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Clubroot caused by Plasmodiophora brassicae is an important disease of crucifer crops worldwide. This study aimed to establish an efficient screening method to determine resistant cultivars of Chinese cabbage against P. brassicae. To do this, we investigated the virulence of seven P. brassicae isolates using seedlings of susceptible Chinese cabbage cultivar. The isolates exhibited different virulence in the plants and were divided into three groups based on their virulence. When we explored the disease occurrence in Chinese cabbage seedlings according to photoperiod after inoculation of P. brassicae and incubation temperature, the plants with all-day light showed higher disease severity than seedlings cultivated under 14 hr of light a day. The occurrence of clubroot disease was most severe at 25°C, followed by 20°C and 18°C, but the fresh weight of clubroot of the seedlings cultivated at 20°C was the highest, followed by plants grown at 25°C and 18°C. When the seedlings of two commercial resistant cultivars were inoculated with the mixed spore suspensions of two different pathotype isolates of P. brassicae, disease severity increased as the spore concentration of the susceptible P. brassicae isolate among the two strains increased, suggesting that the clubroot development by different pathotype isolates was independent and not influenced by each other. Taken together, our results provide a faster and more accurate screening methods to determine the resistance of Chinese cabbage against P. brassicae.

The effects of five fungicides on the spore growth phase of Alternaria dauci, which causes carrot leaf blight, were tested using the spore viability assay (SVA) and agar dilution method (ADM). The average EC50 values for chlorothalonil against seven isolates of A. dauci examined by SVA and ADM were 14.21 μg/ml and more than 100 μg/ml. Dithianon and folpet also had lower EC50 values in SVA than in ADM, while iminoctadine tris-albesilate had lower EC50 value in ADM. For fluazinam, the EC50 values of SVA and ADM were 1.63 and 2.40 μg/ml, respectively. As EC50 values of five fungicides according to the spore growth phase of A. dauci KACC 42997, the efficacy of each fungicide as chlorothalonil, dithianon, and folpet decreased when treated after spore germination rather than when treated with spores before germination. However, iminoctadine tris-albesilate was more effective when treated after spores germinated than when treated before treatment. The excellent effect of fluazinam on the pathogen was maintained until A. dauci KACC 42997 was cultured in potato dextrose broth for 6 hr and the germ tube grew beyond the size of the spore. However, when treated with iminoctadine tris-albesilate and fluazinam after culturing for 12 hr, as the EC50 values of the two fungicides increased to 8.87 and 20.65 μg/ml, their efficacies decreased. The results of this study show that the treatment time of the fungicide should be determined by considering the effect of the fungicide on the spore growth phase of pathogens.

In order to examine the pathogenicity of Alternaria dauci, the causal agent of carrot leaf blight, it is necessary to standardize sporulation conditions to ensure the optimal quantity and quality of spore inoculum. There-fore, in this study, the effects of the growth medium, aeration treatment, and UV treatment with 12-hr photo-period on the sporulation of A. dauci KACC42997 were investigated. A. dauci KACC42997 was pre-cultured for 7 days in a potato dextrose agar medium at 25°C in the dark condition. When the pre-culture, after removing aerial mycelia, was re-incubated for 5 days, with simultaneous aeration treatment and 12-hr cycle UV treatment at 20°C, the largest number of spores was produced. One hundred seventy isolates of A. dauci were isolated from major carrot growing regions such as Pyeongchang, Gumi and Jeju and tested for sporulation under the conditions established in this study. Except for 20 strains, all strains produced spores. Statistically significant differences in the extent of sporulation were found among local populations of A. dauci isolates, but no difference was observed in their pathogenicity on carrots.

Apple grower in the Cheongsong region, Korea has reported the increased loss of apple yield due to severe bitter rot incidence. We noticed that this indience is because the Colletotrichum population has developed resistance to commonly used fungicides. We isolated 39 Colletotrichum isolates from 13 orchards in Cheongsong, and all the isolated Colletotrichum species were identified as C. siamense or C. fructicola. These 39 strains were tested for mycelial growth and conidial germination against 12 fungicides. trifloxystrobin (30–55% in recommended concentrations) was shown lower inhibitory effect on mycelial growth. However, the inhibition of conidial germination was shown higher than mycelial growth (62–100%). Kresoxim-methyl was shown lower inhibitory effect on mycelial growth (29–55%). conidial germination inhibitory effect was shown 51% to 96%. dithianon was shown diversity response to inhibition of mycelial growth (43–100%). tebuconazole was shown high inhibitory effect on mycelial growth (84–100%) and conidial germination inhibitory effect was shown to be 64 to 100%. metconazole has been found to display with high inhibitory effect on mycelial growth (79–100%) and conidial germination (70–80%). fluazinam was shown to possess high inhibitory effect on mycelial growth (87–100%) and conidial germination (94–100%). This study provides basic information for the effective management of apple bitter rot.

Resazurin-based microtiter assay was used to evaluate the inhibitory effect of fungicides on the respiration of Colletotrichum acutatum s. lat. 20JDS8 sensitive and 20CDJ6 resistant to strobilurin fungicides. The spores of C. acutatum s. lat. 20JDS8 were inoculated into potato dextrose broth (PDB) at densities of 1×104, 1×105 and 1×106 spores/ml, respectively. The relative fluorescence unit (RFU) of all treatments inoculated at each spore density started to rise after 12 hr of incubation, and were 1,965.5, 5,412.5, and 10,061.0, respectively, after 24 hr of incubation. To evaluate the inhibitory effect of fungicide on the respiration of the pathogen, the spores of the pathogen were inoculated into the PDB and treated with the fungicides 0, 6, 12, and 24 hr after incubation, respectively. After keeping the pathogen culturing for another 24 hr, PrestoBlue reagent was treated into the PDB culturing the pathogen. The RFU of each treatment was examined 1 hr after the reagent was treated. When dithianon, isopyrazam, pyraclostrobin, and fluazinam were treated at high concentrations in the stages of spores (immediately after inoculation [0 hr]), spore germination (after incubation for 6 hr), and hyphal growth (after incubation for 12 hr), the respiration of pathogens was inhibited by 90–100%. When the fungicides were treated after culturing the pathogen for 24 hr, the respiratory inhibitory effects were greatly reduced. With pyraclostrobin-resistant C. acutatum s. lat. 20CDJ6, azxoystrobin, trifloxystrobin and kresoxim-methyl, which have the same mode of action, had very little or no respiratory inhibitory effect in all growth stages of pathogens. Based on the above results, it was thought that the resazurin-based microtiter assay could quickly and accurately evaluate the inhibitory efficacy of the fungicides that inhibited respiration.

The establishment of a laboratory assay and a greenhouse assay was conducted for evaluating the pathogenicity of Macrophomina phaseolina causing soybean charcoal rot established. In the laboratory assay, microsclerotia and hyphae were used as inoculum. In the laboratory assays using microsclerotia as an inoculum, disease incidences of M. phaseolina NSW17-108 and HSM17-034 were higher at 35 o C than 25 o C. Of the two isolates NSW17-108 and HSM17-034, the disease incidence of HSM17-034 isolated from diseased sesame is higher than that of NSW17-108 isolated from diseased soybean. When the mycelia of M. phaseolina were used as an inoculum, the disease incidence of NSW17-108 and HSM17-034 at 35°C exceeded 80% even after only 5 days of inoculation. Even at 25°C, furthermore, that of HSM17-034 exceeded 80% 5 days later. In the pathogenicity assays at a greenhouse, toothpicks where microsclerotia were produced or microsclerotia harvested from potato dextrose agar medium were used as an inoculum. In all greenhouse assays, M. phaseolina NSW17-108 and HSM17-034 showed 40–60% of disease incidences 35–65 days after inoculation with the pathogen, depending on the inoculation method. Between the two isolates, the pathogenicity of HSM17-034 was stronger than that of NSW17-108, and this result was consistent with laboratory assay results. Since the laboratory and greenhouse test methods tested in this study have different advantages and disadvantages depending on each test method, it is thought that the test method that can meet the purpose of the study should be selected and used.

Colletotrichum species is known as the major causal pathogen of red pepper anthracnose in Korea and various groups of fungicides are registered for the management of the disease. However, the consistent use of fungicides has resulted in the development of resistance in many red pepper-growing areas of Korea. Effective management of the occurrence of fungicide resistance depends on constant monitoring and early detection. Thus, in this study, various methods such as agar dilution method (ADM), gene sequencing, allele-specific polymerase chain reaction (PCR), and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) were applied for the detection of benzimidazole resistance among 24 isolates of Colletotrichum acutatum s. lat. and Colletotrichum gloeosporioides s. lat. The result of the ADM showed that C. gloeosporioides s. lat. was classified into sensitive and resistant isolates to benomyl while C. acutatum s. lat. was insensitive at ≥1 μg/ml of benomyl. The sequence analysis of the β-tubulin gene showed the presence of a single nucleotide mutation at the 198th amino acid position of five isolates (16CACY14, 16CAYY19, 15HN5, 15KJ1, and 16CAYY7) of C. gloeosporioides s. lat. Allele-specific PCR and PCR-RFLP were used to detect point mutation at 198th amino acid position and this was done within a day unlike ADM which usually takes more than one week and thus saving time and resources that are essential in the fungicide resistance management in the field. Therefore, the molecular techniques established in this study can warrant early detection of benzimidazole fungicide resistance for the adoption of management strategies that can prevent yield losses among farmers.

Resistance to pyraclostrobin due to a single nucleotide polymorphism at 143rd amino acid position on the cytochrome b gene has been a major source of concern in red pepper field infected by anthracnose in Korea. Therefore, this study investigated the response of 24 isolates of C. acutatum and C. gloeosporioides isolated from anthracnose infected red pepper fruits using agar dilution method and other molecular techniques such as cytochrome b gene sequencing, polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and allele-specific polymerase chain reaction (PCR). The result showed that four isolates were resistant to pyraclostrobin on agar dilution method and possessed GCT (alanine) codon at 143rd amino acid position, whereas the sensitive isolates possessed GGT (glycine). Furthermore, this study illustrated the difference in the cytochrome b gene structure of C. acutatum and C. gloeosporioides. The use of cDNA in this study suggested that the primer Cacytb-P2 can amplify the cytochrome b gene of both C. acutatum and C. gloeosporioides despite the presence of various introns in the cytochrome b gene structure of C. gloeosporioides. The use of allele-specific PCR and PCR-RFLP provided clear difference between the resistant and sensitive isolates. The application of molecular technique in the evaluation of the resistance status of anthracnose pathogen in red pepper provided rapid, reliable, and accurate results that can be helpful in the early adoption of fungicide-resistant management strategies for the strobilurins in the field.

In order to investigate the cause of wilting symptoms in red pepper field of Korea, the frequency of occurrence of red peppers showing wilting symptoms was investigated in pepper cultivation fields in Goesan, Chungcheongbuk-do for 5 years from 2010 to 2014. There was a difference in the frequency of wilting symptoms depending on the year of investigation, but the frequency of occurrence increased as the investigation period passed from June and July to August. During this period, Ralstonia solanacearum causing the bacterial wilt was isolated at a rate four times higher than Phytophthora capsica causing the Phytophthora late blight. In wilted peppers collected in Goesan of Chungbuk and Andong of Gyeongbuk in 2013 and 2014, R. solanacearum and P. capsici were isolated from 20.3% and 3.8% of the total fields, respectively. In the year with a high rate of wilting symptoms, the average temperature was high, and the disease occurrence date of the bacterial wilt, estimated with disease forecasting model, was also fast. The inconsistency between the number of days at risk of Phytophthora late blight and the frequency of occurrence of wither symptoms is thought to be due to the generalization of the use of cultivars resistant to the Phytophthora late blight in the pepper field. In our study, the wilting symptoms were caused by the bacterial wilt caused by R. solanacearum rather than the Phytophthora late blight caused by P. capsica, which is possibly caused by increasing cultivation of pepper varieties resistant to the Phytophthora late blight in the field.

Colletotrichum acutatum s. lat. 20JDS8 sensitive and 20CDJ6 resistant to pylaclostrobin were used to investigate the cross-resistance with fungicides belonging to the strobilurins and the characteristics of fungicidal controlling activities with different mechanisms against the isolate resistant to the fungicide. The resistant isolate of 20CDJ6 also showed the resistance to azoxystrobin, trifloxystrobin, and kresoxim-methyl, suggesting that there is a cross-resistance relationship. All fungicides with different action mechanisms inhibited mycelial growth of both susceptible and resistant isolates of C. acutatum s. lat., but their disease control effects in fruits were different according to the fungicides. The disease control effect of isopyrazam against 20JDS8 and 20CDJ6 was very low, and fluazinam showed a control effect of 91.9% and 88.1% against 20JDS8 and 20CDJ6 only when it was treated before inoculation by spraying spore suspensions on pepper fruits without wounds. Tebuconazole and prochloraz effectively inhibited not only the mycelial growth of 20JDS8 and 20CDJ6 on potato dextrose agar medium, but also disease incidence in red pepper fruits. As a result of this study, C. acutatum s. lat. 20CDJ6 resistant to pyraclostrobin showed cross-resistance with other strobilurin fungicides. In addition, we think that fluazinam, tebuconazole, and prochloraz can be recommended as alternative fungicides for the control of red-pepper pyranthracnose pathogens resistant pyraclostrobin. However, fluazinam can be effective only if it is treated protectively before the occurrence of the disease.

Anthracnose is a fungal disease caused by Colletotrichum species and has detrimental effects on many crops, including red pepper. This study used Bacillus tequilensis GYUN-300 (GYUN-300), which exhibit antagonistic activity against the fungal pathogen, Colletotrichum acutatum. This pathogen causes anthracnose that manifests primarily as a fruit rot in red pepper. There have been little efforts to identify antagonistic bacteria from mushrooms; this strain of bacteria was identified as B. tequilensis using BIOLOG and 16S rDNA sequencing analysis. The genetic mechanism underpinning the biocontrol traits of GYUN-300 was characterized using the complete genome sequence of GYUN-300, which was closely compared to related strains. GYUN-300 inhibited mycelial growth and spore germination of C. acutatum under in vitro conditions. Important antagonistic traits, such as siderophore production, solubilization of insoluble phosphate, and production of lytic enzymes (cellulase, protease, and amylase), were observed in GYUN-300, These trains promoted growth in terms of seed germination and vigorous seedling growth compared to the non-treated control. When red pepper fruits were treated with GYUN-300, the preventive and curative effects were 66.6 and 38.3% effective, respectively, in wounded red pepper fruits; there was no difference between the preventive and curative effects in non-wounded red pepper fruits. Furthermore, GYUN-300 was resistant to several commercial fungicides, indicating that GYUN-300 bacterial cells may also be used synergistically with chemical fungicides to increase biocontrol efficiency. Based on in vitro results, GYUN-300 played a role to control anthracnose disease effectively in field conditions when compared to other treatments and non-treated controls. The results from this study provide a better understanding of the GYUN-300 strain as an effective biocontrol agent against red pepper anthracnose; this form of biocontrol provides an environment-friendly alternative to chemical fungicides.

Pectobacterium carotovorum subsp. carotovorum (Pcc) causes bacterial soft rot on a wide range of crops worldwide, especially in countries with warm and humid climates. This study was conducted to establish an efficient screening method for resistant cultivars of Chinese cabbage to bacterial soft rot. Resistance degrees of 65 commercial Chinese cabbage cultivars to the Pcc KACC 10225 isolate were investigated. For further study, three Chinse cabbage cultivars (Taebong, Hadaejangkun, CR Alchan) showing different level of resistance to the bacterium were selected. The development of bacterial soft rot on the cultivars was tested according to several conditions such as growth stage of Chinse cabbage seedling, inoculum concentration, and incubation temperature after inoculation. On the basis of the results, we suggest that an efficient screening method for resistant Chinses cabbage to Pcc is to inoculate twenty one-day-old seedlings with a bacterial suspension of Pcc at a concentration of 1×107 cfu/ml, and to incubate the plants in a dew chamber at 25°C for 24 hr and then to cultivate in a growth room at 25°C and 80% relative humidity with 12-hr light per day.

Recently, the severe dieback of apple trees resulting from soil-borne diseases has occurred in South Korea. The casual agents of dieback were surveyed on 74 apple orchards that had been damaged nationwide in 2016–2019. The number of apple orchards affected alone by Phytophthora rot, violet root rot, and white root rot was 31, 34, and 3, respectively. Also, the total number of mixed infection orchards was 6. Out of 9,112 apple trees affected by dieback, the trees damaged by Phytophthora rot, violet root rot, and white root rot were 3,332, 3,831, and 44, respectively. Moreover, the total number of mixed infection apple trees was 1,905. The provinces mainly affected were Gyeongnam, Gyeongbuk, Chungbuk, and Jeonbuk. The survey on these infected apple orchards will be available to form management strategy for the dieback that had been increased by soil-borne fungal pathogens.

Fusarium wilt caused by Fusarium oxysporum f. sp. fragariae (Fof) is the most important diseases of a strawberry field in Korea. We surveyed phylogenetic analysis, pathogenicity test, and fungicide response about Fof isolates isolated from Korea. Twenty-seven isolates of F. oxysporum isolated from strawberry plants were conducted in this study. Specific amplification by Fof specific primer was confirmed in all 26 isolates except Fo080701 isolate. The nuclear ribosomal intergenic spacer region and the translation elongation factor EFlα gene sequences of isolates revealed three main lineages. Most of all isolates were contained DNA lineage group 1, but 2 and 3 group was shown only one and three isolates, respectively. All isolates were shown in pathogenicity with cv. Seolhyang. The EC50 mean values of prochloraz ranged 0.02–0.1 μg/ml except for Fo080701 and effectively inhibited mycelial growth at low concentrations. The EC50 value of metconazole was also 0.04–0.22 μg/ml, showing a similar inhibitory effect to that of prochloraz. The EC50 value of pyraclostrobin was 0.23–168.01 μg/ml, which was different according to the strain. In the field trial, boscalid+fludioxonil, fluxapyroxad+pyraclostrobin, and prochloraz manganese were selected as the effective fungicides for controlling Fusarium wilt.

With 32 fungicides, it was examined the inhibitory effects on the mycelial growth of Alternaria dauci KACC42997 causing Alternaria leaf blight of carrot. Showing the results of the agar dilution method, the fungicides belonging to C2, C5, G1, E2, and E3 group were excellent in inhibiting mycelial growth. Protective fungicides belonging to M group, except for iminoctadine tris-albesilate, and pyraclostrobin belonging to C3 group were effective in inhibiting spore germination of pathogens. The fungicides included into C2 group inhibiting succinate dehydrogenase activity and the G1 group inhibiting demethylase activity showed the excellent inhibitory effect on mycelial growth but the inhibitory effect of spore germination was very low. However, fluazinam belonging to C5 group was excellent in inhibiting spore germination as well as mycelial growth. Especially, when 100 μg/ml of fluxapyroxad belonging to the C2 group was treated, 47.1% of spore formation was inhibited on the medium. In comparison of the resistance factors of 3 fungicide groups, as G, C, and E group, in populations of A. dauci isolates collected from Gumi, Pyeongchang, and Jeju, resistance factor in the population of Jeju was the lowest. However, two isolates resistant to fludioxonil belonging to E2 group were found in the isolate group of Pyeongchang, and both showed crossresistance to iprodione and procymidone.

Stem blight symptom of soybean was severely developed in 2016 in Hwaseong and Yeoncheon. During the seedling period, the damping-off of seedlings and the brown or black spots of cotyledons were observed. After August, the leaves began to be yellowed, and partially browned areas on leaves began to develop. After September, microsclerotia began to form even on the surface of the stems that had exhibited water-soaking symptom. After mid-October of the harvest season, the epidermis of the stem was peeled off, resulting in the formation of a large number of microsclerotia in the cortex. The pathogens isolated from these symptoms were the best in mycelial growth at 32–35°C, and the formation of microsclerotia was the most at 20–28°C. The pathogen was identified as Macrophomina phaseolina through the morphological characteristics of the pathogen and the sequencing of the internal transcribed spacer region gene. In addition, when inoculated with a soybean stem using toothpicks cultured with the pathogen, the same symptoms as seen on the soybean field occurred. When the pathogen was re-isolated at the lesion site, the same pathogen was isolated and identified as Macrophomina phaseolina. Based on the results, the disease is reported as soybean charcoal rot.

Among 6 fungicides, fluazinam, which had an excellent inhibitory effect on mycelial growth and spore germination, was also effective in controlling jujube anthracnose in the field. While EC50 values of metconazole and tebuconazole ranged from 0.2 to 0.9 μg/ml and from 0.4 to 1.1 μg/ml against the mycelial growth, respectively, each inhibitory effect on spore germination was low by 7.4% and 11.1% at 50.0 μg/ml. In the field test, they showed the control value of 80.5% and 77.0%, respectively. The protective fungicides, as mancozeb and folpet, which had a low inhibitory effect on the mycelial growth, but had a high inhibitory effect of spore germination, showed excellent disease control activities by 87.6% and 92.0% in the field. Showing a result of resistance monitoring conducted with the isolates of Colletotricum gloeosporioides, the resistance against carbendazim was already generated in the field, but it was thought that there was no resistance to pyraclostrobin, fluazinam and tebuconazole. However, if the resistance factor value of the population of C. gloeosporioides isolates to pyraclostrobin was high by 160.4, the diversity of the response to the fungicide in the population was high, so it should be taken more attention to the resistance management.

Background and PurposeWe compared treatment outcomes and toxicities of photon radiotherapy versus proton beam therapy (PBT) and evaluated radiation field effects for T1–3 squamous cell carcinoma of the thoracic esophagus (EC) without lymph node metastasis.MethodsMedical records of 77 patients with T1–3N0M0 thoracic EC treated with radiotherapy between 2011 and 2019 were retrospectively analyzed. Among these patients, 61 (79.2%) individuals had T1 EC. The initial clinical target volume encompassed the whole esophagus with or without supraclavicular and/or abdominal lymph nodes (extended-field radiotherapy; 67 patients, 87.0%) or the area 3–5 cm craniocaudally and 1–2 cm radially from the gross tumor volume (involved-field radiotherapy; 10 patients, 13.0%). The final clinical target volume included margins of at least 1 cm from the gross tumor volume, with total radiation doses of 50–66 (median, 66) cobalt gray equivalent. Three-dimensional conformal radiotherapy, intensity-modulated radiotherapy, and PBT were used in twenty-four, five, and forty-eight patients, respectively. Concurrent chemotherapy was administered to 17 (22.0%) patients overall and only five (8.0%) T1 patients.ResultsPBT showed significantly lower lung and heart radiation exposure in mean dose, V5, V10, V20, and V30 than photon radiotherapy. The median follow-up for all patients was 46 (interquartile range, 22–72) months. The 5-year progression-free survival and overall survival rates were 56.5 and 64.9%, respectively, with no significant survival difference between photon radiotherapy and PBT. In patients with T1 EC, 5-year progression-free survival and overall survival rates were 62.6 and 73.5%, respectively.ConclusionsExtended-field radiotherapy using modern radiotherapy techniques without chemotherapy showed satisfactory clinical outcomes for lymph node-negative T1 EC.

Our study investigated the available chlorine content, contact time and difference among strains of each pathogen for sodium hypochlorite (NaOCl) to control chemically against soil-borne fungal pathogens, such as Phytophthora rot by Phytophthora cactorum, violet root rot by Helicobasidium mompa, and white root rot by Rosellinia necatrix, causing die-back symptom on apple trees. As a result, the colony growth of Phytophthora cactorum was inhibited completely by soaking over 5 s in 31.25 ml/l available chlorine content of NaOCl. Those of H. mompa and R. necatrix were inhibited entirely by soaking over 160 s in 62.5 and 125 ml/l available chlorine content in NaOCl, respectively. Also, inhibition effect on available chlorine in NaOCl among strains of each soil-borne pathogen showed no significant difference and was similar to or better than that of fungicides.

Pear scab caused by Venturia nashicola has been reported as an important disease of pear resulting in lowering the quality of pear fruits. In this study, it was conducted to investigate the relationship between resistance of V. nashicola and mutation of β-tubulin gene and the fungicide resistance in field isolate group in benzimidazole fungicides. Responce of V. nashicola to carbendazim could be classified into 3 groups as sensitive that does not grow at all on PDA amended with 0.16 μg/ml of carbendazim, low resistance that could not grow in 4.0 μg/ml medium, and high resistance that can grow even at 100 μg/ml. Thirty isolates of V. nashicola collected from 3 regions as Wonju, Naju, and Okcheon were highly resistant to carbendazim. Analysis of the nucleotide sequence of β-tubulin gene of V. nashicola showed that there was no difference in the nucleotide sequence between the sensitive and the low-resistant isolate, but GAG at codon 198 (glutamic acid) was replaced with GCG (alanine) in the high-resistant isolate. Among 10 isolates obtained from the Okcheon, 5 isolates showed the substitution of glycine for glutamic acid, which were resistant to carbendazim, but more sensitive to the mixture of carbendazim and diethofencarb than others. Through these results, all isolates of V. nashicola isolated in pear orchard were found to be resistant to benzimidazoles. Also, mutants E198A and E198G at β-tubulin were found to be important mechanisms of V. nashicola resistance against benzimidazole fungicides.

This study was conducted to establish a simple mass-screening method for resistant melon to Fusarium wilt caused by Fusarium oxysporum f. sp. melonis (FOM). Root-dipping inoculation method has been used to investigate resistance of melon plants to Fusarium wilt. However, the inoculation method requires a lot of labor and time because of complicate procedure. To develop a simple screening method on melon Fusarium wilt, occurrence of Fusarium wilt on susceptible and resistant cultivars of melon according to inoculation method including root-dipping, soil-drenching, tip, and scalpel methods was investigated. Scalpel and tip methods showed more clear resistant and susceptible responses in the melon cultivars than root-dipping inoculation method, but tip method represented slightly variable disease severity. In contrast, in the case of soil-drenching inoculation method, disease severity of the susceptible cultivars was very low. Thus we selected scalpel method as inoculation method of a simple screening method for melon Fusarium wilt. By using the scalpel inoculation method, resistance degrees of the cultivars according to incubation temperature after inoculation (25 and 30°C) and inoculum concentration (1×106 and 1×107 conidia/ml) were measured. The resistance or susceptibility of the cultivars was hardly affected by all the tested conditions. To look into the effectiveness of scalpel inoculation methods, resistance of 22 commercial melon cultivars to FOM was compare with root-dipping inoculation method. When the melon cultivars were inoculated by scalpel method, resistance responses of all the tested cultivars were clearly distinguished as by root-dipping method. Taken together, we suggest that an efficient simple mass-screening method for resistant melon plant to Fusarium wilt is to sow the seeds of melon in a pot (70 ml of soil) and to grow the seedlings in a greenhouse (25±5°C) for 7 days, to cut the root of seedlings with a scalpel and then pour a 10 ml-aliquot of the spore suspension of 1×106 conidia/ml on soil. The infected plants were cultivated in a growth room at 25 to 30°C for about 3 weeks with 12-hr light a day.

Fungi tolerate exposure to various abiotic stresses, including cytotoxic compounds and fungicides, via their ATP-driven efflux pumps belonging to ATP-binding cassette (ABC) transporters. To clarify the molecular basis of interaction between the fungus and various abiotic stresses including fungicides, we constructed a cDNA library from germinated conidia of Colletotrichum acutatum, a major anthracnose pathogen of pepper (Capsicum annum L.). Over 1,000 cDNA clones were sequenced, of which single clone exhibited significant nucleotide sequence homology to ABC transporter genes. We isolated three fosmid clones containing the C. acutatum ABC1 (CaABC1) gene in full-length from genomic DNA library screening. The CaABC1 gene consists of 4,059 bp transcript, predicting a 1,353-aa protein. The gene contains the typical ABC signature and Walker A and B motifs. The 5′-flanking region contains a CAAT motif, a TATA box, and a Kozak region. Phylogenetic and structural analysis suggested that the CaABC1 is a typical ABC transporter gene highly conserved in various fungal species, as well as in Chromista, Metazoans, and Viridiplantae. We also found that CaABC1 was up-regulated during conidiation and a minimal medium condition. Moreover, CaABC1 was induced in iprobenfos, kresoxim-methyl, thiophanate-methyl, and hygromycin B. These results demonstrate that CaABC1 is necessary for conidiation, abiotic stress, and various fungicide resistances. These results will provide the basis for further study on the function of ABC transporter genes in C. acutatum.

The epidermal growth factor receptor (EGFR) is a well-established target for cancer treatment. EGFR tyrosine kinase (TK) inhibitors, such as gefinitib and erlotinib, have been developed as anti-cancer drugs. Although non-small cell lung carcinoma with an activating EGFR mutation, L858R, responds well to gefinitib and erlotinib, tumors with a doubly mutated EGFR, T790M-L858R, acquire resistance to these drugs. The C. elegans EGFR homolog LET-23 and its downstream signaling pathway have been studied extensively to provide insight into regulatory mechanisms conserved from C. elegans to humans. To develop an in vivo screening system for potential cancer drugs targeting specific EGFR mutants, we expressed three LET-23 chimeras in which the TK domain was replaced with either the human wild-type TK domain (LET-23::hEGFR-TK), a TK domain with the L858R mutation (LET-23::hEGFR-TK[L858R]), or a TK domain with the T790M-L858R mutations (LET-23::hEGFR-TK[T790M-L858R]) in C. elegans vulval cells using the let-23 promoter. The wild-type hEGFR-TK chimeric protein rescued the let-23 mutant phenotype, and the activating mutant hEGFR-TK chimeras induced a multivulva (Muv) phenotype in a wild-type C. elegans background. The anti-cancer drugs gefitinib and erlotinib suppressed the Muv phenotype in LET-23::hEGFR-TK[L858R]-expressing transgenic animals, but not in LET-23::hEGFR-TK[T790M-L858R] transgenic animals. As a pilot screen, 8,960 small chemicals were tested for Muv suppression, and AG1478 (an EGFR-TK inhibitor) and U0126 (a MEK inhibitor) were identified as potential inhibitors of EGFR-mediated biological function. In conclusion, transgenic C. elegans expressing chimeric LET-23::hEGFR-TK proteins are a model system that can be used in mutation-specific screens for new anti-cancer drugs.

Purpose: Information about the impact on the adult health care system is limited for complex rare pediatric diseases, despite their increasing collective prevalence that has paralleled advances in clinical care of children. Within a population-based health care context, we examined costs and multimorbidity in adults with an exemplar of contemporary genetic diagnostics., Methods: We estimated direct health care costs over an 18-year period for adults with molecularly confirmed 22q11.2 microdeletion (cases) and matched controls (total 60,459 person-years of data) by linking the case cohort to health administrative data for the Ontario population (∼15 million people). We used linear regression to compare the relative ratio (RR) of costs and to identify baseline predictors of higher costs., Results: Total adult (age ≥ 18) health care costs were significantly higher for cases compared with population-based (RR 8.5, 95% CI 6.5-11.1) controls, and involved all health care sectors. At study end, when median age was <30 years, case costs were comparable to population-based individuals aged 72 years, likelihood of being within the top 1st percentile of health care costs for the entire (any age) population was significantly greater for cases than controls (odds ratio [OR], for adults 17.90, 95% CI 7.43-43.14), and just 8 (2.19%) cases had a multimorbidity score of zero (vs 1483 (40.63%) controls). The 22q11.2 microdeletion was a significant predictor of higher overall health care costs after adjustment for baseline variables (RR 6.9, 95% CI 4.6-10.5)., Conclusion: The findings support the possible extension of integrative models of complex care used in pediatrics to adult medicine and the potential value of genetic diagnostics in adult clinical medicine., Competing Interests: Conflict of Interest The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Elevated triglyceride (TG) levels are a heritable and modifiable risk factor for cardiovascular disease and have well-established associations with common genetic variation captured in a polygenic risk score (PRS). In young adulthood, the 22q11.2 microdeletion conveys a 2-fold increased risk for mild-moderate hypertriglyceridemia. This study aimed to assess the role of the TG-PRS in individuals with this elevated baseline risk for mild-moderate hypertriglyceridemia., Methods: We studied a deeply phenotyped cohort of adults (n = 157, median age 34 years) with a 22q11.2 microdeletion and available genome sequencing, lipid level, and other clinical data. The association between a previously developed TG-PRS and TG levels was assessed using a multivariable regression model adjusting for effects of sex, BMI, and other covariates. We also constructed receiver operating characteristic (ROC) curves using logistic regression models to assess the ability of TG-PRS and significant clinical variables to predict mild-moderate hypertriglyceridemia status., Results: The TG-PRS was a significant predictor of TG-levels (p = 1.52E-04), along with male sex and BMI, in a multivariable model (p model  = 7.26E-05). The effect of TG-PRS appeared to be slightly stronger in individuals with obesity (BMI ≥ 30) (beta = 0.4617) than without (beta = 0.1778), in a model unadjusted for other covariates (p-interaction = 0.045). Among ROC curves constructed, the inclusion of TG-PRS, sex, and BMI as predictor variables produced the greatest area under the curve (0.749) for classifying those with mild-moderate hypertriglyceridemia, achieving an optimal sensitivity and specificity of 0.746 and 0.707, respectively., Conclusions: These results demonstrate that in addition to significant effects of sex and BMI, genome-wide common variation captured in a PRS also contributes to the variable expression of the 22q11.2 microdeletion with respect to elevated TG levels., (© 2023. The Author(s).)

Objective/background: We aimed to evaluate adult-onset obstructive sleep apnea (OSA) and related risk factors, including history of pediatric palatal/pharyngeal surgery to remediate velopharyngeal dysfunction, in 22q11.2 deletion syndrome (22q11.2DS)., Patients/methods: Using a retrospective cohort design and standard sleep study-based criteria, we determined presence of adult-onset OSA (age ≥16 years) and relevant variables through comprehensive chart review in a well-characterized cohort of 387 adults with typical 22q11.2 microdeletions (51.4% female, median age 32.3, interquartile range 25.0-42.5, years). We used multivariate logistic regression to identify independent risk factors for OSA., Results: Of the 73 adults with sleep study data, 39 (53.4%) met criteria for OSA at median age 33.6 (interquartile range 24.0-40.7) years, indicating a minimum OSA prevalence of 10.1% in this 22q11.2DS cohort. History of pediatric pharyngoplasty (odds ratio 2.56, 95% confidence interval 1.15-5.70) was a significant independent predictor of adult-onset OSA, while accounting for other significant independent predictors (asthma, higher body mass index, older age), and for male sex. An estimated 65.5% of those prescribed continuous positive airway pressure therapy were reported as adherent., Conclusions: In addition to factors of known importance in the general population, delayed effects of pediatric pharyngoplasty may contribute to risk of adult-onset OSA in individuals with 22q11.2DS. The results support increased index of suspicion for OSA in adults with a 22q11.2 microdeletion. Future research with this and other homogeneous genetic models may help to improve outcomes and to better understand genetic and modifiable risk factors for OSA., Competing Interests: Declaration of competing interest None., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: Recurrent chromosome 22q11.2 deletions cause 22q11 deletion syndrome (22q11DS), a multisystem disorder associated with high rates of schizophrenia. Neuroanatomical changes on brain MRI have been reported in relation to 22q11DS. However, to date no 22q11DS neuroimaging studies have examined cerebral blood flow (CBF). This exploratory case-control study seeks to identify differences in regional cerebral blood flow between 22q11DS subjects and controls, and their association with psychotic symptoms., Methods: This study of 23 adults used arterial spin labelling MRI to investigate voxel-wise CBF in 22q11DS individuals compared with age- and sex-matched healthy controls., Results: Four significant clusters, involving the right and left putamen, right fusiform gyrus and left middle temporal gyrus, delineated significantly elevated CBF in individuals with 22q11DS compared to controls. Post-hoc analysis determined that this elevation in CBF trended with psychotic symptom diagnosis within the 22q11DS group., Conclusions: These findings suggest possible relevance to schizophrenia risk and support further functional neuroimaging studies of 22q11DS with larger sample sizes to improve our understanding of the underlying pathophysiology.

The 22q11.2 microdeletion and its associated conditions could affect reproductive outcomes but there is limited information on this important area. We investigated reproductive outcomes in a sample of 368 adults with typical 22q11.2 deletions (median age 32.8, range 17.9-76.3 years; 195 females), and without moderate-severe intellectual disability, who were followed prospectively. We examined all reproductive outcomes and possible effects of diagnosis as a transmitting parent on these outcomes. We used logistic regression to investigate factors relevant to reproductive fitness (liveborn offspring). There were 63 (17.1%) individuals with 157 pregnancy outcomes, 94 (60.3%) of which involved live births. Amongst the remainder involving a form of loss, were seven (5.77%) stillbirths, significantly greater than population norms ( p < 0.0001). For 35 (55.6%) individuals, diagnosis of 22q11.2 deletion syndrome (22q11.2DS) followed diagnosis of an offspring, with disproportionately fewer individuals had major congenital heart disease (CHD) in that transmitting parent subgroup. The regression model indicated that major CHD, in addition to previously identified factors, was a significant independent predictor of reduced reproductive fitness. There was evidence of persisting diagnostic delay and limited prenatal genetic testing. The findings indicate that pregnancy loss is an important health issue for adults with 22q11.2DS. CHD and/or its absence is a factor to consider in reproductive outcome research. Further studies are warranted to better appreciate factors that may contribute to reproductive outcomes, including technological advances. The results suggest the need for ongoing efforts to provide optimal education and supports to individuals with 22q11.2DS, and their clinicians, around reproductive issues and early diagnosis.

The 22q11.2 deletion syndrome (22q11.2DS) manifests as a wide range of medical conditions across a number of systems. Pediatric growth deficiency with some catch-up growth is reported, but there are few studies of final adult height. We aimed to investigate how final adult height in 22q11.2DS compared with general population norms, and to examine predictors of short stature in in a cohort of 397 adults with 22q11.2DS (aged 17.6-76.3 years) with confirmed typical 22q11.2 microdeletion (overlapping the LCR22A to LCR22B region). We defined short stature as <3rd percentile using population norms. For the subset ( n = 314, 79.1%) with 22q11.2 deletion extent, we used a binomial logistic regression model to predict short stature in 22q11.2DS, accounting for effects of sex, age, ancestry, major congenital heart disease (CHD), moderate-to-severe intellectual disability (ID), and 22q11.2 deletion extent. Adult height in 22q11.2DS showed a normal distribution but with a shift to the left, compared with population norms. Those with short stature represented 22.7% of the 22q11.2DS sample, 7.6-fold greater than population expectations ( p < 0.0001). In the regression model, moderate-to-severe ID, major CHD, and the common LCR22A-LCR22D (A-D) deletion were significant independent risk factors for short stature while accounting for other factors (model p = 0.0004). The results suggest that the 22q11.2 microdeletion has a significant effect on final adult height distribution, and on short stature with effects appearing to arise from reduced gene dosage involving both the proximal and distal sub-regions of the A-D region. Future studies involving larger sample sizes with proximal nested 22q11.2 deletions, longitudinal lifetime data, parental heights, and genotype data will be valuable.

Learning and intellectual disabilities are hallmark features of 22q11.2 deletion syndrome. Data are limited, however, regarding influences on full-scale IQ (FSIQ). Here, we investigated possible 22q11.2 deletion parent-of-origin effects. In 535 individuals, we compared FSIQ (≥50), 481 with de novo and 54 with inherited 22q11.2 deletions. In the subsets with data available, we examined parent-of-origin effects on FSIQ. We used linear regression models to account for covariates. Median FSIQ was significantly higher in de novo vs. inherited deletions (77; range 50−116 vs. 67; range 50−96, p < 0.0001). Results remained significant using a regression model accounting for age at IQ testing, sex and cohort site. No significant parent-of-origin differences in FSIQ were observed for de novo deletions (n = 81, 63.0% maternal; p = 0.6882). However, median FSIQ was significantly lower in maternally than in paternally inherited familial deletions (65, range 50−86 vs. 71.5, range 58−96, respectively, p = 0.0350), with the regression model indicating an ~8 point decrement in FSIQ for this variable (p = 0.0061). FSIQ is higher on average in de novo than in inherited 22q11.2 deletions, regardless of parental origin. However, parent-of-origin appears relevant in inherited deletions. The results have potential clinical implications with further research needed to delineate possible actionable mechanisms., Competing Interests: The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Background: Genotype-first and within-family studies can elucidate factors that contribute to psychiatric illness. Combining these approaches, we investigated the patterns of influence of parental scores, a high-impact variant, and schizophrenia on dimensional neurobehavioral phenotypes implicated in major psychiatric disorders., Methods: We quantitatively assessed cognitive (FSIQ, VIQ, PIQ), social, and motor functioning in 82 adult individuals with a de novo 22q11.2 deletion (22 with schizophrenia), and 148 of their unaffected parents. We calculated within-family correlations and effect sizes of the 22q11.2 deletion and schizophrenia, and used linear regressions to assess contributions to neurobehavioral measures., Results: Proband-parent intra-class correlations (ICC) were significant for cognitive measures (e.g. FSIQ ICC = 0.549, p < 0.0001), but not for social or motor measures. Compared to biparental scores, the 22q11.2 deletion conferred significant impairments for all phenotypes assessed (effect sizes -1.39 to -2.07 s.d.), strongest for PIQ. There were further decrements in those with schizophrenia. Regression models explained up to 37.7% of the variance in IQ and indicated that for proband IQ, parental IQ had larger effects than schizophrenia., Conclusions: This study, for the first time, disentangles the impact of a high-impact variant from the modifying effects of parental scores and schizophrenia on relevant neurobehavioral phenotypes. The robust proband-parent correlations for cognitive measures, independent of the impact of the 22q11.2 deletion and of schizophrenia, suggest that, for certain phenotypes, shared genetic variation plays a significant role in expression. Molecular genetic and predictor studies are needed to elucidate shared factors and their contribution to psychiatric illness in this and other high-risk groups.

Tandem repeat expansions (TREs) can cause neurological diseases but their impact in schizophrenia is unclear. Here we analyzed genome sequences of adults with schizophrenia and found that they have a higher burden of TREs that are near exons and rare in the general population, compared with non-psychiatric controls. These TREs are disproportionately found at loci known to be associated with schizophrenia from genome-wide association studies, in individuals with clinically-relevant genetic variants at other schizophrenia loci, and in families where multiple individuals have schizophrenia. We showed that rare TREs in schizophrenia may impact synaptic functions by disrupting the splicing process of their associated genes in a loss-of-function manner. Our findings support the involvement of genome-wide rare TREs in the polygenic nature of schizophrenia., (© 2022. The Author(s).)

Background: There is limited information about sexual knowledge and behaviours in adults with complex care needs, including those with 22q11.2 deletion syndrome (22q) which represents a group predisposed to intellectual disabilities., Methods: We conducted sexual health assessments with 67 adults with 22q, examining whether those with knowledge deficits and a history of engaging in sexual activities with others would be more likely to engage in high-risk behaviours., Results: The majority (65.7%) of adults with 22q were sexually active with others; most (70.1%) had sexual knowledge deficits. Those with intellectual disabilities were more likely (p = .0012) to have deficits in certain topics. In the sexually active subgroup, most (81.8%) engaged in high-risk sexual behaviours, regardless of intellectual disability or knowledge deficits., Conclusion: The results suggest a need for increased dialogue, repeated education, genetic counselling and preventive healthcare measures related to sexuality in 22q and potentially in other complex care conditions., (© 2021 John Wiley & Sons Ltd.)

Objective: Mild to moderate hypertriglyceridemia is a condition often associated with obesity and diabetes, with as yet incomplete knowledge of underlying genetic architecture. The 22q11.2 microdeletion is associated with multimorbidity, including increased risk of obesity and diabetes. In this study, we sought to investigate whether the 22q11.2 microdeletion was associated with mild to moderate hypertriglyceridemia (1.7-10 mmol/L)., Design: This was a cohort study comparing 6793 population-based adults and 267 with a 22q11.2 microdeletion aged 17-69 years, excluding those with diabetes or on statins., Methods: We used binomial logistic regression modeling to identify predictors of hypertriglyceridemia, accounting for the 22q11.2 microdeletion, male sex, BMI, ethnicity, age, and antipsychotic medications., Results: The 22q11.2 microdeletion was a significant independent predictor of mild to moderate hypertriglyceridemia (odds ratio (OR): 2.35, 95% CI: 1.70-3.26). All other factors examined were also significant predictors (OR: 1.23-2.10), except for antipsychotic medication use. Within the 22q11.2 microdeletion subgroup, only male sex (OR: 3.10, 95% CI: 1.77-5.44) and BMI (OR: 1.63, 95% CI: 1.14-1.98) were significant predictors of hypertriglyceridemia, evident at mean age 31.2 years., Conclusions: The 22q11.2 microdeletion is associated with hypertriglyceridemia even when accounting for other known risk factors for elevated triglycerides. This effect is seen in young adulthood (76.6% were <40 years), in the absence of diabetes, and irrespective of antipsychotics, suggesting that the 22q11.2 microdeletion may represent an unrecognized genetic risk factor for hypertriglyceridemia, providing novel opportunities for animal and cellular models. Early dyslipidemia screening and management strategies would appear prudent for individuals with 22q11.2 microdeletions.

PAN2 encodes a subunit of a deadenylation complex with important functions in mRNA stability and post-transcriptional regulation of gene expression. A homozygous frameshift deletion in PAN2 was reported in a single affected individual with developmental delay and multiple congenital anomalies. Here, we describe five additional individuals from three unrelated families with homozygous predicted loss-of-function variants in PAN2. The affected individuals presented with significant overlap in their clinical features, including mild-moderate intellectual disability, hypotonia, sensorineural hearing loss, EEG abnormalities, congenital heart defects (tetralogy of Fallot, septal defects, dilated aortic root), urinary tract malformations, ophthalmological anomalies, short stature with other skeletal anomalies, and craniofacial features including flat occiput, ptosis, long philtrum, and short neck. Our data confirm that biallelic predicted loss-of-function variants in PAN2 cause a syndrome with multiple congenital anomalies, and suggest an important role of mRNA polyA tail length for proper organ formation., (© 2022. The Author(s), under exclusive licence to European Society of Human Genetics.)

The 22q11.2 deletion is associated with >20-fold increased risk for schizophrenia. The presence of gene DGCR8 in the 22q11.2 deletion region has suggested microRNA (miRNA) dysregulation as possibly contributing to this risk. We therefore investigated the role of miRNA target genes in the context of previously identified genome-wide risk for schizophrenia conveyed by additional copy number variation (CNV) in 22q11.2 deletion syndrome (22q11.2DS). Using a cohort of individuals with 22q11.2DS and documented additional rare CNVs overlapping protein coding genes, we compared those with schizophrenia ( n = 100) to those with no psychotic illness ( n = 118), assessing for rare CNVs that overlapped experimentally supported miRNA target genes. We further characterized the contributing miRNA target genes using gene set enrichment analyses and identified the miRNAs most implicated. Consistent with our hypothesis, we found a significantly higher proportion of individuals in the schizophrenia than in the non-psychotic group to have an additional rare CNV that overlapped one or more miRNA target genes (odds ratio = 2.12, p = 0.0138). Gene set analyses identified an enrichment of FMRP targets and genes involved in nervous system development and postsynaptic density amongst these miRNA target genes in the schizophrenia group. The miRNAs most implicated included miR-17-5p, miR-34a-5p and miR-124-3p. These results provide initial correlational evidence in support of a possible role for miRNA perturbation involving genes affected by rare genome-wide CNVs in the elevated risk for schizophrenia in 22q11.2DS, consistent with the multi-hit and multi-layered genetic mechanisms implicated in this and other forms of schizophrenia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ying, Heung, Zhang, Yuen and Bassett.)

Background: Although pathogenic 22q11.2 deletions are an important cause of developmental delays and lifelong disease burden, their variable and complex clinical expression contributes to under-recognition, delayed molecular diagnosis and uncertainty about prevalence. We sought to estimate the contemporary live-birth prevalence of typical 22q11.2 deletions using a population-based newborn screening sample and to examine data available for associated clinical features., Methods: Using DNA available from an unbiased sample of about 12% of all dried blood spots collected for newborn screening in Ontario between January 2017 and September 2018, we prospectively screened for 22q11.2 deletions using multiplex quantitative polymerase chain reaction assays and conducted independent confirmatory studies. We used cross-sectional analyses to compare available clinical and T-cell receptor excision circle (TREC, used in newborn screening for severe combined immunodeficiency) data between samples with and without 22q11.2 deletions., Results: The estimated minimum prevalence of 22q11.2 deletions was 1 in 2148 (4.7 per 10 000) live births (95% confidence interval [CI] 2.5 to 7.8 per 10 000), based on a total of 30 074 samples screened, with 14 having confirmed 22q11.2 deletions. Of term singletons, samples with 22q11.2 deletions had significantly younger median maternal age (25.5 v. 32.0 yr, difference -6.5 yr, 95% CI -7 to -2 yr), a greater proportion with small birth weight for gestational age (odds ratio 7.00, 95% CI 2.36 to 23.18) and lower median TREC levels (108.9 v. 602.5 copies/3 μL, p < 0.001)., Interpretation: These results indicate that the 22q11.2 deletion syndrome is one of the most common of rare genetic conditions and may be associated with relatively younger maternal ages and with prenatal growth abnormalities. The findings support the public health importance of early - prenatal and neonatal - diagnosis that would enable prompt screening for and management of well-known actionable features associated with 22q11.2 deletions., Competing Interests: Competing interests: None declared., (© 2021 CMA Joule Inc. or its licensors.)

Schizophrenia occurs in about one in four individuals with 22q11.2 deletion syndrome (22q11.2DS). The aim of this International Brain and Behavior 22q11.2DS Consortium (IBBC) study was to identify genetic factors that contribute to schizophrenia, in addition to the ~20-fold increased risk conveyed by the 22q11.2 deletion. Using whole-genome sequencing data from 519 unrelated individuals with 22q11.2DS, we conducted genome-wide comparisons of common and rare variants between those with schizophrenia and those with no psychotic disorder at age ≥25 years. Available microarray data enabled direct comparison of polygenic risk for schizophrenia between 22q11.2DS and independent population samples with no 22q11.2 deletion, with and without schizophrenia (total n = 35,182). Polygenic risk for schizophrenia within 22q11.2DS was significantly greater for those with schizophrenia (p adj  = 6.73 × 10 -6 ). Novel reciprocal case-control comparisons between the 22q11.2DS and population-based cohorts showed that polygenic risk score was significantly greater in individuals with psychotic illness, regardless of the presence of the 22q11.2 deletion. Within the 22q11.2DS cohort, results of gene-set analyses showed some support for rare variants affecting synaptic genes. No common or rare variants within the 22q11.2 deletion region were significantly associated with schizophrenia. These findings suggest that in addition to the deletion conferring a greatly increased risk to schizophrenia, the risk is higher when the 22q11.2 deletion and common polygenic risk factors that contribute to schizophrenia in the general population are both present., (© 2020. The Author(s), under exclusive licence to Springer Nature Limited.)