A
bstract
We calculate the neutrino-electron elastic scattering cross section, extending the results previously obtained in ref. 1, in the presence of generic new interactions that take into account ...all the effects caused by finite neutrino masses. We address the potential significance of a heavy neutrino sector during precision measurements, particularly for tau neutrinos scattering with masses in the MeV range, for which the existing upper bounds on |
U
τ
4
|
2
would result in conceivably measurable contributions. Finally, we comment on the possibility to distinguish between Dirac and Majorana neutrinos, including the analysis of the new emerging parameters and its application to illustrative model-dependent scenarios.
An epigenetic characterization of Giemsa bands (G bands) revealed their utility as epigenetic units to investigate the differential distribution of linker histones. GC content is a strong driver in ...histone H1 distribution: H1X is enriched at high GC bands and H1.2 is abundant at low GC, compacted bands. Hi‐C analysis showed that TADs with a high H1.2/H1X ratio strongly overlap with B compartment, inaccessible chromatin and low‐GC bands.
Giemsa staining of metaphase chromosomes results in a characteristic banding useful for identification of chromosomes and its alterations. We have investigated in silico whether Giemsa bands (G bands) correlate with epigenetic and topological features of the interphase genome. Staining of G‐positive bands decreases with GC content; nonetheless, G‐negative bands are GC heterogeneous. High GC bands are enriched in active histone marks, RNA polymerase II, and SINEs and associate with gene richness, gene expression, and early replication. Low GC bands are enriched in repressive marks, lamina‐associated domains, and LINEs. Histone H1 variants distribute heterogeneously among G bands: H1X is enriched at high GC bands and H1.2 is abundant at low GC, compacted bands. According to epigenetic features and H1 content, G bands can be organized in clusters useful to compartmentalize the genome. Indeed, we have obtained Hi‐C chromosome interaction maps and compared topologically associating domains (TADs) and A/B compartments to G banding. TADs with high H1.2/H1X ratio strongly overlap with B compartment, late replicating, and inaccessible chromatin and low GC bands. We propose that GC content is a strong driver of chromatin compaction and 3D genome organization, that Giemsa staining recapitulates this organization denoted by high‐throughput techniques, and that H1 variants distribute at distinct chromatin domains.
Databases
Hi‐C data on T47D breast cancer cells have been deposited in NCBI's Gene Expression Omnibus and are accessible through GEO Series accession number GSE147627.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Fanconi anemia (FA) is caused by biallelic mutations in FA genes. Monoallelic mutations in five of these genes (
and
) increase the susceptibility to breast/ovarian cancer and are used in clinical ...diagnostics as bona-fide hereditary cancer genes. Increasing evidence suggests that monoallelic mutations in other FA genes could predispose to tumor development, especially breast cancer. The objective of this study is to assess the mutational spectrum of 14 additional FA genes (
and
) in a cohort of hereditary cancer patients, to compare with local cancer-free controls as well as GnomAD. A total of 1021 hereditary cancer patients and 194 controls were analyzed using our next generation custom sequencing panel. We identified 35 pathogenic variants in eight genes. A significant association with the risk of breast cancer/breast and ovarian cancer was found for carriers of
mutations (odds ratio (OR) = 3.14 95% confidence interval (CI) 1.4-6.17,
= 0.003). Two patients with early-onset cancer showed a pathogenic FA variant in addition to another germline mutation, suggesting a modifier role for FA variants. Our results encourage a comprehensive analysis of FA genes in larger studies to better assess their role in cancer risk.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The effective-Lagrangian description of Lorentz-invariance violation provided by the so-called Standard Model extension covers all the sectors of the Standard Model, allowing for model-independent ...studies of high-energy phenomena that might leave traces at relatively low energies. In this context, the quantification of the large set of parameters characterizing Lorentz-violating effects is well motivated. In the present work, effects from the Lorentz-nonconserving Yukawa sector on the electromagnetic moments of charged leptons are calculated, estimated, and discussed. Following a perturbative approach, explicit expressions of leading contributions are derived, and upper bounds on Lorentz violation are estimated from current data on electromagnetic moments. Scenarios regarding the coefficients of Lorentz violation are considered. In a scenario of two-point insertions preserving lepton flavor, the bound on the electron electric dipole moment yields limits as stringent as 10−27, whereas muon and tau-lepton electromagnetic moments determine bounds as restrictive as 10−14 and 10−5, respectively. Another scenario defined by the assumption that Lorentz-violating Yukawa couplings are Hermitian leads to less stringent bounds provided by the muon anomalous magnetic moment, which turn out to be as restrictive as 10−14.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
To identify predictors of patient acceptance of non-in-person cancer genetic visits before and after the COVID-19 pandemic and assess the preferences of health-care professionals.
Prospective ...multicenter cohort study (N = 578, 1 February 2018–20 April 2019) and recontacted during the COVID-19 lockdown in April 2020. Health-care professionals participated in May 2020. Association of personality traits and clinical factors with acceptance was assessed with multivariate analysis.
Before COVID-19, videoconference was more accepted than telephone-based visits (28% vs. 16% pretest, 30% vs. 19% post-test). Predictors for telephone visits were age (pretest, odds ratio OR 10-year increment = 0.79; post-test OR 10Y = 0.78); disclosure of panel testing (OR = 0.60), positive results (OR = 0.52), low conscientiousness group (OR = 2.87), and post-test level of uncertainty (OR = 0.93). Predictors for videoconference were age (pretest, OR 10Y = 0.73; post-test, OR 10Y = 0.75), educational level (pretest: OR = 1.61), low neuroticism (pretest, OR = 1.72), and post-test level of uncertainty (OR = 0.96). Patients’ reported acceptance for non-in-person visits after COVID-19 increased to 92% for the pretest and 85% for the post-test. Health-care professionals only preferred non-in-person visits for disclosure of negative results (83%).
These new delivery models need to recognize challenges associated with age and the psychological characteristics of the population and embrace health-care professionals’ preferences.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
ERCC3, a new ovarian cancer susceptibility gene? Stradella, Agostina; del Valle, Jesús; Rofes, Paula ...
European journal of cancer (1990),
December 2020, 2020-12-00, 20201201, Volume:
141
Journal Article
Peer reviewed
Hereditary breast and ovarian cancer syndrome (HBOC) is an inherited disorder with an increased risk of breast cancer (BC) and ovarian cancers (OC). Mutations in BRCA1-BRCA2 explains less than a half ...of cases. In the last decade several genes with different penetrance have been associated with an increased risk of BC or OC. A recurrent heterozygous ERCC3 truncating mutation increases the risk for breast cancer in patients with Ashkenazi Jewish ancestry. Our study aimed to investigate the role of ERCC3 truncating variants in a cohort of patients with suspicion of HBOC.
ERCC3 screening by multigene-panel analysis in 1311 unrelated patients after our regional consensus for genetic testing in hereditary cancer was done. In addition, 453 Spanish cancer-free individuals and 51,343 GnomAD non-Finnish, non-cancer European individuals were used as control populations.
We identified 13 patients with heterozygous ERCC3 truncating variants (0.99%). Five of them also carried a mutation in a high- /moderate-penetrance HBOC gene (BRCA1, BRCA2, CHEK2, and TP53) being Multilocus Inherited Neoplasia Alleles syndrome (MINAS) patients. The frequency in 453 Spanish controls was of 0.22%; similar to that observed in 51,343 non-Finnish European GnomAD population (0.24%). We found an almost statistically significant association of truncating ERCC3 variants with BC (odds ratio OR = 2.25, confidence interval CI = 0.6–5.93, P = 0.11), and we observed for the first time a significant association with OC (OR = 4.74, CI = 1–14.34, P = 0.028), that holds even after removing MINAS cases.
To our knowledge, this is the largest HBOC series comprehensively analysed for ERCC3 mutations, and the first study identifying ERCC3 as a cancer risk for OC.
•Our results confirm the association of ERCC3 truncating mutations with breast cancer.•We also describe their association with ovarian cancer for the first time. Further studies in larger cohorts are needed to more precisely establish the associated cancer risk as well as the relation with other cancer types.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Familial adenomatous polyposis (FAP) is an autosomal dominant syndrome responsible for 1% of colorectal cancers (CRCs). Up to 90% of classic FAPs are caused by inactivating mutations in APC, and ...mosaicism has been previously reported in 20% of de novo cases, usually linked to milder phenotypic manifestations. This study aimed to explore the prevalence of mosaicism in 11 unsolved cases of classic FAP and to evaluate the diagnostic yield of somatic testing. Paired samples of colorectal polyps, tumors, and/or mucosa were analyzed using a custom next-generation sequencing panel targeting 15 polyposis and CRC-predisposing genes. Whenever possible, the extension of mosaicism to blood or sperm was also examined. Of 11 patients with classic adenomatous polyposis, a mosaic pathogenic variant in APC was identified in 7 (64%). No other altered genes were identified. In two of seven patients (29%), mosaicism was found restricted to colonic tissues, whereas in five of seven patients (71%), it was extended to the blood. Germline affectation was confirmed in one patient. We report the first analysis at a somatic level of 15 genes associated with CRC susceptibility, which highlights the role of APC mosaicism in classic FAP etiology. The results further reinforce the importance of testing target tissues when blood test results are negative.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
Histone H1, a vital component in chromatin structure, binds to linker DNA and regulates nuclear processes. We have investigated the distribution of histone H1 variants in a breast cancer ...cell line using ChIP-Seq. Two major groups of variants are identified: H1.2, H1.3, H1.5 and H1.0 are abundant in low GC regions (B compartment), while H1.4 and H1X preferentially localize in high GC regions (A compartment). Examining their abundance within transposable elements (TEs) reveals that H1X and H1.4 are enriched in recently-incorporated TEs (SVA and SINE-Alu), while H1.0/H1.2/H1.3/H1.5 are more abundant in older elements. Notably, H1X is particularly enriched in SVA families, while H1.4 shows the highest abundance in young AluY elements. Although low GC variants are generally enriched in LINE, LTR and DNA repeats, H1X and H1.4 are also abundant in a subset of recent LINE-L1 and LTR repeats. H1X enrichment at SVA and Alu is consistent across multiple cell lines. Further, H1X depletion leads to TE derepression, suggesting its role in maintaining TE repression. Overall, this study provides novel insights into the differential distribution of histone H1 variants among repetitive elements, highlighting the potential involvement of H1X in repressing TEs recently incorporated within the human genome.
Graphical Abstract
Graphical Abstract
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