Whole-genome sequencing of Costa Rican children with asthma identifies CRISPLD2 as a candidate gene for lung function

2018 ◽  
Author(s):  
Bo Chawes ◽  
Julian Hecker ◽  
Christoph Lange ◽  
Scott Weiss ◽  
Jessica Lasky-Su
Keyword(s):  
Lung Function ◽  
Candidate Gene ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Costa Rican ◽  
Whole Genome ◽  
Children With Asthma

scholarly journals Whole Genome Sequencing Identifies CRISPLD2 as a Lung Function Gene in Children With Asthma

CHEST Journal ◽  
2019 ◽  
Vol 156 (6) ◽  
pp. 1068-1079 ◽  
Author(s):  
Priyadarshini Kachroo ◽  
Julian Hecker ◽  
Bo L. Chawes ◽  
Tarunveer S. Ahluwalia ◽  
Michael H. Cho ◽  
...  
Keyword(s):  
Lung Function ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Whole Genome ◽  
Children With Asthma

scholarly journals Whole-Genome Sequencing Identifies Novel Functional Loci Associated with Lung Function in Puerto Rican Youth

2020 ◽  
Vol 202 (7) ◽  
pp. 962-972
Author(s):  
Eunice Y. Lee ◽  
Angel C. Y. Mak ◽  
Donglei Hu ◽  
Satria Sajuthi ◽  
Marquitta J. White ◽  
...  
Keyword(s):  
Lung Function ◽  
Whole Genome Sequencing ◽  
Puerto Rican ◽  
Genome Sequencing ◽  
Whole Genome

scholarly journals Whole genome sequencing of pharmacogenetic drug response in racially and ethnically diverse children with asthma

2017 ◽  
Author(s):  
Angel C.Y. Mak ◽  
Marquitta J. White ◽  
Zachary A. Szpiech ◽  
Walter L. Eckalbar ◽  
Sam S. Oh ◽  
...  
Keyword(s):  
African Americans ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Drug Response ◽  
Puerto Ricans ◽  
Ethnically Diverse ◽  
Asthma Prevalence ◽  
Whole Genome ◽  
Minority Children ◽  
Children With Asthma

ABSTRACTAsthma is the most common chronic disease of children, with significant racial/ethnic differences in prevalence, morbidity, mortality and therapeutic response. Albuterol, a bronchodilator medication, is the first-line therapy for asthma treatment worldwide. We performed the largest whole genome sequencing (WGS) pharmacogenetics study to date using data from 1,441 minority children with asthma who had extremely high or low bronchodilator drug response (BDR). We identified population-specific and shared pharmacogenetic variants associated with BDR, including genome-wide significant (p < 3.53 x 10-7) and suggestive (p < 7.06 x 10-6) loci near genes previously associated with lung capacity (DNAH5), immunity (NFKB1 and PLCB1), and β-adrenergic signaling pathways (ADAMTS3 and COX18). Functional analyses centered on NFKB1 revealed potential regulatory function of our BDR-associated SNPs in bronchial smooth muscle cells. Specifically, these variants are in linkage disequilibrium with SNPs in a functionally active enhancer, and are also expression quantitative trait loci (eQTL) for a neighboring gene, SLC39A8. Given the lack of other asthma study populations with WGS data on minority children, replication of our rare variant associations is infeasible. We attempted to replicate our common variant findings in five independent studies with GWAS data. The age-specific associations previously found in asthma and asthma-related traits suggest that the over-representation of adults in our replication populations may have contributed to our lack of statistical replication, despite the functional relevance of the NFKB1 variants demonstrated by our functional assays. Our study expands the understanding of pharmacogenetic analyses in racially/ethnically diverse populations and advances the foundation for precision medicine in at-risk and understudied minority populations.AUTHOR SUMMARYAsthma is the most common chronic disease among children. Albuterol, a bronchodilator medication, is the first-line therapy for asthma treatment worldwide. In the U.S., asthma prevalence is the highest among Puerto Ricans, intermediate among African Americans and lowest in Whites and Mexicans. Asthma disparities extend to mortality, which is four- to five-fold higher in Puerto Ricans and African Americans compared to Mexicans [1]. Puerto Ricans and African Americans, the populations with the highest asthma prevalence and death rate, also have the lowest albuterol bronchodilator drug response (BDR). We conducted the largest pharmacogenetic study using whole genome sequencing data from 1,441 minority children with asthma who had extremely high or low albuterol bronchodilator drug response. We identified population-specific and shared pharmacogenetic variants associated with BDR. Our findings help inform the direction of future development of asthma medications and our study advances the foundation of precision medicine for at-risk, yet understudied, racially/ethnically diverse populations.

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

Genes ◽  
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.

scholarly journals Whole-Genome Sequencing of Pharmacogenetic Drug Response in Racially Diverse Children with Asthma

2018 ◽  
Vol 197 (12) ◽  
pp. 1552-1564 ◽  
Author(s):  
Angel C. Y. Mak ◽  
Marquitta J. White ◽  
Walter L. Eckalbar ◽  
Zachary A. Szpiech ◽  
Sam S. Oh ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Drug Response ◽  
Whole Genome ◽  
Racially Diverse ◽  
Children With Asthma ◽  
Diverse Children

scholarly journals Detection of Candidate Gene LsACOS5 and Development of InDel Marker for Male Sterility by DdRAD-Seq and Whole-Genome Sequencing in Lettuce (Lactuca Sativa L.)

2021 ◽  
Author(s):  
kousuke seki
Keyword(s):  
Candidate Gene ◽  
Whole Genome Sequencing ◽  
Male Sterility ◽  
Genome Sequencing ◽  
Indel Marker ◽  
Hybrid Breeding ◽  
Whole Genome ◽  
Structural Polymorphism ◽  
Male Sterile ◽  
Breeding Method

Abstract A new breeding method of F1 hybrid using male sterility would open an exciting frontier in lettuce breeding, a self-pollinating crop. Male sterility is a crucial trait in F1 hybrid breeding. It is essential to map the causative gene for using male sterility. The ms-S, male-sterile gene of ‘CGN17397’, was mapped to LG8 by double-digest restriction site-associated DNA sequencing (ddRAD-seq) and narrowed down between two markers using two F2 populations. This region spans approximately 10.16 Mb, where 94 genes were annotated according to the lettuce reference genome sequence (version8 from crisphead cultivar ‘Salinas’). The whole-genome sequencing of the male-sterile and fertile lines of ‘CGN17397’ revealed that only one gene differed in the area of Lsat_1_v5_gn_8_148221.1, a homolog of Arabidopsis acyl-CoA synthetase5 (AtACOS5), and was deleted in the male-sterile lines. It was reported that AtACOS5 was needed for pollen wall formation and that the null mutants of AtACOS5 were entirely male sterility. Thus, I concluded that Lsat_1_v5_gn_8_148221.1 designated as LsACOS5 was a biologically plausible candidate gene for the ms-S locus. By using the structural polymorphism of LsACOS5, an insertion/deletion (InDel) marker was developed to select the male-sterile trait. The results obtained here provide valuable information for the genic male-sterility in lettuce.

scholarly journals Whole Genome Sequencing of Giant Schnauzer Dogs with Progressive Retinal Atrophy Establishes NECAP1 as a Novel Candidate Gene for Retinal Degeneration

Genes ◽  
2019 ◽  
Vol 10 (5) ◽  
pp. 385 ◽  
Author(s):  
Rebekkah J. Hitti ◽  
James A. C. Oliver ◽  
Ellen C. Schofield ◽  
Anina Bauer ◽  
Maria Kaukonen ◽  
...  
Keyword(s):  
Candidate Gene ◽  
Whole Genome Sequencing ◽  
Retinal Degeneration ◽  
Genome Sequencing ◽  
Autosomal Recessive Disorder ◽  
Causal Variant ◽  
Whole Genome ◽  
Gene Encoding ◽  
Progressive Retinal Atrophy ◽  
Dna Test

Canine progressive retinal atrophies (PRA) are genetically heterogeneous diseases characterized by retinal degeneration and subsequent blindness. PRAs are untreatable and affect multiple dog breeds, significantly impacting welfare. Three out of seven Giant Schnauzer (GS) littermates presented with PRA around four years of age. We sought to identify the causal variant to improve our understanding of the aetiology of this form of PRA and to enable development of a DNA test. Whole genome sequencing of two PRA-affected full-siblings and both unaffected parents was performed. Variants were filtered based on those segregating appropriately for an autosomal recessive disorder and predicted to be deleterious. Successive filtering against 568 canine genomes identified a single nucleotide variant in the gene encoding NECAP endocytosis associated 1 (NECAP1): c.544G>A (p.Gly182Arg). Five thousand one hundred and thirty canids of 175 breeds, 10 cross-breeds and 3 wolves were genotyped for c.544G>A. Only the three PRA-affected GS were homozygous (allele frequency in GS, excluding proband family = 0.015). In addition, we identified heterozygotes belonging to Spitz and Dachshund varieties, demonstrating c.544G>A segregates in other breeds of German origin. This study, in parallel with the known retinal expression and role of NECAP1 in clathrin mediated endocytosis (CME) in synapses, presents NECAP1 as a novel candidate gene for retinal degeneration in dogs and other species.

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