| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Lango Allen, Hana, et al.
(författare)
-
Hundreds of variants clustered in genomic loci and biological pathways affect human height.
- 2010
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 467:7317, s. 832-8
-
Tidskriftsartikel (refereegranskat)abstract
- Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P<0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
|
|
| 5. |
|
|
| 6. |
- Reghellin, Daniele, 1984-
(författare)
-
Paleoceanography of the Eastern Equatorial Pacific over the last eight million years
- 2013
-
Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Many studies have investigated the evolution of the Eastern Equatorial Pacific (EEP) Ocean paleoceanography since the late Neogene because of its role in regulating the Earth’s climate and because global climate has undergone major changes during this time period. However, current understanding of the EEP paleoceanography encounters two basic problems. First, this region is characterized by steep east-west and meridional gradients in Sea Surface Temperatures (SSTs) and biological productivity, which can vary from one year to another. Second, the seafloor lies below the lysocline in most of the area, leading to poor preservation of biogenic carbonate. As a result, sediments from the EEP exhibit major changes in their physical and compositional properties over short time, and hence sediment depth, increments. Therefore, the study of bulk sediment properties is crucial to further understand the paleoceanography of EEP during the past 8 Myr. Bulk sediment properties are highly appropriate proxies for achieving highly resolved and time comparable SST and biological productivity data because changes in such properties can be traced across the EEP over large distances.This thesis presents two manuscripts. In Paper 1 we examine the positive second-order relationship between wet bulk density (WBD) and carbonate content of sediments from the EEP. This relationship is important because it can be used to determine high-resolution carbonate content records. In Paper 2 we examine bulk sediment stable isotopes records from the EEP to understand what these records actually represent and whether these records are robust across the EEP. The main conclusions of these studies are (1) a single two-component equation cannot be used to determine carbonate content from the WBD. Instead, the WBD-carbonate relationship can only be described by an infinite series of curves representing the mixing of different components; (2) bulk sediment stable isotope records are robust across the EEP and changes in grain-size are not the primary cause of variations of these records.
|
|
| 7. |
|
|
