The avian eye color, generally referred to the color of the bird's iris, results from both pigments and structural coloration. Avian iris colors exhibit striking interspecies variations that may reflect unique evolutionary history and ecological adaption in different taxa. With a wide range of intraspecific iris color polymorphism, the domestic pigeon (Columba livia) thus serves as an excellent model

Summary: Post-GWAS studies using the results from large consortium meta-analysis often need to correctly take care of the overlapping sample issue. The gold standard approach for resolving this issue is to reperform the GWAS or meta-analysis excluding the overlapped participants. However, such approach is time-consuming and, sometimes, restricted by the available data. deMeta provides a user friendly

Here we propose a simple, robust and effective method for global ancestry inference and grouping from Principal Component Analysis (PCA) of genetic data. The proposed approach is particularly useful for methods that need to be applied in homogeneous samples. First, we show that Euclidean distances in the PCA space are proportional to $F_{ST}$ between populations. Then, we show how to use this PCA-based

Current methods for genotype imputation and phasing exploit the sheer volume of data in haplotype reference panels and rely on hidden Markov models. Existing programs all have essentially the same imputation accuracy, are computationally intensive, and generally require pre-phasing the typed markers. We propose a novel data-mining method for genotype imputation and phasing that substitutes highly efficient

Linkage-Disequilibrium Score Regression (LDSC) is a popular framework for analyzing GWAS summary statistics that allows for estimating SNP heritability, confounding, and functional enrichment of genetic variants with different annotations. Recent work has highlighted the influence of implicit and explicit assumptions of the model on the biological interpretation of the results. In this work, we explored

Polyploid genomes pose several inherent challenges to population genetic analyses. While alignment-based methods are fundamentally limited in their applicability to polyploids, alignment-free methods bypass most of these limits. We investigated the use of Mash, a k-mer analysis tool that uses the MinHash method to reduce complexity in large genomic datasets, for basic population genetic analyses of

Despite the negative impact of common scab (Streptomyces spp.) to the potato industry, little is known about the genetic architecture of resistance to this bacterial disease in the crop. We evaluated a mapping population (~150 full-sibs) derived from a cross between two tetraploid potatoes ('Atlantic' × B1829-5) in three environments (MN11, PA11, ME12) under natural common scab pressure. Three measures

Whereas large-scale statistical analyses can robustly identify disease-gene relationships, they do not accurately capture genotype-phenotype correlations or disease mechanisms. We use multiple lines of independent evidence to show that different variant types in a single gene, SATB1, cause clinically overlapping but distinct neurodevelopmental disorders. Clinical evaluation of 42 individuals carrying

The Middle and Late Bronze Age Near East, a period roughly spanning the second millennium BC (ca. 2000-1200 BC), is frequently referred to as the first ‘international age’, characterized by intense and far-reaching contacts between different entities from the eastern Mediterranean to the Near East and beyond. In a large-scale tandem study of stable isotopes and ancient DNA of individuals excavated

Background: Genome-wide association studies (GWAS) uncovered a wealth of associations between common variants and human phenotypes. These results, widely shared across the scientific community as summary statistics, fostered a flurry of secondary analysis: heritability and genetic correlation assessment, pleiotropy characterization and multitrait association test. Amongst these secondary analyses,

Traditionally, treatments for bacterial infection have focused on killing the microbe or preventing its growth. As antimicrobial resistance becomes more ubiquitous, attention has begun to shift toward disrupting the host-pathogen interaction by improving the host defense. Using a high-throughput, fragment-based screen to identify compounds that alleviate Pseudomonas aeruginosa-mediated killing of Caenorhabditis

Brain morphology has been shown to be highly heritable, yet only a small portion of the heritability is explained by the genetic variants discovered so far. Here we exploit the distributed nature of genetic effects across the brain and apply the Multivariate Omnibus Statistical Test (MOSTest) to genome-wide association studies (GWAS) of vertex-wise structural magnetic resonance imaging (MRI) measures

The molecular mechanism underlying epigenetic inheritance remains largely unknown. Previous studies have shown that transmission of paternally acquired traits through the male germline (i.e., sperm) requires functional DNMT2 to maintain normal profiles of sperm-borne tRNA-derived small RNAs (tsRNAs). Here we report that maternal transmission of a Kit paramutant phenotype (white tail tip) through the

Commercial hybrid breeding operations can be described as decentralized networks of smaller, more or less isolated breeding programs. There is further a tendency for the disproportionate use of successful inbred lines for generating the next generation of recombinants, which has led to a series of significant bottlenecks, particularly in the history of the North American and European maize germplasm

Paramutation is a case of non-Mendelian inheritance, long known, but still incompletely understood. It describes the change of gene expression at a paramutable allele by encounter with a paramutagenic allele, causing an alteration that remains even after segregation of both alleles. While discovery, genetic and mechanistic studies of paramutation were made with alleles that change plant pigmentation

Culex mosquitoes are a globally widespread vector of several human and animal pathogens. Their biology and behavior allow them to thrive in proximity to urban areas, rendering them a constant public health threat. Their mixed bird/mammal feeding behavior further offers a vehicle for zoonotic pathogens transmission to people, and separately, poses a conservation threat to insular bird species. The advent

The African Horn region that includes the Abyssinian is one of the areas in the world that harbor high human genetic diversity manifesting past intermingling of people of different origins attributed to its geographic immediacy to the middle east and being historical trade and religio-cultural hub. Here, we performed a genetic structure analysis of linguistically differentiated populations of Ethiopia

Interpretation of the function of non-coding risk loci for neuropsychiatric disorders and brain-relevant traits via gene expression and alternative splicing is mainly performed in bulk post-mortem adult tissue. However, genetic risk loci are enriched in regulatory elements of cells present during neocortical differentiation, and regulatory effects of risk variants may be masked by heterogeneity in

Due to anatomical and physiological similarities to humans, the common marmoset (Callithrix jacchus) is an ideal organism for the study human diseases. Researchers are currently leveraging genome-editing technologies such as CRISPR/Cas9 to genetically engineer marmosets for the in vivo biomedical modeling of human neuropsychiatric and neurodegenerative diseases. The genome characterization of these

Mutations of PINK1 cause early-onset Parkinson's disease (PD) with selective neurodegeneration in humans. However, current PINK1 knockout mouse and pig models are unable to recapitulate the typical neurodegenerative phenotypes observed in PD patients, indicating that it is essential to generate PINK1 disease models in non-human primates (NHPs) that are highly close to humans, to investigate the unique

The replication of Plasmodium falciparum malaria parasites within red blood cells (RBCs) causes severe disease in humans, especially in Africa. The influence of host erythrocyte variation on parasite replication is largely uncharted, aside from a handful of deleterious alleles like sickle cell. Here, we integrated analyses of exome sequencing, RBC phenotyping, and parasite fitness assays on blood donated

Mendelian Randomization (MR) exploits genetic variants as instrumental variables to estimate the causal effect of an "exposure" trait on an "outcome" trait from observational data. However, the validity of such studies is threatened by population stratification, batch effects, and horizontal pleiotropy. Although a variety of methods have been proposed to partially mitigate those problems, residual

Primary cilia are sensory organelles that are built and maintained by intraflagellar transport (IFT) multi-protein complexes. Deletion of certain ciliary genes in Autosomal Dominant Polycystic Kidney Disease (ADPKD) mouse models markedly attenuates PKD severity, indicating that a component of cilia dysfunction may have potential therapeutic value. To broaden the role of ciliary dysfunction, here we

Transposable elements (TEs) are enriched in cytosine methylation, preventing their mobility within the genome. We previously identified a genome-wide repertoire of candidate intracisternal A particle (IAP) TEs in mice that exhibit inter-individual variability in this methylation (VM-IAPs) with implications for genome function. Here we validate these metastable epialleles and discover a novel class

The establishment of heterochromatin in fission yeast involves methyltransferase Clr4-mediated H3-Lys9 methylation, which is bound specifically by Swi6/HP1. The structure spreads further through cooperative action of Swi6 and Clr4. While the mechanism of establishment and spreading of heterochromatin is somewhat well understood, that of its propagation through multiple cell divisions is not so well

Canonically, heterochromatin formation in fission yeast and metazoans involves di/trimethylation of histone H3 at lysine 9 position (me2/me3-K9-H3) by the histone methyltransferase (HMT) Suv39/Clr4, followed by binding of Swi6/HP1 to me2/me3-K9-H3 via its chromodomain. Subsequent self-association of Swi6/HP1 on adjacent nucleosomes leads to folded heterochromatin structure. An alternate model suggests

Spikelet number per spike (SNS) is a key factor in determining kernel number per spike which has a great effect on wheat grain yield. Modern wheat breeding narrows genetic diversity among cultivars leading to a detrimental effect on future wheat improvement. It is thus of great significance to explore new genetic resources for SNS to increase wheat yield. Here, a tetraploid landrace Ailanmai mult wild

STARR-seq assesses millions of fragments in parallel measuring enhancer activity quantitatively. Here we show that STARR-seq is critically flawed with a systematic error in the cells of Arabidopsis thaliana (A. thaliana). Large amount of self-transcripts (STs) is lost during reverse transcription because these STs are polyadenylated after alternative polyadenylation sites (APAS) inside the test sequences

Vrindavani is an Indian composite cattle breed developed by crossbreeding taurine dairy breeds with native insicine cattle in the 1960s. About 190,000 semen doses of Vrindavni bulls have been distributed to the farmer till date. the animals are under artificial and natural selection for higher milk production and adaptation traits in the Vrindavani genome is not explored. In this study, we provide

Motivation: Gene-gene co-expression networks (GCN) are of biological interest for the useful information they provide for understanding gene-gene interactions. The advent of single cell RNA-sequencing allows us to examine more subtle gene co-expression occurring within a cell type. Many imputation and denoising methods have been developed to deal with the technical challenges observed in single cell

Envirotyping is a core of techniques used to unfold the non-genetic drivers associated with the phenotypic adaptation of living organisms. Here we introduce the EnvRtype R package, a novel toolkit developed to interplay large-scale envirotyping data (enviromics) into quantitative genomics. To start a user-friendly envirotyping pipeline, this package offers: (1) remote sensing tools for collecting (get_weather

Background: CYP2D6 and CYP2C19 are cytochrome P450 enzymes involved in the metabolism of many medications from multiple therapeutic classes. Associations between patterns of variants (known as haplotypes) in the genes encoding them (CYP2D6 and CYP2C19) and enzyme activities are well described. The genes in fact comprise 21% of biomarkers in drug labels. Despite this, genotyping is not common, partly

In total, 39 faba bean ( Vicia faba L.) advanced lines were evaluated for resistance to broomrape Orobanche foetida under highly infested field conditions. The trials were conducted during two consecutive copping seasons at Oued-Beja Research Station in Tunisia. The advanced lines XAR-VF00.13-1-2-1-2-1 and XBJ90.04-2-3-1-1-1-2A expressed high resistance level to O. foetida exceeding those recorded

Objective Ruminant intestine health played a vital role in nutrient absorption and metabolism. Methods In present study, twelve Datong male Yak were randomly selected and slaughtered to determine jejunal digestive enzyme activity, morphology and protein composition between forage-fed and concentrate-fed during cold season in Tibetan Plateau. Results The results showed that Yak jejunum digestive enzyme

Zebrafish have practical features that make them a useful model for higher-throughput tests of gene function using CRISPR/Cas9 editing to create ‘knockout’ models. Due to the large number of available tools to design CRISPR assays and diversity of theories/model systems they were originally built on, we sought to systematically compare computational and empirical approaches for predicting gene-editing

Dimensionality reduction is a common tool for visualization and inference of population structure from genotypes, but popular methods either return too many dimensions for easy plotting (PCA) or fail to preserve global geometry (t-SNE and UMAP). Here we explore the utility of variational autoencoders (VAEs) -- generative machine learning models in which a pair of neural networks seek to first compress

Sequence variants in gene regulatory regions alter gene expression and contribute to phenotypes of individual cells and the whole organism, including disease susceptibility and progression. Single-nucleotide variants in enhancers or promoters may affect gene transcription by altering transcription factor binding sites. Differential transcription factor binding in heterozygous genomic loci provides

The genetic heterogeneity of autism has stymied the search for causes and cures. Even whole-genomic studies on large numbers of families have yielded results of relatively little impact. In the present work, we analyze two genomic databases using a novel strategy that takes prior knowledge of genetic relationships into account and that was designed to boost signal important to our understanding of

The molecular mechanisms for repairing DNA damages and point mutations have been well understood but it remains unclear how a frameshift mutation is repaired. Here we report that frameshift reversion occurs in E. coli more frequently than expected and appears to be a targeted gene repair signaled by premature termination codons (PTCs), producing high-level variations in the repaired genes. Genome resequencing

Heterosis refers to the superior performance of the hybrid over the inbred parental lines. Besides genetic variation, epigenetic difference between the parental lines has been suggested to be involved in heterosis. However, precise nature and extent of parental epigenome difference and reprograming in hybrids governing heterotic gene expression remain unclear. In this work, we analyzed DNA methylomes

Polycystic kidney disease (PKD) is a genetic disorder that affects cilia homeostasis and causes progressive growth of tubular-derived cysts within the kidney. Efforts to find safer drugs for PKD have increased in the past few years after the successful launch of tolvaptan, the first approved drug to combat autosomal dominant PKD progression. Here we investigate the effects of Quinomycin A on progression

Accounting for 10-20% of breast cancer cases, TNBC is associated with a disproportionate number of breast cancer deaths. Despite recent progress, many patients fail to respond to current targeted therapies. Responses to chemotherapy are variable, and the tumor characteristics that determine response are poorly understood. One challenge in studying TNBC is its genomic profile: outside of TP53 loss,

Transcription factors that contain a homeodomain DNA-binding domain have crucial functions in most aspects of cellular function and embryonic development in both animals and plants. Hmx proteins are a sub-family of NK homeodomain-containing proteins that have fundamental roles in development of sensory structures such as the eye and the ear. However, Hmx functions in spinal cord development have not

We report a meta-Genome Wide Association Study involving 73 published studies in soybean (Glycine max L. [Merr.]) covering 17,556 unique accessions, with improved statistical power for robust detection of loci associated with a broad range of traits. De novo GWAS and meta-analysis were conducted for composition traits including fatty acid and amino acid composition traits, disease resistance traits

Background: There are research questions whose answers require record linkage of multiple databases which may be characterized by limited options for full data sharing. For this purpose, the Open Data Infrastructure for Social Science and Economic Innovations (ODISSEI) consortium has supported the development of the ODISSEI Secure Supercomputer (OSSC) platform that allows researchers to link cohort

CHARGE syndrome patients commonly display craniofacial abnormalities. Furthermore, most patients show features of idiopathic scoliosis, reduced bone mineral density and in a few cases osteopenia. While several clinical cases and studies have documented the skeletal deformities in CHARGE syndrome bearing CHD7 mutations, the underlying mechanisms of the disorder remain elusive. Here, we detect and quantitatively

The alkylphosphocholine (APC) class of antineoplastic and antiprotozoal drugs, such as edelfosine and miltefosine, are structural mimics of lyso-phosphatidylcholine (lyso-PC), and are inhibitory to the yeast Saccharomyces cerevisiae at low micromolar concentrations. Cytotoxic effects related to inhibition of phospholipid synthesis, induction of an unfolded protein response, inhibition of oxidative

Behaviors and disorders related to self-regulation, such as substance use, antisocial conduct, and ADHD, are collectively referred to as externalizing and have a shared genetic liability. We applied a multivariate approach that leverages genetic correlations among externalizing traits for genome-wide association analyses. By pooling data from ~1.5 million people, our approach is statistically more

Objective: Two experimental samples from a mouse line containing Cryaa or Cryab modifications on a predominantly C57Bl/6 background using 129Sv mouse strain embryonic stem cells were investigated. The objective was to reexamine the precise genetic background of the mice 10 years after they were converted to the C57Bl/6 background. Results: The genetic backgrounds of the mice were assessed at the DartMouse

During the past decade, genome-wide association studies (GWAS) have been used to successfully identify tens of thousands of genetic variants associated with complex traits included in human, animal, and plant. All common genome-wide association (GWA) methods rely on population structure correction, to avoid false genotype and phenotype associations. However, population structure correction is a stringent

Genotype-by-environment interaction (GxE) occurs when the size of a genetic effect varies systematically across levels of the environment and when the size of an environmental effect varies systematically across levels of the genotype. However, total variance in the phenotype may shift as a function of the moderator irrespective of its etiology such that the proportional effect of the predictor is

Purpose: Depression is genetically influenced, but the mechanisms that underlie these influences are largely unknown. Recently, shared genetic influences were found between depression and both cognitive ability and educational attainment (EA). Although genetic influences are often thought to represent direct biological pathways, they can also reflect indirect pathways, including modifiable environmental

The free-living nematode C. elegans remains one of the most robust and flexible genetic systems for interrogating the complexities of animal biology. Targeted genetic manipulations, such as RNA interference (RNAi), CRISPR or array-based transgenesis, all rely on initial delivery of nucleic acids. Delivery of dsRNA by feeding can be effective, but expression in E. coli is not conducive to experiments

Purine salvage from the host is an obligatory process for all protozoan parasites. In Leishmania donovani, this is accomplished by four membrane nucleoside and nucleobase transporters, or LdNTs. Previously, we demonstrated that purine starvation invokes a robust stress response in Leishmania and characterized the proteomic changes involved. However, because Leishmania do not control the transcription

An increasing number of field studies have shown that the phenotype of an individual plant depends not only on its genotype but also on those of neighboring plants; however, this fact is not taken into consideration in genome-wide association studies (GWAS). Based on the Ising model of ferromagnetism, we incorporated neighbor genotypic identity into a regression model, named "Neighbor GWAS". Our simulations

A substantial fraction of the human genome is difficult to interrogate with short-read DNA sequencing technologies due to paralogy, complex haplotype structures, or tandem repeats. Long-read sequencing technologies, such as Oxford Nanopore's MinION, enable direct measurement of complex loci without introducing many of the biases inherent to short-read methods, though they suffer from relatively lower

6-mercaptopurine (6-MP) is widely used in the treatment of acute lymphoblastic leukemia (ALL), and its cytotoxicity is primarily mediated by thioguanine nucleotide metabolites (TGN). Recent genome-wide association study has identified germline polymorphisms (e.g., rs72846714) in the NT5C2 gene associated with 6-MP metabolism in patients with ALL. However, the full spectrum of genetic variation in NT5C2

Plant breeding programs are designed and operated over multiple cycles to systematically change the genetic makeup of plants to achieve improved trait performance for a Target Population of Environments (TPE). Within each cycle, selection applied to the standing genetic variation within a structured reference population of genotypes (RPG) is the primary mechanism by which breeding programs make the

MutS and its homologues, from prokaryotes to humans, recognize and bind to DNA mismatches generated during DNA replication, initiate DNA mismatch repair and ensures 100-200 fold increase in replication fidelity. In E.coli, through post transcriptional regulation, at least three mechanisms mediate decline of MutS intracellular concentrations during stress conditions. To understand the significance of

An important issue in human population genetics is the ancestry. By extracting the ancestral information retained in the single nucleotide polymorphism (SNP) of genomic DNA, the history of migration and reproduction of the population can be reconstructed. Since the SNP data of population are multidimensional, their dimensionality reduction can demonstrate their potential internal connections. In this