scholarly journals Discovery of runs-of-homozygosity diplotype clusters and their associations with diseases in UK Biobank

2020 ◽  
Author(s):  
Ardalan Naseri ◽  
Degui Zhi ◽  
Shaojie Zhang
Keyword(s):  
Demographic History ◽  
Hfe Gene ◽  
Uk Biobank ◽  
Runs Of Homozygosity ◽  
Genome Wide ◽  
A Genome ◽  
Large Populations ◽  
History Of ◽  
Outbred Populations ◽  
Inbred Populations

AbstractRuns of homozygosity (ROH) segments, contiguous homozygous regions in a genome were traditionally linked to families and inbred populations. However, a growing literature suggests that ROHs are ubiquitous in outbred populations. Still, most existing genetic studies of ROH in populations are limited to aggregated ROH content across the genome, which does not offer the resolution for mapping causal loci. This limitation is mainly due to a lack of methods for efficient identification of shared ROH diplotypes. Here, we present a new method, ROH-DICE, to find large ROH diplotype clusters, sufficiently long ROHs shared by a sufficient number of individuals, in large cohorts. ROH-DICE identified over 1 million ROH diplotypes that span over 100 SNPs and shared by more than 100 UK Biobank participants. Moreover, we found significant associations of clustered ROH diplotypes across the genome with various self-reported diseases, with the strongest associations found between the extended HLA region and autoimmune disorders. We found an association between a diplotype covering the HFE gene and haemochromatosis, even though the well-known causal SNP was not directly genotyped nor imputed. Using genome-wide scan, we identified a putative association between carriers of an ROH diplotype in chromosome 4 and an increase of mortality among COVID-19 patients. In summary, our ROH-DICE method, by calling out large ROH diplotypes in a large outbred population, enables further population genetics into the demographic history of large populations. More importantly, our method enables a new genome-wide mapping approach for finding disease-causing loci with multi-marker recessive effects at population scale.

scholarly journals A genome-wide perspective about the diversity and demographic history of seven Spanish goat breeds

2016 ◽  
Vol 48 (1) ◽  
Author(s):  
Arianna Manunza ◽  
Antonia Noce ◽  
Juan Manuel Serradilla ◽  
Félix Goyache ◽  
Amparo Martínez ◽  
...  
Keyword(s):  
Demographic History ◽  
Genome Wide ◽  
A Genome ◽  
History Of ◽  
Wide Perspective ◽  
Spanish Goat

scholarly journals The genomic landscape of Mexican Indigenous populations brings insights into the peopling of the Americas

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Humberto García-Ortiz ◽  
Francisco Barajas-Olmos ◽  
Cecilia Contreras-Cubas ◽  
Miguel Ángel Cid-Soto ◽  
Emilio J. Córdova ◽  
...  
Keyword(s):  
Demographic History ◽  
Indigenous Populations ◽  
South American ◽  
Genome Wide Analysis ◽  
Genome Wide ◽  
Genomic Landscape ◽  
A Genome ◽  
Peopling Of The Americas ◽  
History Of ◽  
Genetic Makeup

AbstractThe genetic makeup of Indigenous populations inhabiting Mexico has been strongly influenced by geography and demographic history. Here, we perform a genome-wide analysis of 716 newly genotyped individuals from 60 of the 68 recognized ethnic groups in Mexico. We show that the genetic structure of these populations is strongly influenced by geography, and our demographic reconstructions suggest a decline in the population size of all tested populations in the last 15–30 generations. We find evidence that Aridoamerican and Mesoamerican populations diverged roughly 4–9.9 ka, around the time when sedentary farming started in Mesoamerica. Comparisons with ancient genomes indicate that the Upward Sun River 1 (USR1) individual is an outgroup to Mexican/South American Indigenous populations, whereas Anzick-1 was more closely related to Mesoamerican/South American populations than to those from Aridoamerica, showing an even more complex history of divergence than recognized so far.

scholarly journals Genome-Wide Analysis Revealed Homozygosity and Demographic History of Five Chinese Sheep Breeds Adapted to Different Environments

Genes ◽  
2020 ◽  
Vol 11 (12) ◽  
pp. 1480
Author(s):  
Adam Abied ◽  
Lei Xu ◽  
Bahlibi W. Sahlu ◽  
Feng Xing ◽  
Abulgasim Ahbara ◽  
...  
Keyword(s):  
Demographic History ◽  
Adaptive Immune Response ◽  
Conservation Strategies ◽  
Distribution Analysis ◽  
Runs Of Homozygosity ◽  
Sheep Breeds ◽  
Indigenous Sheep ◽  
Genome Wide ◽  
History Of ◽  
Genomic Regions

Homozygosity of long sequence genotypes are a result of parents transmitting identical haplotypes, which can be used to estimate their auto-zygosity. Therefore, we used high-density SNP Chip data to characterize the auto-zygosity of each breed according to the occurrence and distribution of runs of homozygosity (ROH). Subsequently, we identified the genomic regions with high runs of homozygosity frequencies within individuals of each breed. We selected 96 sheep samples from five local Chinese sheep breeds belonging to different geographical locations. We identified 3046 ROHs within the study breed individuals, among which the longer segments (>1–5 Mb) were dominant. On average, ROH segments covered about 12% of the genomes; the coverage rate of OAR20 was the lowest and that of OAR2 was the highest. The distribution analysis of runs of homozygosity showed that the detected ROH mainly distributed between >26 and 28 Mb. The Hetian and Hu sheep showed the lowest ROH distribution. The estimation of homozygosity level reflects the history of modern and ancient inbreeding, which may affect the genomes of Chinese indigenous sheep breeds and indicate that some animals have experienced recent self-pollination events (Yabuyi, Karakul and Wadi). In these sheep breeds, the genomic regions were assumed to be under selection signatures frequently in line with long ROH. These regions included candidate genes associated with disease resistance traits (5S_rRNA), the innate and adaptive immune response (HERC2 and CYFIP1), digestion and metabolism (CENPJ), growth (SPP1), body size and developments (GJB2 and GJA3). This study highlighted new insights into the ROH patterns and provides a basis for future breeding and conservation strategies of Chinese sheep breeds.

scholarly journals A fully integrated machine learning scan of selection in the chimpanzee genome

2020 ◽  
Vol 2 (3) ◽  
Author(s):  
Jessica Nye ◽  
Mayukh Mondal ◽  
Jaume Bertranpetit ◽  
Hafid Laayouni
Keyword(s):  
Machine Learning ◽  
Positive Selection ◽  
Demographic History ◽  
Effective Population ◽  
Fully Integrated ◽  
Genome Wide ◽  
A Genome ◽  
Machine Learning Approach ◽  
History Of ◽  
The Impact

Abstract After diverging, each chimpanzee subspecies has been the target of unique selective pressures. Here, we employ a machine learning approach to classify regions as under positive selection or neutrality genome-wide. The regions determined to be under selection reflect the unique demographic and adaptive history of each subspecies. The results indicate that effective population size is important for determining the proportion of the genome under positive selection. The chimpanzee subspecies share signals of selection in genes associated with immunity and gene regulation. With these results, we have created a selection map for each population that can be displayed in a genome browser (www.hsb.upf.edu/chimp_browser). This study is the first to use a detailed demographic history and machine learning to map selection genome-wide in chimpanzee. The chimpanzee selection map will improve our understanding of the impact of selection on closely related subspecies and will empower future studies of chimpanzee.

scholarly journals Variation in VKORC1 Is Associated with Vascular Dementia

2021 ◽  
Vol 80 (3) ◽  
pp. 1329-1337
Author(s):  
Jure Mur ◽  
Daniel L. McCartney ◽  
Daniel I. Chasman ◽  
Peter M. Visscher ◽  
Graciela Muniz-Terrera ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Vascular Dementia ◽  
Genetic Variant ◽  
Warfarin Dose ◽  
Uk Biobank ◽  
Parental History ◽  
Genome Wide ◽  
History Of ◽  
First Time ◽  
The Relationship

Background: The genetic variant rs9923231 (VKORC1) is associated with differences in the coagulation of blood and consequentially with sensitivity to the drug warfarin. Variation in VKORC1 has been linked in a gene-based test to dementia/Alzheimer’s disease in the parents of participants, with suggestive evidence for an association for rs9923231 (p = 1.8×10–7), which was included in the genome-wide significant KAT8 locus. Objective: Our study aimed to investigate whether the relationship between rs9923231 and dementia persists only for certain dementia sub-types, and if those taking warfarin are at greater risk. Methods: We used logistic regression and data from 238,195 participants from UK Biobank to examine the relationship between VKORC1, risk of dementia, and the interplay with warfarin use. Results: Parental history of dementia, APOE variant, atrial fibrillation, diabetes, hypertension, and hypercholesterolemia all had strong associations with vascular dementia (p < 4.6×10–6). The T-allele in rs9923231 was linked to a lower warfarin dose (βperT - allele = –0.29, p < 2×10–16) and risk of vascular dementia (OR = 1.17, p = 0.010), but not other dementia sub-types. However, the risk of vascular dementia was not affected by warfarin use in carriers of the T-allele. Conclusion: Our study reports for the first time an association between rs9923231 and vascular dementia, but further research is warranted to explore potential mechanisms and specify the relationship between rs9923231 and features of vascular dementia.

Polygenic Risk Scores for Kidney Function and Their Associations with Circulating Proteome, and Incident Kidney Diseases

2021 ◽  
pp. ASN.2020111599
Author(s):  
Zhi Yu ◽  
Jin Jin ◽  
Adrienne Tin ◽  
Anna Köttgen ◽  
Bing Yu ◽  
...  
Keyword(s):  
Kidney Function ◽  
Kidney Diseases ◽  
Association Studies ◽  
Polygenic Risk Score ◽  
Genome Wide Association Studies ◽  
Plasma Proteome ◽  
Uk Biobank ◽  
Polygenic Risk ◽  
Genome Wide ◽  
A Genome

Background: Genome-wide association studies (GWAS) have revealed numerous loci for kidney function (estimated glomerular filtration rate, eGFR). The relationship of polygenic predictors of eGFR, risk of incident adverse kidney outcomes, and the plasma proteome is not known. Methods: We developed a genome-wide polygenic risk score (PRS) for eGFR by applying the LDpred algorithm to summary statistics generated from a multiethnic meta-analysis of CKDGen Consortium GWAS (N=765,348) and UK Biobank GWAS (90% of the cohort; N=451,508), followed by best parameter selection using the remaining 10% of UK Biobank (N=45,158). We then tested the association of the PRS in the Atherosclerosis Risk in Communities (ARIC) study (N=8,866) with incident chronic kidney disease, kidney failure, and acute kidney injury. We also examined associations between the PRS and 4,877 plasma proteins measured at at middle age and older adulthood and evaluated mediation of PRS associations by eGFR. Results: The developed PRS showed significant associations with all outcomes with hazard ratios (95% CI) per 1 SD lower PRS ranged from 1.06 (1.01, 1.11) to 1.33 (1.28, 1.37). The PRS was significantly associated with 132 proteins at both time points. The strongest associations were with cystatin-C, collagen alpha-1(XV) chain, and desmocollin-2. Most proteins were higher at lower kidney function, except for 5 proteins including testican-2. Most correlations of the genetic PRS with proteins were mediated by eGFR. Conclusions: A PRS for eGFR is now sufficiently strong to capture risk for a spectrum of incident kidney diseases and broadly influences the plasma proteome, primarily mediated by eGFR.

scholarly journals Genome-wide diversity and global migration patterns in dromedaries follow ancient caravan routes

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Sara Lado ◽  
Jean Pierre Elbers ◽  
Angela Doskocil ◽  
Davide Scaglione ◽  
Emiliano Trucchi ◽  
...  
Keyword(s):  
Demographic History ◽  
Genomic Diversity ◽  
Phylogeographic Structure ◽  
Arid Environments ◽  
Migration Patterns ◽  
Migration Rates ◽  
Global Migration ◽  
Genome Wide ◽  
A Genome ◽  
Scale Population

AbstractDromedaries have been essential for the prosperity of civilizations in arid environments and the dispersal of humans, goods and cultures along ancient, cross-continental trading routes. With increasing desertification their importance as livestock species is rising rapidly, but little is known about their genome-wide diversity and demographic history. As previous studies using few nuclear markers found weak phylogeographic structure, here we detected fine-scale population differentiation in dromedaries across Asia and Africa by adopting a genome-wide approach. Global patterns of effective migration rates revealed pathways of dispersal after domestication, following historic caravan routes like the Silk and Incense Roads. Our results show that a Pleistocene bottleneck and Medieval expansions during the rise of the Ottoman empire have shaped genome-wide diversity in modern dromedaries. By understanding subtle population structure we recognize the value of small, locally adapted populations and appeal for securing genomic diversity for a sustainable utilization of this key desert species.

scholarly journals Each of 3,323 metabolic innovations in the evolution ofE. coliarose through the horizontal transfer of a single DNA segment

2018 ◽  
Vol 116 (1) ◽  
pp. 187-192 ◽  
Author(s):  
Tin Yau Pang ◽  
Martin J. Lercher
Keyword(s):  
E Coli ◽  
New Genes ◽  
Metabolic Adaptations ◽  
Genome Wide ◽  
A Genome ◽  
Individual Strain ◽  
History Of ◽  
Phenotype Space ◽  
Genome Content ◽  
Metabolic Models

Even closely related prokaryotes often show an astounding diversity in their ability to grow in different nutritional environments. It has been hypothesized that complex metabolic adaptations—those requiring the independent acquisition of multiple new genes—can evolve via selectively neutral intermediates. However, it is unclear whether this neutral exploration of phenotype space occurs in nature, or what fraction of metabolic adaptations is indeed complex. Here, we reconstruct metabolic models for the ancestors of a phylogeny of 53Escherichia colistrains, linking genotypes to phenotypes on a genome-wide, macroevolutionary scale. Based on the ancestral and extant metabolic models, we identify 3,323 phenotypic innovations in the history of theE. coliclade that arose through changes in accessory genome content. Of these innovations, 1,998 allow growth in previously inaccessible environments, while 1,325 increase biomass yield. Strikingly, every observed innovation arose through the horizontal acquisition of a single DNA segment less than 30 kb long. Although we found no evidence for the contribution of selectively neutral processes, 10.6% of metabolic innovations were facilitated by horizontal gene transfers on earlier phylogenetic branches, consistent with a stepwise adaptation to successive environments. Ninety-eight percent of metabolic phenotypes accessible to the combinedE. colipangenome can be bestowed on any individual strain by transferring a single DNA segment from one of the extant strains. These results demonstrate an amazing ability of theE. colilineage to adapt to novel environments through single horizontal gene transfers (followed by regulatory adaptations), an ability likely mirrored in other clades of generalist bacteria.

scholarly journals Inferring the Demographic History of Inbred Species from Genome-Wide SNP Frequency Data

2020 ◽  
Vol 37 (7) ◽  
pp. 2124-2136
Author(s):  
Paul D Blischak ◽  
Michael S Barker ◽  
Ryan N Gutenkunst
Keyword(s):  
Puma Concolor ◽  
Demographic History ◽  
Random Mating ◽  
Simulated Data ◽  
Conservation Agriculture ◽  
Model Fit ◽  
Parameter Estimates ◽  
History Of ◽  
Demographic Inference ◽  
Inbred Populations

Abstract Demographic inference using the site frequency spectrum (SFS) is a common way to understand historical events affecting genetic variation. However, most methods for estimating demography from the SFS assume random mating within populations, precluding these types of analyses in inbred populations. To address this issue, we developed a model for the expected SFS that includes inbreeding by parameterizing individual genotypes using beta-binomial distributions. We then take the convolution of these genotype probabilities to calculate the expected frequency of biallelic variants in the population. Using simulations, we evaluated the model’s ability to coestimate demography and inbreeding using one- and two-population models across a range of inbreeding levels. We also applied our method to two empirical examples, American pumas (Puma concolor) and domesticated cabbage (Brassica oleracea var. capitata), inferring models both with and without inbreeding to compare parameter estimates and model fit. Our simulations showed that we are able to accurately coestimate demographic parameters and inbreeding even for highly inbred populations (F = 0.9). In contrast, failing to include inbreeding generally resulted in inaccurate parameter estimates in simulated data and led to poor model fit in our empirical analyses. These results show that inbreeding can have a strong effect on demographic inference, a pattern that was especially noticeable for parameters involving changes in population size. Given the importance of these estimates for informing practices in conservation, agriculture, and elsewhere, our method provides an important advancement for accurately estimating the demographic histories of these species.

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