28 research outputs found
Power to Detect Risk Alleles Using Genome-Wide Tag SNP Panels
Advances in high-throughput genotyping and the International HapMap Project have enabled association studies at the whole-genome level. We have constructed whole-genome genotyping panels of over 550,000 (HumanHap550) and 650,000 (HumanHap650Y) SNP loci by choosing tag SNPs from all populations genotyped by the International HapMap Project. These panels also contain additional SNP content in regions that have historically been overrepresented in diseases, such as nonsynonymous sites, the MHC region, copy number variant regions and mitochondrial DNA. We estimate that the tag SNP loci in these panels cover the majority of all common variation in the genome as measured by coverage of both all common HapMap SNPs and an independent set of SNPs derived from complete resequencing of genes obtained from SeattleSNPs. We also estimate that, given a sample size of 1,000 cases and 1,000 controls, these panels have the power to detect single disease loci of moderate risk (λ ∼ 1.8–2.0). Relative risks as low as λ ∼ 1.1–1.3 can be detected using 10,000 cases and 10,000 controls depending on the sample population and disease model. If multiple loci are involved, the power increases significantly to detect at least one locus such that relative risks 20%–35% lower can be detected with 80% power if between two and four independent loci are involved. Although our SNP selection was based on HapMap data, which is a subset of all common SNPs, these panels effectively capture the majority of all common variation and provide high power to detect risk alleles that are not represented in the HapMap data
Design of a Bovine Low-Density SNP Array Optimized for Imputation
The Illumina BovineLD BeadChip was designed to support imputation to higher density genotypes in dairy and beef breeds by including single-nucleotide polymorphisms (SNPs) that had a high minor allele frequency as well as uniform spacing across the genome except at the ends of the chromosome where densities were increased. The chip also includes SNPs on the Y chromosome and mitochondrial DNA loci that are useful for determining subspecies classification and certain paternal and maternal breed lineages. The total number of SNPs was 6,909. Accuracy of imputation to Illumina BovineSNP50 genotypes using the BovineLD chip was over 97% for most dairy and beef populations. The BovineLD imputations were about 3 percentage points more accurate than those from the Illumina GoldenGate Bovine3K BeadChip across multiple populations. The improvement was greatest when neither parent was genotyped. The minor allele frequencies were similar across taurine beef and dairy breeds as was the proportion of SNPs that were polymorphic. The new BovineLD chip should facilitate low-cost genomic selection in taurine beef and dairy cattle
Type 2 Diabetes Modifies the association of Cad Genomic Risk Variants With Subclinical atherosclerosis
BACKGROUND: Individuals with type 2 diabetes (T2D) have an increased risk of coronary artery disease (CAD), but questions remain about the underlying pathology. Identifying which CAD loci are modified by T2D in the development of subclinical atherosclerosis (coronary artery calcification [CAC], carotid intima-media thickness, or carotid plaque) may improve our understanding of the mechanisms leading to the increased CAD in T2D.
METHODS: We compared the common and rare variant associations of known CAD loci from the literature on CAC, carotid intima-media thickness, and carotid plaque in up to 29 670 participants, including up to 24 157 normoglycemic controls and 5513 T2D cases leveraging whole-genome sequencing data from the Trans-Omics for Precision Medicine program. We included first-order T2D interaction terms in each model to determine whether CAD loci were modified by T2D. The genetic main and interaction effects were assessed using a joint test to determine whether a CAD variant, or gene-based rare variant set, was associated with the respective subclinical atherosclerosis measures and then further determined whether these loci had a significant interaction test.
RESULTS: Using a Bonferroni-corrected significance threshold of
CONCLUSIONS: These results highlight T2D as an important modifier of rare variant associations in CAD loci with CAC
The Gulf of Ambracia’s common bottlenose dolphins (<i>Tursiops truncatus</i>):a highly dense and yet threatened population
The common bottlenose dolphin Tursiops truncatus is the only cetacean present in the semi-closed waters of the Gulf of Ambracia, western Greece. This increasingly degraded coastal ecosystem hosts one of the highest observed densities in the Mediterranean for this species. Photo-identification data and tissue samples collected through skin-swabbing and remote biopsy sampling techniques during boat-based surveys conducted between 2006-2015 in the Gulf, were used to examine bottlenose dolphin abundance, population trends, site fidelity, genetic differentiation and toxicological status. Bottlenose dolphins showed high levels of year-round site fidelity throughout the 10-year study period. Dolphin population estimates mostly fell between 130 and 170 with CVs averaging about 10%; a trend in population size over the 10 years was a decline of 1.6% per year but this was not significant. A clear genetic differentiation between the bottlenose dolphins of the Gulf and their conspecifics from neighbouring populations was detected and low genetic diversity was also found. In addition, pesticides where identified as factors posing a real toxicological problem for local bottlenose dolphins. Therefore, in the Gulf of Ambracia, high dolphin density does not seem to be indicative of favourable conservation status or pristine habitat
Past Connectivity but Recent Inbreeding in Cross River Gorillas Determined Using Whole Genomes from Single Hairs
The critically endangered western gorillas (Gorilla gorilla) are divided into two subspecies: the western lowland (G. g. gorilla) and the Cross River (G. g. diehli) gorilla. Given the difficulty in sampling wild great ape populations and the small estimated size of the Cross River gorilla population, only one whole genome of a Cross River gorilla has been sequenced to date, hindering the study of this subspecies at the population level. In this study, we expand the number of whole genomes available for wild western gorillas, generating 41 new genomes (25 belonging to Cross River gorillas) using single shed hairs collected from gorilla nests. By combining these genomes with publicly available wild gorilla genomes, we confirm that Cross River gorillas form three population clusters. We also found little variation in genome-wide heterozygosity among them. Our analyses reveal long runs of homozygosity (>10 Mb), indicating recent inbreeding in Cross River gorillas. This is similar to that seen in mountain gorillas but with a much more recent bottleneck. We also detect past gene flow between two Cross River sites, Afi Mountain Wildlife Sanctuary and the Mbe Mountains. Furthermore, we observe past allele sharing between Cross River gorillas and the northern western lowland gorilla sites, as well as with the eastern gorilla species. This is the first study using single shed hairs from a wild species for whole genome sequencing to date. Taken together, our results highlight the importance of implementing conservation measures to increase connectivity among Cross River gorilla sites
Imputation accuracy for Bovine3K and BovineLD genotypes.
<p>Imputation was performed for A) Bovine3K and B) BovineLD genotypes using Beagle software (<a href="http://faculty.washington.edu/browning/beagle/beagle.html" target="_blank">http://faculty.washington.edu/browning/beagle/beagle.html</a>); imputation accuracy is reported by single-nucleotide polymorphism (SNP).</p
Accuracy of imputation<sup>a</sup> from BovineLD or Bovine3K genotypes to BovineSNP50 genotypes for Australian Holsteins with and without a sire in the reference population<sup>b</sup>.
<p><sup><i>a</i></sup>Imputation was done using Beagle software (<a href="http://faculty.washington.edu/browning/beagle/beagle.html" target="_blank">http://faculty.washington.edu/browning/beagle/beagle.html</a>).</p><p><sup><i>b</i></sup>Reference population included 1,831 animals.</p