30 research outputs found
On the nature of the fourth generation neutrino and its implications
We consider the neutrino sector of a Standard Model with four generations.
While the three light neutrinos can obtain their masses from a variety of
mechanisms with or without new neutral fermions, fourth-generation neutrinos
need at least one new relatively light right-handed neutrino. If lepton number
is not conserved this neutrino must have a Majorana mass term whose size
depends on the underlying mechanism for lepton number violation. Majorana
masses for the fourth generation neutrinos induce relative large two-loop
contributions to the light neutrino masses which could be even larger than the
cosmological bounds. This sets strong limits on the mass parameters and mixings
of the fourth generation neutrinos.Comment: To be published. Few typos corrected, references update
Effective Lagrangian approach to neutrinoless double beta decay and neutrino masses
Neutrinoless double beta () decay can in general produce
electrons of either chirality, in contrast with the minimal Standard Model (SM)
extension with only the addition of the Weinberg operator, which predicts two
left-handed electrons in the final state. We classify the lepton number
violating (LNV) effective operators with two leptons of either chirality but no
quarks, ordered according to the magnitude of their contribution to \znbb
decay. We point out that, for each of the three chirality assignments, and , there is only one LNV operator of the corresponding type
to lowest order, and these have dimensions 5, 7 and 9, respectively. Neutrino
masses are always induced by these extra operators but can be delayed to one or
two loops, depending on the number of RH leptons entering in the operator.
Then, the comparison of the decay rate and neutrino masses
should indicate the effective scenario at work, which confronted with the LHC
searches should also eventually decide on the specific model elected by nature.
We also list the SM additions generating these operators upon integration of
the heavy modes, and discuss simple realistic examples of renormalizable
theories for each case.Comment: Accepted for publication. Few misprints corrected and new references
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Identification of constrained sequence elements across 239 primate genomes
Noncoding DNA is central to our understanding of human gene regulation and complex diseases1,2, and measuring the evolutionary sequence constraint can establish the functional relevance of putative regulatory elements in the human genome3–9. Identifying the genomic elements that have become constrained specifically in primates has been hampered by the faster evolution of noncoding DNA compared to protein-coding DNA10, the relatively short timescales separating primate species11, and the previously limited availability of whole-genome sequences12. Here we construct a whole-genome alignment of 239 species, representing nearly half of all extant species in the primate order. Using this resource, we identified human regulatory elements that are under selective constraint across primates and other mammals at a 5% false discovery rate. We detected 111,318 DNase I hypersensitivity sites and 267,410 transcription factor binding sites that are constrained specifically in primates but not across other placental mammals and validate their cis-regulatory effects on gene expression. These regulatory elements are enriched for human genetic variants that affect gene expression and complex traits and diseases. Our results highlight the important role of recent evolution in regulatory sequence elements differentiating primates, including humans, from other placental mammals
Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples
Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts
Vocal responsiveness in male wild chimpanzees: implications for the evolution of language
Vocal responsiveness in male wild chimpanzees: implications for the evolution of language Several captive chimpanzees and bonobos have learned to use symbols and to comprehend syntax. Thus, compared with other nonhumans, these animals appear to have unusual cognitive powers that can be recruited for communicative behavior. This raises the possibility that wild chimpanzee vocal communication is more complex than heretofore demonstrated. To examine this possibility, I investigated whether wild chimpanzee vocal exchanges exhibit uniquely human conversational attributes. The results indicate that wild chimpanzees vocalize at low rates, tend not to respond to calls that they hear, and, when they do respond, tend to give calls that are similar to the ones they have heard. Thus, chimpanzee vocal interactions resemble those of other primate species, and show no special similarity to human conversations. The results support the view that we need to explore cognitive and social continuities and discontinuities with nonhuman primates to understand the origin and evolution of language, but also emphasize the need for fine-grained analyses of wild chimpanzee vocal interactions
Identification of constrained sequence elements across 239 primate genomes
Noncoding DNA is central to our understanding of human gene regulation and complex diseases and measuring the evolutionary sequence constraint can establish the functional relevance of putative regulatory elements in the human genome. Identifying the genomic elements that have become constrained specifically in primates has been hampered by the faster evolution of noncoding DNA compared to protein-coding DNA10, the relatively short timescales separating primate species, and the previously limited availability of whole-genome sequences12. Here we construct a whole-genome alignment of 239 species, representing nearly half of all extant species in the primate order. Using this resource, we identified human regulatory elements that are under selective constraint across primates and other mammals at a 5% false discovery rate. We detected 111,318 DNase I hypersensitivity sites and 267,410 transcription factor binding sites that are constrained specifically in primates but not across other placental mammals and validate their cis-regulatory effects on gene expression. These regulatory elements are enriched for human genetic variants that affect gene expression and complex traits and diseases. Our results highlight the important role of recent evolution in regulatory sequence elements differentiating primates, including humans, from other placental mammals
Infanticide in chimpanzees: Review of cases and a new within-group observation from the Kanyawara study group in Kibale National Park
Sex differences in oncogenic mutational processes
Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research.Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research.Peer reviewe
Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples
The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts.The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that -80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAFPeer reviewe
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Sex differences in oncogenic mutational processes
Funder: Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada (NSERC Canadian Network for Research and Innovation in Machining Technology); doi: https://doi.org/10.13039/501100002790Funder: Genome Canada (Génome Canada); doi: https://doi.org/10.13039/100008762Funder: Canada Foundation for Innovation (Fondation canadienne pour l'innovation); doi: https://doi.org/10.13039/501100000196Funder: Terry Fox Research Institute (Institut de Recherche Terry Fox); doi: https://doi.org/10.13039/501100004376Abstract: Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research