| 1. |
- Gisladottir, Rosa S, et al.
(författare)
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Sequence Variants in TAAR5 and Other Loci Affect Human Odor Perception and Naming.
- 2020
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Ingår i: Current biology : CB. - : Elsevier BV. - 1879-0445 .- 0960-9822. ; 30:23
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Tidskriftsartikel (refereegranskat)abstract
- Olfactory receptor (OR) genes in humans form a special class characterized by unusually high DNA sequence diversity, which should give rise to differences in perception and behavior. In the largest genome-wide association study to date based on olfactory testing, we investigated odor perception and naming with smell tasks performed by 9,122 Icelanders, with replication in a separate sample of 2,204 individuals. We discovered an association between a low-frequency missense variant in TAAR5 and reduced intensity rating of fish odor containing trimethylamine (p.Ser95Pro, pcombined= 5.6× 10-15). We demonstrate that TAAR5 genotype affects aversion to fish odor, reflected by linguistic descriptions of the odor and pleasantness ratings. We also discovered common sequence variants in two canonical olfactory receptor loci that associate with increased intensity and naming of licorice odor (trans-anethole: lead variant p.Lys233Asn in OR6C70, pcombined= 8.8× 10-16 and pcombined= 1.4× 10-9) and enhanced naming of cinnamon (trans-cinnamaldehyde; intergenic variant rs317787-T, pcombined= 5.0× 10-17). Together, our results show that TAAR5 genotype variation influences human odor responses and highlight that sequence diversity in canonical OR genes can lead to enhanced olfactory ability, in contrast to the view that greater tolerance for mutations in the human OR repertoire leads to diminished function.
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| 2. |
- Oddsson, Asmundur, et al.
(författare)
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Deficit of homozygosity among 1.52 million individuals and genetic causes of recessive lethality
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Genotypes causing pregnancy loss and perinatal mortality are depleted among living individuals and are therefore difficult to find. To explore genetic causes of recessive lethality, we searched for sequence variants with deficit of homozygosity among 1.52 million individuals from six European populations. In this study, we identified 25 genes harboring protein-altering sequence variants with a strong deficit of homozygosity (10% or less of predicted homozygotes). Sequence variants in 12 of the genes cause Mendelian disease under a recessive mode of inheritance, two under a dominant mode, but variants in the remaining 11 have not been reported to cause disease. Sequence variants with a strong deficit of homozygosity are over-represented among genes essential for growth of human cell lines and genes orthologous to mouse genes known to affect viability. The function of these genes gives insight into the genetics of intrauterine lethality. We also identified 1077 genes with homozygous predicted loss-of-function genotypes not previously described, bringing the total set of genes completely knocked out in humans to 4785.
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| 3. |
- Styrkarsdottir, Unnur, et al.
(författare)
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Whole-genome sequencing identifies rare genotypes in COMP and CHADL associated with high risk of hip osteoarthritis
- 2017
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 49:5, s. 801-805
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Tidskriftsartikel (refereegranskat)abstract
- We performed a genome-wide association study of total hip replacements, based on variants identified through whole-genome sequencing, which included 4,657 Icelandic patients and 207,514 population controls. We discovered two rare signals that strongly associate with osteoarthritis total hip replacement: a missense variant, c.1141G>C (p.Asp369His), in the COMP gene (allelic frequency = 0.026%, P = 4.0 × 10-12, odds ratio (OR) = 16.7) and a frameshift mutation, rs532464664 (p.Val330Glyfs∗106), in the CHADL gene that associates through a recessive mode of inheritance (homozygote frequency = 0.15%, P = 4.5 × 10-18, OR = 7.71). On average, c.1141G>C heterozygotes and individuals homozygous for rs532464664 had their hip replacement operation 13.5 years and 4.9 years earlier than others (P = 0.0020 and P = 0.0026), respectively. We show that the full-length CHADL transcript is expressed in cartilage. Furthermore, the premature stop codon introduced by the CHADL frameshift mutation results in nonsense-mediated decay of the mutant transcripts.
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| 4. |
- Helgason, Hannes, et al.
(författare)
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Adaptive Multiscale Complexity Analysis of Fetal Heart Rate
- 2011
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Ingår i: IEEE Transactions on Biomedical Engineering. - 0018-9294 .- 1558-2531. ; 58:8, s. 2186-2193
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Tidskriftsartikel (refereegranskat)abstract
- Per partum fetal asphyxia is a major cause of neonatal morbidity and mortality. Fetal heart rate monitoring plays an important role in early detection of acidosis, an indicator for asphyxia. This problem is addressed in this paper by introducing a novel complexity analysis of fetal heart rate data, based on producing a collection of piecewise linear approximations of varying dimensions from which a measure of complexity is extracted. This procedure specifically accounts for the highly nonstationary context of labor by being adaptive and multiscale. Using a reference dataset, made of real per partum fetal heart rate data, collected in situ and carefully constituted by obstetricians, the behavior of the proposed approach is analyzed and illustrated. Its performance is evaluated in terms of the rate of correct acidosis detection versus the rate of false detection, as well as how early the detection is made. Computational cost is also discussed. The results are shown to be extremely promising and further potential uses of the tool are discussed. MATLAB routines implementing the procedure will be made available at the time of publication.
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| 5. |
- Helgason, Hannes, et al.
(författare)
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Framework for Adaptive Multiscale Analysis of Nonhomogeneous Point Processes
- 2011
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Ingår i: 2011 ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY (EMBC). - New York : IEEE. - 9781424441228 ; , s. 7727-7730
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Konferensbidrag (refereegranskat)abstract
- We develop the methodology for hypothesis testing and model selection in nonhomogeneous Poisson processes, with an eye toward the application of modeling and variability detection in heart beat data. Modeling the process' non-constant rate function using templates of simple basis functions, we develop the generalized likelihood ratio statistic for a given template and a multiple testing scheme to model-select from a family of templates. A dynamic programming algorithm inspired by network flows is used to compute the maximum likelihood template in a multiscale manner. In a numerical example, the proposed procedure is nearly as powerful as the super-optimal procedures that know the true template size and true partition, respectively. Extensions to general history-dependent point processes is discussed.
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| 6. |
- Helgason, Hannes, et al.
(författare)
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Multiscale framework for adaptive and robust enhancement of depth in multi-view imagery
- 2012
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Ingår i: Image Processing (ICIP), 2012 19th IEEE International Conference on. - : IEEE. - 9781467325332 ; , s. 13-16
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Konferensbidrag (refereegranskat)abstract
- Depth Image Based Rendering (DIBR) is a standard technique in free viewpoint television for rendering virtual camera views. For synthesis it utilizes one or several reference texture images and associated depth images, which contain information about the 3D structure of the scene. Many popular depth estimation methods infer the depth information by considering texture images in pairs. This often leads to severe inconsistencies among multiple reference depth images, resulting in poor rendering quality. We propose a method which takes as input a set of depth images and returns an enhanced depth map to be used for rendering at the virtual viewpoint. Our framework is data-driven and based on a simple geometric multiscale model of the underlying depth. Inconsistencies and errors in the inputted depth images are handled locally using tools from the field of robust statistics. Numerical comparison shows the method outperform standard MPEG DIBR software.
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| 7. |
- Helgason, Hannes, et al.
(författare)
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Synthesis of multivariate stationary series with prescribed marginal distributions and covariance using circulant matrix embedding
- 2011
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Ingår i: Signal Processing. - : Elsevier BV. - 0165-1684 .- 1872-7557. ; 91:8, s. 1741-1758
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Tidskriftsartikel (refereegranskat)abstract
- The problem of synthesizing multivariate stationary series Y[n] = (Y-1[n],...,Y-p[n](T), n is an element of Z, with prescribed non-Gaussian marginal distributions, and a targeted covariance structure, is addressed. The focus is on constructions based on a memoryless transformation Y-p[n] = f(p)(X-p[n]) of a multivariate stationary Gaussian series X[n] = (X-1[n],...,X-p[n])(T). The mapping between the targeted covariance and that of the Gaussian series is expressed via Hermite expansions. The various choices of the transforms f(p) for a prescribed marginal distribution are discussed in a comprehensive manner. The interplay between the targeted marginal distributions, the choice of the transforms f(p), and on the resulting reachability of the targeted covariance, is discussed theoretically and illustrated on examples. Also, an original practical procedure warranting positive definiteness for the transformed covariance at the price of approximating the targeted covariance is proposed, based on a simple and natural modification of the popular circulant matrix embedding technique. The applications of the proposed methodology are also discussed in the context of network traffic modeling. MATIAB codes implementing the proposed synthesis procedure are publicly available at http://www.hermir.org.
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| 8. |
- Lewis, Cathryn M, et al.
(författare)
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Genome scan meta-analysis of schizophrenia and bipolar disorder, part II : Schizophrenia
- 2003
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Ingår i: American Journal of Human Genetics. - 0002-9297 .- 1537-6605. ; 73:1, s. 34-48
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Tidskriftsartikel (refereegranskat)abstract
- Schizophrenia is a common disorder with high heritability and a 10-fold increase in risk to siblings of probands. Replication has been inconsistent for reports of significant genetic linkage. To assess evidence for linkage across studies, rank-based genome scan meta-analysis (GSMA) was applied to data from 20 schizophrenia genome scans. Each marker for each scan was assigned to 1 of 120 30-cM bins, with the bins ranked by linkage scores (1 = most significant) and the ranks averaged across studies (R(avg)) and then weighted for sample size (N(sqrt)[affected casess]). A permutation test was used to compute the probability of observing, by chance, each bin's average rank (P(AvgRnk)) or of observing it for a bin with the same place (first, second, etc.) in the order of average ranks in each permutation (P(ord)). The GSMA produced significant genomewide evidence for linkage on chromosome 2q (PAvgRnk<.000417). Two aggregate criteria for linkage were also met (clusters of nominally significant P values that did not occur in 1,000 replicates of the entire data set with no linkage present): 12 consecutive bins with both P(AvgRnk) and P(ord)<.05, including regions of chromosomes 5q, 3p, 11q, 6p, 1q, 22q, 8p, 20q, and 14p, and 19 consecutive bins with P(ord)<.05, additionally including regions of chromosomes 16q, 18q, 10p, 15q, 6q, and 17q. There is greater consistency of linkage results across studies than has been previously recognized. The results suggest that some or all of these regions contain loci that increase susceptibility to schizophrenia in diverse populations.
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| 9. |
- Petkov, Petko N., et al.
(författare)
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Feature set augmentation for enhancing the performance of a non-intrusive quality predictor
- 2012
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Ingår i: 2012 4th International Workshop on Quality of Multimedia Experience, QoMEX 2012. - : IEEE. - 9781467307253 ; , s. 121-126
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Konferensbidrag (refereegranskat)abstract
- A non-intrusive quality predictor constitutes a mapping from signal features to a (typically one dimensional) representation of the perceived quality. Assuming that the regression model performing the mapping is suited to the data, the performance of the predictor largely depends on how well the parameters of this regression model can be inferred from the training data. In situations where the training data is scarce, model performance is degraded due to over-fitting. The effects of over-fitting can be mitigated by feature selection but the model performance remains low due to the insufficiently representative training data. The objective we pursue is to enhance the performance of a quality predictor by augmenting the feature set with the output of a pre-trained quality predictor. This approach introduces an implicit dependence of the regression model parameters on a larger amount of training data. In view of the increasing usage of speech signals with higher bandwidth, and the dearth of training data for such signals, an augmentation of particular interest is that of a wide-band feature set with a narrow-band quality prediction. Experimental results for additive noise and non-linear distortions encountered in hearing aids, using quality labels from an intrusive quality predictor, illustrate the performance enhancement capabilities of the proposed approach.
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| 10. |
- Sandoval-Velasco, Marcela, et al.
(författare)
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The ancestry and geographical origins of St Helena's liberated Africans
- 2023
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Ingår i: American Journal of Human Genetics. - : Cell Press. - 0002-9297 .- 1537-6605. ; 110:9, s. 1590-1599
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Tidskriftsartikel (refereegranskat)abstract
- The island of St Helena played a crucial role in the suppression of the transatlantic slave trade. Strategically located in the middle of the South Atlantic, it served as a staging post for the Royal Navy and reception point for enslaved Africans who had been "liberated"from slave ships intercepted by the British. In total, St Helena received approximately 27,000 liberated Africans between 1840 and 1867. Written sources suggest that the majority of these individuals came from West Central Africa, but their precise origins are unknown. Here, we report the results of ancient DNA analyses that we conducted as part of a wider effort to commemorate St Helena's liberated Africans and to restore knowledge of their lives and experiences. We generated partial genomes (0.1-0.53) for 20 individuals whose remains had been recovered during archaeological excavations on the island. We compared their genomes with genotype data for over 3,000 present-day individuals from 90 populations across sub-Saharan Africa and conclude that the individuals most likely originated from different source populations within the general area between northern Angola and Gabon. We also find that the majority (17/20) of the individuals were male, supporting a well-documented sex bias in the latter phase of the transatlantic slave trade. The study expands our understanding of St Helena's liberated African community and illustrates how ancient DNA analyses can be used to investigate the origins and identities of individuals whose lives were bound up in the story of slavery and its abolition.
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