Wild Allele Research Articles

Ischemic stroke susceptibility associated with ALPK1 single nucleotide polymorphisms by inhibiting URAT1 in uric acid hemostasis

ObjectivesIschemic stroke (IS) prevalence rising annually, the necessity of discovering non-interventional genetic influences is progressing. Single nucleotide polymorphism (SNP) plays a pivotal role in stable inheritance of disease susceptibility. Based on the relationship between Alpha- Kinase 1 (ALPK1) and traditional IS risk factors especially hyperuricemia, our study investigated the association and function of ALPK1 SNPs with IS susceptibility. MethodsA case-control study of 1539 patients and 933 controls from northeast China was conducted. Genotyping information of ALPK1 rs2074379 and rs2074388 was collected. Four types of plasmids including rs2074379/rs2074388 G/G, A/G, G/A, and A/A were transfected into 293T cells to observe ALPK1 and SLC22A12 expression. Possible ALPK1 structures of different SNPs were predicted online. ResultsGenotype GG (OR = 1.371, CI = 1.029–1.828, P = 0.031) and GA (OR = 1.326, CI = 1.110–1.584, P = 0.002) of rs2074379 and GA of rs2074388 (OR = 1.359, CI = 1.137–1.624, P = 0.001) were found significantly susceptible to IS, with G allele on sites to be a risk allele. Rs2074379 had a multiplicative interaction with hyperuricemia (OR = 1.637, CI = 1.157–2.315, P = 0.005). Uric acid levels differed in genotypes (P < 0.001). The expression of ALPK1 (P < 0.01) and SLC22A12 in membrane urate transporter 1 (URAT1) protein (P < 0.05) functionally changed with G allele on either site. With glycine changing into aspartic acid at rs2074388, the protein secondary structure changed, but the ALPK1 protein subtype remained still. ConclusionsALPK1 rs2074379 and rs2074388 SNPs were functionally associated with IS susceptibility. The wild allele progressed IS risk probably by reducing ALPK1 expression and inhibiting URAT1 raising the uric acid level, contributing to further exploration of pathogenetic mechanisms of stroke.Chinese Clinical Trial Registration number: ChiCTR-COC-17013559.

Genetic diversity in the Plasmodium falciparum next-generation blood stage vaccine candidate antigen PfCyRPA in Senegal.

The Plasmodium falciparum cysteine-rich protective antigen (PfCyRPA) is a promising target as a next-generation blood-stage malaria vaccine and together with PCRCR complex members, the reticulocyte binding-like homologous protein 5 (PfRh5) and the Rh5-interacting protein (PfRipr), are currently being evaluated in clinical trials. PfCyRPA is essential for merozoite invasion and appears to be highly conserved within the P. falciparum parasite populations. Here, we used a targeted deep amplicon next-generation sequencing approach to assess the breadth of PfCyRPA genetic diversity in 95 P. falciparum clinical isolates from Kédougou, an area with a high seasonal malaria transmission in Senegal. Our data show the dominant prevalence of PfCyRPA wild type reference allele, while we also identify a total of 15 single nucleotide polymorphisms (SNPs). Of these, only five have previously been reported, while the majority of the SNPs were present as singletons within our sampled population. Moreover, the variant read frequency of the identified SNPs varied from 2.6 to 100%, while the majority of the SNPs were present at frequencies greater than 25% in polygenomic samples. We also applied a structure-based modelling approach to thread these SNPs onto PfCyRPA crystal structures and showed that these polymorphisms have different predicted functional impacts on the interactions with binding partner PfRH5 or neutralizing antibodies. Our prediction revealed that the majority of these SNPs have minor effects on PfCyRPA antibodies, while others alter its structure, stability, or interaction with PfRH5. Altogether, our present findings reveal conserved PfCyRPA epitopes which will inform downstream investigations on next-generation structure-guided malaria vaccine design.

OVO positively regulates essential maternal pathways by binding near the transcriptional start sites in the Drosophila female germline

Differentiation of female germline stem cells into a mature oocyte includes the expression of RNAs and proteins that drive early embryonic development in Drosophila. We have little insight into what activates the expression of these maternal factors. One candidate is the zinc-finger protein OVO. OVO is required for female germline viability and has been shown to positively regulate its own expression, as well as a downstream target, ovarian tumor, by binding to the transcriptional start site (TSS). To find additional OVO targets in the female germline and further elucidate OVO’s role in oocyte development, we performed ChIP-seq to determine genome-wide OVO occupancy, as well as RNA-seq comparing hypomorphic and wild type rescue ovo alleles. OVO preferentially binds in close proximity to target TSSs genome-wide, is associated with open chromatin, transcriptionally active histone marks, and OVO-dependent expression. Motif enrichment analysis on OVO ChIP peaks identified a 5’-TAACNGT-3’ OVO DNA binding motif spatially enriched near TSSs. However, the OVO DNA binding motif does not exhibit precise motif spacing relative to the TSS characteristic of RNA polymerase II complex binding core promoter elements. Integrated genomics analysis showed that 525 genes that are bound and increase in expression downstream of OVO are known to be essential maternally expressed genes. These include genes involved in anterior/posterior/germ plasm specification (bcd, exu, swa, osk, nos, aub, pgc, gcl), egg activation (png, plu, gnu, wisp, C(3)g, mtrm), translational regulation (cup, orb, bru1, me31B), and vitelline membrane formation (fs(1)N, fs(1)M3, clos). This suggests that OVO is a master transcriptional regulator of oocyte development and is responsible for the expression of structural components of the egg as well as maternally provided RNAs that are required for early embryonic development.

Haplotype-based Analysis of 6q24-25 for Association with Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a multisystem inflammatory disorder. Family history of RA is an important risk factor as it is strongly linked with the inherited HLA-DR4 (most specifically DR0401 and 0404). The aim of this study is to conduct the haplotype-based analysis of 6q24-25 and evaluate its association with RA. Case-control study which included all patients attending outpatient department (OPD) at Sardar Patel Medical College, Bikaner, Rajasthan and volunteers (only for blood samples). Blood samples of patients were collected. As per inclusion and exclusion criteria, a total of 103 subjects lacking history of disease were included under control group, while 48 cases were recruited as study group. Any significant departure of genotype distribution is evaluated using Hardy-Weinberg equilibrium by Chi-squared test. Case-control association was done using data from 151 genomic deoxyribonucleic acid (DNA) samples, which were allele typed. RA is significantly associated with >305bp (the longer allele of D6S1053 corresponding to 11 tetramer (GATA) repeats. Differences in individual allele frequency within the control population and RA cases were observed which shows the bimodal distribution of the 10 alleles of D6S1053 short tandem repeat (STR) marker observed in the cohort tested by us. No significant association with the risk for RA is shown by the allele for D6S1053 and the mutant allele 118G. Similarly, OPRM1 gene's haplotype frequency for rs1799972 for D6S1053 allele has not shown any added risk with the wild allele 17C compared to controls. The polymorphism showed that 17T depicted a higher odds ratio of 1.3 with an associated risk of 1.15 in the presence of longer allele of DS61053. Significance observed between short allele and RA was lost when haplotype analysis for the two genes were taken together. There was no difference observed between the short or long allele and 17T/C while there was a significant difference observed when haplotype frequencies were compared with alleles of A118G and the long and short allele of DS61053. We concluded that the short allele of µ-opioid receptor (MOR) gene offered a clear protection from a risk of getting RA.

Wild grass-derived alleles represent a genetic architecture for the resilience of modern common wheat to stresses.

This review explores the integration of wild grass-derived alleles into modern bread wheat breeding to tackle the challenges of climate change and increasing food demand. With a focus on synthetic hexaploid wheat, this review highlights the potential of genetic variability in wheat wild relatives, particularly Aegilops tauschii, for improving resilience to multifactorial stresses like drought, heat, and salinity. The evolutionary journey of wheat (Triticum spp.) from diploid to hexaploid species is examined, revealing significant genetic contributions from wild grasses. We also emphasize the importance of understanding incomplete lineage sorting in the genomic evolution of wheat. Grasping this information is crucial as it can guide breeders in selecting the appropriate alleles from the gene pool of wild relatives to incorporate into modern wheat varieties. This approach improves the precision of phylogenetic relationships and increases the overall effectiveness of breeding strategies. This review also addresses the challenges in utilizing the wheat wild genetic resources, such as the linkage drag and cross-compatibility issues. Finally, we culminate the review with future perspectives, advocating for a combined approach of high-throughput phenotyping tools and advanced genomic techniques to comprehensively understand the genetic and regulatory architectures of wheat under stress conditions, paving the way for more precise and efficient breeding strategies.

Meta-QTL and Candidate Gene Analyses of Agronomic Salt Tolerance and Related Traits in an RIL Population Derived from Solanum pimpinellifolium.

Breeding salt-tolerant crops is necessary to reduce food insecurity. Prebreeding populations are fundamental for uncovering tolerance alleles from wild germplasm. To obtain a physiological interpretation of the agronomic salt tolerance and better criteria to identify candidate genes, quantitative trait loci (QTLs) governing productivity-related traits in a population of recombinant inbred lines (RIL) derived from S. pimpinellifolium were reanalyzed using an SNP-saturated linkage map and clustered using QTL meta-analysis to synthesize QTL information. A total of 60 out of 85 QTLs were grouped into 12 productivity MQTLs. Ten of them were found to overlap with other tomato yield QTLs that were found using various mapping populations and cultivation conditions. The MQTL compositions showed that fruit yield was genetically associated with leaf water content. Additionally, leaf Cl- and K+ contents were related to tomato productivity under control and salinity conditions, respectively. More than one functional candidate was frequently found, explaining most productivity MQTLs, indicating that the co-regulation of more than one gene within those MQTLs might explain the clustering of agronomic and physiological QTLs. Moreover, MQTL1.2, MQTL3 and MQTL6 point to the root as the main organ involved in increasing productivity under salinity through the wild allele, suggesting that adequate rootstock/scion combinations could have a clear agronomic advantage under salinity.

Haplotype-resolved gapless genome and chromosome segment substitution lines facilitate gene identification in wild rice

The abundant genetic variation harbored by wild rice (Oryza rufipogon) has provided a reservoir of useful genes for rice breeding. However, the genome of wild rice has not yet been comprehensively assessed. Here, we report the haplotype-resolved gapless genome assembly and annotation of wild rice Y476. In addition, we develop two sets of chromosome segment substitution lines (CSSLs) using Y476 as the donor parent and cultivated rice as the recurrent parents. By analyzing the gapless reference genome and CSSL population, we identify 254 QTLs associated with agronomic traits, biotic and abiotic stresses. We clone a receptor-like kinase gene associated with rice blast resistance and confirm its wild rice allele improves rice blast resistance. Collectively, our study provides a haplotype-resolved gapless reference genome and demonstrates a highly efficient platform for gene identification from wild rice.

Deep genotyping reveals specific adaptation footprints of conventional and organic farming in barley populations—an evolutionary plant breeding approach

Sustainable food production for a growing world population will pose a central challenge in the coming decades. Organic farming is among the feasible approaches to achieving this goal if the yield gap to conventional farming can be decreased. However, uncertainties exist to which extend—and for which phenotypes in particular—organic and conventional agro-ecosystems require differentiated breeding strategies. To answer this question, a heterogeneous spring barley population was established between a wild barley and an elite cultivar to examine this question. This initial population was divided into two sets and sown one in organic and the other in conventional managed agro-ecosystems, without any artificial selection for two decades. A fraction of seeds harvested each year was sown the following year. Various generations, up to the 23th were whole-genome pool-sequenced to identify adaptation patterns towards ecosystem and climate conditions in the allele frequency shifts. Additionally, a meta-data analysis was conducted to link genomic regions’ increased fitness to agronomically related traits. This long-term experiment highlights for the first time that allele frequency pattern difference between the conventional and organic populations grew with subsequent generations. Further, the organic-adapted population showed a higher genetic heterogeneity. The data indicate that adaptations towards new environments happen in few generations. Drastic interannual changes in climate are manifested in significant allele frequency changes. Particular wild form alleles were positively selected in both environments. Clustering these revealed an increased fitness associated with biotic stress resistance, yield physiology, and yield components in both systems. Additionally, the introduced wild alleles showed increased fitness related to root morphology, developmental processes, and abiotic stress responses in the organic agro-ecosystem. Concluding the genetic analysis, we demonstrate that breeding of organically adapted varieties should be conducted in an organically managed agro-ecosystem, focusing on root-related traits, to close the yield gap towards conventional farming.

A Pilot Study for Drug-Resistant Tuberculosis Disease Patients Suggests that A964G (rs153109)—Interleukin 27 may be Protective

Abstract Context: Variation in the transcription of host genes of inflammatory cytokines may underscore variation in their production. Thus, the host-immune status plays a vital role in determining the fate of the invading bacilli. Materials and Methods: Two hundred consenting volunteers and drug-resistant tuberculosis (DR-TB) patients had their blood samples amplified for the A964G (rs153109) gene. The amplicons were digested using the Xhol enzyme for genotyping purpose. Results: Among the cases: AA (homozygous wild type; n = 33), AG (heterozygous wild type; n = 36), GG (homozygous mutant, n = 10), A (wild allele, n = 102), and T (mutant allele; n = 66); while among the healthy volunteers: AA (homozygous wild type; n = 20), AG (heterozygous wild type; n = 40), GG (homozygous mutant, n = 4) A (wild allele, n = 80), and T (mutant allele; n = 48). The Hardy Weinberg Equilibrium (HWE) assessment of the samples from the control participants was statistically significant (P = 0.015). Nevertheless, the assessment of the association between the genotypes and the phenotypes assessed revealed that the healthy volunteers had more (twice) heterozygous genotype (AG) (crude statistics: P =0.045, OR = 1.99 (1.02–3.90)) when compared to the DR-TB patients. Conclusion: Although the AG genotype of A964G (rs153109)—Interleukin 27 gene may have a protective role against the development of MTB/XPERT positive DR-TB disease, the significant HWE finding among the genotype from the samples of the healthy volunteers suggests that this current result may be a false positive finding.

A Pilot Study of Detecting RS920778 and RS1899663 Genetic Variants of HOTAIR in A Cohort of Sporadic Breast Cancer Patients in Sri Lanka

Background: Some functional single nucleotide polymorphisms (SNPs) on the HOTAIR gene are potent to elevate breast cancer risk where rs920778 and rs1899663 are associated with the expression and function of the HOTAIR gene, and these SNPs were detected in the current study. Methods: A cohort of nine sporadic cancer patients and five healthy controls were screened for selected HOTAIR variants using direct sequencing. Results: Among patients, seven were with TT genotype, and other 2 with CT genotype for rs920778 C&gt;T while two healthy controls showed TT, another two were with CT, and the remaining with CC genotypes. Among the cohort, the rs1899663 variant was not found in any patients and healthy controls., Conclusion: In the study, the T allele of rs920778 was prominent among the sporadic breast cancer in the studied cohort while only a wild allele (T) of rs1899663 was more prominent in the patients and healthy controls.

Investigating the genetic control of plant development in spring barley under speed breeding conditions

Key messageThis study found that the genes, PPD-H1 and ELF3, control the acceleration of plant development under speed breeding, with important implications for optimizing the delivery of climate-resilient crops.Speed breeding is a tool to accelerate breeding and research programmes. Despite its success and growing popularity with breeders, the genetic basis of plant development under speed breeding remains unknown. This study explored the developmental advancements of barley genotypes under different photoperiod regimes. A subset of the HEB-25 Nested Association Mapping population was evaluated for days to heading and maturity under two contrasting photoperiod conditions: (1) Speed breeding (SB) consisting of 22 h of light and 2 h of darkness, and (2) normal breeding (NB) consisting of 16 h of light and 8 h of darkness. GWAS revealed that developmental responses under both conditions were largely controlled by two loci: PPDH-1 and ELF3. Allelic variants at these genes determine whether plants display early flowering and maturity under both conditions. At key QTL regions, domesticated alleles were associated with late flowering and maturity in NB and early flowering and maturity in SB, whereas wild alleles were associated with early flowering under both conditions. We hypothesize that this is related to the dark-dependent repression of PPD-H1 by ELF3 which might be more prominent in NB conditions. Furthermore, by comparing development under two photoperiod regimes, we derived an estimate of plasticity for the two traits. Interestingly, plasticity in development was largely attributed to allelic variation at ELF3. Our results have important implications for our understanding and optimization of speed breeding protocols particularly for introgression breeding and the design of breeding programmes to support the delivery of climate-resilient crops.

Impact of CYP3A4 rs2242480 polymorphisms on Imatinib HPLC determined trough concentration and response in Chronic Myeloid Leukaemia in Pakistani patients

Objective To ascertain the impact of CYP3A4 polymorphism on the therapeutic outcome of imatinib and its trough concentration Study design Descriptive analytical study Place and duration of the study This study was conducted in the Department of Pharmacology &amp; Therapeutics, Islamic International Medical College, between December 2020 and February 2022, in collaboration with the Institute of Biomedical Genetic Engineering, KRL Hospital Islamabad. Methods Patients with Chronic Myeloid Leukaemia age range–18-70 years were included in this study. One group comprised responders and the other group comprised non-responders. Imatinib trough levels in both groups were determined using High-performance Liquid Chromatography and compared, and the association was determined with therapeutic outcomes. DNA was extracted, and the PCR restriction fragment length polymorphism technique was used to identify the alleles. The results were analyzed using Statistical Package for Social Sciences (SPSS) version 22.0. Results The imatinib concentration in patients with the homozygous wild allele CC of rs2242480 was higher(1298ng/ml) as compared with the mutant homozygous TT allele (489ng/ml) or heterozygous allele CT(873ng/ml) Conclusion There was a significant association between imatinib trough levels and CYP3A4 polymorphism, and trough concentration was found to be lower in patients with the TT or CT variant of rs2242480 than in patients with the CC genotype.

Analysis of Molecular Genetic Variants of Lgals4 in Esophageal Cancer: A Preliminary Report.

Esophageal cancer is the eighth most common cancer worldwide and fourth most common in developing countries. Altered glycosylation pattern of cell membrane molecules along with inflammation is a characteristic attribute of oncogenesis. Galectin-4, a tandem repeat galectin, has shown effect on cancer progression/metastasis in digestive system cancers. This role of galectin-4 can be attributed to variations in LGALS4, gene encoding galectin-4. The present case-control study was designed to analyze four intronic SNPs in LGALS4 with susceptibility toward esophageal cancer.Esophageal cancer cases and age- and gender-matched apparently healthy individuals were recruited for the present study. Genotyping of rs8113319, rs4802886, rs4802887, and rs12610990 was carried out using Sanger sequencing and PCR-RFLP. MedCalc software, SNPStats and SHEsis online platform were used for statistical analysis.Genotypic analyses revealed an overall increased heterozygosity of rs12610990, rs4802886, and rs4802887, and AA genotype of rs8113319 in the study participants. Haplotypic analyses also revealed a predominance of AAAT haplotype in the cases. Moreover, combined presence of wild alleles of rs4802886 and rs4802887 could influence protection toward disease, and combined presence of wild alleles of rs12610990 and rs8113319 could influence disease susceptibility. Furthermore, a strong linkage disequilibrium was also observed between the SNPs. Further studies are underway to validate galectin-4 and its genetic variants as blood-based biomarkers in early disease diagnosis, improving treatment outcome.

CFTR function is impaired in a subset of patients with pancreatitis carrying rare CFTR variants

BackgroundMany affected by pancreatitis harbor rare variants of the cystic fibrosis (CF) gene, CFTR, which encodes an epithelial chloride/bicarbonate channel. We investigated CFTR function and the effect of CFTR modulator drugs in pancreatitis patients carrying CFTR variants. MethodsNext-generation sequencing was performed to identify CFTR variants. Sweat tests and nasal potential difference (NPD) assays were performed to assess CFTR function in vivo. Intestinal current measurement (ICM) was performed on rectal biopsies. Patient-derived intestinal epithelial monolayers were used to evaluate chloride and bicarbonate transport and the effects of a CFTR modulator combination: elexacaftor, tezacaftor and ivacaftor (ETI). ResultsOf 32 pancreatitis patients carrying CFTR variants, three had CF-causing mutations on both alleles and yielded CF-typical sweat test, NPD and ICM results. Fourteen subjects showed a more modest elevation in sweat chloride levels, including three that were provisionally diagnosed with CF. ICM indicated impaired CFTR function in nine out of 17 non-CF subjects tested. This group of nine included five carrying a wild type CFTR allele. In epithelial monolayers, a reduction in CFTR-dependent chloride transport was found in six out of 14 subjects tested, whereas bicarbonate secretion was reduced in only one individual. In epithelial monolayers of four of these six subjects, ETI improved CFTR function. ConclusionsCFTR function is impaired in a subset of pancreatitis patients carrying CFTR variants. Mutations outside the CFTR locus may contribute to the anion transport defect. Bioassays on patient-derived intestinal tissue and organoids can be used to detect such defects and to assess the effect of CFTR modulators.

A wild rice CSSL population facilitated identification of salt tolerance genes and rice germplasm innovation.

Salt stress is one of the major factors that limits rice production. Therefore, identification of salt-tolerant alleles from wild rice is important for rice breeding. In this study, we constructed a set of chromosome segment substitution lines (CSSLs) using wild rice as the donor parent and cultivated rice Nipponbare (Nip) as the recurrent parent. Salt tolerance germinability (STG) was evaluated, and its association with genotypes was determined using this CSSL population. We identified 17 QTLs related to STG. By integrating the transcriptome and genome data, four candidate genes were identified, including the previously reported AGO2 and WRKY53. Compared with Nip, wild rice AGO2 has a structure variation in its promoter region and the expression levels were upregulated under salt treatments; wild rice WRKY53 also has natural variation in its promoter region, and the expression levels were downregulated under salt treatments. Wild rice AGO2 and WRKY53 alleles have combined effects for improving salt tolerance at the germination stage. One CSSL line, CSSL118 that harbors these two alleles was selected. Compared with the background parent Nip, CSSL118 showed comprehensive salt tolerance and higher yield, with improved transcript levels of reactive oxygen species scavenging genes. Our results provided promising genes and germplasm resources for future rice salt tolerance breeding.

Introgressed eggplant lines with the wild Solanum incanum evaluated under drought stress conditions1

As access to irrigation water becomes increasingly limited, introgression of relevant genomic regions from drought-tolerant wild genotypes is a promising breeding strategy for crop plants. In this study, nine eggplant (Solanum melongena) introgression lines (ILs) covering altogether 71.6% of the genome of the donor wild relative parent S. incanum were evaluated for drought tolerance under water stress conditions. Plants at the five true leaves stage were irrigated at either 100% (control) or 30% (water stress) field capacity for 14 days, and growth and biochemical traits were measured. Reduced irrigation resulted in decreased growth and increased levels of stress markers such as proline and malondialdehyde. Most ILs had lower growth and biomass production than the cultivated parent under both conditions. However, the wild alleles for two genomic regions related to stem and root dry weight (dwt8 and dwr6%) conferred improved tolerance to water stress. In addition, several S. incanum alleles had a positive effect on important traits that may improve yield under drought conditions, such as leaf water content (lwc12%), water use efficiency (wue1%) and chlorophyll content (chl2 and chl8%). Fine-mapping of the genomic regions for tolerance and reducing linkage drag with regions affecting growth will be crucial for significantly improving eggplant drought tolerance through introgression breeding.

The impact of MIR196A2 and MIR423 genes polymorphisms on the development of type 2 diabetes mellitus in a sample of the Iraqi population

PurposeMicro-RNAs, play a significant role in regulating essential physiological processes by controlling post-transcriptional gene expression. Several disorders have been linked to variations in the miRNA genes that generate sequences of mature micro-RNA. The current research aims to determine if the genetic variations rs6505162; C > A in the MIR423 gene and rs11614913; T > C in the MIR196A2 gene are associated with type 2 diabetes mellitus (T2DM). MethodThe tetra-primers amplification refractory mutation system-polymerase chain reaction technique was used to identify these two single nucleotide polymorphisms (SNPs). ResultsThe allele frequency of MIR423- rs6505162; C > A SNP was 0.47 for the wild allele (A) and 0.53 for the mutant allele (C) in the control group, while in the patients group the frequency was 0.54 and 0.46 for the A and C alleles respectively. No association was discovered between this SNP and T2DM (O.R = 0.75, P = 0.47 for AC genotype, and O.R = 0.53, P = 0.15 for CC genotype). The wild type of MIR196A2 rs11614913; C > T SNP showed a 100% prevalence in the study subjects, thus this SNP has no association with T2DM as well. ConclusionThe current investigation demonstrates that the incidence of T2DM is not associated with the MIR196A2-rs11614913; C > T, and MIR423-rs6505162; C > A SNPs.

Genetic polymorphism of WNT9A is functionally associated with thumb osteoarthritis in the Chinese population

BackgroundIn a recent genome-wide association study, novel genetic variations of WNT9A were reported to be involved in the etiopathogenesis of thumb osteoarthritis (TOA) in Caucasians. Our purposes were to replicate the association of WNT9A with the development of TOA in the Chinese population and to further unveil the functional role of the risk variants.MethodsSNP rs11588850 of WNT9A were genotyped in 953 TOA patients and 1124 healthy controls. The differences of genotype and allele distributions between the patients and healthy controls were evaluated using the Chi-square test. Luciferase Reporter Assay was performed to investigate the influence of variant on the gene expression.ResultsThere was significantly lower frequency of genotype AA in TOA patients than in the controls 74.9% vs. 81.9%, p < 0.001). The frequency of allele A was remarkably lower in the patients than in the controls (86.3% vs. 90.5%, p < 0.001), with an odds ratio of 0.66 (95% CI = 0.54–0.80). Luciferase Reporter Assay showed that the construct containing mutant allele G of rs11588850 displayed 29.1% higher enhancer activity than the wild allele A construct (p < 0.05).ConclusionsAllele G of rs11588850 was associated with the increased risk of TOA possibly via up-regulation of WNT9A expression. Further functional analysis into the regulatory role of rs11588850 in WNT9A expression can shed new light on the genetic architecture of TOA.

A wild barley nested association mapping population shows a wide variation for yield-associated traits to be used for breeding in Australian environment

This study aimed to identify wild barley alleles controlling grain size and weight with the potential to improve barley yield in Australia and worldwide. The HEB-25 nested association mapping population was used, which samples 25 different wild barley accessions in a ‘Barke’ genetic background. The HEB-25 population was evaluated in field conditions at Strathalbyn in South Australia in 2015 and 2016. Seven yield component traits reflecting ear length, grain number per ear and grain dimension were measured. Among 114 quantitative trait loci (QTL) identified for the seven traits in both years, many co-localise with known genes controlling flowering and spike morphology. There were 18 QTL hotspots associated with four loci or more, of which one at the beginning of chromosome 5H had wild alleles that increased both grain number per ear and thousand-grain weight. A wide range of effects was found for wild alleles for each trait across all QTL identified, providing a rich source of genetic diversity that barley breeders can exploit to enhance barley yield.

A study of pod constriction in a peanut population with mixed wild and cultivated genetics

AbstractWild relatives comprise a diverse genetic source from which to introduce beneficial alleles for peanut breeding. However, when using wild species for breeding, unadapted agronomic characteristics are often co‐inherited along with favorable traits. Previously, an advanced backcross population was developed from a cross between Arachis hypogaea and the wild‐derived induced allotetraploid (Arachis batizocoi × Arachis stenosperma)4x to incorporate nematode resistance genes into elite peanut. We observed additional wild alleles unintentionally inherited throughout the genome, possibly causing variation in several pod and seed characteristics. To identify the wild introgressions controlling the variation in pod constriction (PC), a critical trait for peanut's acceptability and marketability, we performed an association analysis using 419 SNPs and phenotypic data of 72 BC3F2/3 families. An introgression on the top of chromosome B08 (pod constriction‐quantitative trait locus [PC‐QTL], 3.7 Mbp) derived from A. batizocoi was found to be controlling 47.3% of the PC variation. To confirm the PC‐QTL, six BC3F4 families harboring the wild loci in a homozygous or heterozygous state were selected and used for segregation analysis. All progenies from the backcross families carrying the homozygous allele had severely constricted pods, whereas progenies from families with the heterozygous allele were segregated for PC. Finally, analyses using end‐point genotyping with four linked SNP assays confirmed the association of the PC‐QTL with PC. The present work studied PC and developed DNA markers to assist the selection against constricted pods while retaining the new and beneficial wild‐derived genes.