Genome-wide Association Approach Research Articles

Genome-wide association study for carcass traits in a composite beef cattle breed

Improvement of carcass traits is highly emphasized in beef cattle production in order to meet consumer demands. Discovering and understanding genes and genetic variants that control these traits is of paramount importance. In this study, different genome wide association approaches (single step GBLUP GWAS, Bayes A and Bayes B) were implemented and compared for three ultrasound carcass traits: fat thickness (FAT), intramuscular fat (IMF) and ribeye area (REA) of a composite beef cattle breed. The results showed different SNP marker windows associated with carcass traits explaining a small percentage of the genetic variance. The SNP marker window with the highest percentage of genetic variance (1.83%) associated with FAT was located on BTA14 in position 24 Mb. Surveying candidate genes in the regions associated with these traits revealed genes such as LYPLA, and LYN genes which have been associated with feed intake and growth in beef cattle. This study supported previous results from GWAS of carcass traits and revealed additional regions in the bovine genome associated with these economically important traits. Comparing the top 5 SNP windows for each trait across the GWAS methods revealed that only a few of these windows overlap.

Molecular diversity and landscape genomics of the crop wild relative Triticum urartu across the Fertile Crescent.

Modern plant breeding can benefit from the allelic variation that exists in natural populations of crop wild relatives that evolved under natural selection in varying pedoclimatic conditions. In this study, next-generation sequencing was used to generate 1.3 million genome-wide single nucleotide polymorphisms (SNPs) on ex situ collections of Triticum urartu L., the wild donor of the Au subgenome of modern wheat. A set of 75511 high-quality SNPs were retained to describe 298 T. urartu accessions collected throughout the Fertile Crescent. Triticum urartu showed a complex pattern of genetic diversity, with two main genetic groups distributed sequentially from west to east. The incorporation of geographical information on sampling points showed that genetic diversity was correlated to the geographical distance (R2 =0.19) separating samples from Jordan and Lebanon, from Syria and southern Turkey, and from eastern Turkey, Iran and Iraq. The wild emmer genome was used to derive the physical positions of SNPs on the seven chromosomes of the Au subgenome, allowing us to describe a relatively slow decay of linkage disequilibrium in the collection. Outlier loci were described on the basis of the geographic distribution of the T. urartu accessions, identifying a hotspot of directional selection on chromosome 4A. Bioclimatic variation was derived from grid data and related to allelic variation using a genome-wide association approach, identifying several marker-environment associations (MEAs). Fifty-seven MEAs were associated with altitude and temperature measures while 358 were associated with rainfall measures. The most significant MEAs and outlier loci were used to identify genomic loci with adaptive potential (some already reported in wheat), including dormancy and frost resistance loci. We advocate the application of genomics and landscape genomics on ex situ collections of crop wild relatives to efficiently identify promising alleles and genetic materials for incorporation into modern crop breeding.

Genetic Variants in CPA6 and PRPF31 Are Associated With Variation in Response to Metformin in Individuals With Type 2 Diabetes.

Metformin is the first-line treatment for type 2 diabetes (T2D). Although widely prescribed, the glucose-lowering mechanism for metformin is incompletely understood. Here, we used a genome-wide association approach in a diverse group of individuals with T2D from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) clinical trial to identify common and rare variants associated with HbA1c response to metformin treatment and followed up these findings in four replication cohorts. Common variants in PRPF31 and CPA6 were associated with worse and better metformin response, respectively (P < 5 × 10-6), and meta-analysis in independent cohorts displayed similar associations with metformin response (P = 1.2 × 10-8 and P = 0.005, respectively). Previous studies have shown that PRPF31(+/-) knockout mice have increased total body fat (P = 1.78 × 10-6) and increased fasted circulating glucose (P = 5.73 × 10-6). Furthermore, rare variants in STAT3 associated with worse metformin response (q <0.1). STAT3 is a ubiquitously expressed pleiotropic transcriptional activator that participates in the regulation of metabolism and feeding behavior. Here, we provide novel evidence for associations of common and rare variants in PRPF31, CPA6, and STAT3 with metformin response that may provide insight into mechanisms important for metformin efficacy in T2D.

Identification of novel loci associated with maturity and yield traits in early maturity soybean plant introduction lines

BackgroundTo continue to meet the increasing demands of soybean worldwide, it is crucial to identify key genes regulating flowering and maturity to expand the cultivated regions into short season areas. Although four soybean genes have been successfully utilized in early maturity breeding programs, new genes governing maturity are continuously being identified suggesting that there remains as yet undiscovered loci governing agronomic traits of interest. The objective of this study was to identify novel loci and genes involved in a diverse set of early soybean maturity using genome-wide association (GWA) analyses to identify loci governing days to maturity (DTM), flowering (DTF) and pod filling (DTPF), as well as yield and 100 seed weight in Canadian environments. To do so, soybean plant introduction lines varying significantly for maturity, but classified as early varieties, were used. Plants were phenotyped for the five agronomic traits for five site-years and GWA approaches used to identify candidate loci and genes affecting each trait.ResultsGenotyping using genotyping-by-sequencing and microarray methods identified 67,594 single nucleotide polymorphisms, of which 31,283 had a linkage disequilibrium < 1 and minor allele frequency > 0.05 and were used for GWA analyses. A total of 9, 6, 4, 5 and 2 loci were detected for GWA analyses for DTM, DTF, DTPF, 100 seed weight and yield, respectively. Regions of interest, including a region surrounding the E1 gene for flowering and maturity, and several novel loci, were identified, with several loci having pleiotropic effects. Novel loci affecting maturity were identified on chromosomes five and 13 and reduced maturity by 7.2 and 3.3 days, respectively. Novel loci for maturity and flowering contained genes orthologous to known Arabidopsis flowering genes, while loci affecting yield and 100 seed weight contained genes known to cause dwarfism.ConclusionsThis study demonstrated substantial variation in soybean agronomic traits of interest, including maturity and flowering dates as well as yield, and the utility of GWA analyses in identifying novel genetic factors underlying important agronomic traits. The loci and candidate genes identified serve as promising targets for future studies examining the mechanisms underlying the related soybean traits.

Identification of relevant drugable targets in diffuse large B-cell lymphoma using a genome-wide unbiased CD20 guilt-by association approach.

Forty percent of patients with diffuse large B-cell lymphoma (DLBCL) show resistant disease to standard chemotherapy (CHOP) in combination with the anti-CD20 monoclonal antibody rituximab (R). Although many new anti-cancer drugs were developed in the last years, it is unclear which of these drugs can be safely combined to improve standard therapy without antagonizing anti-CD20 efficacy. In this study, we aimed to identify rituximab compatible drug-target combinations for DLBCL. For this, we collected gene expression profiles of 1,804 DLBCL patient samples. Subsequently, we performed a guilt-by-association analysis with MS4A1 (CD20) and prioritized the 500 top-ranked CD20-associated gene probes for drug-target interactions. This analysis showed the well-known genes involved in DLBCL pathobiology, but also revealed several genes that are relatively unknown in DLBCL, such as WEE1 and PARP1. To demonstrate potential clinical relevance of these targets, we confirmed high protein expression of WEE1 and PARP1 in patient samples. Using clinically approved WEE1 and PARP1 inhibiting drugs in combination with rituximab, we demonstrated significantly improved DLBCL cell killing, also in rituximab-insensitive cell lines. In conclusion, as exemplified by WEE1 and PARP1, our CD20-based genome-wide analysis can be used as an approach to identify biological relevant drug-targets that are rituximab compatible and may be implemented in phase 1/2 clinical trials to improve DLBCL treatment.

Linking genotype to phenotype in a changing ocean: inferring the genomic architecture of a blue mussel stress response with genome-wide association.

A key component to understanding the evolutionary response to a changing climate is linking underlying genetic variation to phenotypic variation in stress response. Here, we use a genome-wide association approach (GWAS) to understand the genetic architecture of calcification rates under simulated climate stress. We take advantage of the genomic gradient across the blue mussel hybrid zone (Mytilus edulis and Mytilus trossulus) in the Gulf of Maine (GOM) to link genetic variation with variance in calcification rates in response to simulated climate change. Falling calcium carbonate saturation states are predicted to negatively impact many marine organisms that build calcium carbonate shells - like blue mussels. We sampled wild mussels and measured net calcification phenotypes after exposing mussels to a 'climate change' common garden, where we raised temperature by 3°C, decreased pH by 0.2 units and limited food supply by filtering out planktonic particles >5μm, compared to ambient GOM conditions in the summer. This climate change exposure greatly increased phenotypic variation in net calcification rates compared to ambient conditions. We then used regression models to link the phenotypic variation with over 170000 single nucleotide polymorphism loci (SNPs) generated by genotype by sequencing to identify genomic locations associated with calcification phenotype, and estimate heritability and architecture of the trait. We identified at least one of potentially 2-10 genomic regions responsible for 30% of the phenotypic variation in calcification rates that are potential targets of natural selection by climate change. Our simulations suggest a power of 13.7% with our study's average effective sample size of 118 individuals and rare alleles, but a power of >90% when effective sample size is 900.

Real-life helping behaviours in North America: A genome-wide association approach.

In humans, prosocial behaviour is essential for social functioning. Twin studies suggest this distinct human trait to be partly hardwired. In the last decade research on the genetics of prosocial behaviour focused on neurotransmitters and neuropeptides, such as oxytocin, dopamine, and their respective pathways. Recent trends towards large scale medical studies targeting the genetic basis of complex diseases such as Alzheimer’s disease and schizophrenia pave the way for new directions also in behavioural genetics.Based on data from 10,713 participants of the American Health and Retirement Study we estimated heritability of helping behaviour–its total variance explained by 1.2 million single nucleotide polymorphisms–to be 11%. Both, fixed models and mixed linear models identified rs11697300, an intergene variant on chromosome 20, as a candidate variant moderating this particular helping behaviour. We assume that this so far undescribed area is worth further investigation in association with human prosocial behaviour.

Analysis of single nucleotide polymorphisms variation associated with important economic and computed tomography measured traits in Texel sheep

Sheep are an important part of the global agricultural economy. Growth and meat production traits are significant economic traits in sheep. The Texel breed is the most popular terminal sire breed in the UK, mainly selected for muscle growth and lean carcasses. This is a study based on a genome-wide association approach that investigates the links between some economically important traits, including computed tomography (CT) measurements, and molecular polymorphisms in UK Texel sheep. Our main aim was to identify single nucleotide polymorphisms (SNP) associated with growth, carcass, health and welfare traits of the Texel sheep breed. This study used data from 384 Texel rams. Data comprised ten traits, including two CT measured traits. The phenotypic data were placed in four categories: growth traits, carcass traits, health traits and welfare traits. De-regressed estimated breeding values (EBV) for these traits together with sire genotypes derived with the Ovine 50 K SNP array of Illumina were jointly analysed in a genome wide association analysis. Eight novel chromosome-wise significant associations were found for carcass, growth, health and welfare traits. Three significant markers were intronic variants and the remainder intergenic variants. This study is a first step to search for genomic regions controlling CT-based productivity traits related to body and carcass composition in a terminal sire sheep breed using a 50 K SNP genome-wide array. Results are important for the further development of strategies to identify causal variants associated with CT measures and other commercial traits in sheep. Independent studies are needed to confirm these results and identify candidate genes for the studied traits.

Genetic dissection of Sharka disease tolerance in peach (P. persica L. Batsch)

BackgroundPlum pox virus (PPV), agent of Sharka disease, is the most important quarantine pathogen of peach (P. persica L. Batsch). Extensive evaluation of peach germplasm has highlighted the lack of resistant sources, while suggesting the presence of a quantitative disease resistance, expressed as reduction in the intensity of symptoms. Unravelling the genetic architecture of peach response to PPV infection is essential for pyramiding resistant genes and for developing more tolerant varieties. For this purpose, a genome-wide association (GWA) approach was applied in a panel of accessions phenotyped for virus susceptibility and genotyped with the IPSC peach 9 K SNP Array, and coupled with an high-coverage resequencing of the tolerant accession ‘Kamarat’.ResultsGenome-wide association identified three highly significant associated loci on chromosome 2 and 3, accounting for most of the reduction in PPV-M susceptibility within the analysed peach population. The exploration of associated intervals through whole-genome comparison of the tolerant accession ‘Kamarat’ and other susceptible accessions, including the PPV-resistant wild-related species P. davidiana, allow the identification of allelic variants in promising candidate genes, including an RTM2-like gene already characterized in A. thaliana.ConclusionsThe present study is the first effort to identify genetic factors involved in Sharka disease in peach germplasm through a GWA approach. We provide evidence of the presence of quantitative resistant loci in a collection of peach accessions, identifying major loci and highly informative SNPs that could be useful for marker assisted selection. These results could serve as reference bases for future research aimed at the comprehension of genetic mechanism regulating the complex peach-PPV interaction.

An Unexpectedly Complex Architecture for Skin Pigmentation in Africans

Approximately 15 genes have been directly associated with skin pigmentation variation in humans, leading to its characterization as a relatively simple trait. However, by assembling a global survey of quantitative skin pigmentation phenotypes, we demonstrate that pigmentation is more complex than previously assumed, with genetic architecture varying by latitude. We investigate polygenicity in the KhoeSan populations indigenous to southern Africa who have considerably lighter skin than equatorial Africans. We demonstrate that skin pigmentation is highly heritable, but known pigmentation loci explain only a small fraction of the variance. Rather, baseline skin pigmentation is a complex, polygenic trait in the KhoeSan. Despite this, we identify canonical and non-canonical skin pigmentation loci, including near SLC24A5, TYRP1, SMARCA2/VLDLR, and SNX13, using a genome-wide association approach complemented by targeted resequencing. By considering diverse, under-studied African populations, we show how the architecture of skin pigmentation can vary across humans subject to different local evolutionary pressures.

Improving Genomic Prediction for Pre‐Harvest Sprouting Tolerance in Wheat by Weighting Large‐Effect Quantitative Trait Loci

Preharvest sprouting (PHS) is a major problem in wheat (Triticum aestivum L.) that occurs when grains in a mature spike germinate before harvest, resulting in reduced yield, quality, and grain sale price. Improving PHS tolerance is a challenge to wheat breeders because it is quantitatively inherited and tedious to score. Genomic selection (GS) is particularly useful for predicting phenotypes that are costly and time consuming to assess. In our study, single nucleotide polymorphism (SNP) markers obtained by genotyping‐by‐sequencing were used to identify significant marker trait associations and develop predictive models for PHS tolerance. A panel of 1118 breeding lines and cultivars (genotypes) representative of U.S. Great Plains hard winter wheat germplasm was scored for PHS tolerance over multiple years. A genomewide association approach was used to identify quantitative trait loci (QTL) among the individuals. Two primary factors were examined for their influence on model accuracy: the effect of including identified QTL and kernel color as fixed effects in the model and increasing marker number. Model accuracy did not improve with kernel color information, but weighting QTL increased predictive performance. Thus, the combination of marker‐assisted and genomic selection outperformed all other methods. Optimum marker number was reached at 4000 SNPs. Overall, model accuracies were promising (0.49 to 0.62) and confirm effectiveness of GS for predicting PHS tolerance in wheat.

Regional enrichment analyses on genetic profiles for schizophrenia and bipolar disorder

Both schizophrenia (SZ) and bipolar disorder (BD) are highly heritable psychiatric disorders. The significant genomic risk loci are of great importance but with no guarantee of known functional impact and they cannot totally explain the genetic inheritance. In this study we present regional enrichment analyses across the genome, aiming to strike a balance between individual risk loci and integrated regional effects. Chromosomes were partitioned into 2 million base-pair regions (indicated by an underscore sign in the cytogenetic bands) on which enrichment tests are performed. In the discovery phase, we leverage the Psychiatric Genomics Consortium SZ and BD initial association test results for European Ancestry (EA) population and dbGAP SNP data for African Ancestry (AA) population. 78 and 48 regions show significantly enriched associations with SZ and BD respectively in the EA population, and nine are in common including MHC, 3p21.1, 7p22.3_2, 2q32.3_2, 8q24.3_4, and 19q13.33_1. The most unique SZ associated region is 1p21.3_3, while the most unique BD associated region is 6q25.2_1. For the AA population fewer regions are discovered with only 10% overlapping with that of EA population. A replication test using Wellcome Trust Case Control Consortium data for EA population verified 9% of the SZ enriched regions and 40% of the BD enriched regions. In summary, we showed that regional enrichment analyses produce reliable genetic association profiles using about one tenth of samples compared to single base-pair genome wide association approach. The identified association regions will be useful for further genetic functional studies.

Genetic epidemiology in kidney disease.

Familial aggregation of chronic kidney disease and its component phenotypes-reduced glomerular filtration rate, proteinuria and renal histologic changes-has long been recognized. Rates of severe kidney disease are also known to differ markedly between populations based on ancestry. These epidemiologic observations support the existence of nephropathy susceptibility genes. Several molecular genetic technologies are now available to identify causative loci. The present article summarizes available strategies useful for identifying nephropathy susceptibility genes, including candidate gene association, family-based linkage, genome-wide association and admixture mapping (mapping by admixture linkage disequilibrium) approaches. Examples of loci detected using these techniques are provided. Epigenetic studies and future directions are also discussed. The identification of nephropathy susceptibility genes, coupled with modifiable environmental triggers impacting their function, is likely to improve risk prediction and transform care. Development of novel therapies to prevent progression of kidney disease will follow.

대장암 환자의 옥살리플라틴(oxaliplatin) 유도 말초신경병증에 대한 약물유전학적 접근: 체계적 문헌고찰

Purpose: Peripheral neuropathy is common among colorectal cancer (CRC) patients who undergo oxaliplatin-based (OXL) chemotherapy. A pharmacogenetic approach can be used to identify patients at high-risk of developing severe neuropathy. This type of approach can also help clinicians determine the best treatment option and prevent severe neurotoxicity. The purpose of this study is to investigate the evidence of pharmacogenetic markers for OXL-induced peripheral neuropathy (OXIPN) in patients with CRC. Methods: A systematic literature search was conducted using the following databases up to December 2017: Pubmed, EMBASE, and CINAHL. We reviewed the genetic risk factors for OXIPN in observational studies and randomized controlled clinical trials (RCTs). All processes were performed independently by two reviewers. Results: Sixteen studies published in English between 2006 and 2017 were included in this review. A genome-wide association approach was used in one study and various candidate genes were tested, based on their functions (e.g., DNA damage or repair, ion channels, anti-oxidants, and nerve growth etc.). The genes associated with incidence or severity of OXIPN were ABCG2, GSTP1, XRCC1, TAC1, and ERCC1. Conclusion: This study highlighted the need and the importance of conducting pharmacogenetic studies to generate evidence of personalized OXIPN symptoms management. Additional studies are warranted to accelerate the tailored interventions used for OXIPN in patients with CRC (NRF-2014R1A1A3054386).

A genome-wide association study of seed composition traits in wild soybean (Glycine soja)

BackgroundCultivated soybean (Glycine max) is a major agricultural crop that provides a crucial source of edible protein and oil. Decreased amounts of saturated palmitic acid and increased amounts of unsaturated oleic acid in soybean oil are considered optimal for human cardiovascular health and therefore there has considerable interest by breeders in discovering genes affecting the relative concentrations of these fatty acids. Using a genome-wide association (GWA) approach with nearly 30,000 single nucleotide polymorphisms (SNPs), we investigated the genetic basis of protein, oil and all five fatty acid levels in seeds from a sample of 570 wild soybeans (Glycine soja), the progenitor of domesticated soybean, to identify quantitative trait loci (QTLs) affecting these seed composition traits.ResultsWe discovered 29 SNPs located on ten different chromosomes that are significantly associated with the seven seed composition traits in our wild soybean sample. Eight SNPs co-localized with QTLs previously uncovered in linkage or association mapping studies conducted with cultivated soybean samples, while the remaining SNPs appeared to be in novel locations. Twenty-four of the SNPs significantly associated with fatty acid variation, with the majority located on chromosomes 14 (6 SNPs) and seven (8 SNPs). Two SNPs were common for two or more fatty acids, suggesting loci with pleiotropic effects. We also identified some candidate genes that are involved in fatty acid metabolism and regulation. For each of the seven traits, most of the SNPs produced differences between the average phenotypic values of the two homozygotes of about one-half standard deviation and contributed over 3% of their total variability.ConclusionsThis is the first GWA study conducted on seed composition traits solely in wild soybean populations, and a number of QTLs were found that have not been previously discovered. Some of these may be useful to breeders who select for increased protein/oil content or altered fatty acid ratios in the seeds. The results also provide additional insight into the genetic architecture of these traits in a large sample of wild soybean, and suggest some new candidate genes whose molecular effects on these traits need to be further studied.

Transporters for the Intestinal Absorption of Cholesterol, Vitamin E, and Vitamin K.

Humans cannot synthesize fat-soluble vitamins such as vitamin E and vitamin K. For this reason, they must be obtained from the diet via intestinal absorption. As the deficiency or excess of these vitamins has been reported to cause several types of diseases and disorders in humans, the intestinal absorption of these nutrients must be properly regulated to ensure good health. However, the mechanism of their intestinal absorption remains poorly understood. Recent studies on cholesterol using genome-edited mice, genome-wide association approaches, gene mutation analyses, and the development of cholesterol absorption inhibitors have revealed that several membrane proteins play crucial roles in the intestinal absorption of cholesterol. Surprisingly, detailed analyses of these cholesterol transporters have revealed that they can also transport vitamin E and vitamin K, providing clues to uncover the molecular mechanisms underlying the intestinal absorption of these fat-soluble vitamins. In this review, we focus on the membrane proteins (Niemann-Pick C1 like 1, scavenger receptor class B type I, cluster of differentiation 36, and ATP-binding cassette transporter A1) that are (potentially) involved in the intestinal absorption of cholesterol, vitamin E, and vitamin K and discuss their physiological and pharmacological importance. We also discuss the related uncertainties that need to be explored in future studies.

An Analysis of Two Genome-wide Association Meta-analyses Identifies a New Locus for Broad Depression Phenotype

BackgroundThe genetics of depression has been explored in genome-wide association studies that focused on either major depressive disorder or depressive symptoms with mostly negative findings. A broad depression phenotype including both phenotypes has not been tested previously using a genome-wide association approach. We aimed to identify genetic polymorphisms significantly associated with a broad phenotype from depressive symptoms to major depressive disorder. MethodsWe analyzed two prior studies of 70,017 participants of European ancestry from general and clinical populations in the discovery stage. We performed a replication meta-analysis of 28,328 participants. Single nucleotide polymorphism (SNP)-based heritability and genetic correlations were calculated using linkage disequilibrium score regression. Discovery and replication analyses were performed using a p-value-based meta-analysis. Lifetime major depressive disorder and depressive symptom scores were used as the outcome measures. ResultsThe SNP-based heritability of major depressive disorder was 0.21 (SE = 0.02), the SNP-based heritability of depressive symptoms was 0.04 (SE = 0.01), and their genetic correlation was 1.001 (SE = 0.2). We found one genome-wide significant locus related to the broad depression phenotype (rs9825823, chromosome 3: 61,082,153, p = 8.2 × 10–9) located in an intron of the FHIT gene. We replicated this SNP in independent samples (p = .02) and the overall meta-analysis of the discovery and replication cohorts (1.0 × 10–9). ConclusionsThis large study identified a new locus for depression. Our results support a continuum between depressive symptoms and major depressive disorder. A phenotypically more inclusive approach may help to achieve the large sample sizes needed to detect susceptibility loci for depression.

Genetic architecture of nonadditive inheritance in Arabidopsis thaliana hybrids

The ubiquity of nonparental hybrid phenotypes, such as hybrid vigor and hybrid inferiority, has interested biologists for over a century and is of considerable agricultural importance. Although examples of both phenomena have been subject to intense investigation, no general model for the molecular basis of nonadditive genetic variance has emerged, and prediction of hybrid phenotypes from parental information continues to be a challenge. Here we explore the genetics of hybrid phenotype in 435 Arabidopsis thaliana individuals derived from intercrosses of 30 parents in a half diallel mating scheme. We find that nonadditive genetic effects are a major component of genetic variation in this population and that the genetic basis of hybrid phenotype can be mapped using genome-wide association (GWA) techniques. Significant loci together can explain as much as 20% of phenotypic variation in the surveyed population and include examples that have both classical dominant and overdominant effects. One candidate region inherited dominantly in the half diallel contains the gene for the MADS-box transcription factor AGAMOUS-LIKE 50 (AGL50), which we show directly to alter flowering time in the predicted manner. Our study not only illustrates the promise of GWA approaches to dissect the genetic architecture underpinning hybrid performance but also demonstrates the contribution of classical dominance to genetic variance.

Yield-related salinity tolerance traits identified in a nested association mapping (NAM) population of wild barley.

Producing sufficient food for nine billion people by 2050 will be constrained by soil salinity, especially in irrigated systems. To improve crop yield, greater understanding of the genetic control of traits contributing to salinity tolerance in the field is needed. Here, we exploit natural variation in exotic germplasm by taking a genome-wide association approach to a new nested association mapping population of barley called HEB-25. The large population (1,336 genotypes) allowed cross-validation of loci, which, along with two years of phenotypic data collected from plants irrigated with fresh and saline water, improved statistical power. We dissect the genetic architecture of flowering time under high salinity and we present genes putatively affecting this trait and salinity tolerance. In addition, we identify a locus on chromosome 2H where, under saline conditions, lines homozygous for the wild allele yielded 30% more than did lines homozygous for the Barke allele. Introgressing this wild allele into elite cultivars could markedly improve yield under saline conditions.

Analysis of Common Single Nucleotide Polymorphisms in Complex Regional Pain Syndrome: Genome Wide Association Study Approach and Pooled DNA Strategy.

The objective of this study was to use a genome-wide association (GWAS) approach and pooled DNA strategy to search for new genomic loci associated with complex regional pain syndrome (CRPS). The study cohort consisted of 230 patients with established diagnosis of CRPS. The control group consisted of 230 age- and gender-matched subjects without chronic pain. We tested the association of common single nucleotide polymorphisms (SNPs), genotyped using a high-density microarray platform, with CRPS phenotype. This was followed by individual genotyping of the most significant SNPs identified in the microarray genomic scan, in both original discovery (N = 115) and independent verification (N = 115) groups of patients with CRPS, as well as in the appropriate matched control subjects. The results of our study provide no support for the initial hypothesis of the existence of an association between any investigated genomic targets (including GWAS for all genomic loci available on the microarray, and focused scan of the HLA locus on chromosome 6) and CRPS phenotype. Despite the fact that we interrogated about 83% of all of common SNPs in the human genome, we did not find evidence that any of the investigated common SNPs may be associated with CRPS phenotype.