Genome-wide association study provides insights into the genetic architecture of bone size and mass in chickens

Bone size is an important trait for chickens because of its association with osteoporosis in layers and meat production in broilers. Here, we employed high density genotyping platforms to detect candidate genes for bone traits. Estimates of the narrow heritabilities ranged from 0.37 ± 0.04 for shank length to 0.59 ± 0.04 for tibia length. The dominance heritability was 0.12 ± 0.04 for shank length. Using a linear mixed model approach, we identified a promising locus within NCAPG on chromosome 4, which was associated with tibia length and mass, femur length and area, and shank length. In addition, three other loci were associated with bone size or mass at a Bonferroni-corrected genome-wide significance threshold of 1%. One region on chicken chromosome 1 between 168.38 and 171.82 Mb harbored HTR2A, LPAR6, CAB39L, and TRPC4. A second region that accounted for 2.2% of the phenotypic variance was located around WNT9A on chromosome 2, where allele substitution was predicted to be associated with tibia length. Four candidate genes identified on chromosome 27 comprising SPOP, NGFR, GIP, and HOXB3 were associated with tibia length and mass, femur length and area, and shank length. Genome partitioning analysis indicated that the variance explained by each chromosome was proportional to its length.

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Genome-Wide Association Studies Reveal Susceptibility Loci for Noninfectious Claw Lesions in Holstein Dairy Cattle

Frontiers in Genetics ◽

10.3389/fgene.2021.657375 ◽

2021 ◽

Vol 12 ◽

Author(s):

Ellen Lai ◽

Alexa L. Danner ◽

Thomas R. Famula ◽

Anita M. Oberbauer

Keyword(s):

Dairy Cattle ◽

Candidate Genes ◽

Linear Mixed Model ◽

Association Studies ◽

Genome Wide Association ◽

Phenotypic Variance ◽

Genome Wide Association Studies ◽

Susceptibility Loci ◽

Genome Wide ◽

Claw Lesions

Sole ulcers (SUs) and white line disease (WLD) are two common noninfectious claw lesions (NICL) that arise due to a compromised horn production and are frequent causes of lameness in dairy cattle, imposing welfare and profitability concerns. Low to moderate heritability estimates of SU and WLD susceptibility indicate that genetic selection could reduce their prevalence. To identify the susceptibility loci for SU, WLD, SU and/or WLD, and any type of noninfectious claw lesion, genome-wide association studies (GWAS) were performed using generalized linear mixed model (GLMM) regression, chunk-based association testing (CBAT), and a random forest (RF) approach. Cows from five commercial dairies in California were classified as controls having no lameness records and ≥6 years old (n = 102) or cases having SU (n = 152), WLD (n = 117), SU and/or WLD (SU + WLD, n = 198), or any type of noninfectious claw lesion (n = 217). The top single nucleotide polymorphisms (SNPs) were defined as those passing the Bonferroni-corrected suggestive and significance thresholds in the GLMM analysis or those that a validated RF model considered important. Effects of the top SNPs were quantified using Bayesian estimation. Linkage disequilibrium (LD) blocks defined by the top SNPs were explored for candidate genes and previously identified, functionally relevant quantitative trait loci. The GLMM and CBAT approaches revealed the same regions of association on BTA8 for SU and BTA13 common to WLD, SU + WLD, and NICL. These SNPs had effects significantly different from zero, and the LD blocks they defined explained a significant amount of phenotypic variance for each dataset (6.1–8.1%, p < 0.05), indicating the small but notable contribution of these regions to susceptibility. These regions contained candidate genes involved in wound healing, skin lesions, bone growth and mineralization, adipose tissue, and keratinization. The LD block defined by the most significant SNP on BTA8 for SU included a SNP previously associated with SU. The RF models were overfitted, indicating that the SNP effects were very small, thereby preventing meaningful interpretation of SNPs and any downstream analyses. These findings suggested that variants associated with various physiological systems may contribute to susceptibility for NICL, demonstrating the complexity of genetic predisposition.

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Genome-wide association study reveals candidate genes for flowering time in cowpea (Vigna unguiculata [L.] Walp)

10.1101/2021.04.01.438123 ◽

2021 ◽

Author(s):

Dev Paudel ◽

Rocheteau Dareus ◽

Julia Rosenwald ◽

Maria Munoz-Amatriain ◽

Esteban Rios

Keyword(s):

Flowering Time ◽

Candidate Genes ◽

Vigna Unguiculata ◽

Association Studies ◽

Snp Markers ◽

Genome Wide Association ◽

Human Consumption ◽

Phenotypic Variance ◽

Genome Wide Association Studies ◽

Genome Wide

Cowpea (Vigna unguiculata [L.] Walp., diploid, 2n = 22) is a major crop used as a protein source for human consumption as well as a quality feed for livestock. It is drought and heat tolerant and has been bred to develop varieties that are resilient to changing climates. Plant adaptation to new climates and their yield are strongly affected by flowering time. Therefore, understanding the genetic basis of flowering time is critical to advance cowpea breeding. The aim of this study was to perform genome-wide association studies (GWAS) to identify marker trait associations for flowering time in cowpea using single nucleotide polymorphism (SNP) markers. A total of 367 accessions from a cowpea mini-core collection were evaluated in Ft. Collins, CO in 2019 and 2020, and 292 accessions were evaluated in Citra, FL in 2018. These accessions were genotyped using the Cowpea iSelect Consortium Array that contained 51,128 SNPs. GWAS revealed seven reliable SNPs for flowering time that explained 8-12% of the phenotypic variance. Candidate genes including FT, GI, CRY2, LSH3, UGT87A2, LIF2, and HTA9 that are associated with flowering time were identified for the significant SNP markers. Further efforts to validate these loci will help to understand their role in flowering time in cowpea, and it could facilitate the transfer of some of this knowledge to other closely related legume species.

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Identification of candidate genes that underlie the QTL on chromosome 1 that mediates genetic differences in stress-ethanol interactions

Physiological Genomics ◽

10.1152/physiolgenomics.00114.2014 ◽

2015 ◽

Vol 47 (8) ◽

pp. 308-317 ◽

Cited By ~ 12

Author(s):

Melloni N. Cook ◽

Jessica A. Baker ◽

Scott A. Heldt ◽

Robert W. Williams ◽

Kristin M. Hamre ◽

...

Keyword(s):

Candidate Genes ◽

Genome Wide Association Study ◽

Zinc Finger Protein ◽

Genetic Differences ◽

Chromosome 1 ◽

Protein Tyrosine ◽

Finger Protein ◽

Genome Wide ◽

Trait Locus ◽

Tyrosine Phosphate

Alcoholism, stress, and anxiety are strongly interacting heritable, polygenetic traits. In a previous study, we identified a quantitative trait locus (QTL) on murine chromosome (Chr) 1 between 23.0 and 31.5 Mb that modulates genetic differences in the effects of ethanol on anxiety-related phenotypes. The goal of the present study was to extend the analysis of this locus with a focus on identifying candidate genes using newly available data and tools. Anxiety-like behavior was evaluated with an elevated zero maze following saline or ethanol injections (1.8 g/kg) in C57BL/6J, DBA2J, and 72 BXD strains. We detected significant effects of strain and treatment and their interaction on anxiety-related behaviors, although surprisingly, sex was not a significant factor. The Chr1 QTL is specific to the ethanol-treated cohort. Candidate genes in this locus were evaluated using now standard bioinformatic criteria. Collagen 19a1 ( Col19a1) and family sequence 135a ( Fam135a) met most criteria but have lower expression levels and lacked biological verification and, therefore, were considered less likely candidates. In contrast, two other genes, the prenylated protein tyrosine phosphate family member Ptp4a1 (protein tyrosine phosphate 4a1) and the zinc finger protein Phf3 (plant homeoDomain finger protein 3) met each of our bioinformatic criteria and are thus strong candidates. These findings are also of translational relevance because both Ptp4a1 and Phf3 have been nominated as candidates genes for alcohol dependence in a human genome-wide association study. Our findings support the hypothesis that variants in one or both of these genes modulate heritable differences in the effects of ethanol on anxiety-related behaviors.

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Identification of a Goat Intersexuality-Associated Novel Variant Through Genome-Wide Resequencing and Hi-C

Frontiers in Genetics ◽

10.3389/fgene.2020.616743 ◽

2021 ◽

Vol 11 ◽

Author(s):

Guang-Xin E ◽

Dong-Ke Zhou ◽

Zhu-Qing Zheng ◽

Bai-Gao Yang ◽

Xiang-Long Li ◽

...

Keyword(s):

Candidate Genes ◽

Molecular Genetic ◽

Genetic Mechanism ◽

Chromosome 1 ◽

Future Research ◽

Whole Genome ◽

Chromosome Conformation ◽

Next Generation Sequencing Technology ◽

Genome Wide ◽

Novel Variant

Background: Polled intersex syndrome (PIS) leads to reproductive disorders in goats and exerts a heavy influence on goat breeding. Since 2001, the core variant of an 11.7 kb deletion at ~129 Mb on chromosome 1 (CHI1) has been widely used as a genetic diagnostic criterion. In 2020, a ~0.48 Mb insertion within the PIS deletion was identified by sequencing in XX intersex goats. However, the suitability of this variation for the diagnosis of intersex goats worldwide and its further molecular genetic mechanism need to be clarified.Results: The whole-genome selective sweep of intersex goats from China was performed with whole-genome next-generation sequencing technology for large sample populations and a case–control study on interbreeds. A series of candidate genes related to the goat intersexuality phenotype were found. We further confirmed that a ~0.48 Mb duplicated fragment (including ERG and KCNJ15) downstream of the ~20 Mb PIS region was reversely inserted into the PIS locus in intersex Chinese goats and was consistent with that in European Saanen and Valais black-necked goats. High-throughput chromosome conformation capture (Hi-C) technology was then used to compare the 3D structures of the PIS variant neighborhood in CHI1 between intersex and non-intersex goats. A newly found structure was validated as an intrachromosomal rearrangement. This inserted duplication changed the original spatial structure of goat CHI1 and caused the appearance of several specific loop structures in the adjacent ~20 kb downstream region of FOXL2.Conclusions: Results suggested that the novel complex PIS variant genome was sufficient as a broad-spectrum clinical diagnostic marker of XX intersexuality in goats from Europe and China. A series of private dense loop structures caused by segment insertion into the PIS deletion might affect the expression of FOXL2 or other neighboring novel candidate genes. However, these structures require further in-depth molecular biological experimental verification. In general, this study provided new insights for future research on the molecular genetic mechanism underlying female-to-male sex reversal in goats.

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Novel Organ-Specific Genetic Factors for Quantitative Resistance to Late Blight in Potato

10.1101/567289 ◽

2019 ◽

Author(s):

Deissy Katherine Juyo Rojas ◽

Johana Carolina Soto Sedano ◽

Agim Ballvora ◽

Jens Léon ◽

Teresa Mosquera Vásquez

Keyword(s):

Late Blight ◽

Candidate Genes ◽

Genome Wide Association Study ◽

Quantitative Resistance ◽

Genotyping By Sequencing ◽

Phenotypic Variance ◽

Resistance Response ◽

Genome Wide ◽

A Genome ◽

Organ Specific

AbstractPotato, Solanum tuberosum, is one of the highest consumed food in the world, being the basis of the diet of millions of people. The main limiting and destructive disease of potato is late blight, caused by Phytophtora infestans. Here, we present a multi-environmental analysis of the response to P. infestans using an association panel of 150 accessions of S. tuberosum Group Phureja, evaluated in two localities in Colombia. Disease resistance data were merged with a genotyping matrix of 83,862 SNPs obtained by 2b-restriction site–associated DNA and Genotyping by sequencing approaches into a Genome-wide association study. We are reporting 16 organ-specific QTL conferring resistance to late blight. These QTL explain from 13.7% to 50.9% of the phenotypic variance. Six and ten QTL were detected for resistance response in leaves and stem, respectively. In silico analysis revealed 15 candidate genes for resistance to late blight. Four of them have no functional genome annotation, while eleven candidate genes code for diverse proteins, including one leucine-rich repeat kinase.

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Identification of genetic loci and candidate genes related to soybean flowering through genome wide association study

BMC Genomics ◽

10.1186/s12864-019-6324-7 ◽

2019 ◽

Vol 20 (1) ◽

Author(s):

Minmin Li ◽

Ying Liu ◽

Yahan Tao ◽

Chongjing Xu ◽

Xin Li ◽

...

Keyword(s):

Association Study ◽

Flowering Time ◽

Candidate Genes ◽

Genome Wide Association Study ◽

Growth Period ◽

Snp Markers ◽

Genome Wide Association ◽

Chromosome 1 ◽

Genome Wide ◽

A Genome

Abstract Background As a photoperiod-sensitive and self-pollinated species, the growth periods traits play important roles in the adaptability and yield of soybean. To examine the genetic architecture of soybean growth periods, we performed a genome-wide association study (GWAS) using a panel of 278 soybean accessions and 34,710 single nucleotide polymorphisms (SNPs) with minor allele frequencies (MAF) higher than 0.04 detected by the specific-locus amplified fragment sequencing (SLAF-seq) with a 6.14-fold average sequencing depth. GWAS was conducted by a compressed mixed linear model (CMLM) involving in both relative kinship and population structure. Results GWAS revealed that 37 significant SNP peaks associated with soybean flowering time or other growth periods related traits including full bloom, beginning pod, full pod, beginning seed, and full seed in two or more environments at -log10(P) > 3.75 or -log10(P) > 4.44 were distributed on 14 chromosomes, including chromosome 1, 2, 3, 5, 6, 9, 11, 12, 13, 14, 15, 17, 18, 19. Fourteen SNPs were novel loci and 23 SNPs were located within known QTLs or 75 kb near the known SNPs. Five candidate genes (Glyma.05G101800, Glyma.11G140100, Glyma.11G142900, Glyma.19G099700, Glyma.19G100900) in a 90 kb genomic region of each side of four significant SNPs (Gm5_27111367, Gm11_10629613, Gm11_10950924, Gm19_34768458) based on the average LD decay were homologs of Arabidopsis flowering time genes of AT5G48385.1, AT3G46510.1, AT5G59780.3, AT1G28050.1, and AT3G26790.1. These genes encoding FRI (FRIGIDA), PUB13 (plant U-box 13), MYB59, CONSTANS, and FUS3 proteins respectively might play important roles in controlling soybean growth periods. Conclusions This study identified putative SNP markers associated with soybean growth period traits, which could be used for the marker-assisted selection of soybean growth period traits. Furthermore, the possible candidate genes involved in the control of soybean flowering time were predicted.

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Single-Step Genome Wide Association Study Identifies QTL Signals for Untrimmed and Trimmed Thigh Weight in Italian Crossbred Pigs for Dry-Cured Ham Production

Animals ◽

10.3390/ani11061612 ◽

2021 ◽

Vol 11 (6) ◽

pp. 1612

Author(s):

Valentino Palombo ◽

Mariasilvia D’Andrea ◽

Danilo Licastro ◽

Simeone Dal Monego ◽

Sandy Sgorlon ◽

...

Keyword(s):

Candidate Genes ◽

Carcass Traits ◽

Single Step ◽

Genome Wide Association ◽

Chromosome 1 ◽

Genome Wide Association Studies ◽

Breeding Programs ◽

Genome Wide ◽

Dry Cured Ham ◽

Heritability Estimation

Protected Designation of Origin (PDO) dry-cured ham is the most important product in the Italian pig breeding industry, mainly oriented to produce heavy pig carcasses to obtain hams of the right weight and maturity. Recently, along with the traditional traits swine breeding programs have aimed to include novel carcass traits. The identification at the genome level of quantitative trait loci (QTLs) affecting such new traits helps to reveal their genetic determinism and may provide information to be integrated in prediction models in order to improve prediction accuracy as well as to identify candidate genes underlying such traits. This study aimed to estimate genetic parameters and perform a single step genome wide association studies (ssGWAS) on novel carcass traits such as untrimmed (UTW) and trimmed thigh weight (TTW) in two pig crossbred lines approved for the ham production of the Italian PDO. With this purpose, phenotypes were collected from ~1800 animals and 240 pigs were genotyped with Illumina PorcineSNP60 Beadchip. The single-step genomic BLUP procedure was used for the heritability estimation and to implement the ssGWAS. QTL were characterized based on the variance of 10-SNP sliding window genomic estimated breeding values. Moderate heritabilities were detected and QTL signals were identified on chromosome 1, 4, 6, 7, 11 and 15 for both traits. As expected, the genetic correlation among the two traits was very high (~0.99). The QTL regions encompassed a total of 249 unique candidate genes, some of which were already reported in association with growth, carcass or ham weight traits in pigs. Although independent studies are required to further verify our findings and disentangle the possible effects of specific linkage disequilibrium in our population, our results support the potential use of such new QTL information in future breeding programs to improve the reliability of genomic prediction.

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Genome-wide Association Study of Individual Sugar Content and Sugar Conversion in Fruit of Japanese Pear (Pyrus spp.)

10.21203/rs.3.rs-170038/v1 ◽

2021 ◽

Author(s):

Sogo Nishio ◽

Takeshi Hayashi ◽

Kenta Shirasawa ◽

Toshihiro Saito ◽

Shingo Terakami ◽

...

Keyword(s):

Candidate Genes ◽

Sugar Content ◽

Genome Wide Association ◽

Sugar Accumulation ◽

Phenotypic Variance ◽

Fruit Traits ◽

Chromosome 11 ◽

Breeding Populations ◽

Genome Wide ◽

Sugar Conversion

Abstract Background: Sweetness is one of the most important traits determining fruit quality. Sweetness is controlled not only by the total sugar content but also by the contents of individual sugars. The major sugars in mature Rosaceae fruits are sucrose, fructose, glucose, and sorbitol, which have different levels of sweetness. Among these, sucrose and fructose have high sweetness, whereas glucose and sorbitol have low sweetness. The objective of this study was to identify the quantitative trait loci (QTLs) associated with fruit traits including individual sugar accumulation and conversion, to infer the candidate genes underlying the QTLs, and to assess the potential of genomic selection for breeding pear fruit traits.Results: We evaluated 10 fruit traits and conducted genome-wide association studies (GWAS) for 106 cultivars and 17 breeding populations (1112 F1 individuals) using 3484 tag single-nucleotide polymorphisms (SNPs) genotyped by double-digest restriction-site associated DNA sequencing (ddRAD-Seq). By implementing a mixed linear model and a Bayesian multiple-QTL model in GWAS, 56 SNPs associated with fruit traits were identified. Four loci were presumed to be associated with sugar conversion because the SNPs were significant for more than one individual sugar and the individual sugar contents associated with each SNP genotype were negatively correlated. In particular, a SNP located close to acid invertase gene PPAIV3 on chromosome 7 and a newly identified SNP on chromosome 11 had quite large effects on sugar conversion. We used ‘Golden Delicious’ doubled haploid (GDDH) 13, an apple reference genome to infer the candidate genes for the identified SNPs. In the region flanking the SNP on chromosome 11, there is a tandem repeat of early responsive to dehydration (ERD6)-like sugar transporter genes which might play a role in the phenotypes observed.Conclusions: SNPs associated with sugar accumulation and conversion were newly identified at several loci, and candidate genes underlying QTLs were inferred using advanced apple genome information. Several QTLs showed clear effects with more than 10% of phenotypic variance explained by those SNPs in the breeding populations. By combining the effects of multiple QTLs, breeders would be able to select seedlings that will later bear fruit with high sucrose and fructose content.

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Genome-Wide Analysis for Early Growth-Related Traits of the Locally Adapted Egyptian Barki Sheep

Genes ◽

10.3390/genes12081243 ◽

2021 ◽

Vol 12 (8) ◽

pp. 1243

Author(s):

Ibrahim Abousoliman ◽

Henry Reyer ◽

Michael Oster ◽

Eduard Murani ◽

Ismail Mohamed ◽

...

Keyword(s):

Candidate Genes ◽

Growth Traits ◽

Critical Role ◽

Fixation Index ◽

Meat Production ◽

Livestock Sector ◽

Genome Wide ◽

A Genome ◽

Performance Traits ◽

Genomic Regions

Sheep play a critical role in the agricultural and livestock sector in Egypt. For sheep meat production, growth traits such as birth and weaning weights are very important and determine the supply and income of local farmers. The Barki sheep originates from the northeastern coastal zone of Africa, and due to its good adaptation to the harsh environmental conditions, it contributes significantly to the meat production in these semi-arid regions. This study aimed to use a genome-wide SNP panel to identify genomic regions that are diversified between groups of individuals of Egyptian Barki sheep with high and low growth performance traits. In this context, from a phenotyped population of 140 lambs of Barki sheep, 69 lambs were considered for a genome-wide scan with the Illumina OvineSNP50 V2 BeadChip. The selected lambs were grouped into divergent subsets with significantly different performance for birth weight and weaning weight. After quality control, 63 animals and 40,383 SNPs were used for analysis. The fixation index (FST) for each SNP was calculated between the groups. The results verified genomic regions harboring some previously proposed candidate genes for traits related to body growth, i.e., EYA2, GDF2, GDF10, MEF2B, SLC16A7, TBX15, TFAP2B, and TNNC2. Moreover, novel candidate genes were proposed with known functional implications on growth processes such as CPXM2 and LRIG3. Subsequent association analysis showed significant effects of the considered SNPs on birth and weaning weights. Results highlight the genetic diversity associated with performance traits and thus the potential to improve growth traits in the Barki sheep breed.

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Genome-wide mediation analysis: bridging the divide between genotype and phenotype via transcriptomic data in maize

10.1101/2021.04.09.439238 ◽

2021 ◽

Author(s):

Zhikai Yang ◽

Gen Xu ◽

Qi Zhang ◽

TOSHIHIRO OBATA ◽

Jinliang Yang

Keyword(s):

Causal Inference ◽

Candidate Genes ◽

Mediation Analysis ◽

Genome Wide Association Study ◽

Agronomic Traits ◽

Causal Chain ◽

Phenotypic Variance ◽

Omics Data ◽

Metabolic Traits ◽

Genome Wide

Mapping genotype to phenotype is an essential topic in genetics and genomics research. As the Omics data become increasingly available, genome-wide association study (GWAS) has been widely applied to establish the relationship between genotype and phenotype. However, signals detected by GWAS usually span broad genomic regions with many underneath candidate genes, making it challenging to interpret and validate the molecular functions of the candidate genes. Under the context of genetics research, we hypothesized a causal chain from genotype to phenotype partially mediated by intermediate molecular processes, i.e., gene expression. To test this hypothesis, we applied the high dimensional mediation analysis, a class of causal inference method with an assumed causal chain from the exposure to the mediator to the outcome, and implemented it to the maize diversity panel (N=280 lines). Using 40 publicly available agronomic traits, 66 newly generated metabolic traits, and published RNA-seq data from seven different tissues, we detected N=736 unique mediating genes, explaining an average of 12.7\% phenotypic variance due to mediation. Noticeably, 83/736 (11\%) genes were identified in mediating more than one trait, suggesting the prevalence of pleiotropic mediating effects. Among those pleiotropic mediators, benzoxazinone synthesis 13 (Bx13), a well-characterized gene encoding a 2-oxoglutarate-dependent dioxygenase, was identified mediating 37 different agronomic and metabolic traits. Further genetic and genomic analyses of the bx13 and adjacent mediating genes suggested a 3D co-regulation modulation likely affect their expression levels and eventually lead to phenotypic consequences. Our results suggested the genome-wide mediation analysis is a powerful tool to integrate Omics data in providing causal inference to connect genotype to phenotype.

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