| 1. |
- Antoniou, Antonis C., et al.
(författare)
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A locus on 19p13 modifies risk of breast cancer in BRCA1 mutation carriers and is associated with hormone receptor-negative breast cancer in the general population
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:10, s. 885-892
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Tidskriftsartikel (refereegranskat)abstract
- Germline BRCA1 mutations predispose to breast cancer. To identify genetic modifiers of this risk, we performed a genome-wide association study in 1,193 individuals with BRCA1 mutations who were diagnosed with invasive breast cancer under age 40 and 1,190 BRCA1 carriers without breast cancer diagnosis over age 35. We took forward 96 SNPs for replication in another 5,986 BRCA1 carriers (2,974 individuals with breast cancer and 3,012 unaffected individuals). Five SNPs on 19p13 were associated with breast cancer risk (P-trend = 2.3 x 10(-9) to Ptrend = 3.9 x 10(-7)), two of which showed independent associations (rs8170, hazard ratio (HR) = 1.26, 95% CI 1.17-1.35; rs2363956 HR = 0.84, 95% CI 0.80-0.89). Genotyping these SNPs in 6,800 population-based breast cancer cases and 6,613 controls identified a similar association with estrogen receptor-negative breast cancer (rs2363956 per-allele odds ratio (OR) = 0.83, 95% CI 0.75-0.92, P-trend = 0.0003) and an association with estrogen receptor-positive disease in the opposite direction (OR = 1.07, 95% CI 1.01-1.14, P-trend = 0.016). The five SNPs were also associated with triple-negative breast cancer in a separate study of 2,301 triple-negative cases and 3,949 controls (Ptrend = 1 x 10(-7) to Ptrend = 8 x 10(-5); rs2363956 per-allele OR = 0.80, 95% CI 0.74-0.87, P-trend = 1.1 x 10(-7)).
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| 2. |
- Quimby, Robert M., et al.
(författare)
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Spectra of Hydrogen-poor Superluminous Supernovae from the Palomar Transient Factory
- 2018
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 855:1, s. 1-57
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Tidskriftsartikel (refereegranskat)abstract
- Most Type I superluminous supernovae (SLSNe-I) reported to date have been identified by their high peak luminosities and spectra lacking obvious signs of hydrogen. We demonstrate that these events can be distinguished from normal-luminosity SNe (including Type Ic events) solely from their spectra over a wide range of light-curve phases. We use this distinction to select 19 SLSNe-I and four possible SLSNe-I from the Palomar Transient Factory archive (including seven previously published objects). We present 127 new spectra of these objects and combine these with 39 previously published spectra, and we use these to discuss the average spectral properties of SLSNe-I at different spectral phases. We find that Mn II most probably contributes to the ultraviolet spectral features after maximum light, and we give a detailed study of the O II features that often characterize the early-time optical spectra of SLSNe-I. We discuss the velocity distribution of O II, finding that for some SLSNe-I this can be confined to a narrow range compared to relatively large systematic velocity shifts. Mg II and Fe II favor higher velocities than O II and C II, and we briefly discuss how this may constrain power-source models. We tentatively group objects by how well they match either SN 2011ke or PTF12dam and discuss the possibility that physically distinct events may have been previously grouped together under the SLSN-I label.
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| 3. |
- Rubin, Adam, et al.
(författare)
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TYPE II SUPERNOVA ENERGETICS AND COMPARISON OF LIGHT CURVES TO SHOCK-COOLING MODELS
- 2016
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 820:1
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Tidskriftsartikel (refereegranskat)abstract
- During the first few days after explosion, Type II supernovae (SNe) are dominated by relatively simple physics. Theoretical predictions regarding early-time SN light curves in the ultraviolet (UV) and optical bands are thus quite robust. We present, for the first time, a sample of 57 R-band SN II light curves that are well-monitored during their rise, with > 5 detections during the first 10 days after discovery, and a well-constrained time of explosion to within 1-3 days. We show that the energy per unit mass (E/M) can be deduced to roughly a factor of five by comparing early-time optical data to the 2011 model of Rabinak & Waxman, while the progenitor radius cannot be determined based on R-band data alone. We find that SN II explosion energies span a range of E/M = (0.2-20) x 10(51) erg/(10 M-circle dot), and have a mean energy per unit mass of < E/M > = 0.85 x 10(51) erg/(10 M-circle dot), corrected for Malmquist bias. Assuming a small spread in progenitor masses, this indicates a large intrinsic diversity in explosion energy. Moreover, E/M is positively correlated with the amount of Ni-56 produced in the explosion, as predicted by some recent models of core-collapse SNe. We further present several empirical correlations. The peak magnitude is correlated with the decline rate (Delta m(15)), the decline rate is weakly correlated with the rise time, and the rise time is not significantly correlated with the peak magnitude. Faster declining SNe are more luminous and have longer rise times. This limits the possible power sources for such events.
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| 4. |
- Thomassen, Mads, et al.
(författare)
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Clinical, splicing, and functional analysis to classify BRCA2 exon 3 variants : Application of a points-based ACMG/AMP approach
- 2022
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Ingår i: Human Mutation. - : Hindawi Limited. - 1059-7794 .- 1098-1004. ; 43:12, s. 1921-1944
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Tidskriftsartikel (refereegranskat)abstract
- Skipping of BRCA2 exon 3 (∆E3) is a naturally occurring splicing event, complicating clinical classification of variants that may alter ∆E3 expression. This study used multiple evidence types to assess pathogenicity of 85 variants in/near BRCA2 exon 3. Bioinformatically predicted spliceogenic variants underwent mRNA splicing analysis using minigenes and/or patient samples. ∆E3 was measured using quantitative analysis. A mouse embryonic stem cell (mESC) based assay was used to determine the impact of 18 variants on mRNA splicing and protein function. For each variant, population frequency, bioinformatic predictions, clinical data, and existing mRNA splicing and functional results were collated. Variant class was assigned using a gene-specific adaptation of ACMG/AMP guidelines, following a recently proposed points-based system. mRNA and mESC analysis combined identified six variants with transcript and/or functional profiles interpreted as loss of function. Cryptic splice site use for acceptor site variants generated a transcript encoding a shorter protein that retains activity. Overall, 69/85 (81%) variants were classified using the points-based approach. Our analysis shows the value of applying gene-specific ACMG/AMP guidelines using a points-based approach and highlights the consideration of cryptic splice site usage to appropriately assign PVS1 code strength.
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| 5. |
- Thöne, Christina C., et al.
(författare)
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NGC 2770 : A Supernova Ib Factory?
- 2009
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 698:2, s. 1307-1320
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Tidskriftsartikel (refereegranskat)abstract
- NGC 2770 has been the host of three supernovae (SNe) of Type Ib during the last ten years, SN 1999eh, SN 2007uy, and SN 2008D. SN 2008D attracted special attention due to the serendipitous discovery of an associated X-ray transient. In this paper, we study the properties of NGC 2770 and specifically the three SN sites to investigate whether this galaxy is in any way peculiar to cause a high frequency of SNe Ib. We model the global spectral energy distribution of the galaxy from broadband data and derive a star formation and SN rate comparable to the values of the Milky Way. We further study the galaxy using longslit spectroscopy covering the major axis and the three SN sites. From the spectroscopic study we find subsolar metallicities for the SN sites, a high extinction and a moderate star formation rate. In a high-resolution spectrum, we also detect diffuse interstellar bands in the line of sight toward SN 2008D. A comparison of NGC 2770 to the global properties of a galaxy sample with high SN occurrence (>= 3 SN in the last 100 years) suggests that NGC 2770 is not particularly destined to produce such an enhancement of observed SNe. Its properties are also very different from gamma-ray burst host galaxies. Statistical considerations on SN Ib detection rates give a probability of ~1.5% to find a galaxy with three Ib SNe detected in ten years. The high number of rare Ib SNe in this galaxy is therefore likely to be a coincidence rather than special properties of the galaxy itself. NGC 2770 has a small irregular companion, NGC 2770B, which is highly star-forming, has a very low mass and one of the lowest metallicities detected in the nearby universe as derived from longslit spectroscopy. In the most metal poor part, we even detect Wolf-Rayet (WR) features, which is at odds with most current models of WR stars which require high metallicities. Based on observations with the Nordic Optical Telescope, ESO proposal 080.D-0526, the GALEX and NED databases.
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| 6. |
- Vreeswijk, Paul M., et al.
(författare)
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ON THE EARLY-TIME EXCESS EMISSION IN HYDROGEN-POOR SUPERLUMINOUS SUPERNOVAE
- 2017
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 835:1
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Tidskriftsartikel (refereegranskat)abstract
- We present the light curves of the hydrogen-poor superluminous supernovae (SLSNe I) PTF 12dam and iPTF 13dcc, discovered by the (intermediate) Palomar Transient Factory. Both show excess emission at early times and a slowly declining light curve at late times. The early bump in PTF 12dam is very similar in duration (similar to 10 days) and brightness relative to the main peak (2-3 mag fainter) compared to that observed in other SLSNe I. In contrast, the long-duration (>30 days) early excess emission in iPTF 13dcc, whose brightness competes with that of the main peak, appears to be of a different nature. We construct bolometric light curves for both targets, and fit a variety of light-curve models to both the early bump and main peak in an attempt to understand the nature of these explosions. Even though the slope of the late-time decline in the light curves of both SLSNe is suggestively close to that expected from the radioactive decay of Ni-56 and Co-56, the amount of nickel required to power the full light curves is too large considering the estimated ejecta mass. The magnetar model including an increasing escape fraction provides a reasonable description of the PTF 12dam observations. However, neither the basic nor the double-peaked magnetar model is capable of reproducing the light curve of iPTF 13dcc. A model combining a shock breakout in an extended envelope with late-time magnetar energy injection provides a reasonable fit to the iPTF 13dcc observations. Finally, we find that the light curves of both PTF 12dam and iPTF 13dcc can be adequately fit with the model involving interaction with the circumstellar medium.
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| 7. |
- Vreeswijk, Paul M., et al.
(författare)
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THE HYDROGEN-POOR SUPERLUMINOUS SUPERNOVA iPTF 13ajg AND ITS HOST GALAXY IN ABSORPTION AND EMISSION
- 2014
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 797:1, s. 24-
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Tidskriftsartikel (refereegranskat)abstract
- We present imaging and spectroscopy of a hydrogen-poor superluminous supernova (SLSN) discovered by the intermediate Palomar Transient Factory, iPTF 13ajg. At a redshift of z = 0.7403, derived from narrow absorption lines, iPTF 13ajg peaked at an absolute magnitude of M-u,M-AB = -22.5, one of the most luminous supernovae to date. The observed bolometric peak luminosity of iPTF 13ajg is 3.2 x 10(44) erg s(-1), while the estimated total radiated energy is 1.3 x 10(51) erg. We detect narrow absorption lines of Mg I, Mg II, and Fe II, associated with the cold interstellar medium in the host galaxy, at two different epochs with X-shooter at the Very Large Telescope. From Voigt profile fitting, we derive the column densities log N(Mg I) = 11.94 +/- 0.06, log N(Mg II) = 14.7 +/- 0.3, and log N(Fe II) = 14.25 +/- 0.10. These column densities, as well as the Mg I and Mg II equivalent widths of a sample of hydrogen-poor SLSNe taken from the literature, are at the low end of those derived for gamma-ray bursts (GRBs) whose progenitors are also thought to be massive stars. This suggests that the environments of hydrogen-poor SLSNe and GRBs are different. From the nondetection of Fe II fine-structure absorption lines, we derive a lower limit on the distance between the supernova and the narrow-line absorbing gas of 50 pc. The neutral gas responsible for the absorption in iPTF 13ajg exhibits a single narrow component with a low velocity width, Delta V = 76 km s(-1), indicating a low-mass host galaxy. No host galaxy emission lines are detected, leading to an upper limit on the unobscured star formation rate (SFR) of SFR[O II] < 0.07 M-circle dot yr(-1). Late-time imaging shows the iPTF 13ajg host galaxy to be faint, with g(AB) approximate to 27.0 and R-AB >= 26.0 mag, corresponding to M-B,M-Vega greater than or similar to -17.7 mag.
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| 8. |
- Zanti, Maria, et al.
(författare)
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A Likelihood Ratio Approach for Utilizing Case-Control Data in the Clinical Classification of Rare Sequence Variants : Application to BRCA1 and BRCA2
- 2023
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Ingår i: Human Mutation. - : John Wiley & Sons. - 1059-7794 .- 1098-1004. ; 2023
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Tidskriftsartikel (refereegranskat)abstract
- A large number of variants identified through clinical genetic testing in disease susceptibility genes are of uncertain significance (VUS). Following the recommendations of the American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP), the frequency in case-control datasets (PS4 criterion) can inform their interpretation. We present a novel case-control likelihood ratio-based method that incorporates gene-specific age-related penetrance. We demonstrate the utility of this method in the analysis of simulated and real datasets. In the analysis of simulated data, the likelihood ratio method was more powerful compared to other methods. Likelihood ratios were calculated for a case-control dataset of BRCA1 and BRCA2 variants from the Breast Cancer Association Consortium (BCAC) and compared with logistic regression results. A larger number of variants reached evidence in favor of pathogenicity, and a substantial number of variants had evidence against pathogenicity-findings that would not have been reached using other case-control analysis methods. Our novel method provides greater power to classify rare variants compared with classical case-control methods. As an initiative from the ENIGMA Analytical Working Group, we provide user-friendly scripts and preformatted Excel calculators for implementation of the method for rare variants in BRCA1, BRCA2, and other high-risk genes with known penetrance.
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