patients may provide clues to the genes involved in this disease. For this reason, a chromosomal analysis of samples from 62 schizophrenics and 70 controls was performed with trypsin-Giemsa banding and fluorescence in situ hybridization of the X chromosome. A clonal pericentric inversion on chromosome 9 was detected in one male patient, and we also discovered mosaicism associated with X chromosome aneuploidy in female patients, primarily detected in schizophrenic and normal female controls over 40 years old. When compared with age-matched female controls, the frequency of X chromosome loss was not significantly different between schizophrenics and controls, except for the 40- to 49-year-old age group. Our findings suggest that the X chromosome loss seen in schizophrenic patients is inherent to the normal cellular aging process. However, our data also suggest that X chromosome gain may be correlated with schizophrenia in this Brazilian population.

  19. Chromosomal instability determines taxane response

    DEFF Research Database (Denmark)

    Swanton, C.; Nicke, B.; Schuett, M.;

    2009-01-01

    -positive breast cancer and occurs frequently in basal-like and Her2-positive cases. In diploid cells, but not in chromosomally unstable cells, paclitaxel causes repression of CIN-survival genes, followed by cell death. In the OV01 ovarian cancer clinical trial, a high level of CIN was associated with taxane...... chromosomal instability (CIN). Silencing 22/50 of these genes, many of which are involved in DNA repair, caused cancer cell death, suggesting that these genes are involved in the survival of aneuploid cells. Overexpression of these "CIN-survival'' genes is associated with poor outcome in estrogen receptor...... resistance but carboplatin sensitivity, indicating that CIN may determine MTS response in vivo. Thus, pretherapeutic assessment of CIN may optimize treatment stratification and clinical trial design using these agents....

  20. Microdissection and chromosome painting of the alien chromosome in an addition line of wheat-Thinopyrum intermedium

    Science.gov (United States)

    The chromosome painting is an efficient tool for chromosome research. However, plant chromosome painting is relatively underdeveloped. In this study, chromosome painting was developed and used to identify alien chromosomes in TAi-27, a wheat-Thinopyrum intermedium addition line, and chromosomes of...

  1. Bacterial Chromosome Organization and Segregation

    OpenAIRE

    Toro, Esteban; Shapiro, Lucy

    2010-01-01

    Bacterial chromosomes are generally ∼1000 times longer than the cells in which they reside, and concurrent replication, segregation, and transcription/translation of this crowded mass of DNA poses a challenging organizational problem. Recent advances in cell-imaging technology with subdiffraction resolution have revealed that the bacterial nucleoid is reliably oriented and highly organized within the cell. Such organization is transmitted from one generation to the next by progressive segrega...

  2. Environmental pollution, chromosomes, and health

    Science.gov (United States)

    Bell, Peter M.

    In mid-May, 1980, President Carter declared a state of emergency at the Love Canal area, near Niagara Falls, New York. The reason for this was for the U.S. to underwrite the relocation costs ($3-5 million) of some 2500 residents who, according to a report by the EPA (Environmental Protection Agency) may have suffered damaged chromosomes. These injuries were apparently caused by contact with toxic wastes that had been dumped in the area in the years prior to development for housing.That the toxic compounds exist in the Love Canal and Niagara Falls subsurface zones, including public water supplies, appears to be established fact. That the residents of the Love Canal area suffered chromosomal damage may be established fact as well. Whether or not these two findings can be linked to ill health of the residents is another matter. Recently, the EPA report has been described as having ‘close to zero scientific significance,’ and has been ‘discredited’(Science, 208, 123a, 1980). The reasons for this disparity go beyond differences of opinion, beyond possible inadequacies of the EPA study, and even beyond problems that probably will arise from future studies, including those now in the planning stages. The problem is that even if victims have easily recognizable injuries from toxic substances (injury that apparently has not occurred to Love Canal residents), medical science usually cannot show a causal relationship. Even chromosomal damage is, at best, difficult to interpret. In ideal studies of significant populations and control groups, the association of toxic chemical to chromosome damage and to cancer and birth defects is indirect and, up to now, has been shown to have little or no significance to an individual member of the exposed population.

  3. GSK-3 inhibitors induce chromosome instability

    Directory of Open Access Journals (Sweden)

    Staples Oliver D

    2007-08-01

    Full Text Available Abstract Background Several mechanisms operate during mitosis to ensure accurate chromosome segregation. However, during tumour evolution these mechanisms go awry resulting in chromosome instability. While several lines of evidence suggest that mutations in adenomatous polyposis coli (APC may promote chromosome instability, at least in colon cancer, the underlying mechanisms remain unclear. Here, we turn our attention to GSK-3 – a protein kinase, which in concert with APC, targets β-catenin for proteolysis – and ask whether GSK-3 is required for accurate chromosome segregation. Results To probe the role of GSK-3 in mitosis, we inhibited GSK-3 kinase activity in cells using a panel of small molecule inhibitors, including SB-415286, AR-A014418, 1-Azakenpaullone and CHIR99021. Analysis of synchronised HeLa cells shows that GSK-3 inhibitors do not prevent G1/S progression or cell division. They do, however, significantly delay mitotic exit, largely because inhibitor-treated cells have difficulty aligning all their chromosomes. Although bipolar spindles form and the majority of chromosomes biorient, one or more chromosomes often remain mono-oriented near the spindle poles. Despite a prolonged mitotic delay, anaphase frequently initiates without the last chromosome aligning, resulting in chromosome non-disjunction. To rule out the possibility of "off-target" effects, we also used RNA interference to selectively repress GSK-3β. Cells deficient for GSK-3β exhibit a similar chromosome alignment defect, with chromosomes clustered near the spindle poles. GSK-3β repression also results in cells accumulating micronuclei, a hallmark of chromosome missegregation. Conclusion Thus, not only do our observations indicate a role for GSK-3 in accurate chromosome segregation, but they also raise the possibility that, if used as therapeutic agents, GSK-3 inhibitors may induce unwanted side effects by inducing chromosome instability.

  4. Mechanisms of Chromosome Congression during Mitosis

    Science.gov (United States)

    Maiato, Helder; Gomes, Ana Margarida; Sousa, Filipe; Barisic, Marin

    2017-01-01

    Chromosome congression during prometaphase culminates with the establishment of a metaphase plate, a hallmark of mitosis in metazoans. Classical views resulting from more than 100 years of research on this topic have attempted to explain chromosome congression based on the balance between opposing pulling and/or pushing forces that reach an equilibrium near the spindle equator. However, in mammalian cells, chromosome bi-orientation and force balance at kinetochores are not required for chromosome congression, whereas the mechanisms of chromosome congression are not necessarily involved in the maintenance of chromosome alignment after congression. Thus, chromosome congression and maintenance of alignment are determined by different principles. Moreover, it is now clear that not all chromosomes use the same mechanism for congressing to the spindle equator. Those chromosomes that are favorably positioned between both poles when the nuclear envelope breaks down use the so-called “direct congression” pathway in which chromosomes align after bi-orientation and the establishment of end-on kinetochore-microtubule attachments. This favors the balanced action of kinetochore pulling forces and polar ejection forces along chromosome arms that drive chromosome oscillatory movements during and after congression. The other pathway, which we call “peripheral congression”, is independent of end-on kinetochore microtubule-attachments and relies on the dominant and coordinated action of the kinetochore motors Dynein and Centromere Protein E (CENP-E) that mediate the lateral transport of peripheral chromosomes along microtubules, first towards the poles and subsequently towards the equator. How the opposite polarities of kinetochore motors are regulated in space and time to drive congression of peripheral chromosomes only now starts to be understood. This appears to be regulated by position-dependent phosphorylation of both Dynein and CENP-E and by spindle microtubule

  5. Mechanisms of Chromosome Congression during Mitosis

    Directory of Open Access Journals (Sweden)

    Helder Maiato

    2017-02-01

    Full Text Available Chromosome congression during prometaphase culminates with the establishment of a metaphase plate, a hallmark of mitosis in metazoans. Classical views resulting from more than 100 years of research on this topic have attempted to explain chromosome congression based on the balance between opposing pulling and/or pushing forces that reach an equilibrium near the spindle equator. However, in mammalian cells, chromosome bi-orientation and force balance at kinetochores are not required for chromosome congression, whereas the mechanisms of chromosome congression are not necessarily involved in the maintenance of chromosome alignment after congression. Thus, chromosome congression and maintenance of alignment are determined by different principles. Moreover, it is now clear that not all chromosomes use the same mechanism for congressing to the spindle equator. Those chromosomes that are favorably positioned between both poles when the nuclear envelope breaks down use the so-called “direct congression” pathway in which chromosomes align after bi-orientation and the establishment of end-on kinetochore-microtubule attachments. This favors the balanced action of kinetochore pulling forces and polar ejection forces along chromosome arms that drive chromosome oscillatory movements during and after congression. The other pathway, which we call “peripheral congression”, is independent of end-on kinetochore microtubule-attachments and relies on the dominant and coordinated action of the kinetochore motors Dynein and Centromere Protein E (CENP-E that mediate the lateral transport of peripheral chromosomes along microtubules, first towards the poles and subsequently towards the equator. How the opposite polarities of kinetochore motors are regulated in space and time to drive congression of peripheral chromosomes only now starts to be understood. This appears to be regulated by position-dependent phosphorylation of both Dynein and CENP-E and by spindle

  6. Chromosome aberration assays in Allium

    Energy Technology Data Exchange (ETDEWEB)

    Grant, W.F.

    1982-01-01

    The common onion (Allium cepa) is an excellent plant for the assay of chromosome aberrations after chemical treatment. Other species of Allium (A. cepa var. proliferum, A. carinatum, A. fistulosum and A. sativum) have also been used but to a much lesser extent. Protocols have been given for using root tips from either bulbs or seeds of Allium cepa to study the cytological end-points, such as chromosome breaks and exchanges, which follow the testing of chemicals in somatic cells. It is considered that both mitotic and meiotic end-points should be used to a greater extent in assaying the cytogenetic effects of a chemical. From a literature survey, 148 chemicals are tabulated that have been assayed in 164 Allium tests for their clastogenic effect. Of the 164 assays which have been carried out, 75 are reported as giving a positive reaction, 49 positive and with a dose response, 1 positive and temperature-related, 9 borderline positive, and 30 negative; 76% of the chemicals gave a definite positive response. It is proposed that the Allium test be included among those tests routinely used for assessing chromosomal damage induced by chemicals.

  7. Whole-Genome Resequencing of a Cucumber Chromosome Segment Substitution Line and Its Recurrent Parent to Identify Candidate Genes Governing Powdery Mildew Resistance

    Science.gov (United States)

    Yu, Ting; Xu, Xuewen; Yan, Yali; Qi, Xiaohua; Chen, Xuehao

    2016-01-01

    Cucumber is an economically important vegetable crop worldwide. Powdery mildew (PM) is one of the most severe diseases that can affect cucumber crops. There have been several research efforts to isolate PM resistance genes for breeding PM-resistant cucumber. In the present study, we used a chromosome segment substitution line, SSL508-28, which carried PM resistance genes from the donor parent, JIN5-508, through twelve generations of backcrossing with a PM-susceptible inbred line, D8. We performed whole-genome resequencing of SSL508-28 and D8 to identify single nucleotide polymorphisms (SNPs), and insertions and deletions (indels). When compared against the reference genome of the inbred cucumber line 9930, a total of 468,616 SNPs and 67,259 indels were identified in SSL508-28, and 537,352 SNPs and 91,698 indels were identified in D8. Of these, 3,014 non-synonymous SNPs and 226 frameshift indels in SSL508-28, and 3,104 non-synonymous SNPs and 251 frameshift indels in D8, were identified. Bioinformatics analysis of these variations revealed a total of 15,682 SNPs and 6,262 indels between SSL508-28 and D8, among which 120 non-synonymous SNPs and 30 frameshift indels in 94 genes were detected between SSL508-28 and D8. Finally, out of these 94 genes, five resistance genes with nucleotide-binding sites and leucine-rich repeat domains were selected for qRT-PCR analysis. This revealed an upregulation of two transcripts, Csa2M435460.1 and Csa5M579560.1, in SSL508-28. Furthermore, the results of qRT-PCR analysis of these two genes in ten PM resistant and ten PM susceptible cucumber lines showed that when exposed to PM, Csa2M435460.1 and Csa5M579560.1 exhibited a higher expression level of resistant lines than susceptible lines. This indicates that Csa2M435460.1 and Csa5M579560.1 are candidate genes for PM resistance in cucumber. In addition, the non-synonymous SNPs in Csa2M435460.1 and Csa5M579560.1, identified in SSL508-28 and D8, might be the key to high PM-resistance in

  8. Mutations and/or close relatives? Six case work examples where 49 autosomal SNPs were used as supplementary markers.

    Science.gov (United States)

    Børsting, Claus; Morling, Niels

    2011-06-01

    Six case work examples are presented, where the individuals were typed for 15 autosomal short tandem repeats (STRs) and 49 autosomal single nucleotide polymorphisms (SNPs). The 15 STRs were typed with the AmpFlSTR Identifiler PCR Amplification Kit and the 49 SNPs were typed with the SNPforID multiplex assay. The six cases included two duos, two trios and two cases, where the alleged father was not available for testing and one or two of his close relatives were tested instead. The SNP investigation was more informative than the STR investigation in all six cases. In two cases, the alleged father would have been falsely included based on the STR results, while the SNP results showed that the alleged father was not the true parent. These case work examples underline the importance of performing supplementary investigations in selected cases and demonstrate the usefulness of the SNPforID multiplex assay.

  9. Analysis of SNPs and haplotypes in vitamin D pathway genes and renal cancer risk.

    Directory of Open Access Journals (Sweden)

    Sara Karami

    Full Text Available In the kidney vitamin D is converted to its active form. Since vitamin D exerts its activity through binding to the nuclear vitamin D receptor (VDR, most genetic studies have primarily focused on variation within this gene. Therefore, analysis of genetic variation in VDR and other vitamin D pathway genes may provide insight into the role of vitamin D in renal cell carcinoma (RCC etiology. RCC cases (N = 777 and controls (N = 1,035 were genotyped to investigate the relationship between RCC risk and variation in eight target genes. Minimum-p-value permutation (Min-P tests were used to identify genes associated with risk. A three single nucleotide polymorphism (SNP sliding window was used to identify chromosomal regions with a False Discovery Rate of <10%, where subsequently, haplotype relative risks were computed in Haplostats. Min-P values showed that VDR (p-value = 0.02 and retinoid-X-receptor-alpha (RXRA (p-value = 0.10 were associated with RCC risk. Within VDR, three haplotypes across two chromosomal regions of interest were identified. The first region, located within intron 2, contained two haplotypes that increased RCC risk by approximately 25%. The second region included a haplotype (rs2239179, rs12717991 across intron 4 that increased risk among participants with the TC (OR = 1.31, 95% CI = 1.09-1.57 haplotype compared to participants with the common haplotype, TT. Across RXRA, one haplotype located 3' of the coding sequence (rs748964, rs3118523, increased RCC risk 35% among individuals with the variant haplotype compared to those with the most common haplotype. This study comprehensively evaluated genetic variation across eight vitamin D pathway genes in relation to RCC risk. We found increased risk associated with VDR and RXRA. Replication studies are warranted to confirm these findings.

  10. GLIDERS - A web-based search engine for genome-wide linkage disequilibrium between HapMap SNPs

    Directory of Open Access Journals (Sweden)

    Broxholme John

    2009-10-01

    Full Text Available Abstract Background A number of tools for the examination of linkage disequilibrium (LD patterns between nearby alleles exist, but none are available for quickly and easily investigating LD at longer ranges (>500 kb. We have developed a web-based query tool (GLIDERS: Genome-wide LInkage DisEquilibrium Repository and Search engine that enables the retrieval of pairwise associations with r2 ≥ 0.3 across the human genome for any SNP genotyped within HapMap phase 2 and 3, regardless of distance between the markers. Description GLIDERS is an easy to use web tool that only requires the user to enter rs numbers of SNPs they want to retrieve genome-wide LD for (both nearby and long-range. The intuitive web interface handles both manual entry of SNP IDs as well as allowing users to upload files of SNP IDs. The user can limit the resulting inter SNP associations with easy to use menu options. These include MAF limit (5-45%, distance limits between SNPs (minimum and maximum, r2 (0.3 to 1, HapMap population sample (CEU, YRI and JPT+CHB combined and HapMap build/release. All resulting genome-wide inter-SNP associations are displayed on a single output page, which has a link to a downloadable tab delimited text file. Conclusion GLIDERS is a quick and easy way to retrieve genome-wide inter-SNP associations and to explore LD patterns for any number of SNPs of interest. GLIDERS can be useful in identifying SNPs with long-range LD. This can highlight mis-mapping or other potential association signal localisation problems.

  11. Transcriptome assembly and identification of genes and SNPs associated with growth traits in largemouth bass (Micropterus salmoides).

    Science.gov (United States)

    Li, Shengjie; Liu, Hao; Bai, Junjie; Zhu, Xinping

    2017-04-01

    Growth is one of the most crucial economic traits of all aquaculture species, but the molecular mechanisms involved in growth of largemouth bass (Micropterus salmoides) are poorly understood. The objective of this study was to screen growth-related genes of M. salmoides by RNA sequencing and identify growth-related single-nucleotide polymorphism (SNP) markers through a growth association study. The muscle transcriptomes of fast- and slow-growing largemouth bass were obtained using the RNA-Seq technique. A total of 54,058,178 and 54,742,444 qualified Illumina read pairs were obtained for the fast-growing and slow-growing groups, respectively, giving rise to 4,865,236,020 and 4,926,819,960 total clean bases, respectively. Gene expression profiling showed that 3,530 unigenes were differentially expressed between the fast-growing and slow-growing phenotypes (false discovery rate ≤0.001, the absolute value of log2 (fold change) ≥1), including 1,441 up-regulated and 2,889 down-regulated unigenes in the fast-growing largemouth bass. Analysis of these genes revealed that several signalling pathways, including the growth hormone-insulin-like growth factor 1 axis and signalling pathway, the glycolysis pathway, and the myostatin/transforming growth factor beta signalling pathway, as well as heat shock protein, cytoskeleton, and myofibril component genes might be associated with muscle growth. From these genes, 10 genes with putative SNPs were selected, and 17 SNPs were genotyped successfully. Marker-trait analysis in 340 individuals of Youlu No. 1 largemouth bass revealed three SNPs associated with growth in key genes (phosphoenolpyruvate carboxykinase 1, FOXO3b, and heat shock protein beta-1). This research provides information about key genes and SNPs related to growth, providing new clues to understanding the molecular basis of largemouth bass growth.

  12. Replication and Characterization of Association between ABO SNPs and Red Blood Cell Traits by Meta-Analysis in Europeans.

    Science.gov (United States)

    McLachlan, Stela; Giambartolomei, Claudia; White, Jon; Charoen, Pimphen; Wong, Andrew; Finan, Chris; Engmann, Jorgen; Shah, Tina; Hersch, Micha; Podmore, Clara; Cavadino, Alana; Jefferis, Barbara J; Dale, Caroline E; Hypponen, Elina; Morris, Richard W; Casas, Juan P; Kumari, Meena; Ben-Shlomo, Yoav; Gaunt, Tom R; Drenos, Fotios; Langenberg, Claudia; Kuh, Diana; Kivimaki, Mika; Rueedi, Rico; Waeber, Gerard; Hingorani, Aroon D; Price, Jacqueline F; Walker, Ann P

    2016-01-01

    Red blood cell (RBC) traits are routinely measured in clinical practice as important markers of health. Deviations from the physiological ranges are usually a sign of disease, although variation between healthy individuals also occurs, at least partly due to genetic factors. Recent large scale genetic studies identified loci associated with one or more of these traits; further characterization of known loci and identification of new loci is necessary to better understand their role in health and disease and to identify potential molecular mechanisms. We performed meta-analysis of Metabochip association results for six RBC traits-hemoglobin concentration (Hb), hematocrit (Hct), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), mean corpuscular volume (MCV) and red blood cell count (RCC)-in 11 093 Europeans from seven studies of the UCL-LSHTM-Edinburgh-Bristol (UCLEB) Consortium. We identified 394 non-overlapping SNPs in five loci at genome-wide significance: 6p22.1-6p21.33 (with HFE among others), 6q23.2 (with HBS1L among others), 6q23.3 (contains no genes), 9q34.3 (only ABO gene) and 22q13.1 (with TMPRSS6 among others), replicating previous findings of association with RBC traits at these loci and extending them by imputation to 1000 Genomes. We further characterized associations between ABO SNPs and three traits: hemoglobin, hematocrit and red blood cell count, replicating them in an independent cohort. Conditional analyses indicated the independent association of each of these traits with ABO SNPs and a role for blood group O in mediating the association. The 15 most significant RBC-associated ABO SNPs were also associated with five cardiometabolic traits, with discordance in the direction of effect between groups of traits, suggesting that ABO may act through more than one mechanism to influence cardiometabolic risk.

  13. A new approach to in silico SNP detection and some new SNPs in the Bacillus anthracis genome

    OpenAIRE

    Francoeur Joe; Brodzik Andrzej K

    2011-01-01

    Abstract Background Bacillus anthracis is one of the most monomorphic pathogens known. Identification of polymorphisms in its genome is essential for taxonomic classification, for determination of recent evolutionary changes, and for evaluation of pathogenic potency. Findings In this work three strains of the Bacillus anthracis genome are compared and previously unpublished single nucleotide polymorphisms (SNPs) are revealed. Moreover, it is shown that, despite the highly monomorphic nature o...

  14. Chromosomal divergence and evolutionary inferences in Rhodniini based on the chromosomal location of ribosomal genes

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    Sebastian Pita

    2013-05-01

    Full Text Available In this study, we used fluorescence in situ hybridisation to determine the chromosomal location of 45S rDNA clusters in 10 species of the tribe Rhodniini (Hemiptera: Reduviidae: Triatominae. The results showed striking inter and intraspecific variability, with the location of the rDNA clusters restricted to sex chromosomes with two patterns: either on one (X chromosome or both sex chromosomes (X and Y chromosomes. This variation occurs within a genus that has an unchanging diploid chromosome number (2n = 22, including 20 autosomes and 2 sex chromosomes and a similar chromosome size and genomic DNA content, reflecting a genome dynamic not revealed by these chromosome traits. The rDNA variation in closely related species and the intraspecific polymorphism in Rhodnius ecuadoriensis suggested that the chromosomal position of rDNA clusters might be a useful marker to identify recently diverged species or populations. We discuss the ancestral position of ribosomal genes in the tribe Rhodniini and the possible mechanisms involved in the variation of the rDNA clusters, including the loss of rDNA loci on the Y chromosome, transposition and ectopic pairing. The last two processes involve chromosomal exchanges between both sex chromosomes, in contrast to the widely accepted idea that the achiasmatic sex chromosomes of Heteroptera do not interchange sequences.

  15. Whole chromosome painting of B chromosomes of the red-eye tetra Moenkhausia sanctaefilomenae (Teleostei, Characidae).

    Science.gov (United States)

    Scudeler, Patricia Elda Sobrinho; Diniz, Débora; Wasko, Adriane Pinto; Oliveira, Claudio; Foresti, Fausto

    2015-01-01

    B chromosomes are dispensable genomic elements found in different groups of animals and plants. In the present study, a whole chromosome probe was generated from a specific heterochromatic B chromosome occurring in cells of the characidae fish Moenkhausia sanctaefilomenae (Steindachner, 1907). The chromosome painting probes were used in fluorescence in situ hybridization (FISH) experiments for the assessment of metaphase chromosomes obtained from individuals from three populations of Moenkhausia sanctaefilomenae. The results revealed that DNA sequences were shared between a specific B chromosome and many chromosomes of the A complement in all populations analyzed, suggesting a possible intra-specific origin of these B chromosomes. However, no hybridization signals were observed in other B chromosomes found in the same individuals, implying a possible independent origin of B chromosome variants in this species. FISH experiments using 18S rDNA probes revealed the presence of non-active ribosomal genes in some B chromosomes and in some chromosomes of the A complement, suggesting that at least two types of B chromosomes had an independent origin. The role of heterochromatic segments and ribosomal sequences in the origin of B chromosomes were discussed.

  16. Characterization of genome-wide SNPs for the water flea Daphnia pulicaria generated by genotyping-by-sequencing (GBS)

    Science.gov (United States)

    Muñoz, Joaquín; Chaturvedi, Anurag; De Meester, Luc; Weider, Lawrence J.

    2016-01-01

    The keystone aquatic herbivore Daphnia has been studied for more than 150 years in the context of evolution, ecology and ecotoxicology. Although it is rapidly becoming an emergent model for environmental and population genomics, there have been limited genome-wide level studies in natural populations. We report a unique resource of novel Single Nucleotide Polymorphic (SNP) markers for Daphnia pulicaria using the reduction in genomic complexity with the restriction enzymes approach, genotyping-by-sequencing. Using the genome of D. pulex as a reference, SNPs were scored for 53 clones from five natural populations that varied in lake trophic status. Our analyses resulted in 32,313 highly confident and bi-allelic SNP markers. 1,364 outlier SNPs were mapped on the annotated D. pulex genome, which identified 2,335 genes, including 565 within functional genes. Out of 885 EuKaryotic Orthologous Groups that we found from outlier SNPs, 294 were involved in three metabolic and four regulatory pathways. Bayesian-clustering analyses showed two distinct population clusters representing the possible combined effects of geography and lake trophic status. Our results provide an invaluable tool for future population genomics surveys in Daphnia targeting informative regions related to physiological processes that can be linked to the ecology of this emerging eco-responsive taxon. PMID:27346179

  17. Identification of single nucleotide polymorphisms (SNPs) in the 16S rRNA gene of foodborne Bacillus spp.

    Science.gov (United States)

    Fernández-No, I C; Böhme, K; Caamaño-Antelo, S; Barros-Velázquez, J; Calo-Mata, P

    2015-04-01

    The main goal of this work was the identification of single nucleotide polymorphisms (SNPs) in the 16S rRNA gene of foodborne Bacillus spp. that may be useful for typing purposes. These species include, among others, Bacillus cereus, an important pathogenic species involved in food poisoning, and Bacillus licheniformis, Bacillus subtilis and Bacillus pumilus, which are causative agents of food spoilage described as responsible for foodborne disease outbreaks. With this purpose in mind, 52 Bacillus strains isolated from culture collections and fresh and processed food were considered. SNP type "Y" at sites 212 and 476 appeared in the majority of B. licheniformis studied strains. SNP type "R" at site 278 was detected in many strains of the B. subtilis/Bacillus amyloliquefaciens group, while polymorphism "Y" at site 173 was characteristic of the majority of strains of B. cereus/Bacillus thuringiensis group. The analysis of SNPs provided more intra-specific information than phylogenetic analysis in the cases of B. cereus and B. subtilis. Moreover, this study describes novel SNPs that should be considered when designing 16S rRNA-based primers and probes for multiplex-PCR, Real-Time PCR and microarray systems for foodborne Bacillus spp.

  18. Characterization of genome-wide SNPs for the water flea Daphnia pulicaria generated by genotyping-by-sequencing (GBS).

    Science.gov (United States)

    Muñoz, Joaquín; Chaturvedi, Anurag; De Meester, Luc; Weider, Lawrence J

    2016-06-27

    The keystone aquatic herbivore Daphnia has been studied for more than 150 years in the context of evolution, ecology and ecotoxicology. Although it is rapidly becoming an emergent model for environmental and population genomics, there have been limited genome-wide level studies in natural populations. We report a unique resource of novel Single Nucleotide Polymorphic (SNP) markers for Daphnia pulicaria using the reduction in genomic complexity with the restriction enzymes approach, genotyping-by-sequencing. Using the genome of D. pulex as a reference, SNPs were scored for 53 clones from five natural populations that varied in lake trophic status. Our analyses resulted in 32,313 highly confident and bi-allelic SNP markers. 1,364 outlier SNPs were mapped on the annotated D. pulex genome, which identified 2,335 genes, including 565 within functional genes. Out of 885 EuKaryotic Orthologous Groups that we found from outlier SNPs, 294 were involved in three metabolic and four regulatory pathways. Bayesian-clustering analyses showed two distinct population clusters representing the possible combined effects of geography and lake trophic status. Our results provide an invaluable tool for future population genomics surveys in Daphnia targeting informative regions related to physiological processes that can be linked to the ecology of this emerging eco-responsive taxon.

  19. Large-scale parentage inference with SNPs: an efficient algorithm for statistical confidence of parent pair allocations.

    Science.gov (United States)

    Anderson, Eric C

    2012-11-08

    Advances in genotyping that allow tens of thousands of individuals to be genotyped at a moderate number of single nucleotide polymorphisms (SNPs) permit parentage inference to be pursued on a very large scale. The intergenerational tagging this capacity allows is revolutionizing the management of cultured organisms (cows, salmon, etc.) and is poised to do the same for scientific studies of natural populations. Currently, however, there are no likelihood-based methods of parentage inference which are implemented in a manner that allows them to quickly handle a very large number of potential parents or parent pairs. Here we introduce an efficient likelihood-based method applicable to the specialized case of cultured organisms in which both parents can be reliably sampled. We develop a Markov chain representation for the cumulative number of Mendelian incompatibilities between an offspring and its putative parents and we exploit it to develop a fast algorithm for simulation-based estimates of statistical confidence in SNP-based assignments of offspring to pairs of parents. The method is implemented in the freely available software SNPPIT. We describe the method in detail, then assess its performance in a large simulation study using known allele frequencies at 96 SNPs from ten hatchery salmon populations. The simulations verify that the method is fast and accurate and that 96 well-chosen SNPs can provide sufficient power to identify the correct pair of parents from amongst millions of candidate pairs.

  20. Prediction of disease causing non-synonymous SNPs by the Artificial Neural Network Predictor NetDiseaseSNP.

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    Morten Bo Johansen

    Full Text Available We have developed a sequence conservation-based artificial neural network predictor called NetDiseaseSNP which classifies nsSNPs as disease-causing or neutral. Our method uses the excellent alignment generation algorithm of SIFT to identify related sequences and a combination of 31 features assessing sequence conservation and the predicted surface accessibility to produce a single score which can be used to rank nsSNPs based on their potential to cause disease. NetDiseaseSNP classifies successfully disease-causing and neutral mutations. In addition, we show that NetDiseaseSNP discriminates cancer driver and passenger mutations satisfactorily. Our method outperforms other state-of-the-art methods on several disease/neutral datasets as well as on cancer driver/passenger mutation datasets and can thus be used to pinpoint and prioritize plausible disease candidates among nsSNPs for further investigation. NetDiseaseSNP is publicly available as an online tool as well as a web service: http://www.cbs.dtu.dk/services/NetDiseaseSNP.

  1. Pathway analysis of expression-related SNPs on genome-wide association study of basal cell carcinoma

    Science.gov (United States)

    Li, Xin; Liang, Liming; De Vivo, Immaculata; Tang, Jean Y.; Han, Jiali

    2016-01-01

    Genome-wide association studies (GWASs) have primarily focused on the association between individual genetic markers and risk of disease. We applied a novel approach that integrates skin expression-related single-nucleotide polymorphisms (eSNPs) and pathway analysis for GWAS of basal cell carcinoma (BCC) to identify potential novel biological pathways. We evaluated the associations between 70,932 skin eSNPs and risk of BCC among 2,323 cases and 7,275 controls of European ancestry, and then assigned them to the pathways defined by KEGG, GO, and BioCarta databases. Three KEGG pathways (colorectal cancer, actin cytoskeleton, and BCC), two GO pathways (cellular component disassembly in apoptosis, and nucleus organization), and four BioCarta pathways (Ras signaling, T cell receptor signaling, natural killer cell-mediated cytotoxicity, and links between Pyk2 and Map Kinases) showed significant association with BCC risk with p-value<0.05 and FDR<0.2. These pathways also ranked at top in sensitivity analyses. Two positive controls in KEGG, the hedgehog pathway and the BCC pathway, showed significant association with BCC risk in both main and sensitivity analyses. Our results indicate that SNPs that are undetectable by conventional GWASs are significantly associated with BCC when tested as pathways. Biological studies of these gene groups suggest their potential roles in the etiology of BCC. PMID:27367190

  2. Influence of Gender and SNPs in GPX1 Gene on Biomarkers of Selenium Status in Healthy Brazilians

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    Janaina L. S. Donadio

    2016-05-01

    Full Text Available Selenium (Se status varies worldwide as a result of natural variation of Se content in soils, dietary pattern, and the presence of SNPs. Further, Se status in Brazilians and its relationship between genetic variation and Se biomarkers is unknown. This work investigated the association between SNPs in glutathione peroxidase genes and biomarkers of Se status in healthy Brazilians. The study was conducted in 116 healthy adults in São Paulo, Brazil. Plasma and erythrocyte Se were measured by HGFAAS. Erythrocyte GPx (eGPx activity was measured spectrometrically in a biochemical analyzer. Genotypes were determined by real-time PCR using Taqman® Assays. eGPx activity was higher in females compared with males. Lower erythrocyte Se concentrations were found in heterozygous GC carriers for GPX1 rs8179169. eGPx activity was higher in females with the common genotypes, except for rs8179169. GC carriers for rs8179169 had lower erythrocyte Se in both genders, and only male carriers of the variant alleles of both rs1050450 and rs1800668 had higher eGPx activity. In conclusion, the genotype for SNPs in GPX1 and gender affected biomarkers of Se status in this pilot study with healthy Brazilians.

  3. SNPs in DNA repair or oxidative stress genes and late subcutaneous fibrosis in patients following single shot partial breast irradiation

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    Falvo Elisabetta

    2012-01-01

    Full Text Available Abstract Background The aim of this study was to evaluate the potential association between single nucleotide polymorphisms related response to radiotherapy injury, such as genes related to DNA repair or enzymes involved in anti-oxidative activities. The paper aims to identify marker genes able to predict an increased risk of late toxicity studying our group of patients who underwent a Single Shot 3D-CRT PBI (SSPBI after BCS (breast conserving surgery. Methods A total of 57 breast cancer patients who underwent SSPBI were genotyped for SNPs (single nucleotide polymorphisms in XRCC1, XRCC3, GST and RAD51 by Pyrosequencing technology. Univariate analysis (ORs and 95% CI was performed to correlate SNPs with the risk of developing ≥ G2 fibrosis or fat necrosis. Results A higher significant risk of developing ≥ G2 fibrosis or fat necrosis in patients with: polymorphic variant GSTP1 (Ile105Val (OR = 2.9; 95%CI, 0.88-10.14, p = 0.047. Conclusions The presence of some SNPs involved in DNA repair or response to oxidative stress seem to be able to predict late toxicity. Trial Registration ClinicalTrials.gov: NCT01316328

  4. Functional interaction between SNPs and microsatellite in the transcriptional regulation of insulin-like growth factor 1.

    Science.gov (United States)

    Chen, Holly Y; Huang, Wei; Leung, Vincent H K; Fung, Simon L M; Ma, Suk Ling; Jiang, Hongling; Tang, Nelson L S

    2013-09-01

    A CA-repeat microsatellite in insulin-like growth factor 1 (IGF1) promoter was associated with interindividual variation of circulating IGF1 level. Previously, we reported that such association was due to variation of haplotype unit in a linkage disequilibrium block composed of microsatellite and single-nucleotide polymorphisms (SNPs), suggesting the presence of an interaction between them. In this study, reporter assays were performed to investigate the regulatory effect and interaction of genetic variants on gene expression. We used an in vitro system to compare the transcriptional activities of haplotypes (rs35767:T>C, the CA-repeat microsatellite, rs5742612:T>C, and rs2288377:T>A) in evolutionarily conserved region of IGF1 promoter. In haplotype C-T-T, a longer microsatellite had a lower transcriptional activity (17.6 ± 2.4-fold for 17 repeats and 8.3 ± 1.1-fold for 21 repeats), whereas in haplotype T-C-A, such trend could not be observed, as the microsatellite with 21 repeats had the highest transcriptional activity (17.5 ± 2.3-fold). Because the microsatellite and SNPs affected the transcriptional activity of each other, there may be an interaction between them in the regulation of IGF1 expression. For the first time, we demonstrated that a noncoding microsatellite polymorphism could act as a functional unit and interact with SNPs in the regulation of transcription in human genome.

  5. A new approach to in silico SNP detection and some new SNPs in the Bacillus anthracis genome

    Directory of Open Access Journals (Sweden)

    Francoeur Joe

    2011-04-01

    Full Text Available Abstract Background Bacillus anthracis is one of the most monomorphic pathogens known. Identification of polymorphisms in its genome is essential for taxonomic classification, for determination of recent evolutionary changes, and for evaluation of pathogenic potency. Findings In this work three strains of the Bacillus anthracis genome are compared and previously unpublished single nucleotide polymorphisms (SNPs are revealed. Moreover, it is shown that, despite the highly monomorphic nature of Bacillus anthracis, the SNPs are (1 abundant in the genome and (2 distributed relatively uniformly across the sequence. Conclusions The findings support the proposition that SNPs, together with indels and variable number tandem repeats (VNTRs, can be used effectively not only for the differentiation of perfect strain data, but also for the comparison of moderately incomplete, noisy and, in some cases, unknown Bacillus anthracis strains. In the case when the data is of still lower quality, a new DNA sequence fingerprinting approach based on recently introduced markers, based on combinatorial-analytic concepts and called cyclic difference sets, can be used.

  6. A novel relationship for schizophrenia, bipolar and major depressive disorder Part 7: A hint from chromosome 7 high density association screen.

    Science.gov (United States)

    Chen, Xing; Long, Feng; Cai, Bin; Chen, Xiaohong; Chen, Gang

    2015-10-15

    Convergent evidence from genetics, symptology and psychopharmacology imply that there are intrinsic connection between schizophrenia (SCZ), bipolar disorder (BPD) and major depressive disorder (MDD). Also, any two or even three of these disorders could co-existe in some families. A total of 47,144 single nucleotide polymorphism (SNPs) on chromosome 7 were genotyped by Affymetrix Genome-Wide Human SNP array 6.0 on 119 SCZ, 253 BPD (type-I), 177 MDD, and 1000 controls. Associated SNP loci were comprehensively revealed and outstanding susceptibility genes were identified including CNTNAP2. a neurexin family gene. Unexpectedly, flanking genes for up to 94.74 % of of the associated SNPs were replicated (P≤9.9 E-8) in an enlarged cohort of 986 SCZ patients. Considering other convergent evidence, our results further implicate that BPD and MDD are subtypes of SCZ.

  7. The origin of Mosuo people as revealed by mtDNA and Y chromosome variation

    Institute of Scientific and Technical Information of China (English)

    WEN; Bo; SHI; Hong; REN; Ling; XI; Huifeng; LI; Kaiyuan; ZHA

    2004-01-01

    The Mosuo, living in the Lugu Lake area in northwest Yunnan Province, China, is the only matriarchal population in China. The Mosuo was officially identified as Naxi nationality although its relationship with Naxi remains controversial. We studied the genetic relationship between the Mosuo and five other ethnic groups currently residing in northwest Yunnan, i.e. Naxi, Tibetan, Bai, Yi and Pumi, by typing the genetic variations in mtDNA HVS1 and 21 Y chromosome markers (13 SNPs & 8 STR markers). We showed that the maternal lineages of the Mosuo bear the strongest resemblance with those found in Naxi while its paternal lineages are more similar to those that are prevalent in Yunnan Tibetan. The marked difference between paternal and maternal lineages may be attributable to the genetic history, matriarchal structure, and visiting marriage.

  8. Y chromosomes of 40% Chinese descend from three Neolithic super-grandfathers.

    Science.gov (United States)

    Yan, Shi; Wang, Chuan-Chao; Zheng, Hong-Xiang; Wang, Wei; Qin, Zhen-Dong; Wei, Lan-Hai; Wang, Yi; Pan, Xue-Dong; Fu, Wen-Qing; He, Yun-Gang; Xiong, Li-Jun; Jin, Wen-Fei; Li, Shi-Lin; An, Yu; Li, Hui; Jin, Li

    2014-01-01

    Demographic change of human populations is one of the central questions for delving into the past of human beings. To identify major population expansions related to male lineages, we sequenced 78 East Asian Y chromosomes at 3.9 Mbp of the non-recombining region, discovered >4,000 new SNPs, and identified many new clades. The relative divergence dates can be estimated much more precisely using a molecular clock. We found that all the Paleolithic divergences were binary; however, three strong star-like Neolithic expansions at ∼6 kya (thousand years ago) (assuming a constant substitution rate of 1×10(-9)/bp/year) indicates that ∼40% of modern Chinese are patrilineal descendants of only three super-grandfathers at that time. This observation suggests that the main patrilineal expansion in China occurred in the Neolithic Era and might be related to the development of agriculture.

  9. Y chromosomes of 40% Chinese descend from three Neolithic super-grandfathers.

    Directory of Open Access Journals (Sweden)

    Shi Yan

    Full Text Available Demographic change of human populations is one of the central questions for delving into the past of human beings. To identify major population expansions related to male lineages, we sequenced 78 East Asian Y chromosomes at 3.9 Mbp of the non-recombining region, discovered >4,000 new SNPs, and identified many new clades. The relative divergence dates can be estimated much more precisely using a molecular clock. We found that all the Paleolithic divergences were binary; however, three strong star-like Neolithic expansions at ∼6 kya (thousand years ago (assuming a constant substitution rate of 1×10(-9/bp/year indicates that ∼40% of modern Chinese are patrilineal descendants of only three super-grandfathers at that time. This observation suggests that the main patrilineal expansion in China occurred in the Neolithic Era and might be related to the development of agriculture.

  10. Novel Y-chromosome Short Tandem Repeat Variants Detected Through the Use of Massively Parallel Sequencing

    Institute of Scientific and Technical Information of China (English)

    David H Warshauer; Jennifer D Churchill; Nicole Novroski; Jonathan L King; Bruce Budowle

    2015-01-01

    Massively parallel sequencing (MPS) technology is capable of determining the sizes of short tandem repeat (STR) alleles as well as their individual nucleotide sequences. Thus, single nucleotide polymorphisms (SNPs) within the repeat regions of STRs and variations in the pattern of repeat units in a given repeat motif can be used to differentiate alleles of the same length. In this study, MPS was used to sequence 28 forensically-relevant Y-chromosome STRs in a set of 41 DNA samples from the 3 major U.S. population groups (African Americans, Caucasians, and Hispanics). The resulting sequence data, which were analyzed with STRait Razor v2.0, revealed 37 unique allele sequence variants that have not been previously reported. Of these, 19 sequences were variations of documented sequences resulting from the presence of intra-repeat SNPs or alternative repeat unit patterns. Despite a limited sampling, two of the most frequently-observed variants were found only in African American samples. The remaining 18 variants represented allele sequences for which there were no published data with which to compare. These findings illustrate the great potential of MPS with regard to increasing the resolving power of STR typing and emphasize the need for sample population characterization of STR alleles.

  11. Novel Y-chromosome Short Tandem Repeat Variants Detected Through the Use of Massively Parallel Sequencing

    Directory of Open Access Journals (Sweden)

    David H. Warshauer

    2015-08-01

    Full Text Available Massively parallel sequencing (MPS technology is capable of determining the sizes of short tandem repeat (STR alleles as well as their individual nucleotide sequences. Thus, single nucleotide polymorphisms (SNPs within the repeat regions of STRs and variations in the pattern of repeat units in a given repeat motif can be used to differentiate alleles of the same length. In this study, MPS was used to sequence 28 forensically-relevant Y-chromosome STRs in a set of 41 DNA samples from the 3 major U.S. population groups (African Americans, Caucasians, and Hispanics. The resulting sequence data, which were analyzed with STRait Razor v2.0, revealed 37 unique allele sequence variants that have not been previously reported. Of these, 19 sequences were variations of documented sequences resulting from the presence of intra-repeat SNPs or alternative repeat unit patterns. Despite a limited sampling, two of the most frequently-observed variants were found only in African American samples. The remaining 18 variants represented allele sequences for which there were no published data with which to compare. These findings illustrate the great potential of MPS with regard to increasing the resolving power of STR typing and emphasize the need for sample population characterization of STR alleles.

  12. Chromosome aberrations induced by zebularine in triticale.

    Science.gov (United States)

    Ma, Xuhui; Wang, Qing; Wang, Yanzhi; Ma, Jieyun; Wu, Nan; Ni, Shuang; Luo, Tengxiao; Zhuang, Lifang; Chu, Chenggen; Cho, Seong-Woo; Tsujimoto, Hisashi; Qi, Zengjun

    2016-07-01

    Chromosome engineering is an important approach for generating wheat germplasm. Efficient development of chromosome aberrations will facilitate the introgression and application of alien genes in wheat. In this study, zebularine, a DNA methylation transferase inhibitor, was successfully used to induce chromosome aberrations in the octoploid triticale cultivar Jinghui#1. Dry seeds were soaked in zebularine solutions (250, 500, and 750 μmol/L) for 24 h, and the 500 μmol/L treatment was tested in three additional treatment times, i.e., 12, 36, and 48 h. All treatments induced aberrations involving wheat and rye chromosomes. Of the 920 cells observed in 67 M1 plants, 340 (37.0%) carried 817 aberrations with an average of 0.89 aberrations per cell (range: 0-12). The aberrations included probable deletions, telosomes and acentric fragments (49.0%), large segmental translocations (28.9%), small segmental translocations (17.1%), intercalary translocations (2.6%), long chromosomes that could carry more than one centromere (2.0%), and ring chromosomes (0.5%). Of 510 M2 plants analyzed, 110 (21.6%) were found to carry stable aberrations. Such aberrations included 79 with varied rye chromosome numbers, 7 with wheat and rye chromosome translocations, 15 with possible rye telosomes/deletions, and 9 with complex aberrations involving variation in rye chromosome number and wheat-rye translocations. These indicated that aberrations induced by zebularine can be steadily transmitted, suggesting that zebularine is a new efficient agent for chromosome manipulation.

  13. The importance of having two X chromosomes.

    Science.gov (United States)

    Arnold, Arthur P; Reue, Karen; Eghbali, Mansoureh; Vilain, Eric; Chen, Xuqi; Ghahramani, Negar; Itoh, Yuichiro; Li, Jingyuan; Link, Jenny C; Ngun, Tuck; Williams-Burris, Shayna M

    2016-02-19

    Historically, it was thought that the number of X chromosomes plays little role in causing sex differences in traits. Recently, selected mouse models have been used increasingly to compare mice with the same type of gonad but with one versus two copies of the X chromosome. Study of these models demonstrates that mice with one X chromosome can be strikingly different from those with two X chromosomes, when the differences are not attributable to confounding group differences in gonadal hormones. The number of X chromosomes affects adiposity and metabolic disease, cardiovascular ischaemia/reperfusion injury and behaviour. The effects of X chromosome number are likely the result of inherent differences in expression of X genes that escape inactivation, and are therefore expressed from both X chromosomes in XX mice, resulting in a higher level of expression when two X chromosomes are present. The effects of X chromosome number contribute to sex differences in disease phenotypes, and may explain some features of X chromosome aneuploidies such as in Turner and Klinefelter syndromes.

  14. Chromosome analysis of arsenic affected cattle

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    S. Shekhar

    2014-10-01

    Full Text Available Aim: The aim was to study the chromosome analysis of arsenic affected cattle. Materials and Methods: 27 female cattle (21 arsenic affected and 6 normal were selected for cytogenetical study. The blood samples were collected, incubated, and cultured using appropriate media and specific methods. The samples were analyzed for chromosome number and morphology, relative length of the chromosome, arm ratio, and centromere index of X chromosome and chromosomal abnormalities in arsenic affected cattle to that of normal ones. Results: The diploid number of metaphase chromosomes in arsenic affected cattle as well as in normal cattle were all 2n=60, 58 being autosomes and 2 being sex chromosomes. From the centromeric position, karyotyping studies revealed that all the 29 pair of autosomes was found to be acrocentric or telocentric, and the sex chromosomes (XX were submetacentric in both normal and arsenic affected cattle. The relative length of all the autosome pairs and sex chrosomosome pair was found to be higher in normal than that of arsenic affected cattle. The mean arm ratio of X-chromosome was higher in normal than that of arsenic affected cattle, but it is reverse in case of centromere index value of X-chromosome. There was no significant difference of arm ratio and centromere index of X-chromosomes between arsenic affected and normal cattle. No chromosomal abnormalities were found in arsenic affected cattle. Conclusion: The chromosome analysis of arsenic affected cattle in West Bengal reported for the first time in this present study which may serve as a guideline for future studies in other species. These reference values will also help in comparison of cytological studies of arsenic affected cattle to that of various toxicants.

  15. eQTL networks unveil enriched mRNA master integrators downstream of complex disease-associated SNPs.

    Science.gov (United States)

    Li, Haiquan; Pouladi, Nima; Achour, Ikbel; Gardeux, Vincent; Li, Jianrong; Li, Qike; Zhang, Hao Helen; Martinez, Fernando D; Garcia, Joe G N 'Skip'; Lussier, Yves A

    2015-12-01

    The causal and interplay mechanisms of Single Nucleotide Polymorphisms (SNPs) associated with complex diseases (complex disease SNPs) investigated in genome-wide association studies (GWAS) at the transcriptional level (mRNA) are poorly understood despite recent advancements such as discoveries reported in the Encyclopedia of DNA Elements (ENCODE) and Genotype-Tissue Expression (GTex). Protein interaction network analyses have successfully improved our understanding of both single gene diseases (Mendelian diseases) and complex diseases. Whether the mRNAs downstream of complex disease genes are central or peripheral in the genetic information flow relating DNA to mRNA remains unclear and may be disease-specific. Using expression Quantitative Trait Loci (eQTL) that provide DNA to mRNA associations and network centrality metrics, we hypothesize that we can unveil the systems properties of information flow between SNPs and the transcriptomes of complex diseases. We compare different conditions such as naïve SNP assignments and stringent linkage disequilibrium (LD) free assignments for transcripts to remove confounders from LD. Additionally, we compare the results from eQTL networks between lymphoblastoid cell lines and liver tissue. Empirical permutation resampling (p<0.001) and theoretic Mann-Whitney U test (p<10(-30)) statistics indicate that mRNAs corresponding to complex disease SNPs via eQTL associations are likely to be regulated by a larger number of SNPs than expected. We name this novel property mRNA hubness in eQTL networks, and further term mRNAs with high hubness as master integrators. mRNA master integrators receive and coordinate the perturbation signals from large numbers of polymorphisms and respond to the personal genetic architecture integratively. This genetic signal integration contrasts with the mechanism underlying some Mendelian diseases, where a genetic polymorphism affecting a single protein hub produces a divergent signal that affects a large

  16. Genome-wide association study identified a narrow chromosome 1 region associated with chicken growth traits.

    Directory of Open Access Journals (Sweden)

    Liang Xie

    Full Text Available Chicken growth traits are important economic traits in broilers. A large number of studies are available on finding genetic factors affecting chicken growth. However, most of these studies identified chromosome regions containing putative quantitative trait loci and finding causal mutations is still a challenge. In this genome-wide association study (GWAS, we identified a narrow 1.5 Mb region (173.5-175 Mb of chicken (Gallus gallus chromosome (GGA 1 to be strongly associated with chicken growth using 47,678 SNPs and 489 F2 chickens. The growth traits included aggregate body weight (BW at 0-90 d of age measured weekly, biweekly average daily gains (ADG derived from weekly body weight, and breast muscle weight (BMW, leg muscle weight (LMW and wing weight (WW at 90 d of age. Five SNPs in the 1.5 Mb KPNA3-FOXO1A region at GGA1 had the highest significant effects for all growth traits in this study, including a SNP at 8.9 Kb upstream of FOXO1A for BW at 22-48 d and 70 d, a SNP at 1.9 Kb downstream of FOXO1A for WW, a SNP at 20.9 Kb downstream of ENSGALG00000022732 for ADG at 29-42 d, a SNP in INTS6 for BW at 90 d, and a SNP in KPNA3 for BMW and LMW. The 1.5 Mb KPNA3-FOXO1A region contained two microRNA genes that could bind to messenger ribonucleic acid (mRNA of IGF1, FOXO1A and KPNA3. It was further indicated that the 1.5 Mb GGA1 region had the strongest effects on chicken growth during 22-42 d.

  17. Intronic Polymorphisms in the CDKN2B-AS1 Gene Are Strongly Associated with the Risk of Myocardial Infarction and Coronary Artery Disease in the Saudi Population

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    Sayed AbdulAzeez

    2016-03-01

    Full Text Available Recent genome-wide association studies identified single nucleotide polymorphisms (SNPs on the chromosome 9p21.3 conferring the risk for CAD (coronary artery disease in individuals of Caucasian ancestry. We performed a genetic association study to investigate the effect of 12 candidate SNPs within 9p21.3 locus on the risk of CAD in the Saudi population of the Eastern Province of Saudi Arabia. A total of 250 Saudi CAD patients who had experienced an myocardial infarction (MI and 252 Saudi age-matched healthy controls were genotyped using TaqMan assay. Controls with evidenced lack of CAD provided 90% of statistical power at the type I error rate of 0.05. Five percent of the results were rechecked for quality control using Sanger sequencing, the results of which concurred with the TaqMan genotyping results. Association analysis of 12 SNPs indicated a significant difference in the genotype distribution for four SNPs between cases and controls (rs564398 p = 0.0315, χ2 = 4.6, odds ratio (OD = 1.5; rs4977574 p = 0.0336, χ2 = 4.5, OD = 1.4; rs2891168 p = 1.85 × 10 − 10, χ2 = 40.6, OD = 2.1 and rs1333042 p = 5.14 × 10 − 9, χ2 = 34.1, OD = 2.2. The study identified three protective haplotypes (TAAG p = 1.00 × 10 − 4; AGTA p = 0.022 and GGGCC p = 0.0175 and a risk haplotype (TGGA p = 2.86 × 10 − 10 for the development of CAD. This study is in line with others that indicated that the SNPs located in the intronic region of the CDKN2B-AS1 gene are associated with CAD.

  18. Deciphering evolutionary strata on plant sex chromosomes and fungal mating-type chromosomes through compositional segmentation.

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    Pandey, Ravi S; Azad, Rajeev K

    2016-03-01

    Sex chromosomes have evolved from a pair of homologous autosomes which differentiated into sex determination systems, such as XY or ZW system, as a consequence of successive recombination suppression between the gametologous chromosomes. Identifying the regions of recombination suppression, namely, the "evolutionary strata", is central to understanding the history and dynamics of sex chromosome evolution. Evolution of sex chromosomes as a consequence of serial recombination suppressions is well-studied for mammals and birds, but not for plants, although 48 dioecious plants have already been reported. Only two plants Silene latifolia and papaya have been studied until now for the presence of evolutionary strata on their X chromosomes, made possible by the sequencing of sex-linked genes on both the X and Y chromosomes, which is a requirement of all current methods that determine stratum structure based on the comparison of gametologous sex chromosomes. To circumvent this limitation and detect strata even if only the sequence of sex chromosome in the homogametic sex (i.e. X or Z chromosome) is available, we have developed an integrated segmentation and clustering method. In application to gene sequences on the papaya X chromosome and protein-coding sequences on the S. latifolia X chromosome, our method could decipher all known evolutionary strata, as reported by previous studies. Our method, after validating on known strata on the papaya and S. latifolia X chromosome, was applied to the chromosome 19 of Populus trichocarpa, an incipient sex chromosome, deciphering two, yet unknown, evolutionary strata. In addition, we applied this approach to the recently sequenced sex chromosome V of the brown alga Ectocarpus sp. that has a haploid sex determination system (UV system) recovering the sex determining and pseudoautosomal regions, and then to the mating-type chromosomes of an anther-smut fungus Microbotryum lychnidis-dioicae predicting five strata in the non

  19. Scaling Chromosomes for an Evolutionary Karyotype: A Chromosomal Tradeoff between Size and Number across Woody Species.

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    Liang, Guolu; Chen, Hong

    2015-01-01

    This study aims to examine the expected scaling relationships between chromosome size and number across woody species and to clarify the importance of the scaling for the maintenance of chromosome diversity by analyzing the scaling at the inter- & intra-chromosomal level. To achieve for the goals, chromosome trait data were extracted for 191 woody species (including 56 evergreen species and 135 deciduous species) from the available literature. Cross-species analyses revealed a tradeoff among chromosomes between chromosome size and number, demonstrating there is selective mechanism crossing chromosomes among woody species. And the explanations for the result were presented from intra- to inter-chromosome contexts that the scaling may be compromises among scale symmetry, mechanical requirements, and resource allocation across chromosomes. Therein, a 3/4 scaling pattern was observed between total chromosomes and m-chromosomes within nucleus which may imply total chromosomes may evolve from more to less. In addition, the primary evolutionary trend of karyotype and the role of m-chromosomes in the process of karyotype evolution were also discussed.

  20. Microdissection and chromosome painting of X and B chromosomes in Locusta migratoria.

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    Teruel, María; Cabrero, Josefa; Montiel, Eugenia E; Acosta, Manuel J; Sánchez, Antonio; Camacho, Juan Pedro M

    2009-01-01

    Acquisition of knowledge of the nature and DNA content of B chromosomes has been triggered by a collection of molecular techniques, one of which, microdissection, has provided interesting results in a number of B chromosome systems. Here we provide the first data on the molecular composition of B chromosomes in Locusta migratoria, after microdissection of the B and X chromosomes, DNA amplification by one (B) or two (X) different methods, and chromosome painting. The results showed that B chromosomes share at least two types of repetitive DNA sequences with the A chromosomes, suggesting that Bs in this species most likely arose intraspecifically. One of these repetitive DNAs is located on the heterochromatic distal half of the B chromosome and in the pericentromeric regions of about half of the A chromosomes, including the X. The other type of repetitive DNA is located interspersedly over the non-centromeric euchromatic regions of all A chromosomes and in an interstitial part of the proximal euchromatic half of the B chromosome. Chromosome painting, however, did not provide results sufficiently reliable to determine, in this species, which A chromosome gave rise to the B; this might be done by detailed analysis of the microdissected DNA sequences.

  1. Chromosome-specific segmentation revealed by structural analysis of individually isolated chromosomes.

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    Kitada, Kunio; Taima, Akira; Ogasawara, Kiyomoto; Metsugi, Shouichi; Aikawa, Satoko

    2011-04-01

    Analysis of structural rearrangements at the individual chromosomal level is still technologically challenging. Here we optimized a chromosome isolation method using fluorescent marker-assisted laser-capture and laser-beam microdissection and applied it to structural analysis of two aberrant chromosomes found in a lung cancer cell line. A high-density array-comparative genomic hybridization (array-CGH) analysis of DNA samples prepared from each of the chromosomes revealed that these two chromosomes contained 296 and 263 segments, respectively, ranging from 1.5 kb to 784.3 kb in size, derived from different portions of chromosome 8. Among these segments, 242 were common in both aberrant chromosomes, but 75 were found to be chromosome-specific. Sequences of 263 junction sites connecting the ends of segments were determined using a PCR/Sanger-sequencing procedure. Overlapping microhomologies were found at 169 junction sites. Junction partners came from various portions of chromosome 8 and no biased pattern in the positional distribution of junction partners was detected. These structural characteristics suggested the occurrence of random fragmentation of the entire chromosome 8 followed by random rejoining of these fragments. Based on that, we proposed a model to explain how these aberrant chromosomes are formed. Through these structural analyses, it was demonstrated that the optimized chromosome isolation method described here can provide high-quality chromosomal DNA for high resolution array-CGH analysis and probably for massively parallel sequencing analysis.

  2. The massive mitochondrial genome of the angiosperm Silene noctiflora is evolving by gain or loss of entire chromosomes.

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    Wu, Zhiqiang; Cuthbert, Jocelyn M; Taylor, Douglas R; Sloan, Daniel B

    2015-08-18

    Across eukaryotes, mitochondria exhibit staggering diversity in genomic architecture, including the repeated evolution of multichromosomal structures. Unlike in the nucleus, where mitosis and meiosis ensure faithful transmission of chromosomes, the mechanisms of inheritance in fragmented mitochondrial genomes remain mysterious. Multichromosomal mitochondrial genomes have recently been found in multiple species of flowering plants, including Silene noctiflora, which harbors an unusually large and complex mitochondrial genome with more than 50 circular-mapping chromosomes totaling ∼7 Mb in size. To determine the extent to which such genomes are stably maintained, we analyzed intraspecific variation in the mitochondrial genome of S. noctiflora. Complete genomes from two populations revealed a high degree of similarity in the sequence, structure, and relative abundance of mitochondrial chromosomes. For example, there are no inversions between the genomes, and there are only nine SNPs in 25 kb of protein-coding sequence. Remarkably, however, these genomes differ in the presence or absence of 19 entire chromosomes, all of which lack any identifiable genes or contain only duplicate gene copies. Thus, these mitochondrial genomes retain a full gene complement but carry a highly variable set of chromosomes that are filled with presumably dispensable sequence. In S. noctiflora, conventional mechanisms of mitochondrial sequence divergence are being outstripped by an apparently nonadaptive process of whole-chromosome gain/loss, highlighting the inherent challenge in maintaining a fragmented genome. We discuss the implications of these findings in relation to the question of why mitochondria, more so than plastids and bacterial endosymbionts, are prone to the repeated evolution of multichromosomal genomes.

  3. Building bridges within the bacterial chromosome.

    Science.gov (United States)

    Song, Dan; Loparo, Joseph J

    2015-03-01

    All organisms must dramatically compact their genomes to accommodate DNA within the cell. Bacteria use a set of DNA-binding proteins with low sequence specificity called nucleoid-associated proteins (NAPs) to assist in chromosome condensation and organization. By bending or bridging DNA, NAPs also facilitate chromosome segregation and regulate gene expression. Over the past decade, emerging single-molecule and chromosome conformation capture techniques have investigated the molecular mechanisms by which NAPs remodel and organize the bacterial chromosome. In this review we describe how such approaches reveal the biochemical mechanisms of three NAPs that are believed to facilitate DNA bridging: histone-like nucleoid structuring protein (H-NS), ParB, and structural maintenance of chromosomes (SMC). These three proteins form qualitatively different DNA bridges, leading to varied effects on transcription and chromosome segregation.