| 1. |
- Machiela, Mitchell J., et al.
(författare)
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Characterization of Large Structural Genetic Mosaicism in Human Autosomes
- 2015
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 96:3, s. 487-497
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Tidskriftsartikel (refereegranskat)abstract
- Analyses of genome-wide association study (GWAS) data have revealed that detectable genetic mosaicism involving large (>2 Mb) structural autosomal alterations occurs in a fraction of individuals. We present results for a set of 24,849 genotyped individuals (total GWAS set II [TGSII]) in whom 341 large autosomal abnormalities were observed in 168 (0.68%) individuals. Merging data from the new TGSII set with data from two prior reports (the Gene-Environment Association Studies and the total GWAS set I) generated a large dataset of 127,179 individuals; we then conducted a meta-analysis to investigate the patterns of detectable autosomal mosaicism (n = 1,315 events in 925 [0.73%] individuals). Restricting to events >2 Mb in size, we observed an increase in event frequency as event size decreased. The combined results underscore that the rate of detectable mosaicism increases with age (p value = 5.5 x 3 10(-31)) and is higher in men (p value = 0.002) but lower in participants of African ancestry (p value = 0.003). In a subset of 47 individuals from whom serial samples were collected up to 6 years apart, complex changes were noted over time and showed an overall increase in the proportion of mosaic cells as age increased. Our large combined sample allowed for a unique ability to characterize detectable genetic mosaicism involving large structural events and strengthens the emerging evidence of non-random erosion of the genome in the aging population.
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| 2. |
- O'Mara, TA, et al.
(författare)
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Identification of nine new susceptibility loci for endometrial cancer
- 2018
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 3166-
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Tidskriftsartikel (refereegranskat)abstract
- Endometrial cancer is the most commonly diagnosed cancer of the female reproductive tract in developed countries. Through genome-wide association studies (GWAS), we have previously identified eight risk loci for endometrial cancer. Here, we present an expanded meta-analysis of 12,906 endometrial cancer cases and 108,979 controls (including new genotype data for 5624 cases) and identify nine novel genome-wide significant loci, including a locus on 12q24.12 previously identified by meta-GWAS of endometrial and colorectal cancer. At five loci, expression quantitative trait locus (eQTL) analyses identify candidate causal genes; risk alleles at two of these loci associate with decreased expression of genes, which encode negative regulators of oncogenic signal transduction proteins (SH2B3 (12q24.12) and NF1 (17q11.2)). In summary, this study has doubled the number of known endometrial cancer risk loci and revealed candidate causal genes for future study.
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| 3. |
- Brogaard, K., et al.
(författare)
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The blue straggler V106 in NGC6791 : A prototype progenitor of old single giants masquerading as young
- 2018
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Ingår i: Monthly Notices of the Royal Astronomical Society. - 0035-8711. ; 481:4, s. 5062-5072
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Tidskriftsartikel (refereegranskat)abstract
- We determine the properties of the binary star V106 in the old open cluster NGC6791. We identify the system to be a blue straggler cluster member by using a combination of groundbased and Kepler photometry and multi-epoch spectroscopy. The properties of the primary component are found to be Mp ~ 1.67M⊙, more massive than the cluster turn-off, with Rp ~ 1.91R⊙ and Teff = 7110 ± 100 K. The secondary component is highly oversized and overluminous for its low mass with Ms ~ 0.182M⊙, R⊙ ~ 0.864R⊙, and T⊙ =6875±200 K. We identify this secondary star as a bloated (proto) extremely low-mass helium white dwarf. These properties of V106 suggest that it represents a typical Algol-paradox system and that it evolved through a mass-transfer phase, which provides insight into its past evolution. We present a detailed binary stellar evolution model for the formation of V106 using the MESA code and find that the mass-transfer phase only ceased about 40 Myr ago. Due to the short orbital period (P = 1.4463 d), another mass-transfer phase is unavoidable once the current primary star evolves towards the red giant phase. We argue that V106 will evolve through a common-envelope phase within the next 100 Myr and merge to become a single overmassive giant. The high mass will make it appear young for its true age, which is revealed by the cluster properties. Therefore, V106 is potentially a prototype progenitor of old field giants masquerading as young.
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