Whole-Genome Sequencing on 220 Alfalfa (Medicago sativa L.) Accessions Identified Loci Associated with Fall Dormancy

Abstract Fall dormancy (FD) is one of the most important traits of alfalfa (Medicago sativa) for cultivar selection to overcome winter damage. Regrowth plant height following autumn clipping is an indirect way to evaluate FD. Although transcriptomics, proteomics analysis, and QTL mapping have revealed some important genes correlated with FD, the genetic architecture of this trait is still unclear. There are no applicable genes or markers for selection, which hinders progress in the genetic research and molecular breeding for the trait. We conducted whole-genome sequencing (WGS) on 220 alfalfa accessions at 10x depth. Among the 875,023 SNPs, seven of them were associated with FD using genome-wide association study (GWAS). One SNP located on chromosome 6 is in linkage disequilibrium with dehydration-responsive element-binding protein 1C (DREB1C). Furthermore, seven DREB genes are clustered in this region, one of which has previously been shown to enhance freezing tolerance in the model plant Medicago truncatula. The candidate genes uncovered by our research will benefit the transgenic and CRISPR-Cas9 research of FD in alfalfa. This gene will also be useful for marker development and assisted selection of FD for alfalfa.

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Whole-Genome Sequencing on 220 Alfalfa (Medicago sativa L.) Accessions Identified Association of DREB1C Gene with Fall Dormancy Height

10.1101/2021.03.29.437533 ◽

2021 ◽

Author(s):

Fan Zhang ◽

Junmei Kang ◽

Ruicai Long ◽

Mingna Li ◽

Yan Sun ◽

...

Keyword(s):

Medicago Sativa ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Genetic Research ◽

Whole Genome ◽

Cultivar Selection ◽

Fall Dormancy ◽

Element Binding Protein ◽

Responsive Element ◽

Molecular Marker Development

Fall dormancy (FD) is one of the most important traits of alfalfa (Medicago sativa) for cultivar selection to overcome winter stress. Although transcriptomics, proteomics analysis, and QTL mapping have revealed some important genes correlated with FD, the genetic architecture of this trait is still unclear. There are no applicable genes or markers for selection, which hinders progress in the genetic research and molecular breeding for the trait. We conducted whole-genome sequencing (WGS) on 220 alfalfa accessions at 10x depth. Among the 875,023 SNPs, four of them were associated with FD height using GWAS. One SNP located on chromosome 6 is in linkage disequilibrium with dehydration-responsive element-binding protein 1C (DREB1C). Furthermore, seven DREB genes are clustered in this region, one of which has previously been shown to enhance freezing tolerance in the model plant Medicago truncatula. The candidate genes uncovered by our research will benefit the transgenic and CRISPR-Cas9 research of FD in alfalfa. This gene will also be useful for molecular marker development and marker-associated breeding of FD for alfalfa.

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Whole-genome sequencing analysis of clozapine-induced myocarditis

10.1101/2021.07.26.21261157 ◽

2021 ◽

Author(s):

Ankita Narang ◽

Paul Lacaze ◽

Kathlyn Ronaldson ◽

John McNeil ◽

Mahesh Jayaram ◽

...

Keyword(s):

Whole Genome Sequencing ◽

Genome Sequencing ◽

Genome Wide Association Study ◽

Copy Number Variants ◽

Whole Genome Sequencing Data ◽

Whole Genome ◽

Sequencing Analysis ◽

Sequencing Data ◽

Dna Variation ◽

Rare Genetic Variants

One of the concerns limiting the use of clozapine in schizophrenia treatment is the risk of rare but potentially fatal myocarditis. Our previous genome-wide association study and human leucocyte antigen analyses identified putative loci associated with clozapine-induced myocarditis. However, the contribution of DNA variation in cytochrome P450 genes, copy number variants and rare deleterious variants have not been investigated. We explored these unexplored classes of DNA variation using whole-genome sequencing data from 25 cases with clozapine-induced myocarditis and 25 demographically-matched clozapine-tolerant control subjects. We identified 15 genes based on rare variant gene-burden analysis (MLLT6, CADPS, TACC2, L3MBTL4, NPY, SLC25A21, PARVB, GPR179, ACAD9, NOL8, C5orf33, FAM127A, AFDN, SLC6A11, PXDN) nominally associated (p<0.05) with clozapine-induced myocarditis. Of these genes, 13 were expressed in human myocardial tissue. Although independent replication of these findings is required, our study provides preliminary insights into the potential role of rare genetic variants in susceptibility to clozapine-induced myocarditis.

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Genome-wide association study and whole-genome sequencing identify a deletion in LRIT3 associated with canine congenital stationary night blindness

Scientific Reports ◽

10.1038/s41598-019-50573-7 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 4

Author(s):

Rueben G. Das ◽

Doreen Becker ◽

Vidhya Jagannathan ◽

Orly Goldstein ◽

Evelyn Santana ◽

...

Keyword(s):

Association Study ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Night Blindness ◽

Genome Wide Association Study ◽

Genome Wide Association ◽

Whole Genome ◽

Congenital Stationary Night Blindness ◽

Genome Wide ◽

A Genome

Abstract Congenital stationary night blindness (CSNB), in the complete form, is caused by dysfunctions in ON-bipolar cells (ON-BCs) which are secondary neurons of the retina. We describe the first disease causative variant associated with CSNB in the dog. A genome-wide association study using 12 cases and 11 controls from a research colony determined a 4.6 Mb locus on canine chromosome 32. Subsequent whole-genome sequencing identified a 1 bp deletion in LRIT3 segregating with CSNB. The canine mutant LRIT3 gives rise to a truncated protein with unaltered subcellular expression in vitro. Genetic variants in LRIT3 have been associated with CSNB in patients although there is limited evidence regarding its apparently critical function in the mGluR6 pathway in ON-BCs. We determine that in the canine CSNB retina, the mutant LRIT3 is correctly localized to the region correlating with the ON-BC dendritic tips, albeit with reduced immunolabelling. The LRIT3-CSNB canine model has direct translational potential enabling studies to help understand the CSNB pathogenesis as well as to develop new therapies targeting the secondary neurons of the retina.

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Whole genome sequencing identified a 16 kilobase deletion on ECA13 associated with distichiasis in Friesian horses

BMC Genomics ◽

10.1186/s12864-020-07265-8 ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

E. A. Hisey ◽

H. Hermans ◽

Z. T. Lounsberry ◽

F. Avila ◽

R. A. Grahn ◽

...

Keyword(s):

Whole Genome Sequencing ◽

Genome Sequencing ◽

Genome Wide Association Study ◽

Secondary Infection ◽

Whole Genome Sequencing Data ◽

Incomplete Penetrance ◽

Whole Genome ◽

Genome Wide ◽

A Genome

Abstract Background Distichiasis, an ocular disorder in which aberrant cilia (eyelashes) grow from the opening of the Meibomian glands of the eyelid, has been reported in Friesian horses. These misplaced cilia can cause discomfort, chronic keratitis, and corneal ulceration, potentially impacting vision due to corneal fibrosis, or, if secondary infection occurs, may lead to loss of the eye. Friesian horses represent the vast majority of reported cases of equine distichiasis, and as the breed is known to be affected with inherited monogenic disorders, this condition was hypothesized to be a simply inherited Mendelian trait. Results A genome wide association study (GWAS) was performed using the Axiom 670 k Equine Genotyping array (MNEc670k) utilizing 14 cases and 38 controls phenotyped for distichiasis. An additive single locus mixed linear model (EMMAX) approach identified a 1.83 Mb locus on ECA5 and a 1.34 Mb locus on ECA13 that reached genome-wide significance (pcorrected = 0.016 and 0.032, respectively). Only the locus on ECA13 withstood replication testing (p = 1.6 × 10− 5, cases: n = 5 and controls: n = 37). A 371 kb run of homozygosity (ROH) on ECA13 was found in 13 of the 14 cases, providing evidence for a recessive mode of inheritance. Haplotype analysis (hapQTL) narrowed the region of association on ECA13 to 163 kb. Whole-genome sequencing data from 3 cases and 2 controls identified a 16 kb deletion within the ECA13 associated haplotype (ECA13:g.178714_195130del). Functional annotation data supports a tissue-specific regulatory role of this locus. This deletion was associated with distichiasis, as 18 of the 19 cases were homozygous (p = 4.8 × 10− 13). Genotyping the deletion in 955 horses from 54 different breeds identified the deletion in only 11 non-Friesians, all of which were carriers, suggesting that this could be causal for this Friesian disorder. Conclusions This study identified a 16 kb deletion on ECA13 in an intergenic region that was associated with distichiasis in Friesian horses. Further functional analysis in relevant tissues from cases and controls will help to clarify the precise role of this deletion in normal and abnormal eyelash development and investigate the hypothesis of incomplete penetrance.

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Whole genome sequencing of a sporadic primary immunodeficiency cohort

10.1101/499988 ◽

2018 ◽

Cited By ~ 2

Author(s):

James E. D. Thaventhiran ◽

Hana Lango Allen ◽

Oliver S. Burren ◽

William Rae ◽

Daniel Greene ◽

...

Keyword(s):

Whole Genome Sequencing ◽

Genome Sequencing ◽

Primary Immunodeficiency ◽

Genome Wide Association Study ◽

Diagnostic Yield ◽

Genetic Diagnosis ◽

Whole Genome ◽

Common Variants ◽

Phenotypic Complexity ◽

A Genome

AbstractPrimary immunodeficiency (PID) is characterised by recurrent and often life-threatening infections, autoimmunity and cancer, and it presents major diagnostic and therapeutic challenges. Although the most severe forms present in early childhood, the majority of patients present in adulthood, typically with no apparent family history and a variable clinical phenotype of widespread immune dysregulation: about 25% of patients have autoimmune disease, allergy is prevalent, and up to 10% develop lymphoid malignancies1–3. Consequently, in sporadic PID genetic diagnosis is difficult and the role of genetics is not well defined. We addressed these challenges by performing whole genome sequencing (WGS) of a large PID cohort of 1,318 participants. Analysis of coding regions of 886 index cases found disease-causing mutations in known monogenic PID genes in 10.3%, while a Bayesian approach (BeviMed4) identified multiple potential new candidate genes, including IVNS1ABP. Exploration of the non-coding genome revealed deletions in regulatory regions which contribute to disease causation. Finally, a genome-wide association study (GWAS) identified PID-associated loci and uncovered evidence for co-localisation of, and interplay between, novel high penetrance monogenic variants and common variants (at the PTPN2 and SOCS1 loci). This begins to explain the contribution of common variants to variable penetrance and phenotypic complexity in PID. Thus, a cohort-based WGS approach to PID diagnosis can increase diagnostic yield while deepening our understanding of the key pathways influencing human immune responsiveness.

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A Missense Mutation in the KLF7 Gene Is a Potential Candidate Variant for Congenital Deafness in Australian Stumpy Tail Cattle Dogs

Genes ◽

10.3390/genes12040467 ◽

2021 ◽

Vol 12 (4) ◽

pp. 467

Author(s):

Fangzheng Xu ◽

Shuwen Shan ◽

Susan Sommerlad ◽

Jennifer M. Seddon ◽

Bertram Brenig

Keyword(s):

Candidate Gene ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Heart Development ◽

Genome Wide Association Study ◽

Whole Genome ◽

Potential Candidate ◽

Congenital Deafness ◽

Cardiovascular Development ◽

A Genome

Congenital deafness is prevalent among modern dog breeds, including Australian Stumpy Tail Cattle Dogs (ASCD). However, in ASCD, no causative gene has been identified so far. Therefore, we performed a genome-wide association study (GWAS) and whole genome sequencing (WGS) of affected and normal individuals. For GWAS, 3 bilateral deaf ASCDs, 43 herding dogs, and one unaffected ASCD were used, resulting in 13 significantly associated loci on 6 chromosomes, i.e., CFA3, 8, 17, 23, 28, and 37. CFA37 harbored a region with the most significant association (−log10(9.54 × 10−21) = 20.02) as well as 7 of the 13 associated loci. For whole genome sequencing, the same three affected ASCDs and one unaffected ASCD were used. The WGS data were compared with 722 canine controls and filtered for protein coding and non-synonymous variants, resulting in four missense variants present only in the affected dogs. Using effect prediction tools, two variants remained with predicted deleterious effects within the Heart development protein with EGF like domains 1 (HEG1) gene (NC_006615.3: g.28028412G>C; XP_022269716.1: p.His531Asp) and Kruppel-like factor 7 (KLF7) gene (NC_006619.3: g.15562684G>A; XP_022270984.1: p.Leu173Phe). Due to its function as a regulator in heart and vessel formation and cardiovascular development, HEG1 was excluded as a candidate gene. On the other hand, KLF7 plays a crucial role in the nervous system, is expressed in the otic placode, and is reported to be involved in inner ear development. 55 additional ASCD samples (28 deaf and 27 normal hearing dogs) were genotyped for the KLF7 variant, and the variant remained significantly associated with deafness in ASCD (p = 0.014). Furthermore, 24 dogs with heterozygous or homozygous mutations were detected, including 18 deaf dogs. The penetrance was calculated to be 0.75, which is in agreement with previous reports. In conclusion, KLF7 is a promising candidate gene causative for ASCD deafness.

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Genome-Wide Association Study Using Whole-Genome Sequencing Identifies a Genomic Region on Chromosome 6 Associated With Comb Traits in Nandan-Yao Chicken

Frontiers in Genetics ◽

10.3389/fgene.2021.682501 ◽

2021 ◽

Vol 12 ◽

Author(s):

Zhuliang Yang ◽

Leqin Zou ◽

Tiantian Sun ◽

Wenwen Xu ◽

Linghu Zeng ◽

...

Keyword(s):

Whole Genome Sequencing ◽

Genome Sequencing ◽

Genetic Improvement ◽

Genome Wide Association Study ◽

Association Studies ◽

Genome Wide Association ◽

Genome Wide Association Studies ◽

Chromosome 6 ◽

Whole Genome ◽

Genome Wide

Comb traits have potential economic value in the breeding of indigenous chickens in China. Identifying and understanding relevant molecular markers for comb traits can be beneficial for genetic improvement. The purpose of this study was to utilize genome-wide association studies (GWAS) to detect promising loci and candidate genes related to comb traits, namely, comb thickness (CT), comb weight (CW), comb height, comb length (CL), and comb area. Genome-wide single-nucleotide polymorphisms (SNPs) and small insertions/deletions (INDELs) in 300 Nandan-Yao chickens were detected using whole-genome sequencing. In total, we identified 134 SNPs and 25 INDELs that were strongly associated with the five comb traits. A remarkable region spanning from 29.6 to 31.4 Mb on chromosome 6 was found to be significantly associated with comb traits in both SNP- and INDEL-based GWAS. In this region, two lead SNPs (6:30,354,876 for CW and CT and 6:30,264,318 for CL) and one lead INDEL (a deletion from 30,376,404 to 30,376,405 bp for CL and CT) were identified. Additionally, two genes were identified as potential candidates for comb development. The nearby gene fibroblast growth factor receptor 2 (FGFR2)—associated with epithelial cell migration and proliferation—and the gene cytochrome b5 reductase 2 (CYB5R2)—identified on chromosome 5 from INDEL-based GWAS—are significantly correlated with collagen maturation. The findings of this study could provide promising genes and biomarkers to accelerate genetic improvement of comb development based on molecular marker-assisted breeding in Nandan-Yao chickens.

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Genetic tools to improve reproduction traits in dairy cattle

Reproduction Fertility and Development ◽

10.1071/rd14379 ◽

2015 ◽

Vol 27 (1) ◽

pp. 14 ◽

Cited By ~ 6

Author(s):

A. Capitan ◽

P. Michot ◽

A. Baur ◽

R. Saintilan ◽

C. Hozé ◽

...

Keyword(s):

Dairy Cattle ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Genetic Research ◽

Detection Methods ◽

Whole Genome ◽

Sequencing Data ◽

Lethal Mutations ◽

Embryonic Lethal ◽

Embryonic Lethal Mutations

Fertility is a major concern in the dairy cattle industry and has been the subject of numerous studies over the past 20 years. Surprisingly, most of these studies focused on rough female phenotypes and, despite their important role in reproductive success, male- and embryo-related traits have been poorly investigated. In recent years, the rapid and important evolution of technologies in genetic research has led to the development of genomic selection. The generalisation of this method in combination with the achievements of the AI industry have led to the constitution of large databases of genotyping and sequencing data, as well as refined phenotypes and pedigree records. These resources offer unprecedented opportunities in terms of fundamental and applied research. Here we present five such examples with a focus on reproduction-related traits: (1) detection of quantitative trait loci (QTL) for male fertility and semen quality traits; (2) detection of QTL for refined phenotypes associated with female fertility; (3) identification of recessive embryonic lethal mutations by depletion of homozygous haplotypes; (4) identification of recessive embryonic lethal mutations by mining whole-genome sequencing data; and (5) the contribution of high-density single nucleotide polymorphism chips, whole-genome sequencing and imputation to increasing the power of QTL detection methods and to the identification of causal variants.

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