| 11. |
|
|
| 12. |
- Clark, DW, et al.
(författare)
-
Associations of autozygosity with a broad range of human phenotypes
- 2019
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4957-
-
Tidskriftsartikel (refereegranskat)abstract
- In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding.
|
|
| 13. |
|
|
| 14. |
- Abdo, A. A., et al.
(författare)
-
FERMI DISCOVERY OF GAMMA-RAY EMISSION FROM NGC 1275
- 2009
-
Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 699:1, s. 31-39
-
Tidskriftsartikel (refereegranskat)abstract
- We report the discovery of high-energy (E > 100 MeV) gamma-ray emission from NGC 1275, a giant elliptical galaxy lying at the center of the Perseus cluster of galaxies, based on observations made with the Large Area Telescope (LAT) of the Fermi Gamma-ray Space Telescope. The positional center of the gamma-ray source is only approximate to 3' away from the NGC 1275 nucleus, well within the 95% LAT error circle of approximate to 5'. The spatial distribution of gamma-ay photons is consistent with a point source. The average flux and power-law photon index measured with the LAT from 2008 August 4 to 2008 December 5 are F-gamma = (2.10 +/- 0.23) x 10(-7) ph (>100 MeV) cm(-2) s(-1) and Gamma = 2.17 +/- 0.05, respectively. The measurements are statistically consistent with constant flux during the four-month LAT observing period. Previous EGRET observations gave an upper limit of F-gamma < 3.72 x 10(-8) ph (>100 MeV) cm(-2) s(-1) to the gamma-ray flux from NGC 1275. This indicates that the source is variable on timescales of years to decades, and therefore restricts the fraction of emission that can be produced in extended regions of the galaxy cluster. Contemporaneous and historical radio observations are also reported. The broadband spectrum of NGC 1275 is modeled with a simple one-zone synchrotron/synchrotron self-Compton model and a model with a decelerating jet flow.
|
|
| 15. |
|
|
| 16. |
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
- Isobe, T, et al.
(författare)
-
Multi-omics analysis defines highly refractory RAS burdened immature subgroup of infant acute lymphoblastic leukemia
- 2022
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 4501-
-
Tidskriftsartikel (refereegranskat)abstract
- KMT2A-rearranged infant acute lymphoblastic leukemia (ALL) represents the most refractory type of childhood leukemia. To uncover the molecular heterogeneity of this disease, we perform RNA sequencing, methylation array analysis, whole exome and targeted deep sequencing on 84 infants with KMT2A-rearranged leukemia. Our multi-omics clustering followed by single-sample and single-cell inference of hematopoietic differentiation establishes five robust integrative clusters (ICs) with different master transcription factors, fusion partners and corresponding stages of B-lymphopoietic and early hemato-endothelial development: IRX-type differentiated (IC1), IRX-type undifferentiated (IC2), HOXA-type MLLT1 (IC3), HOXA-type MLLT3 (IC4), and HOXA-type AFF1 (IC5). Importantly, our deep mutational analysis reveals that the number of RAS pathway mutations predicts prognosis and that the most refractory subgroup of IC2 possesses 100% frequency and the heaviest burden of RAS pathway mutations. Our findings highlight the previously under-appreciated intra- and inter-patient heterogeneity of KMT2A-rearranged infant ALL and provide a rationale for the future development of genomics-guided risk stratification and individualized therapy.
|
|
| 20. |
|
|
