Low Linkage Disequilibrium Research Articles

Rare variant contribution to the heritability of coronary artery disease

Whole genome sequences (WGS) enable discovery of rare variants which may contribute to missing heritability of coronary artery disease (CAD). To measure their contribution, we apply the GREML-LDMS-I approach to WGS of 4949 cases and 17,494 controls of European ancestry from the NHLBI TOPMed program. We estimate CAD heritability at 34.3% assuming a prevalence of 8.2%. Ultra-rare (minor allele frequency ≤ 0.1%) variants with low linkage disequilibrium (LD) score contribute ~50% of the heritability. We also investigate CAD heritability enrichment using a diverse set of functional annotations: i) constraint; ii) predicted protein-altering impact; iii) cis-regulatory elements from a cell-specific chromatin atlas of the human coronary; and iv) annotation principal components representing a wide range of functional processes. We observe marked enrichment of CAD heritability for most functional annotations. These results reveal the predominant role of ultra-rare variants in low LD on the heritability of CAD. Moreover, they highlight several functional processes including cell type-specific regulatory mechanisms as key drivers of CAD genetic risk.

Whole-genome analyses reveal selective signals in four Xinjiang cattle breeds

Xinjiang is home to three indigenous cattle breeds (Xinjiang Mongolian, Altay white-headed, and Kazakh cattle) and one crossbreed (Xinjiang Brown cattle), each possessing distinct and remarkable characteristics. In this study, we conducted comprehensive genome analyses of these four breeds in comparison with eight representative cattle breeds from around the world. Despite being predominantly Bos taurus, the proportion of Bos indicus ancestry in these indigenous breeds decreases with increasing latitude. This mixed genomic composition contributes to higher nucleotide diversity, lower linkage disequilibrium, and larger effective population sizes. Notably, Xinjiang Brown cattle exhibited higher LD at short distances, faster LD decay, and the largest effective population size, indicative of hybrid characteristics. Furthermore, we identified selective signals for lipids dynamics and coat colour in Altay white-headed cattle, immune resistance to local pathogens in Kazakh cattle, hydro-electrolyte balance and immune response in Xinjiang Mongolian cattle, and rapid growth and large body size in Xinjiang Brown cattle, as well as substance metabolism in three indigenous cattle. Our findings not only deepen the understanding of breed origins and diversity but also provide a foundation for exploring the genetic mechanisms underlying breed characteristics and facilitating further breed improvement.

The causal relationship between androgenetic alopecia and serum uric acid: A bidirectional Mendelian randomization analysis.

Despite numerous studies investigating the association between androgenetic alopecia (AGA) and serum uric acid (SUA), the causal relationship between AGA and SUA remains unknown. We utilized bidirectional Mendelian randomization (MR) to explore the causality between AGA and SUA. Our study chose single nucleotide polymorphisms associated with genome-wide significance (p<5×10-8) for the exposure and showing low linkage disequilibrium (R2<0.001) as IVs. Various MR methods were employed to evaluate causality, including inverse-variance weighted (IVW), Weighted Median, MR-Egger, Weighted Mode and Simple Mode. Sensitivity analyses were performed to test the robustness of the results. Using the IVW method, we did not find a significant causal relationship between AGA and SUA (OR=1.00, 95% CI 0.99-1.01; p=0.451). Similarly, the IVW method did not reveal evidence of causality between SUA and AGA (OR=0.97, 95% CI=0.91-1.03; p=0.301). The results from other methods were consistent with those of the IVW approach. The study did not identify a causal relationship between AGA and SUA. Future research should involve larger cohorts and advanced methods to validate the findings and explore the complex interactions between AGA and SUA levels in different populations.

Virulence and Molecular Characterization Reveal Signs of Sexual Genetic Recombination of Puccinia striiformis f. sp. tritici and Puccinia striiformis f. sp. hordei in Tibet.

Stripe rust of wheat and barley is caused by different formae speciales, Puccinia striiformis f. sp. tritici (Pst) and P. striiformis f. sp. hordei (Psh), respectively. To understand the relationship between the populations of the two formae speciales, a total of 260 P. striiformis isolates, including 140 from barley and 120 from wheat collected from Linzhi, Tibet, China, from 2018 to 2020, were tested on 18 barley and 13 wheat genotypes and genotyped with 26 single-nucleotide polymorphism (SNP)-based Kompetitive allele-specific PCR (KASP) markers. As a result, 260 isolates were identified as 83 virulence phenotypes (VPs), 115 of which as 9 VPs and could infect only wheat (wheat population), 111 as 54 VPs and could infect only barley (barley population), and 34 belonged to 20 VPs that could infect both wheat and barley (mixed population). Of the 149 multilocus genotypes (MLGs) that were identified, 92 were from wheat, 56 from barley, and 1 from both wheat and barley. Phenotypic and genotypic diversity was high in the populations from wheat and barley. Low linkage disequilibrium was found in most of the sampling sites of both crops, indicating strong signs of sexual reproduction (|r̄d| = 0.022 to 0.393, P = 0.004 to 0.847), whereas it was not observed in the overall population (wheat and barley sources) and the wheat, barley, and mixed populations, which may be because of the complex composition of isolates. Population structure analyses based on phenotyping and SNP-KASP genotypes supported the separation of the two formae speciales. However, MLGs and clusters containing isolates from both wheat and barley obviously indicated sexual genetic recombination between the two formae speciales. The results of the study provided an insight into evolution of Pst and Psh and showed the importance of management strategies for stripe rust of wheat and barley in regions where both crops are grown.

Disparities in ABO blood type determination across diverse ancestries: a systematic review and validation in the All of Us Research Program.

ABO blood types have widespread clinical use and robust associations with disease. The purpose of this study is to evaluate the portability and suitability of tag single-nucleotide polymorphisms (tSNPs) used to determine ABO alleles and blood types across diverse populations in published literature. Bibliographic databases were searched for studies using tSNPs to determine ABO alleles. We calculated linkage between tSNPs and functional variants across inferred continental ancestry groups from 1000 Genomes. We compared r2 across ancestry and assessed real-world consequences by comparing tSNP-derived blood types to serology in a diverse population from the All of Us Research Program. Linkage between functional variants and O allele tSNPs was significantly lower in African (median r2 = 0.443) compared to East Asian (r2 = 0.946, P = 1.1 × 10-5) and European (r2 = 0.869, P = .023) populations. In All of Us, discordance between tSNP-derived blood types and serology was high across all SNPs in African ancestry individuals and linkage was strongly correlated with discordance across all ancestries (ρ = -0.90, P = 3.08 × 10-23). Many studies determine ABO blood types using tSNPs. However, tSNPs with low linkage disequilibrium promote misinference of ABO blood types, particularly in diverse populations. We observe common use of inappropriate tSNPs to determine ABO blood type, particularly for O alleles and with some tSNPs mistyping up to 58% of individuals. Our results highlight the lack of transferability of tSNPs across ancestries and potential exacerbation of disparities in genomic research for underrepresented populations. This is especially relevant as more diverse cohorts are made publicly available.

Whole-genome resequencing uncovers diversity and selective sweep in Kazakh cattle.

The Kazakh cattle in the Xinjiang Uygur Autonomous Region of China are highly adaptable and have multiple uses, including milk and meat production, and use as draft animals. They are an excellent original breed that could be enhanced by breeding and hybrid improvement. However, the genomic diversity and signature of selection underlying the germplasm characteristics require further elucidation. Herein, we evaluated 26 Kazakh cattle genomes in comparison with 103 genomes of seven other cattle breeds from regions around the world to assess the Kazakh cattle genetic variability. We revealed that the relatively low linkage disequilibrium at large SNP distances was strongly correlated with the largest effective population size among Kazakh cattle. Using population structural analysis, we next demonstrated a taurine lineage with restricted Bos indicus introgression among Kazakh cattle. Notably, we identified putative selected genes associated with resistance to disease and body size within Kazakh cattle. Together, our findings shed light on the evolutionary history and breeding profile of Kazakh cattle, as well as offering indispensable resources for germplasm resource conservation and crossbreeding program implementation.

Comparison of ddRADseq and EUChip60K SNP genotyping systems for population genetics and genomic selection in Eucalyptus dunnii (Maiden).

Eucalyptus dunnii is one of the most important Eucalyptus species for short-fiber pulp production in regions where other species of the genus are affected by poor soil and climatic conditions. In this context, E. dunnii holds promise as a resource to address and adapt to the challenges of climate change. Despite its rapid growth and favorable wood properties for solid wood products, the advancement of its improvement remains in its early stages. In this work, we evaluated the performance of two single nucleotide polymorphism, (SNP), genotyping methods for population genetics analysis and Genomic Selection in E. dunnii. Double digest restriction-site associated DNA sequencing (ddRADseq) was compared with the EUChip60K array in 308 individuals from a provenance-progeny trial. The compared SNP set included 8,011 and 19,008 informative SNPs distributed along the 11 chromosomes, respectively. Although the two datasets differed in the percentage of missing data, genome coverage, minor allele frequency and estimated genetic diversity parameters, they revealed a similar genetic structure, showing two subpopulations with little differentiation between them, and low linkage disequilibrium. GS analyses were performed for eleven traits using Genomic Best Linear Unbiased Prediction (GBLUP) and a conventional pedigree-based model (ABLUP). Regardless of the SNP dataset, the predictive ability (PA) of GBLUP was better than that of ABLUP for six traits (Cellulose content, Total and Ethanolic extractives, Total and Klason lignin content and Syringyl and Guaiacyl lignin monomer ratio). When contrasting the SNP datasets used to estimate PAs, the GBLUP-EUChip60K model gave higher and significant PA values for six traits, meanwhile, the values estimated using ddRADseq gave higher values for three other traits. The PAs correlated positively with narrow sense heritabilities, with the highest correlations shown by the ABLUP and GBLUP-EUChip60K. The two genotyping methods, ddRADseq and EUChip60K, are generally comparable for population genetics and genomic prediction, demonstrating the utility of the former when subjected to rigorous SNP filtering. The results of this study provide a basis for future whole-genome studies using ddRADseq in non-model forest species for which SNP arrays have not yet been developed.

The causal relationship between psoriasis and chronic obstructive pulmonary disease: A bidirectional mendelian randomization study.

Although many studies have investigated the association between psoriasis and chronic obstructive pulmonary disease (COPD), the causal relationship between psoriasis and COPD is still unknown. We employed bidirectional Mendelian randomization to investigate the causal relationship between psoriasis and COPD. Genetic instruments for exposure were selected from two distinct genome-wide association study databases. Single nucleotide polymorphisms associated with exposures at the genome-wide significance level (p<5 × 10^-8 ) and exhibiting low linkage disequilibrium (r^2 <0.001) were chosen as instrumental variables. Causality was assessed using multiple MR methods, including Inverse-Variance Weighted (IVW), MR-Egger, Weighted Median, Simple Mode, and Weighted Mode. A significance level of p<0.05 was considered statistically significant. Heterogeneity was examined using Cochran's Q test, and MR-Egger regression was employed to detect pleiotropy. The robustness and reliability of the results were further evaluated through leave-one-out analysis. We found a positive causal association between psoriasis and COPD [IVW: odds ratio (OR): 1.0006; p=0.0056]. Heterogeneity and pleiotropy have not been discovered, so the results of the study are reliable. In the reverse analysis, no causal association between CPOD and psoriasis was found. Our findings revealed that psoriasis was associated with an elevated risk of COPD. However, no causal association between COPD and psoriasis was identified in our study.

Whole-genome resequencing provides insights into the diversity and adaptation to desert environment in Xinjiang Mongolian cattle

BackgroundXinjiang Mongolian cattle is an indigenous breed that inhabits the Taklimakan Desert and is characterized by its small body size. However, the genomic diversity, origin, and genetic basis underlying the adaptation to the desert environment have been poorly studied.ResultsWe analyzed patterns of Xinjiang Mongolian cattle genetic variation by sequencing 20 genomes together with seven previously sequenced genomes and comparing them to the 134 genomes of nine representative breeds worldwide. Among the breeds of Bos taurus, we found the highest nucleotide diversity (0.0024) associated with the lower inbreeding coefficient (2.0110-6), the lowest linkage disequilibrium (r2 = 0.3889 at distance of 10 kb), and the highest effective population size (181 at 20 generations ago) in Xinjiang Mongolian cattle. The genomic diversity pattern could be explained by a limited introgression of Bos indicus genes. More importantly, similarly to desert-adapted camel and same-habitat sheep, we also identified signatures of selection including genes, GO terms, and/or KEGG pathways controlling water reabsorption and osmoregulation, metabolic regulation and energy balance, as well as small body size in Xinjiang Mongolian cattle.ConclusionsOur results imply that Xinjiang Mongolian cattle might have acquired distinct genomic diversity by virtue of the introgression of Bos indicus, which helps understand the demographic history. The identification of selection signatures can provide novel insights into the genomic basis underlying the adaptation of Xinjiang Mongolian cattle to the desert environment.

A Statistical Testing Strategy Accounting for Random and Nonrandom (Skewed) X-Chromosome Inactivation Identifies Lung Cancer Susceptibility Loci among Smokers.

Lung cancer is the most common cancer worldwide in mortality and the second in incidence. Epidemiological studies found a higher lung cancer risk for smoking women in comparison to men, but these sex differences, irrespective of smoking habits, remain controversial. One of the hypotheses concerns the genetic contribution of the sex chromosomes. However, while genome-wide association studies identified many lung cancer susceptibility loci, these analyses have excluded X-linked loci. To account for nongenetic factors, we first presented an association test based on an additive-multiplicative hazard model accounting for random/nonrandom X-inactivation process. A simulation study was performed to investigate the properties of the proposed test as compared with the Wald test from a Cox model with random X-inactivation process and the partial likelihood ratio test proposed by Xu et al. accounting for nonrandom X-inactivation process. Then, we performed an X chromosome-wide association study on 9,261 individuals from the population-based cohort CARTaGENE to identify susceptibility loci for lung cancer among current and past smokers. We adjusted for the PLCOm2012 lung cancer risk score used in screening programs. Simulation results show the good behavior of the proposed test in terms of power and type I error probability as compared to the Xu et al. and the Wald test. Using the proposed test statistic and adjusting for the PLCOm2012 score, the X chromosome-wide statistical analysis identified two SNPs in low-linkage disequilibrium located in the IL1RAPL1 (IL-1 R accessory protein-like) gene: rs12558491 (p = 2.75×10-9) and rs12835699 (p = 1.26×10-6). For both SNPs, the minor allele was associated with lower lung cancer risk. Adjusting for multiple testing, no signal was detected using the Wald or the Xu et al. likelihood ratio tests. By taking into account smoking behavior and the X-inactivation process, the investigation of the X chromosome has shed a new light on the association between X-linked loci and lung cancer. We identified two loci associated with lung cancer located in the IL1RAPL1 gene. This finding would have been overlooked by examining only results from other test statistics.

#209 : The Association Between Autoimmune Diseases and Gestational Diabetes Mellitus: A Mendelian Randomization Study

Background and Aims: As a common complication of pregnancy, gestational diabetes mellitus (GDM) may lead to a serious negative impact on pregnant women and their children. Autoimmune diseases are chronic pathologies triggered by abnormal responses of the human immune system that result in damage and disorders in the body. Recently, several studies have demonstrated that autoimmune diseases could be related to the risk of GDM. However, several other studies of this relationship have yielded conflicting results. We explored the causal relationship between autoimmune diseases and GDM risk through a two-sample Mendelian randomization (2SMR) study. Method: We obtained exposure data for rheumatoid arthritis (RA) from a genome-wide association study (GWAS) pooled dataset, which consisted of 361,194 participants. We selected single-nucleotide polymorphisms (SNPs) that had a relationship with RA and were at a significance level of not only p &lt; 5 × 10[Formula: see text] but also at a low linkage disequilibrium (LD) level (r2 &lt; 0.01). The results included 5,687 GDM cases and 117,892 controls. For detailed Methods, please see the Methods section in this article’s Online Repository at https://www.jacionline.org Results: The results of inverse variance weight (IVW) analysis suggested a positive correlation between RA and GDM risk. In addition, no validity was observed in the statistical models for heterogeneity and pleiotropy. However, for multiple sclerosis (MS), no causal relationship between it and GDM risk was found in our study. Conclusion: Our results suggest a strong casual association between RA and the risk of GDM. The results suggested the importance of enhanced antenatal care and early intervention among pregnant women with RA as well as clues for novel risk factors for GDM.

Genome-wide association study of powdery mildew resistance in cultivated soybean from Northeast China.

Powdery mildew (PMD), caused by the pathogen Microsphaera diffusa, leads to substantial yield decreases in susceptible soybean under favorable environmental conditions. Effective prevention of soybean PMD damage can be achieved by identifying resistance genes and developing resistant cultivars. In this study, we genotyped 331 soybean germplasm accessions, primarily from Northeast China, using the SoySNP50K BeadChip, and evaluated their resistance to PMD in a greenhouse setting. To identify marker-trait associations while effectively controlling for population structure, we conducted genome-wide association studies utilizing factored spectrally transformed linear mixed models, mixed linear models, efficient mixed-model association eXpedited, and compressed mixed linear models. The results revealed seven single nucleotide polymorphism (SNP) loci strongly associated with PMD resistance in soybean. Among these, one SNP was localized on chromosome (Chr) 14, and six SNPs with low linkage disequilibrium were localized near or in the region of previously mapped genes on Chr 16. In the reference genome of Williams82, we discovered 96 genes within the candidate region, including 17 resistance (R)-like genes, which were identified as potential candidate genes for PMD resistance. In addition, we performed quantitative real-time reverse transcription polymerase chain reaction analysis to evaluate the gene expression levels in highly resistant and susceptible genotypes, focusing on leaf tissues collected at different times after M. diffusa inoculation. Among the examined genes, three R-like genes, including Glyma.16G210800, Glyma.16G212300, and Glyma.16G213900, were identified as strong candidates associated with PMD resistance. This discovery can significantly enhance our understanding of soybean resistance to PMD. Furthermore, the significant SNPs strongly associated with resistance can serve as valuable markers for genetic improvement in breeding M. diffusa-resistant soybean cultivars.

Refine localizations of functional variants affecting eggshell color of Lueyang black-boned chicken in the SLCO1B3

Table eggs with color-uniformity shell are visually attractive for consumers. Lueyang black-boned chicken (LBC) lays colorful eggs, which is undesirable for sale of table eggs, but provides a segregating population for mapping functional variants affecting eggshell color. SLCO1B3 was identified as the causative gene for blue eggs in the Dongxiang and Araucana chickens. The aim of this study is to map functional variants associated with chicken eggshell color in the SLCO1B3. Eggshell color of LBC (n=383) was measured using the L*a*b color space. SLCO1B3 was resequencing using a subset (n=30) of 383 samples. Linkage disequilibrium among 139 SNP was analyzed. Association of 16 SNP in the SLCO1B3 and 8 in CPOX, ALAS1, and ABCG2 genes with L*a*b were tested by a polygenic model (LMM) and a polygenic/oligogenic mixed model (BSLMM). Chromatin state annotations were retrieved from the UCSC database. Effect of SLCO1B3 variants distributed in mapping and upstream 1.6-kb regions on promoter activities were analyzed using dual-luciferase reporter assay. One hundred and thirty-nine variants maintained low linkage disequilibrium with 80% of r2 less than 0.226. Fifteen SLCO1B3 variants were significantly associated with a*, of which 1B3_SNP108 was showed the strongest association and the largest effect on a*. In the BSLMM, 1B3_SNP108 alone appeared in the Markov chain Monte Carlo as major variants in 100% of posterior inclusion probability. None of variants in CPOX, ALAS1, and ABCG2 were significantly associated with color indexes except that 2 ALAS1 variants were associated with L*. 1B3_SNP108 distributes in the Intron4 where 6 active enhancers and 1 ATAC island were enriched. However, 1B3_SNP108-containing constructs showed negligible activities in the reporter assay. No significant differences of activities between haplotypes were found for five 5'-deleted promoter constructs. The data recognizes 1B3_SNP108 as a valuable marker for breeding of eggshell color. Functional variants are localized in the region adjacent to the 1B3_SNP108 due to low linkage disequilibrium in the LBC. Our findings extend the role of SLCO1B3 from a causative gene for blue eggs to a major regulator driving continuous variation of LBC eggshell color.

Evidence for cryptic sex in parthenogenetic stick insects of the genus Timema.

Obligately parthenogenetic species are expected to be short lived since the lack of sex and recombination should translate into a slower adaptation rate and increased accumulation of deleterious alleles. Some, however, are thought to have been reproducing without males for millions of years. It is not clear how these old parthenogens can escape the predicted long-term costs of parthenogenesis, but an obvious explanation is cryptic sex. In this study, we screen for signatures of cryptic sex in eight populations of four parthenogenetic species of Timema stick insects, some estimated to be older than 1 Myr. Low genotype diversity, homozygosity of individuals and high linkage disequilibrium (LD) unaffected by marker distances support exclusively parthenogenetic reproduction in six populations. However, in two populations (namely, of the species Timema douglasi and T. monikensis) we find strong evidence for cryptic sex, most likely mediated by rare males. These populations had comparatively high genotype diversities, lower LD, and a clear LD decay with genetic distance. Rare sex in species that are otherwise largely parthenogenetic could help explain the unusual success of parthenogenesis in the Timema genus and raises the question whether episodes of rare sex are in fact the simplest explanation for the persistence of many old parthenogens in nature.

Limitation of gene flow by distance in the common yellow jasmine (Chrysojasminum fruticans, Oleaceae): implications for the study of its mating strategies

Abstract The common yellow jasmine (Chrysojasminum fruticans, Oleaceae) is a distylous shrub occurring in the wild in south-western Europe and the Mediterranean Basin. Little is known about the genetics of its populations and such information would be necessary to investigate its spread and mating strategies. Here, the organization of its genetic diversity was investigated among and between 13 populations from southern France, including a 35-year-old experimental plot (‘CEFE’, CNRS Montpellier). Markers (microsatellites and indels) were developed to screen polymorphisms in nuclear, chloroplast, and mitochondrial genomes. Low linkage disequilibrium was observed between chloroplast and mitochondrial haplotypes probably resulting from paternal leaks in their inheritance as reported in other species of tribe Jasmineae. Yet, analyses of 36 progenies issued from parents with distinct chloroplast and/or mitochondrial DNA haplotypes only revealed a maternal contribution. Natural populations of C. fruticans are moderately to highly differentiated at the regional scale with a strong isolation-by-distance pattern detected on nuclear data, indicating limited gene flow. An isolated site (‘Moulis’), located on the marginal distribution area, was remarkably genetically depauperate and highly differentiated from other populations. Further studies on the variation of mating strategies in C. fruticans should consider populations with contrasting patterns of genetic diversity. The artificial ‘CEFE’ population also offers opportunities for experiments in a closed system.

Using residual regressions to quantify and map signal leakage in genomic prediction

BackgroundMost genomic prediction applications in animal breeding use genotypes with tens of thousands of single nucleotide polymorphisms (SNPs). However, modern sequencing technologies and imputation algorithms can generate ultra-high-density genotypes (including millions of SNPs) at an affordable cost. Empirical studies have not produced clear evidence that using ultra-high-density genotypes can significantly improve prediction accuracy. However, (whole-genome) prediction accuracy is not very informative about the ability of a model to capture the genetic signals from specific genomic regions. To address this problem, we propose a simple methodology that detects chromosome regions for which a specific model (e.g., single-step genomic best linear unbiased prediction (ssGBLUP)) may fail to fully capture the genetic signal present in such segments—a phenomenon that we refer to as signal leakage. We propose to detect regions with evidence of signal leakage by testing the association of residuals from a pedigree or a genomic model with SNP genotypes. We discuss how this approach can be used to map regions with signals that are poorly captured by a model and to identify strategies to fix those problems (e.g., using a different prior or increasing marker density). Finally, we explored the proposed approach to scan for signal leakage of different models (pedigree-based, ssGBLUP, and various Bayesian models) applied to growth-related phenotypes (average daily gain and backfat thickness) in pigs.ResultsWe report widespread evidence of signal leakage for pedigree-based models. Including a percentage of animals with SNP data in ssGBLUP reduced the extent of signal leakage. However, local peaks of missed signals remained in some regions, even when all animals were genotyped. Using variable selection priors solves leakage points that are caused by excessive shrinkage of marker effects. Nevertheless, these models still miss signals in some regions due to low linkage disequilibrium between the SNPs on the array used and causal variants. Thus, we discuss how such problems could be addressed by adding sequence SNPs from those regions to the prediction model.ConclusionsResidual single-marker regression analysis is a simple approach that can be used to detect regional genomic signals that are poorly captured by a model and to indicate ways to fix such problems.

Potential of genomic selection for growth, meat content and colour traits in mixed-family breeding designs for the Pacific oyster Crassostrea gigas

Selective breeding programs have been initiated worldwide for the Pacific oyster Crassostrea gigas to improve economically important traits such as growth and disease resistance. The emergence of genomic tools has allowed novel perspectives for using genomic selection (GS) in mixed-family breeding designs, which are cheaper and easier to develop than classical breeding schemes. In this study, we evaluated the potential of GS for different growth-related and shell colour traits in two independent commercially selected populations (P1 and P2), based on mixed-family designs. From ≈14.5K informative SNPs genotyped with the bi-species Axiom Affymetrix 57K oyster array, ≈12.5K were mapped on the reference genome. A strong heterogeneity of marker density between and within chromosomes was reported, with a low linkage disequilibrium (below 0.1 at 0.1 Mb) between pairs of SNPs. The within-population structure was homogenous for each population, with effective sizes of 107 for P1 and 76 for P2. Heritability was estimated for each trait and population and ranged from 0.08 ± 0.04 (for mean darkness intensity in P1) to 0.56 ± 0.08 (for the mean upper valve b* value in P2) for a pedigree-based model and from 0.04 ± 0.02 (for mean darkness intensity in P1) to 0.69 ± 0.04 (for the mean darkness intensity in P2) for a genomic-based model. Growth-related traits were generally highly genetically and positively correlated with each other, but weakly correlated with colour traits. Accuracy of prediction was generally higher with the genomic model (GBLUP) than with the classical BLUP model, with a maximum gain of accuracy (from 0.38 to 0.66) for flesh weight adjusted by total weight in P2. Accuracy of breeding values was slightly higher for colour traits for P2, with higher heritability estimates. Overall, our results indicate that GS has a good potential to be implemented in mixed-family breeding programs in a shellfish such as C. gigas.

Investigating genetic diversity and population structure of Egyptian goats across four breeds and seven regions

This study investigated the genetic diversity and population structure of 157 Egyptian adult goat females from four breed groups (Saidi, Barki, Wahati, and E. Nubian / Zaraibi), and distributed over eight geographic regions. Results from various analyses revealed high levels of genotypic diversity. Shannon values ranging from 3.89 in the Serw region population (within the Zaraibi breed) to 2 in the Kharga region population(within Wahati goats), and low linkage disequilibrium. The Simpson index for diversity varied with values ranging from 0.97 in the Serw population to 0.875 in Kharga population. Analysis of gene diversity using Nei’s unbiased method found high levels of heterozygosity, with values ranging from 0.38 in Aswan and Assuit to 0.3 in Serw populations. Principal component analysis separated the studied populations into three groups. The first group displayed Zaraibi and Saidi populations as genetically distinct populations, and the second group showed interbreeding between Barki desert breed, and Wahati oasis breed. Bayesian Information Criterion identified four distinct subpopulations, and the discriminant analysis of principal components revealed intermingling between Wahati and Barki populations, as well as the independence of Zaraibi population. Structure analysis of the subpopulations revealed six gene pools with admixture of Wahati and Barki goats, which were confirmed by the kinship analysis. In conclusion, the study revealed clear diversity between the studied populations, with the regions having their own distinct breeds. These findings suggest that interbreeding between some populations may be due to the exchange of genetic stocks and hybridization programs could be necessary to sustain Egyptian breeds and produce offspring that can survive environmental diversity and CC.

Physical Activity, Sedentary Behavior, and Type 2 Diabetes: Mendelian Randomization Analysis.

The causality and pathways of the associations between physical activity and inactivity and the risk of type 2 diabetes remain inconclusive. We conducted an updated mendelian randomization (MR) study to explore the associations of moderate-to-vigorous physical activity (MVPA) and leisure screen time (LST) with type 2 diabetes mellitus (T2DM). Genetic variants strongly associated with MVPA or LST with low linkage disequilibrium were selected as instrumental variables from a genome-wide meta-analysis including more than 600 000 individuals. Summary-level data on T2DM were obtained from the DIAbetes Genetics Replication And Meta-analysis consortium including 898 130 individuals. Data on possible intermediates (adiposity indicators, lean mass, glycemic traits, and inflammatory biomarkers) were extracted from large-scale genome-wide association studies (n = 21 758-681 275). Univariable and multivariable MR analyses were performed to estimate the total and direct effects of MVPA and LST on T2DM. Methylation MR analysis was performed for MVPA in relation to diabetes. The odds ratio of T2DM was 0.70 (95% CI, 0.55-0.88; P = .002) per unit increase in the log-odds ratio of having MVPA and 1.45 (95% CI, 1.30-1.62; P = 7.62 × 10-11) per SD increase in genetically predicted LST. These associations attenuated in multivariable MR analyses adjusted for genetically predicted waist-to-hip ratio, body mass index, lean mass, and circulating C-reactive protein. The association between genetically predicted MVPA and T2DM attenuated after adjusting for genetically predicted fasting insulin levels. Two physical activity-related methylation biomarkers (cg17332422 in ADAMTS2 and cg09531019) were associated with the risk of T2DM (P < .05). The study suggests causal associations of MVPA and LST with T2DM that appear to be mediated by obesity, lean mass, and chronic low-grade inflammation.

A comprehensive analysis of copy number variations in diverse apple populations

BackgroundAs an important source of genetic variation, copy number variation (CNV) can alter the dosage of DNA segments, which in turn may affect gene expression level and phenotype. However, our knowledge of CNV in apple is still limited. Here, we obtained high-confidence CNVs and investigated their functional impact based on genome resequencing data of two apple populations, cultivars and wild relatives.ResultsIn this study, we identified 914,610 CNVs comprising 14,839 CNV regions (CNVRs) from 346 apple accessions, including 289 cultivars and 57 wild relatives. CNVRs summed to 71.19 Mb, accounting for 10.03% of the apple genome. Under the low linkage disequilibrium (LD) with nearby SNPs, they could also accurately reflect the population structure of apple independent of SNPs. Furthermore, A total of 3,621 genes were covered by CNVRs and functionally involved in biological processes such as defense response, reproduction and metabolic processes. In addition, the population differentiation index ({V}_{st}) analysis between cultivars and wild relatives revealed 127 CN-differentiated genes, which may contribute to trait differences in these two populations.ConclusionsThis study was based on identification of CNVs from 346 diverse apple accessions, which to our knowledge was the largest dataset for CNV analysis in apple. Our work presented the first comprehensive CNV map and provided valuable resources for understanding genomic variations in apple.