Strategies to Identify Pharmacogenomic Biomarkers: Candidate Gene, Pathway-Based, and Genome-Wide Approaches

2008 ◽  
pp. 353-370 ◽  
Author(s):  
Xifeng Wu ◽  
Jian Gu ◽  
Margaret R. Spitz
Keyword(s):  
Candidate Gene ◽  
Gene Pathway ◽  
Genome Wide

scholarly journals Genome-Wide Association Study (GWAS) to Identify Salt-Tolerance QTLs Carrying Novel Candidate Genes in Rice During Early Vegetative Stage

Rice ◽  
2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Leila Nayyeripasand ◽  
Ghasem Ali Garoosi ◽  
Asadollah Ahmadikhah
Keyword(s):  
Association Study ◽  
Candidate Gene ◽  
Candidate Genes ◽  
Salinity Tolerance ◽  
Genome Wide Association Study ◽  
Dry Weight ◽  
Genome Wide Association ◽  
Vegetative Stage ◽  
Genome Wide ◽  
Genomic Regions

Abstract Background Rice is considered as a salt-sensitive plant, particularly at early vegetative stage, and its production is suffered from salinity due to expansion of salt affected land in areas under cultivation. Hence, significant increase of rice productivity on salinized lands is really necessary. Today genome-wide association study (GWAS) is a method of choice for fine mapping of QTLs involved in plant responses to abiotic stresses including salinity stress at early vegetative stage. In this study using > 33,000 SNP markers we identified rice genomic regions associated to early stage salinity tolerance. Eight salinity-related traits including shoot length (SL), root length (RL), root dry weight (RDW), root fresh weight (RFW), shoot fresh weight (SFW), shoot dry weight (SDW), relative water content (RWC) and TW, and 4 derived traits including SL-R, RL-R, RDW-R and RFW-R in a diverse panel of rice were evaluated under salinity (100 mM NaCl) and normal conditions in growth chamber. Genome-wide association study (GWAS) was applied based on MLM(+Q + K) model. Results Under stress conditions 151 trait-marker associations were identified that were scattered on 10 chromosomes of rice that arranged in 29 genomic regions. A genomic region on chromosome 1 (11.26 Mbp) was identified which co-located with a known QTL region SalTol1 for salinity tolerance at vegetative stage. A candidate gene (Os01g0304100) was identified in this region which encodes a cation chloride cotransporter. Furthermore, on this chromosome two other candidate genes, Os01g0624700 (24.95 Mbp) and Os01g0812000 (34.51 Mbp), were identified that encode a WRKY transcription factor (WRKY 12) and a transcriptional activator of gibberellin-dependent alpha-amylase expression (GAMyb), respectively. Also, a narrow interval on the same chromosome (40.79–42.98 Mbp) carries 12 candidate genes, some of them were not so far reported for salinity tolerance at seedling stage. Two of more interesting genes are Os01g0966000 and Os01g0963000, encoding a plasma membrane (PM) H+-ATPase and a peroxidase BP1 protein. A candidate gene was identified on chromosome 2 (Os02g0730300 at 30.4 Mbp) encoding a high affinity K+ transporter (HAK). On chromosome 6 a DnaJ-encoding gene and pseudouridine synthase gene were identified. Two novel genes on chromosome 8 including the ABI/VP1 transcription factor and retinoblastoma-related protein (RBR), and 3 novel genes on chromosome 11 including a Lox, F-box and Na+/H+ antiporter, were also identified. Conclusion Known or novel candidate genes in this research were identified that can be used for improvement of salinity tolerance in molecular breeding programmes of rice. Further study and identification of effective genes on salinity tolerance by the use of candidate gene-association analysis can help to precisely uncover the mechanisms of salinity tolerance at molecular level. A time dependent relationship between salt tolerance and expression level of candidate genes could be recognized.

scholarly journals Association Mapping and Functional Analysis of Rice Cold Tolerance QTLs at the Bud Burst Stage

Rice ◽  
2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Dan Wang ◽  
Zhuo Liu ◽  
Yinghui Xiao ◽  
Xionglun Liu ◽  
Yue Chen ◽  
...  
Keyword(s):  
Candidate Gene ◽  
Cold Tolerance ◽  
Genome Wide Association Study ◽  
Gene Knockout ◽  
Micro Rna ◽  
Negative Regulator ◽  
Bud Burst ◽  
Rab Protein ◽  
Genome Wide ◽  
Direct Seeded

AbstractCold tolerance at the bud burst stage (CTB) is a key trait for direct-seeded rice. Although quantitative trait loci (QTL) affecting CTB in rice have been mapped using traditional linkage mapping and genome-wide association study (GWAS) methods, the underlying genes remain unknown. In this study, we evaluated the CTB phenotype of 339 cultivars in the Rice Diversity Panel II (RDP II) collection. GWAS identified four QTLs associated with CTB (qCTBs), distributed on chromosomes 1–3. Among them, qCTB-1-1 overlaps with Osa-miR319b, a known cold tolerance micro RNA gene. The other three qCTBs have not been reported. In addition, we characterised the candidate gene OsRab11C1 for qCTB-1-2 that encodes a Rab protein belonging to the small GTP-binding protein family. Overexpression of OsRab11C1 significantly reduced CTB, while gene knockout elevated CTB as well as cold tolerance at the seedling stage, suggesting that OsRab11C1 negatively regulates rice cold tolerance. Molecular analysis revealed that OsRab11C1 modulates cold tolerance by suppressing the abscisic acid signalling pathway and proline biosynthesis. Using RDP II and GWAS, we identified four qCTBs that are involved in CTB and determined the function of the candidate gene OsRab11C1 in cold tolerance. Our results demonstrate that OsRab11C1 is a negative regulator of cold tolerance and knocking out of the gene by genome-editing may provide enhanced cold tolerance in rice.

Abstract 1743: Identification of a Novel Susceptibility Locus at 9q21 for Familial Bicuspid Aortic Valve Disease

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Stephen H McKellar ◽  
Marineh Yagubyan ◽  
Ramanath Majumdar ◽  
David J Tester ◽  
Mariza de Andrade ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Linkage Analysis ◽  
Microsatellite Markers ◽  
Candidate Gene ◽  
Candidate Genes ◽  
Bicuspid Aortic Valve ◽  
Fine Mapping ◽  
Aortic Valve Disease ◽  
Biological Plausibility ◽  
Genome Wide

Background: Bicuspid aortic valve disease (BAV), the most common congenital cardiovascular malformation, has an incidence of 0.5–1.0% of live births. While most cases of BAV appear to be sporadic, familial inheritance patterns have been observed consistent with autosomal dominant inheritance with variable penetrance. However, little is known about specific genetic loci responsible for familial BAV. Here, we performed linkage analysis on a large multi-generational pedigree affected with BAV. Methods: We identified a large, five-generation pedigree (136 family members) with 10 individuals having BAV. Two-dimensional echocardiography was used to assign aortic valve phenotype. Genome-wide linkage analysis using 430 microsatellite markers (Marshfield Clinic) and fine mapping using 100 single nucleotide polymorphisms (Affymetrix) on chromosome 9 was performed on genomic DNA from all available family members. Logarithm of odds (LOD) scores of >2.0 were considered suggestive of linkage. Comprehensive splice site/open reading frame mutational analysis of candidate genes residing in the putative locus is underway using PCR, DHPLC, and DNA sequencing. A candidate gene, KLF9, Krüppel-like factor 9 was analyzed for mutations because of its role in cardiogenesis. Results: Multi-point genome-wide linkage analysis demonstrated a 7 cM region on chromosome 9q21 that was suggestive of linkage for familial BAV with a maximum multipoint LOD score of 2.8 flanked by the microsatellite markers GATA7D12 and D9S1834. This region contains several candidate genes with biological plausibility for BAV phenotype. KLF9- encoded Krüppel-like factor 9, localized to chromosome 9q21, was targeted as a prime candidate gene for familial BAV. However, no mutations involving the translated exons of KLF9 were detected. Further fine mapping studies and candidate gene analysis are currently underway. Conclusions: We report a novel susceptibility locus on chromosome 9q21 for BAV in a large multi-generational family. Although coding region mutations in KLF9 are not responsible for BAV in this pedigree, several candidate genes with biological plausibility for the development of congenital BAV lie within this region and warrant further scrutiny.

scholarly journals Genetics of Keratoconus: Where Do We Stand?

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Khaled K. Abu-Amero ◽  
Abdulrahman M. Al-Muammar ◽  
Altaf A. Kondkar
Keyword(s):  
Risk Factors ◽  
Candidate Gene ◽  
Genetic Risk ◽  
Current Knowledge ◽  
Genetic Risk Factors ◽  
Factors Associated ◽  
Genetic Components ◽  
Genome Wide ◽  
Molecular Etiology

Keratoconus is a progressive thinning and anterior protrusion of the cornea that results in steepening and distortion of the cornea, altered refractive powers, and reduced vision. Keratoconus has a complex multifactorial etiology, with environmental, behavioral, and multiple genetic components contributing to the disease pathophysiology. Using genome-wide and candidate gene approaches several genomic loci and genes have been identified that highlight the complex molecular etiology of this disease. The review focuses on current knowledge of these genetic risk factors associated with keratoconus.

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