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

2019 ◽  
Vol 9 (1) ◽  
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.

A chemical genetic roadmap to improved tomato flavor

Science ◽  
2017 ◽  
Vol 355 (6323) ◽  
pp. 391-394 ◽  
Author(s):  
Denise Tieman ◽  
Guangtao Zhu ◽  
Marcio F. R. Resende ◽  
Tao Lin ◽  
Cuong Nguyen ◽  
...  
Keyword(s):  
Association Study ◽  
Genome Sequencing ◽  
Molecular Breeding ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Whole Genome ◽  
Chemical Genetic ◽  
Genome Wide ◽  
A Genome ◽  
Wild Accessions

Modern commercial tomato varieties are substantially less flavorful than heirloom varieties. To understand and ultimately correct this deficiency, we quantified flavor-associated chemicals in 398 modern, heirloom, and wild accessions. A subset of these accessions was evaluated in consumer panels, identifying the chemicals that made the most important contributions to flavor and consumer liking. We found that modern commercial varieties contain significantly lower amounts of many of these important flavor chemicals than older varieties. Whole-genome sequencing and a genome-wide association study permitted identification of genetic loci that affect most of the target flavor chemicals, including sugars, acids, and volatiles. Together, these results provide an understanding of the flavor deficiencies in modern commercial varieties and the information necessary for the recovery of good flavor through molecular breeding.

Genome-wide association study using whole-genome sequencing rapidly identifies new genes influencing agronomic traits in rice

2016 ◽  
Vol 48 (8) ◽  
pp. 927-934 ◽  
Author(s):  
Kenji Yano ◽  
Eiji Yamamoto ◽  
Koichiro Aya ◽  
Hideyuki Takeuchi ◽  
Pei-ching Lo ◽  
...  
Keyword(s):  
Association Study ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Genome Wide Association Study ◽  
Agronomic Traits ◽  
Genome Wide Association ◽  
Whole Genome ◽  
New Genes ◽  
Genome Wide

scholarly journals Genome-wide association study for longevity with whole-genome sequencing in 3 cattle breeds

2016 ◽  
Vol 99 (9) ◽  
pp. 7289-7298 ◽  
Author(s):  
Qianqian Zhang ◽  
Bernt Guldbrandtsen ◽  
Jørn Rind Thomasen ◽  
Mogens Sandø Lund ◽  
Goutam Sahana
Keyword(s):  
Association Study ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Whole Genome ◽  
Cattle Breeds ◽  
Genome Wide

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

BMC Genomics ◽  
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.

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

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.

scholarly journals NUDT15 Genetic Variation Is the Strongest Predictive Marker of Tolerance to 6-Mercaptopurine in Japanese Childhood ALL Patients: A Genome-Wide Association Study

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1347-1347
Author(s):  
Yoichi Tanaka ◽  
Kevin Y Urayama ◽  
Makiko Mori ◽  
Daisuke Hasegawa ◽  
Yasushi Noguchi ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Predictive Marker ◽  
Age At Diagnosis ◽  
Genome Wide Association ◽  
Whole Genome ◽  
Japanese Study ◽  
Genome Wide ◽  
A Genome

Introduction In Asians, NUDT15 genetic variants have been reported to be associated with low tolerance to 6-mercaptopurine (6-MP). However, variation in 6-MP tolerance is still observed among patients without the NUDT15 variants. Some patients required high doses of 6-MP to obtain treatment effect. We performed a genome-wide association study (GWAS) in Japanese to confirm reported associations as well as to identify additional genetic loci associated with variation of 6-MP tolerance in childhood acute lymphoblastic leukemia (ALL) patients. Methods We included ALL patients enrolled into a Tokyo Children's Cancer Study Group (TCCSG) trial who started maintenance therapy by normal protocol dose (30-50 mg/m2/day). Whole genome single nucleotide polymorphism (SNP) microarray genotyping was performed followed by whole genome SNP imputation (Japanese reference genome). Data for over six million SNPs were available for analysis. Association analysis was performed adjusting for age at diagnosis and considering average 6-MP dose during 168 days from maintenance therapy initiation as the outcome. Results A total of 224 patients were included in the analysis. The median age at diagnosis was 4.7 (range = 0.9-15.7) years old and boys comprised 56.3%. The average 6-MP dose during the 168 days of maintenance therapy was 41.1 (range = 13.3-78.5) mg/m2/day. Variants representing 10 genomic regions showed potential association (P < 5 x 10-6) with average 6-MP dose, in which one locus was genome-wide significant (13q14.2, rs116855232). Variant rs116855232 is located in the previously identified NUDT15 gene and represents the strongest association with average 6-MP dose within our Japanese study (β = -11.45, P = 8.5 x 10-10). In contrast, the TPMT locus, which is predictive of 6-MP intolerance in populations of European ancestry, was not associated with 6-MP dose in Japanese. Among the suggestive loci requiring further follow-up is a locus residing in AFF3 (2q11.2, P = 2.1 x 10-6), a gene previously implicated in childhood leukemia. Conclusion We have validated that NUDT15 rs116855232 is a locus with strong association with 6-MP tolerable dose, and it currently represents the most meaningful clinically predictive marker in Japanese. These findings indicated that NUDT15 genotyping should be considered prior to initiation of 6-MP treatment. Prospects for the identification of additional loci of 6-MP tolerance are high after further validation of suggestive loci observed in this Japanese study. Figure Disclosures No relevant conflicts of interest to declare.

scholarly journals Choosing the optimal population for a genome‐wide association study: A simulation of whole‐genome sequences from rice

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Kosuke Hamazaki ◽  
Hiromi Kajiya‐Kanegae ◽  
Masanori Yamasaki ◽  
Kaworu Ebana ◽  
Shiori Yabe ◽  
...  
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Whole Genome ◽  
Genome Sequences ◽  
Genome Wide ◽  
A Genome ◽  
Optimal Population

scholarly journals Whole genome sequencing in the Middle Eastern Qatari population identifies genetic associations with 45 clinically relevant traits

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Gaurav Thareja ◽  
◽  
Yasser Al-Sarraj ◽  
Aziz Belkadi ◽  
Maryam Almotawa ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Genome Wide Association Study ◽  
Clinical Laboratory ◽  
Medical Decision ◽  
Future Application ◽  
Whole Genome ◽  
Genome Wide ◽  
A Genome ◽  
Polygenic Scores

AbstractClinical laboratory tests play a pivotal role in medical decision making, but little is known about their genetic variability between populations. We report a genome-wide association study with 45 clinically relevant traits from the population of Qatar using a whole genome sequencing approach in a discovery set of 6218 individuals and replication in 7768 subjects. Trait heritability is more similar between Qatari and European populations (r = 0.81) than with Africans (r = 0.44). We identify 281 distinct variant-trait-associations at genome wide significance that replicate known associations. Allele frequencies for replicated loci show higher correlations with European (r = 0.94) than with African (r = 0.85) or Japanese (r = 0.80) populations. We find differences in linkage disequilibrium patterns and in effect sizes of the replicated loci compared to previous reports. We also report 17 novel and Qatari-predominate signals providing insights into the biological pathways regulating these traits. We observe that European-derived polygenic scores (PGS) have reduced predictive performance in the Qatari population which could have implications for the translation of PGS between populations and their future application in precision medicine.

Sign in / Sign up

Export Citation Format

Share Document