| 951. |
- Migliorini, Gabriele, et al.
(author)
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Variation at 10p12.2 and 10p14 influences risk of childhood B-cell acute lymphoblastic leukemia and phenotype
- 2013
-
In: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 122:19, s. 3298-3307
-
Journal article (peer-reviewed)abstract
- Acute lymphoblastic leukemia (ALL) is the major pediatric cancer diagnosed in economically developed countries with B-cell precursor (BCP)-ALL, accounting for approximately 70% of ALL. Recent genome-wide association studies (GWAS) have provided the first unambiguous evidence for common inherited susceptibility to BCP-ALL, identifying susceptibility loci at 7p12.2, 9p21.3, 10q21.2, and 14q11.2. To identify additional BCP-ALL susceptibility loci, we conducted a GWAS and performed a meta-analysis with a published GWAS totaling 1658 cases and 4723 controls, with validation in 1449 cases and 1488 controls. Combined analysis identified novel loci mapping to 10p12.2 (rs10828317, odds ratio [OR] = 1.23; P = 2.30 x 10(-9)) and 10p14marked by rs3824662(OR = 1.31; P = 8.62 x 10(-12)). The single nucleotide polymorphism rs10828317 is responsible for the N215S polymorphism in exon 7 of PIP4K2A, and rs3824662 localizes to intron 3 of the transcription factor and putative tumor suppressor gene GATA3. The rs10828317 association was shown to be specifically associated with hyperdiploid ALL, whereas the rs3824662-associated risk was confined to nonhyperdiploid non-TEL-AML1 + ALL. The risk allele of rs3824662 was correlated with older age at diagnosis (P < .001) and significantly worse event-free survivorship (P < .0001). These findings provide further insights into the genetic and biological basis of inherited genetic susceptibility to BCP-ALL and the influence of constitutional genotype on disease development.
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| 952. |
- Mitchell, Jonathan S., et al.
(author)
-
Genome-wide association study identifies multiple susceptibility loci for multiple myeloma
- 2016
-
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
-
Journal article (peer-reviewed)abstract
- Multiple myeloma (MM) is a plasma cell malignancy with a significant heritable basis. Genome-wide association studies have transformed our understanding of MM predisposition, but individual studies have had limited power to discover risk loci. Here we perform a meta-analysis of these GWAS, add a new GWAS and perform replication analyses resulting in 9,866 cases and 239,188 controls. We confirm all nine known risk loci and discover eight new loci at 6p22.3 (rs34229995, P = 1.31 x 10(-8)), 6q21 (rs9372120, P = 9.09 x 10(-15)), 7q36.1 (rs7781265, P = 9.71 x 10(-9)), 8q24.21 (rs1948915, P = 4.20 x 10(-11)), 9p21.3 (rs2811710, P = 1.72 x 10(-13)), 10p12.1 (rs2790457, P = 1.77 x 10(-8)), 16q23.1 (rs7193541, P = 5.00 x 10(-12)) and 20q13.13 (rs6066835, P = 1.36 x 10(-13)), which localize in or near to JARID2, ATG5, SMARCD3, CCAT1, CDKN2A, WAC, RFWD3 and PREX1. These findings provide additional support for a polygenic model of MM and insight into the biological basis of tumour development.
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| 953. |
|
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| 954. |
- Müller, Christoph, et al.
(author)
-
Substantial Differences in Crop Yield Sensitivities Between Models Call for Functionality-Based Model Evaluation
- 2024
-
In: Earth's Future. - 2328-4277. ; 12:3
-
Journal article (peer-reviewed)abstract
- Crop models are often used to project future crop yield under climate and global change and typically show a broad range of outcomes. To understand differences in modeled responses, we analyzed modeled crop yield response types using impact response surfaces along four drivers of crop yield: carbon dioxide (C), temperature (T), water (W), and nitrogen (N). Crop yield response types help to understand differences in simulated responses per driver and their combinations rather than aggregated changes in yields as the result of simultaneous changes in various drivers. We find that models' sensitivities to the individual drivers are substantially different and often more different across models than across regions. There is some agreement across models with respect to the spatial patterns of response types but strong differences in the distribution of response types across models and their configurations suggests that models need to undergo further scrutiny. We suggest establishing standards in model evaluation based on emergent functionality not only against historical yield observations but also against dedicated experiments across different drivers to analyze emergent functional patterns of crop models.
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| 955. |
- Mulvaney, Robert, et al.
(author)
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The ST22 chronology for the Skytrain Ice Rise ice core - Part 2 : An age model to the last interglacial and disturbed deep stratigraphy
- 2023
-
In: Climate of the Past. - 1814-9324. ; 19:4, s. 851-864
-
Journal article (peer-reviewed)abstract
- We present an age model for the 651g€¯m deep ice core from Skytrain Ice Rise, situated inland of the Ronne Ice Shelf, Antarctica. The top 2000 years have previously been dated using age markers interpolated through annual layer counting. Below this, we align the Skytrain core to the AICC2012 age model using tie points in the ice and air phase, and we apply the Paleochrono program to obtain the best fit to the tie points and glaciological constraints. In the gas phase, ties are made using methane and, in critical sections, δ18Oair; in the ice phase ties are through 10Be across the Laschamps event and through ice chemistry related to long-range dust transport and deposition. This strategy provides a good outcome to about 108g€¯ka (g1/4g€¯605g€¯m). Beyond that there are signs of flow disturbance, with a section of ice probably repeated. Nonetheless values of CH4 and δ18Oair confirm that part of the last interglacial (LIG), from about 117-126g€¯ka (617-627g€¯m), is present and in chronological order. Below this there are clear signs of stratigraphic disturbance, with rapid oscillation of values in both the ice and gas phase at the base of the LIG section, below 628g€¯m. Based on methane values, the warmest part of the LIG and the coldest part of the penultimate glacial are missing from our record. Ice below 631g€¯m appears to be of ageg€¯>g€¯150g€¯ka.
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| 956. |
- Niemann, C., Rosmej, F.B., Tauschwitz, A., Neff, S., Penache, D., Birkner, R., Constantin, C., Knobloch, R., Presura, R., Hoffmann, D.H.H., Yu, S.S., Lee, R.W.
(author)
-
pectroscopic density and temperature measurements and modelling of a discharge plasma for neutralized ion-beam transport.
- 2003
-
In: J.Physics D-Appl. Physics. ; 36, s. 2102-9
-
Journal article (peer-reviewed)
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| 957. |
|
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| 958. |
- Oidtmann, B, et al.
(author)
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Detection of genomic DNA of the crayfish plague fungus Aphanomyces astaci (Oomycete) in clinical samples by PCR.
- 2004
-
In: Veterinary Microbiology. - : Elsevier BV. - 0378-1135 .- 1873-2542. ; 100:3-4, s. 269-82
-
Journal article (peer-reviewed)abstract
- A diagnostic procedure, based on a polymerase chain reaction method (PCR) was developed to detect infection of crayfish with the Oomycete Aphanomyces astaci. A set of oligonucleotide primers was designed to specifically amplify A. astaci DNA in the ITS region surrounding the 5.8S rDNA gene. The PCR amplifies a 115 bp amplicon. The specificity of the primers was demonstrated by testing on 27 A. astaci strains and against 20 non-A. astaci Oomycetes and 5 fungal species. Most of the non-A. astaci Oomycete or fungal species included in the study are either known parasites of freshwater crayfish cuticle or can be found in their natural environment. Specificity was also tested against crayfish tissue and some known parasites and bacteria infecting crayfish.A protocol for the extraction of A. astaci DNA from infected crayfish tissue was developed. The optimised method allows the detection of two genome equivalents of purified A. astaci genomic DNA.The method was tested on noble crayfish (Astacus astacus), artificially infected with A. astaci. Detection of A. astaci was possible at the very first time of sampling, which was 2 days after the beginning of spore exposure
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| 959. |
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| 960. |
- O'Seaghdha, Conall M., et al.
(author)
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Meta-Analysis of Genome-Wide Association Studies Identifies Six New Loci for Serum Calcium Concentrations
- 2013
-
In: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 9:9, s. e1003796-
-
Journal article (peer-reviewed)abstract
- Calcium is vital to the normal functioning of multiple organ systems and its serum concentration is tightly regulated. Apart from CASR, the genes associated with serum calcium are largely unknown. We conducted a genome-wide association meta-analysis of 39,400 individuals from 17 population-based cohorts and investigated the 14 most strongly associated loci in <= 21,679 additional individuals. Seven loci (six new regions) in association with serum calcium were identified and replicated. Rs1570669 near CYP24A1 (P = 9.1E-12), rs10491003 upstream of GATA3 (P = 4.8E-09) and rs7481584 in CARS (P = 1.2E-10) implicate regions involved in Mendelian calcemic disorders: Rs1550532 in DGKD (P = 8.2E-11), also associated with bone density, and rs7336933 near DGKH/KIAA0564 (P = 9.1E-10) are near genes that encode distinct isoforms of diacylglycerol kinase. Rs780094 is in GCKR. We characterized the expression of these genes in gut, kidney, and bone, and demonstrate modulation of gene expression in bone in response to dietary calcium in mice. Our results shed new light on the genetics of calcium homeostasis.
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