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Background: High neonatal mortality rates continue to be a major public health issue in Ethiopia. Despite different maternal and neonatal care interventions, neonatal mortality in Ethiopia is at a steady state. This could be due to the low utilization of neonatal checkups. Thus, nationally assessing the level and predictors of postnatal checkups could provide important information for further improving neonatal healthcare services., Materials and Methods: A secondary data analysis of the 2016 Ethiopia Demographic and Health Survey (EDHS) was performed on 7,586 women who had live births in the 2 years before the survey. All variables with a p -value of ≤0.25 in the bivariable analysis were entered into the final model for multivariable analysis, and the level of statistical significance was declared at a P -value of <0.05., Results: According to the national survey, only 8.3% [95% CI: 8.19, 8.41] of neonates received postnatal checkups. About two-thirds of women, 62.8% had antenatal care visits, 67.9%, gave birth at home, and 95.7% were unaware of neonatal danger signs. Distance from health care institutions [AOR = 1.42; 95% CI: 1.06, 1.89], giving birth in a healthcare facility [AOR = 1.55; 95% CI: 1.12, 2.15], antenatal care visit [AOR = 3.0; 95% CI: 1.99, 4.53], and neonatal danger signs awareness [AOR = 3.06; 95% CI: 2.09, 4.5] were all associated with postnatal care visits., Conclusion: The number of neonates who had a postnatal checkup was low. Increasing antenatal care visit utilization, improving institutional delivery, raising awareness about neonatal danger signs, increasing access to health care facilities, and implementing home-based neonatal care visits by healthcare providers could all help to improve postnatal checkups., 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 Birhane, Bayih, Mekonen, Chanie, Demis, Shimelis, Asferie, Abebe, Addisu, Nibret, Endalamaw, Munye, Jember, Nebiyu, Tiruneh and Belay.)

Breeding for climate-resilient, high-yielding, and nutrient-rich sorghum cultivars is essential for sustainable food systems and enhanced livelihoods in sub-Saharan Africa. Therefore, this study aimed to determine the genetic diversity among East African sorghum germplasm collections through agronomic and nutritional quality traits to select promising lines for direct production or breeding. A collection of 348 sorghum germplasm was field evaluated at two locations in Uganda using an augmented design, and grain iron (Fe) and zinc (Zn) contents were profiled. Data were collected on 20 sorghum agro-morphological traits and Fe and Zn compositions. A significant (P ≤ 0.05) variation was detected amongst the test genotypes for all the assessed traits, suggesting the presence of sufficient genetic diversity for selection. High heritability (H 2 > 0.60) and genetic advance as percent of the mean (GA >20%) were computed for grain yield, Zn content, and selected agronomic traits, ensuring genetic gains through selection. A significant positive correlation was recorded between Fe and Zn concentrations (r = 0.32, P < 0.001), allowing simultaneous selection for the two nutrient compositions. Cluster analysis based on phenotypic traits resolved the test sorghum genotypes into four distinct genetic groups. Six genotypes with superior agronomic traits and high Fe and Zn contents were identified for production or potential parents for quality breeding. Overall, the current study found considerable genetic variation among East African sorghum germplasm collections for strategic conservation and breeding in Uganda or similar agro-ecologies., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s).)

Increased root biomass allocation could serve as a proxy trait for selecting crop ideotypes with drought tolerance and carbon sequestration potential in agricultural soils. The objective of this study was to assess the magnitude of the relationship between root biomass and yield components and to identify influential traits so as to optimise genotype selection for enhanced biomass allocation, drought tolerance and carbon sequestration potential in bread wheat (Triticum aestivum L.). One-hundred wheat genotypes consisting of 10 parents and 90 derived F2 families were evaluated under drought-stressed and non-stressed conditions at two different sites. Data were collected for days to heading (DTH), days to maturity (DTM), plant height, productive tiller number (TN), spike length, spikelets per spike (SPS), kernels per spike (KPS), thousand kernel weight (TKW), shoot biomass, root biomass, total plant biomass (PB), root-to-shoot ratio (RS) and grain yield. There was significant (p < 0.05) genetic variation in most assessed traits, TN and RS being exceptions. Root biomass had significant positive correlations with grain yield under drought-stressed (r = 0.28) and non-stressed (r = 0.41) conditions, but a non-significant correlation was recorded for RS and grain yield. Notably, both root biomass and shoot biomass had significant positive correlations under both water regimes, revealing the potential of increasing both traits with minimal biomass trade-offs. The highest positive direct effects on grain yield were found for KPS and PB under both water regimes. The present study demonstrated that selection based on KPS and PB rather than RS will be more effective in ideotype selection of segregating populations for drought tolerance and carbon sequestration potential.

Wheat production and productivity are challenged by recurrent droughts associated with climate change globally. Drought and heat stress resilient cultivars can alleviate yield loss in marginal production agro-ecologies. The ability of some crop genotypes to thrive and yield in drought conditions is attributable to the inherent genetic variation and environmental adaptation, presenting opportunities to develop drought-tolerant varieties. Understanding the underlying genetic, physiological, biochemical, and environmental mechanisms and their interactions is key critical opportunity for drought tolerance improvement. Therefore, the objective of this review is to document the progress, challenges, and opportunities in breeding for drought tolerance in wheat. The paper outlines the following key aspects: (1) challenges associated with breeding for adaptation to drought-prone environments, (2) opportunities such as genetic variation in wheat for drought tolerance, selection methods, the interplay between above-ground phenotypic traits and root attributes in drought adaptation and drought-responsive attributes and (3) approaches, technologies and innovations in drought tolerance breeding. In the end, the paper summarises genetic gains and perspectives in drought tolerance breeding in wheat. The review will serve as baseline information for wheat breeders and agronomists to guide the development and deployment of drought-adapted and high-performing new-generation wheat varieties.

The cyclin-dependent kinase inhibitor p27 (Kip1) is an important regulator of the G1/S checkpoint. It is degraded by the SCF-SKP2 complex in late G1 thereby allowing cells to progress to the S phase. Here we investigated the role of the E3 ubiquitin ligase RNF6 (Ring Finger Protein 6) in cell cycle progression in prostate cancer cells. Our data demonstrate that RNF6 can promote cell cycle progression by reducing the levels of p27. Knockdown of RNF6 led to an increase in the stability of p27 and to the arrest of cells in the G1 phase. RNF6 interacted with p27 via its KIL domain and this interaction was found to be phosphorylation independent. RNF6 enhanced ubiquitination and subsequent degradation of p27 in the early G0/G1 phase of the cell cycle. Knockdown of RNF6 expression by short hairpin RNA led to inhibition of the CDK2/Cyclin E complex thereby reducing phosphorylation of Retinoblastoma protein (Rb) and to a subsequent decrease in cell cycle progression and proliferation. Our data suggest that RNF6 acts as a negative regulator for p27 kip1 leading to its proteasome-dependent degradation in the early G0/G1 phase of the cell cycle.

Fruit quality traits of sweet watermelon ( Citrullus lanatus var. lanatus ) are crucial for new product development and commercialization. Sweet watermelon fruit quality traits are affected by the compositions of phytochemical compounds, phytohormones, and fruit flesh firmness which are affected by genes, the growing environment and their interaction. These compositions determine fruit ripening, eating quality, and postharvest shelf-life. Knowledge of the genetic profile and analyses of quality traits in watermelon is vital to develop improved cultivars with enhanced nutritional compositions, consumer-preferred traits, and extended storage life. This review aims to present the opportunities and progress made on the genetic analysis of fruit quality traits in watermelon as a guide for quality breeding based on economic and end-user attributes. The first section of the review highlights the genetic mechanisms involved in the biosynthesis of phytochemical compounds (i.e., sugars, carotenoids, amino acids, organic acids, and volatile compounds), phytohormones (i.e., ethylene and abscisic acid) and fruit flesh structural components (i.e., cellulose, hemicellulose, and pectin) elicited during watermelon fruit development and ripening. The second section pinpoints the progress on the development of molecular markers and quantitative trait loci (QTL) analysis for phytochemical compounds, phytohormones and fruit quality attributes. The review presents gene-editing technology and innovations associated with fruit quality traits for selection and accelerated cultivar development. Finally, the paper discussed gene actions conditioning fruit ripening in citron watermelon ( C. lanatus var. citroides [L. H. Bailey] Mansf. ex Greb.) as reference genetic resources to guide current and future breeding. Information presented in this review is useful for watermelon variety design, product profiling and development to serve the diverse value chains of the crop., 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 Mashilo, Shimelis, Ngwepe and Thungo.)

Malnutrition remains one of the major human health issues affecting millions of people in sub-Saharan Africa (SSA). Hence, the objective of this study was to quantify the nutritional and phytochemical compositions of immature pods of pigeonpea genotypes to select promising lines with unique nutritional quality for production and cultivar development. Seven preliminarily tested and identified pigeonpea genotypes were grown under field conditions using a randomized complete block design with three replicates to quantify the nutritional and phytochemical contents in the immature pods. Significant ( P ≤ 0.01) genotype effect was detected for the assessed nutritional and phytochemical compositions. Relatively higher contents of iron (15.53 mg/100g), zinc (1.59 mg/100g), magnesium (114.60 mg/100g) and total flavonoid (8.47 mg CE/g) were present in genotype Ilonga&#95;14m1 ICEAP-0054. Higher compositions of beta-carotene (2.84 mg/100g), total phenolics (20.42 mg GAE/g), and vitamin-C (95.84 mg/100g) were detected in genotypes, Mali ICEAP-00046, PigeonP-3018 and Kiboko ICEAP-00932, respectively. Cluster analysis allocated the tested genotypes into three main groups. Significant ( P ≤ 0.05) positive correlations were recorded among the assessed nutritional and phytochemical compositions that will allow direct and indirect selection of the evaluated genotypes for nutritional and phytochemical quality improvement. The principal component analysis resolved four components that cumulatively explained 76.85% of the total genetic variation in nutritional and phytochemical compositions among the tested genotypes of pigeonpea. Genotype PigeonP-3021 exhibited high levels of beta-carotene and vitamin C, while Kiboko ICEAP-00932 and PigeonP-3018 had high contents of aluminium, iron, phosphorus and total phenolics. Genotype Ilonga&#95;14m1 ICEAP-0054 had high compositions of zinc, potassium, magnesium, copper and calcium. Unique pigeonpea genotypes (i.e., PigeonP-3021, Kiboko ICEAP-00932, and PigeonP-3018) were identified for quality breeding or direct production with promising nutrient profiles for food and nutrition security., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s).)

BRCA2 is essential for homologous recombination DNA repair. BRCA2 mutations lead to genome instability and increased risk of breast and ovarian cancer. Similarly, mutations in BRCA2-interacting proteins are also known to modulate sensitivity to DNA damage agents and are established cancer risk factors. Here we identify the tumor suppressor CDK5RAP3 as a novel BRCA2 helical domain-interacting protein. CDK5RAP3 depletion induced DNA damage resistance, homologous recombination and single-strand annealing upregulation, and reduced spontaneous and DNA damage-induced genomic instability, suggesting that CDK5RAP3 negatively regulates double-strand break repair in the S-phase. Consistent with this cellular phenotype, analysis of transcriptomic data revealed an association between low CDK5RAP3 tumor expression and poor survival of breast cancer patients. Finally, we identified common genetic variations in the CDK5RAP3 locus as potentially associated with breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. Our results uncover CDK5RAP3 as a critical player in DNA repair and breast cancer outcomes.

Background: Watermelons and pumpkins are cultivated in Uganda for their leaves, fruits, and seeds, thereby contributing to food, nutrition and income security. However, there is limited research and information on constraints affecting their production. This study assessed the current production constraints for watermelons and pumpkins, management practices, sources of production inputs to guide research and decision making in production of these crops., Methodology: Watermelon and pumpkin fields totalling 105 located in 28 districts from nine sub-regions of Uganda were surveyed. Purposive sampling was conducted based on the importance and availability of watermelon and pumpkin fields in the sub-regions using a questionnaire administered to farmers on different practices, management strategies, and current production constraints. Data were analysed to determine the relationship between the source of seed, sale of their produce, constraints, and control measures of biotic constraints in the different sub-regions., Results: Pumpkins and watermelons were grown by 85.7% and 14.3% of respondent farmers, respectively. The constraints as ranked by the farmers were pests, diseases, drought, high transport and labour costs. Bacterial wilt, downy mildews, anthracnose powdery mildews and virus diseases in this order were the most common and important disease constraints.The whitefly ( Bemisia tabaci,  Gennadius), order hemiptera family aleyrodidae, aphids ( Myzus Persicae , Sulzer), order hemiptera family aphidadae, melon fly ( Bactrocera cucurbitae, Coquillett), order diptera family tephritidae and cutworm ( Agrotis ipsilon, Hufnagel), order lepidoptera family noctuidae, were reported as the most limiting pests of watermelon and pumpkin production. Mixing of several agrochemicals was observed in watermelon fields coupled with gross lack of knowledge of proper usage or purpose of these chemicals may result in pesticide resistance, health and environmental hazards., Conclusion: Pests, diseases, and drought constitute the main constraints affecting watermelon and pumpkin cultivation in Uganda. Whereas weeding using hand hoes is the most common method of weed control, application of ash was the main strategy for pest management in pumpkin, while in watermelons, pheromone traps and pesticides were frequently used., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2022.)

Despite Rwanda's impressive economic success over the last decade, household food insecurity persists, particularly in rural areas. Empirical evidence is therefore deemed necessary to inform policies addressing food insecurity, hunger and poverty in general. This study examines household food security and its determinants in the rural areas of Southern and Northern provinces of Rwanda. Using cross-sectional data collected from 534 farming households, we estimated household food security status by Food Consumption Score (FCS) and Food Insecurity Experience Scale (FIES) and applied ordered Probit model to identify drivers of household food security. The results indicate that a significant proportion (74.4%) of households had an acceptable FCS, but 36.52% of the farming households experienced moderate and severe food insecurity when assessed with FIES. Ownership of livestock was identified as a key determinant of food security using both metrics, which affirms the importance of combating hunger and food insecurity in Rwanda through their 'one cow per household policy' and recommends that this policy be strengthened.

In warm-humid ago-ecologies of the world, sorghum [Sorghum bicolor (L.) Moench] production is severely affected by anthracnose disease caused by Colletotrichum sublineolum Henn. New sources of anthracnose resistance should be identified to introgress novel genes into susceptible varieties in resistance breeding programs. The objective of this study was to determine genome-wide association of Diversity Arrays Technology Sequencing (DArTseq) based single nucleotide polymorphisms (SNP) markers and anthracnose resistance genes in diverse sorghum populations for resistance breeding. Three hundred sixty-six sorghum populations were assessed for anthracnose resistance in three seasons in western Ethiopia using artificial inoculation. Data on anthracnose severity and the relative area under the disease progress curve were computed. Furthermore, the test populations were genotyped using SNP markers with DArTseq protocol. Population structure analysis and genome-wide association mapping were undertaken based on 11,643 SNPs with <10% missing data. The evaluated population was grouped into eight distinct genetic clusters. A total of eight significant (P < 0.001) marker-trait associations (MTAs) were detected, explaining 4.86-15.9% of the phenotypic variation for anthracnose resistance. Out of which the four markers were above the cutoff point. The significant MTAs in the assessed sorghum population are useful for marker-assisted selection (MAS) in anthracnose resistance breeding programs and for gene and quantitative trait loci (QTL) mapping., Competing Interests: The authors declare that they have no competing interests.

Profiling the genetic composition and relationships among groundnut germplasm collections is essential for the breeding of new cultivars. The objectives of this study were to assess the genetic diversity and population structure among 100 improved groundnut genotypes using agronomic traits and high-density single nucleotide polymorphism (SNP) markers. The genotypes were evaluated for agronomic traits and drought tolerance at the International Crop Research Institute for the Semi-Arid Tropics (ICRISAT)/India across two seasons. Ninety-nine of the test genotypes were profiled with 16363 SNP markers. Pod yield per plant (PY), seed yield per plant (SY), and harvest index (HI) were significantly (p < 0.05) affected by genotype × environment interaction effects. Genotypes ICGV 07222, ICGV 06040, ICGV 01260, ICGV 15083, ICGV 10143, ICGV 03042, ICGV 06039, ICGV 14001, ICGV 11380, and ICGV 13200 ranked top in terms of pod yield under both drought-stressed and optimum conditions. PY exhibited a significant (p ≤ 0.05) correlation with SY, HI, and total biomass (TBM) under both test conditions. Based on the principal component (PC) analysis, PY, SY, HSW, shelling percentage (SHP), and HI were allocated in PC 1 and contributed to the maximum variability for yield under the two water regimes. Hence, selecting these traits could be successful for screening groundnut genotypes under drought-stressed and optimum conditions. The model-based population structure analysis grouped the studied genotypes into three sub-populations. Dendrogram for phenotypic and genotypic also grouped the studied 99 genotypes into three heterogeneous clusters. Analysis of molecular variance revealed that 98% of the total genetic variation was attributed to individuals, while only 2% of the total variance was due to variation among the subspecies. The genetic distance between the Spanish bunch and Virginia bunch types ranged from 0.11 to 0.52. The genotypes ICGV 13189, ICGV 95111, ICGV 14421, and ICGV 171007 were selected for further breeding based on their wide genetic divergence. Data presented in this study will guide groundnut cultivar development emphasizing economic traits and adaptation to water-limited agro-ecologies, including in Ethiopia., Competing Interests: The authors declare no conflict of interest.

To evaluate the racial and ethnic differences in prevalence of germline pathogenic variants (PVs) and the effect of race and ethnicity on breast cancer (BC) risk among carriers, results of multigene testing of 77 900 women with BC (non-Hispanic White [NHW] = 57 003; Ashkenazi-Jewish = 4798; Black = 6722; Hispanic = 5194; and Asian = 4183) were analyzed, and the frequency of PVs in each gene were compared between BC patients (cases) and race- and ethnicity-matched gnomAD reference controls. Compared with NHWs, BRCA1 PVs were enriched in Ashkenazi-Jews and Hispanics, whereas CHEK2 PVs were statistically significantly lower in Blacks, Hispanics, and Asians (all 2-sided P < .05). In case-control studies, BARD1 PVs were associated with high risks (odds ratio > 4.00) of BC in Blacks, Hispanics, and Asians; ATM PVs were associated with increased risk of BC among all races and ethnicities except Asians, whereas CHEK2 and BRIP1 PVs were associated with increased risk of BC among NHWs and Hispanics only. These findings suggest a need for personalized management of BC risk in PV carriers based on race and ethnicity., (© The Author(s) 2020. Published by Oxford University Press.)

Groundnut rust caused by Puccinia arachidis Speg. is a major cause of yield and quality losses in groundnut (Arachis hypogaea L.) in the warm-humid tropics including Tanzania. Breeding and deployment of rust resistant cultivars with farmer-preferred attributes will bolster groundnut production and productivity. The objective of this study was to determine the combining ability effects and gene action controlling rust resistance in groundnut genotypes for breeding. Twelve selected and complementary parental lines were crossed in a diallel design, to develop F 1 progenies, which were advanced to the F 2 for individual plant selection. Thirty-three successful partial crosses and the 12 parents were field evaluated using a 5 × 9 alpha lattice designs with two replications over two seasons in Tanzania. The tested genotypes exhibited significant (P < 0.05) variation for rust resistance, yield and yield-related traits. There existed significant (P < 0.05) difference on the general combining ability (GCA) effect of parents and the specific combining ability (SCA) effect of progeny for the assessed traits indicating that both additive and non-additive gene effects conditioned trait inheritance. The Bakers' ratios indicated that the non-additive gene effects predominantly controlling rust resistance and yield components. This suggested that transgressive segregants could be selected for improved rust resistance and yield gains in the advanced pure line generations. Genotypes ICGV-SM 05570 and ICGV-SM 15567 were the best general combiners for rust resistance and grain yield. The crosses ICGV-SM 16589 × Narinut and ICGV-SM 15557 × ICGV-SM 15559 were identified as the best specific combiners for rust resistance with moderate yield levels and medium maturity. Genotypes with desirable GCA or SCA effects were selected for further breeding., (© 2021. The Author(s).)

Ethiopia is one of the centers of genetic diversity of sesame ( Sesamum indicum L.). The sesame genetic resources present in the country should be explored for local, regional, and international genetic improvement programs to design high-performing and market-preferred varieties. This study's objective was to determine the extent of genetic variation among 100 diverse cultivated sesame germplasm collections of Ethiopia using phenotypic traits and simple sequence repeat (SSR) markers to select distinct and complementary genotypes for breeding. One hundred sesame entries were field evaluated at two locations in Ethiopia for agro-morphological traits and seed oil content using a 10 × 10 lattice design with two replications. Test genotypes were profiled using 27 polymorphic SSR markers at the Oil Crops Research Institute of the Chinese Academy of Agricultural Sciences. Analysis of variance revealed significant ( p ≤ 0.05) entry by environment interaction for plant height, internode length, number of secondary branches, and grain yield. Genotypes such as Hirhir Kebabo Hairless-9, Setit-3, Orofalc ACC-2, Hirhir Humera Sel-6, ABX = 2-01-2, and Setit-1 recorded grain yield of >0.73 ton ha -1 with excellent performance in yield component such as oil yield per hectare. Grain yield had positive and significant ( p < 0.01) associations with oil yield ( r = 0.99), useful for simultaneous selection for yield improvement in sesame. The SSR markers revealed gene diversity and polymorphic information content values of 0.30 and 0.25, respectively, showing that the tested sesame accessions were genetically diverse. Cluster analysis resolved the accessions into two groups, while population structure analysis revealed four major heterotic groups, thus enabling selection and subsequent crossing to develop breeding populations for cultivar development. Based on phenotypic and genomic divergence, the following superior and complementary genotypes: Hirhir Humera Sel-6, Setit-3, Hirhir Kebabo Hairless Sel-4, Hirhir Nigara 1st Sel-1, Humera-1 and Hirhir Kebabo Early Sel-1 (from cluster II-a), Hirhir kebabo hairless-9, NN-0029(2), NN0068-2 and Bawnji Fiyel Kolet, (from cluster II-b). The selected genotypes will serve as parents in the local breeding program in Ethiopia.

The bean fly (Ophiomyia spp) is a key insect pest causing significant crop damage and yield loss in common bean (Phaseolus vulgaris L., 2n = 2x = 22). Development and deployment of agronomic superior and bean fly resistant common bean varieties aredependent on genetic variation and the identification of genes and genomic regions controlling economic traits. This study's objective was to determine the population structure of a diverse panel of common bean genotypes and deduce associations between bean fly resistance and agronomic traits based on single nucleotide polymorphism (SNP) markers. Ninety-nine common bean genotypes were phenotyped in two seasons at two locations and genotyped with 16 565 SNP markers. The genotypes exhibited significant variation for bean fly damage severity (BDS), plant mortality rate (PMR), and pupa count (PC). Likewise, the genotypes showed significant variation for agro-morphological traits such as days to flowering (DTF), days to maturity (DTM), number of pods per plant (NPP), number of seeds per pod (NSP), and grain yield (GYD). The genotypes were delineated into two populations, which were based on the Andean and Mesoamerican gene pools. The genotypes exhibited a minimum membership coefficient of 0.60 to their respective populations. Eighty-three significant (P<0.01) markers were identified with an average linkage disequilibrium of 0.20 at 12Mb across the 11 chromosomes. Three markers were identified, each having pleiotropic effects on two traits: M100049197 (BDS and NPP), M3379537 (DTF and PC), and M13122571 (NPP and GYD). The identified markers are useful for marker-assisted selection in the breeding program to develop common bean genotypes with resistance to bean fly damage., Competing Interests: The authors have declared that no competing interests exist.

Groundnut ( Arachis hypogaea L.) is a multi-purpose legume serving millions of farmers and their value chain actors globally. Use of old poor-performing cultivars contributes to low yields (< 1 t/ha) of groundnut in sub-Saharan Africa including Tanzania. The objectives of this study were to determine the extent of genetic variation among diverse groundnut collections using phenotypic traits and simple sequence repeat (SSR) markers to select distinct and complementary genotypes for breeding. One hundred and nineteen genotypes were evaluated under field conditions for agronomic traits and susceptibility to rust and leaf spot diseases. The study was conducted in two locations across two seasons. In addition, the 119 accessions were profiled with 13 selected SSR markers. Genotype and genotype by environment interaction effects were significant ( p  < 0.05) for days to flowering (DTF), late leaf spot score at 85 and 100 days after planting, pod yield (PDY), kernel yield (KY), hundred seed weight (HSW) and shelling percentage (SP). Principal components analysis revealed that plant stand, KY, SP, NPP (number of pods per plant), late leaf spot and rust disease scores accounted for the largest proportion of the total variation (71.9%) among the tested genotypes. Genotypes ICGV-SM 08587 and ICGV-SM 16579 had the most stable yields across the test environments. Moderate genetic variation was recorded with mean polymorphic information content of 0.34 and gene diversity of 0.63 using the SSR markers. The majority (74%) of genotypes showed high membership coefficients to their respective sub-populations, while 26% were admixtures after structure analysis. Much of the variation (69%) was found within populations due to genotypic differences. The present study identified genotypes ICGV-SM 06737, ICGV-SM 16575, ICG 12725 and ICGV-SM 16608 to be used for development of mapping population, which will be useful for groundnut improvement. This study provided a baseline information on characterization and selection of a large sample of groundnut genotypes in Tanzania for effective breeding and systematic conservation., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Author(s) 2020.)

Knowledge of genetic diversity in plant germplasm and the relationship between genetic factors and phenotypic expression is vital for crop improvement. This study's objectives were to understand the extent of genetic diversity and population structure in 60 common bean genotypes from East and Southern Africa. The common bean genotypes exhibited significant (p<0.05) levels of variability for traits such as days to flowering (DTF), days to maturity (DTM), number of pods per plant (NPP), number of seeds per pod (NSP), and grain yield per hectare in kilograms (GYD). About 47.82 per cent of the variation among the genotypes was explained by seven principal components (PC) associated with the following agronomic traits: NPP, NFF (nodes to first flower), DTF, GH (growth habit) and GYD. The SNP markers revealed mean gene diversity and polymorphic information content values of 0.38 and 0.25, respectively, which suggested the presence of considerable genetic variation among the assessed genotypes. Analysis of molecular variance showed that 51% of the genetic variation were between the gene pools, while 49% of the variation were within the gene pools. The genotypes were delineated into two distinct groups through the population structure, cluster and phylogenetic analyses. Genetically divergent genotypes such as DRK57, MW3915, NUA59, and VTTT924/4-4 with high yield and agronomic potential were identified, which may be useful for common bean improvement., Competing Interests: The authors have declared that no competing interests exist.

Background: The germline cancer predisposition genes associated with increased risk of each clinical subtype of breast cancer, defined by estrogen receptor (ER), progesterone receptor (PR), and HER2, are not well defined., Methods: A total of 54 555 invasive breast cancer patients with 56 480 breast tumors were subjected to clinical hereditary cancer multigene panel testing. Heterogeneity for predisposition genes across clinical breast cancer subtypes was assessed by comparing mutation frequencies by gene among tumor subtypes and by association studies between each tumor subtype and reference controls., Results: Mutations in 15 cancer predisposition genes were detected in 8.6% of patients with ER+/HER2-; 8.9% with ER+/HER2+; 7.7% with ER-/HER2+; and 14.4% of ER-/PR-/HER2- tumors. BRCA1, BRCA2, BARD1, and PALB2 mutations were enriched in ER- and HER2- tumors; RAD51C and RAD51D mutations were enriched in ER- tumors only; TP53 mutations were enriched in HER2+ tumors, and ATM and CHEK2 mutations were enriched in both ER+ and/or HER2+ tumors. All genes were associated with moderate (odds ratio > 2.00) or strong (odds ratio > 5.00) risks of at least one subtype of breast cancer in case-control analyses. Mutations in ATM, BARD1, BRCA1, BRCA2, CHEK2, PALB2, RAD51C, RAD51D, and TP53 had predicted lifetime absolute risks of at least 20.0% for breast cancer., Conclusions: Germline mutations in hereditary cancer panel genes confer subtype-specific risks of breast cancer. Combined tumor subtype, age at breast cancer diagnosis, and family history of breast and/or ovarian cancer information provides refined categorical estimates of mutation prevalence for women considering genetic testing., (© The Author(s) 2020. Published by Oxford University Press.)

Understanding the genetic diversity present amongst crop genotypes is an efficient utilization of germplasm for genetic improvement. The present study was aimed at evaluating genetic diversity and population structure of 48 pigeonpea genotypes from four populations collected from diverse sources. The 48 pigeonpea entries were genotyped using 33 simple sequence repeat (SSR) markers that are polymorphic to assess molecular genetic diversity and genetic relatedness. The informative marker combinations revealed a total of 155 alleles at 33 loci, with an average of 4.78 alleles detected per marker with the mean polymorphic information content (PIC) value of 0.46. Population structure analysis using model based revealed that the germplasm was grouped into two subpopulations. The analysis of molecular variance (AMOVA) revealed that 53.3% of genetic variation existed within individuals. Relatively low population differentiation was recorded amongst the test populations indicated by the mean fixation index (Fst) value of 0.032. The Tanzanian pigeonpea germplasm collection was grouped into three major clusters. The clustering pattern revealed a lack of relationship between geographic origin and genetic diversity. This study provides a foundation for the selection of parental material for genetic improvement.

Background: Productivity of cowpea [Vigna unguiculata (L.) Walp] in sub-Sahara Africa is curtailed by a lack of farmer-preferred and improved cultivars and modern production technologies. The objectives of the study were to determine the extent of genetic diversity present among a collection of cowpea accessions from Zambia and Malawi using phenotypic traits and single nucleotide polymorphism (SNP) markers and, to select distinct and complementary parental lines for cultivar development. One hundred cowpea genotypes were evaluated for agronomic traits in two selected sites in Zambia, using a 10 × 10 alpha lattice design with two replications. Ninety-four of the test genotypes were profiled with 14,116 SNP markers., Results: Number of pods plant - 1 (NPP), pod length (PDL), and number of seeds pod - 1 (NSP), were significantly (p < 0.05) affected by genotype × environment interaction effects. Genotypes such as CP411, CP421, CP645, CP732, Chimponongo, and MS1-8-1-4 exhibited higher grain yield of > 1200 kg/ha with excellent performance in yield components such as NSP, PDL, HSW and GYD. Grain yield had significant (p < 0.05) associations with NPP (r = 0.50), NSP (r = 0.46) and PDL (r = 0.42) useful for simultaneous selection for yield improvement in cowpea. The SNP markers revealed gene diversity and polymorphic information content of 0.22 and 0.17, respectively, showing that the tested cowpea accessions were genetically diverse. Test genotypes were classified into four genetic groups irrespective of source of collection allowing selection and subsequent crosses to develop breeding populations for cultivar development., Conclusions: Genotypes Bubebe, CP411, CP421, CP645, Chimponogo and MS1-8-1-4 were identified to be the most genetically divergent and high yielding making them ideal parental lines for breeding. This study provided a baseline information and identified promising cowpea genetic resources for effective breeding and systematic conservation.

Success in inducing genetic variation through mutagenic agents is dependent on the source and dose of application. The objective of this study was to determine the optimum doses of a single and combined use of gamma radiation and ethylmethane sulfonate (EMS) for effective mutation breeding in sorghum. The study involved two concurrent experiments as follows: in experiment I, the seeds of four sorghum genotypes ('Parbhani Moti', 'Parbhani Shakti', 'ICSV 15013', and 'Macia') were treated using gamma radiation (0, 300, 400, 500 and 600 Gy), EMS (0, 0.5 and 1.0%), and gamma radiation followed by EMS (0 and 300 Gy and 0.1% EMS; 400 Gy and 0.05% EMS). In experiment II, the seeds of two genotypes ('Macia' and 'Red sorghum') were treated with seven doses of gamma radiation only (0, 100, 200, 300, 400, 500 and 600 Gy). Overall, the combined applied doses of gamma radiation and EMS are not recommended due to poor seedling emergence and seedling survival rate below LD 50 . The best dosage of gamma radiation for genotypes Red sorghum, Parbhani Moti, Macia, ICSV 15013 and Parbhani Shakti ranged between 392 and 419 Gy, 311 and 354 Gy, 256 and 355 Gy, 273 and 304 Gy, and 266 and 297 Gy, respectively. The EMS optimum dosage ranges for genotypes Parbhani Shakti, ICSV 15013, Parbhani Moti and Macia were between 0.41% and 0.60%, 0.48% and 0.58%, 0.46% and 0.51%, and 0.36% and 0.45%, respectively. The above dose rates are useful to induce genetic variation in the tested sorghum genotypes for greater mutation events in sorghum breeding programs.

Leaf or brown rust of wheat caused by Puccinia triticina ( Pt ) is one of the most damaging diseases globally. Considerable progress has been made to control leaf rust through crop protection chemicals and host plant resistance breeding in southern Africa. However, frequent changes in the pathogen population still present a major challenge to achieve durable resistance. Disease surveillance and monitoring of the pathogen have revealed the occurrence of similar races across the region, justifying the need for concerted efforts by countries in southern Africa to develop and deploy more efficient and sustainable strategies to manage the disease. Understanding the genetic variability and composition of Pt is a pre-requisite for cultivar release with appropriate resistance gene combinations for sustainable disease management. This review highlights the variability and distribution of the Pt population, and the current control strategies, challenges and future prospects of breeding wheat varieties with durable leaf rust resistance in southern Africa. The importance of regular, collaborative and efficient surveillance of the pathogen and germplasm development across southern Africa is discussed, coupled with the potential of using modern breeding technologies to produce wheat cultivars with durable resistance., (Copyright © 2020 Figlan, Ntushelo, Mwadzingeni, Terefe, Tsilo and Shimelis.)

In silico predictions of missense variants is an important consideration when interpreting variants of uncertain significance (VUS) in the BRCA1 and BRCA2 genes. We trained and evaluated hundreds of machine learning algorithms based on results from validated functional assays to better predict missense variants in these genes as damaging or neutral. This new optimal "BRCA-ML" model yielded a substantially more accurate method than current algorithms for interpreting the functional impact of variants in these genes, making BRCA-ML a valuable addition to data sources for VUS classification., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2020.)

Purpose: Genetic testing of individuals often results in identification of genomic variants of unknown significance (VUS). Multiple lines of evidence are used to help determine the clinical significance of these variants., Methods: We analyzed ~138,000 individuals tested by multigene panel testing (MGPT). We used logistic regression to predict carrier status based on personal and family history of cancer. This was applied to 4644 tested individuals carrying 2383 BRCA1/2 variants to calculate likelihood ratios informing pathogenicity for each. Heterogeneity tests were performed for specific classes of variants defined by in silico predictions., Results: Twenty-two variants labeled as VUS had odds of >10:1 in favor of pathogenicity. The heterogeneity analysis found that among variants in functional domains that were predicted to be benign by in silico tools, a significantly higher proportion of variants were estimated to be pathogenic than previously indicated; that missense variants outside of functional domains should be considered benign; and that variants predicted to create de novo donor sites were also largely benign., Conclusion: The evidence presented here supports the use of personal and family history from MGPT in the classification of VUS and will be integrated into ongoing efforts to provide large-scale multifactorial classification.

Genome wide association studies (GWAS) are important in discerning the genetic architecture of complex traits such as biomass allocation for improving drought tolerance and carbon sequestration potential of wheat. The objectives of this study were to deduce the population structure and marker-trait association for biomass traits in wheat under drought-stressed and non-stressed conditions. A 100-wheat (Triticum aestivum L.) genotype panel was phenotyped for days to heading (DTH), days to maturity (DTM), shoot biomass (SB), root biomass (RB), root to shoot ratio (RS) and grain yield (GY). The panel was sequenced using 15,600 single nucleotide polymorphism (SNPs) markers and subjected to genetic analysis using the compressed mixed linear model (CMLM) at false discovery rate (FDR < 0.05). Population structure analysis revealed six sub-clusters with high membership ancestry coefficient of ≤0.65 to their assigned sub-clusters. A total of 75 significant marker-trait associations (MTAs) were identified with a linkage disequilibrium threshold of 0.38 at 5cM. Thirty-seven of the MTAs were detected under drought-stressed condition and 48% were on the B genome, where most quantitative trait loci (QTLs) for RB, SB and GY were previously identified. There were seven pleiotropic markers for RB and SB that may facilitate simultaneous selection. Thirty-seven putative candidate genes were mined by gene annotation on the IWGSC RefSeq 1.1. The significant MTAs observed in this study will be useful in devising strategies for marker-assisted breeding for simultaneous improvement of drought tolerance and to enhance C sequestration capacity of wheat., Competing Interests: The authors have declared that no competing interests exist.

Enhanced grain yield has been achieved in bread wheat ( Triticum aestivum L.) through development and cultivation of superior genotypes incorporating yield-related agronomic and physiological traits derived from genetically diverse and complementary genetic pool. Despite significant breeding progress, yield levels in wheat have remained relatively low and stagnant under marginal growing environments. There is a need for genetic improvement of wheat using yield-promoting morpho-physiological attributes and desired genotypes under the target production environments to meet the demand for food and feed. This review presents breeding progress in wheat for yield gains using agronomic and physiological traits. Further, the paper discusses globally available wheat genetic resources to identify and select promising genotypes possessing useful agronomic and physiological traits to enhance water, nutrient-, and radiation-use efficiency to improve grain yield potential and tolerance to abiotic stresses (i.e. elevated CO 2 , high temperature, and drought stresses). Finally, the paper highlights quantitative trait loci (QTL) linked to agronomic and physiological traits to aid breeding of high-performing wheat genotypes., (Copyright © 2019 Tshikunde, Mashilo, Shimelis and Odindo.)

Purpose: Several genes on hereditary breast and ovarian cancer susceptibility test panels have not been systematically examined for strength of association with disease. We employed the Clinical Genome Resource (ClinGen) clinical validity framework to assess the strength of evidence between selected genes and breast or ovarian cancer., Methods: Thirty-one genes offered on cancer panel testing were selected for evaluation. The strength of gene-disease relationship was systematically evaluated and a clinical validity classification of either Definitive, Strong, Moderate, Limited, Refuted, Disputed, or No Reported Evidence was assigned., Results: Definitive clinical validity classifications were made for 10/31 and 10/32 gene-disease pairs for breast and ovarian cancer respectively. Two genes had a Moderate classification whereas, 6/31 and 6/32 genes had Limited classifications for breast and ovarian cancer respectively. Contradictory evidence resulted in Disputed or Refuted assertions for 9/31 genes for breast and 4/32 genes for ovarian cancer. No Reported Evidence of disease association was asserted for 5/31 genes for breast and 11/32 for ovarian cancer., Conclusion: Evaluation of gene-disease association using the ClinGen clinical validity framework revealed a wide range of classifications. This information should aid laboratories in tailoring appropriate gene panels and assist health-care providers in interpreting results from panel testing.

Genotype-by-environment interaction analysis is key for selection and cultivar release, and to identify suitable production and test environments. The objective of this study was to determine the magnitude of genotype-by-environment interaction (GEI) for storage root yield, yield-related traits and sweet potato virus disease (SPVD) resistance among candidate sweet potato genotypes in Tanzania. Twenty-three newly bred clones and three check varieties were evaluated across six diverse environments using a randomized complete block design with three replications. The Additive Main Effect and Multiplicative Interaction (AMMI) and genotype and genotype-by-environment (GGE) biplot analyses were used to determine GEI of genotypes. Genotype, environment and GEI effects were highly significant ( P ≤ 0.01) for the assessed traits. Further, AMMI analysis of variance revealed highly significant ( P ≤ 0.001) differences among genotypes, environments and G × E interaction effects for all the studied traits. Both AMMI and GGE biplot analyses identified the following promising genotypes: G2 (Resisto × Ukerewe), G3 (Ukerewe × Ex-Msimbu-1), G4 (03-03 x SPKBH008), G12 (Ukerewe × SPKBH008) and G18 (Resisto × Simama) with high yields, high dry matter content and SPVD resistance across all test environments. The candidate genotypes are recommended for further stability tests and release in Tanzania or similar environments.

Background: Increased risk of malignancies other than pancreatic cancer (PC) has been reported among first-degree relatives (FDRs) of PC patients; however, the roles of susceptibility gene mutations are unclear. We assessed risk for 15 cancers among FDRs of unselected PC probands., Methods: Data on 17 162 FDRs, with more than 336 000 person-years at risk, identified through 2305 sequential PC probands enrolled at Mayo Clinic (2000-2016) were analyzed. Family history data were provided by the probands. Standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated, comparing malignancies observed among the FDRs with that expected using Surveillance, Epidemiology, and End Results (SEER) data. Genetic testing was performed among a subset of probands (n = 2094), enabling stratified analyses among FDRs based on whether the related proband tested positive or negative for inherited mutation in 22 sequenced cancer susceptibility genes. All statistical tests were two-sided., Results: Compared with SEER, PC risk was twofold higher among FDRs of PC probands (SIR = 2.04, 95% CI = 1.78 to 2.31, P < .001). Primary liver cancer risk was elevated among female FDRs (SIR = 2.10, 95% CI = 1.34 to 3.12, P < .001). PC risk was more elevated among FDRs of mutation-positive probands (SIR = 4.32, 95% CI = 3.10 to 5.86) than FDRs of mutation-negative probands (SIR = 1.77, 95% CI = 1.51 to 2.05, between-group P < .001). FDR PC risk was higher when the related proband was younger than age 60 years at diagnosis and mutation-positive (SIR = 5.24, 95% CI = 2.93 to 8.64) than when the proband was younger than age 60 years but mutation-negative (SIR = 1.76, 95% CI = 1.21 to 2.47, between-group P < .001). Breast (SIR = 1.29, 95% CI = 1.01 to 1.63) and ovarian (SIR = 2.38, 95% CI = 1.30 to 4.00) cancers were elevated among FDRs of mutation-positive probands., Conclusions: Our study substantiates twofold risk of PC among FDRs of PC patients and suggests increased risk for primary liver cancer among female FDRs. FDRs of susceptibility mutation carriers had substantially increased risk for PC and increased risk for breast and ovarian cancers., (© The Author(s) 2018. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purpose: To improve methods for predicting the impact of missense variants of uncertain significance (VUS) in BRCA1 and BRCA2 on protein function., Methods: Functional data for 248 BRCA1 and 207 BRCA2 variants from assays with established high sensitivity and specificity for damaging variants were used to recalibrate 40 in silico algorithms predicting the impact of variants on protein activity. Additional random forest (RF) and naïve voting method (NVM) metapredictors for both BRCA1 and BRCA2 were developed to increase predictive accuracy., Results: Optimized thresholds for in silico prediction models significantly improved the accuracy of predicted functional effects for BRCA1 and BRCA2 variants. In addition, new BRCA1-RF and BRCA2-RF metapredictors showed area under the curve (AUC) values of 0.92 (95% confidence interval [CI]: 0.88-0.96) and 0.90 (95% CI: 0.84-0.95), respectively. Similarly, the BRCA1-NVM and BRCA2-NVM models had AUCs of 0.93 and 0.90. The RF and NVM models were used to predict the pathogenicity of all possible missense variants in BRCA1 and BRCA2., Conclusion: The recalibrated algorithms and new metapredictors significantly improved upon current models for predicting the impact of variants in cancer risk-associated domains of BRCA1 and BRCA2. Prediction of the functional impact of all possible variants in BRCA1 and BRCA2 provides important information about the clinical relevance of variants in these genes.

Purpose BRCA1/2 mutations are frequent in patients with triple-negative breast cancer (TNBC). These patients are often treated with primary systemic chemotherapy. The aim of this study was to analyze the effects of BRCA1/2 mutations on pathologic complete response (pCR) and disease-free survival (DFS) in a cohort of patients with TNBC treated with anthracycline and taxane-containing chemotherapy, with or without bevacizumab. Patients and Methods Germline DNA was sequenced to identify mutations in BRCA1 and BRCA2 in 493 patients with TNBC from the GeparQuinto study. The pCR rates were compared in patients with and without mutation, as well as in patients treated with and without bevacizumab. In addition, the influence of BRCA1/2 mutation status and pCR status on DFS was evaluated relative to treatment. Results BRCA1/2 mutations were detected in 18.3% of patients with TNBC. Overall, patients with mutations had a pCR rate of 50%, compared with 31.5% in patients without a mutation (odds ratio [OR], 2.17; 95% CI, 1.37 to 3.46; P = .001). The pCR rate among patients treated with bevacizumab was 61.5% for BRCA1/2 mutation carriers and 35.6% for those without mutations (OR, 2.90; 95% CI, 1.43 to 5.89; P = .004). pCR was a strong predictor of DFS for patients without BRCA1/2 mutations (hazard ratio, 0.18; 95% CI, 0.11 to 0.31) but not for patients with BRCA1/2 mutations (hazard ratio, 0.74; 95% CI, 0.32 to 1.69). Conclusion The addition of bevacizumab may increase the pCR after standard neoadjuvant chemotherapy for patients with TNBC with BRCA1/2 mutations. In patients treated with anthracycline and taxane-based chemotherapy (with or without bevacizumab), pCR was a weaker predictor of DFS for BRCA1/2 mutation carriers than for patients without mutations.

Background: Germline genetic testing with hereditary cancer gene panels can identify women at increased risk of breast cancer. However, those at increased risk of triple-negative (estrogen receptor-negative, progesterone receptor-negative, human epidermal growth factor receptor-negative) breast cancer (TNBC) cannot be identified because predisposition genes for TNBC, other than BRCA1, have not been established. The aim of this study was to define the cancer panel genes associated with increased risk of TNBC., Methods: Multigene panel testing for 21 genes in 8753 TNBC patients was performed by a clinical testing laboratory, and testing for 17 genes in 2148 patients was conducted by a Triple Negative Breast Cancer Consortium (TNBCC) of research studies. Associations between deleterious mutations in cancer predisposition genes and TNBC were evaluated using results from TNBC patients and reference controls., Results: Germline pathogenic variants in BARD1, BRCA1, BRCA2, PALB2, and RAD51D were associated with high risk (odds ratio > 5.0) of TNBC and greater than 20% lifetime risk for overall breast cancer among Caucasians. Pathogenic variants in BRIP1, RAD51C, and TP53 were associated with moderate risk (odds ratio > 2) of TNBC. Similar trends were observed for the African American population. Pathogenic variants in these TNBC genes were detected in 12.0% (3.7% non-BRCA1/2) of all participants., Conclusions: Multigene hereditary cancer panel testing can identify women with elevated risk of TNBC due to mutations in BARD1, BRCA1, BRCA2, PALB2, and RAD51D. These women can potentially benefit from improved screening, risk management, and cancer prevention strategies. Patients with mutations may also benefit from specific targeted therapeutic strategies., (© The Author(s) 2018. Published by Oxford University Press.)

Importance: Individuals genetically predisposed to pancreatic cancer may benefit from early detection. Genes that predispose to pancreatic cancer and the risks of pancreatic cancer associated with mutations in these genes are not well defined., Objective: To determine whether inherited germline mutations in cancer predisposition genes are associated with increased risks of pancreatic cancer., Design, Setting, and Participants: Case-control analysis to identify pancreatic cancer predisposition genes; longitudinal analysis of patients with pancreatic cancer for prognosis. The study included 3030 adults diagnosed as having pancreatic cancer and enrolled in a Mayo Clinic registry between October 12, 2000, and March 31, 2016, with last follow-up on June 22, 2017. Reference controls were 123 136 individuals with exome sequence data in the public Genome Aggregation Database and 53 105 in the Exome Aggregation Consortium database., Exposures: Individuals were classified based on carrying a deleterious mutation in cancer predisposition genes and having a personal or family history of cancer., Main Outcomes and Measures: Germline mutations in coding regions of 21 cancer predisposition genes were identified by sequencing of products from a custom multiplex polymerase chain reaction-based panel; associations of genes with pancreatic cancer were assessed by comparing frequency of mutations in genes of pancreatic cancer patients with those of reference controls., Results: Comparing 3030 case patients with pancreatic cancer (43.2% female; 95.6% non-Hispanic white; mean age at diagnosis, 65.3 [SD, 10.7] years) with reference controls, significant associations were observed between pancreatic cancer and mutations in CDKN2A (0.3% of cases and 0.02% of controls; odds ratio [OR], 12.33; 95% CI, 5.43-25.61); TP53 (0.2% of cases and 0.02% of controls; OR, 6.70; 95% CI, 2.52-14.95); MLH1 (0.13% of cases and 0.02% of controls; OR, 6.66; 95% CI, 1.94-17.53); BRCA2 (1.9% of cases and 0.3% of controls; OR, 6.20; 95% CI, 4.62-8.17); ATM (2.3% of cases and 0.37% of controls; OR, 5.71; 95% CI, 4.38-7.33); and BRCA1 (0.6% of cases and 0.2% of controls; OR, 2.58; 95% CI, 1.54-4.05)., Conclusions and Relevance: In this case-control study, mutations in 6 genes associated with pancreatic cancer were found in 5.5% of all pancreatic cancer patients, including 7.9% of patients with a family history of pancreatic cancer and 5.2% of patients without a family history of pancreatic cancer. Further research is needed for replication in other populations.

Microarray-based markers such as Diversity Arrays Technology (DArT) have become the genetic markers of choice for construction of high-density maps, quantitative trait loci (QTL) mapping and genetic diversity analysis based on their efficiency and low cost. More recently, the DArT technology was further developed in combination with high-throughput next-generation sequencing (NGS) technologies to generate the DArTseq platform representing a new sequencing tool of complexity-reduced representations. In this study, we used DArTseq markers to investigate genetic diversity and genome-wide association studies (GWAS) of grain quality traits in rice (Oryza sativa L.). The study was performed using 59 rice genotypes with 525 SNPs derived from DArTseq platform. Population structure analysis revealed only two distinct genetic clusters where genotypes were grouped based on environmental adaptation and pedigree information. Analysis of molecular variance indicated a low degree of differentiation among populations suggesting the need for broadening the genetic base of the current germplasm collection. GWAS revealed 22 significant associations between DArTseq-derived SNP markers and rice grain quality traits in the test genotypes. In general, 2 of the 22 significant associations were in chromosomal regions where the QTLs associated with the given traits had previously been reported, the other 20 significant SNP marker loci were indicative of the likelihood discovery of novel alleles associated with rice grain quality traits. DArTseq-derived SNP markers that include SNP12&#95;100006178, SNP13&#95;3052560 and SNP14&#95;3057360 individually co-localised with two functional gene groups that were associated with QTLs for grain width and grain length to width ratio on chromosome 3, indicating trait dependency or pleiotropic-effect loci. This study demonstrated that DArTseq markers were useful genomic resources for genome-wide association studies of rice grain quality traits to accelerate varietal development and release., Competing Interests: The authors have declared that no competing interests exist.

Gene-panel sequencing allows comprehensive analysis of multiple genes simultaneously and is now routinely used in clinical mutation testing of high-risk breast and ovarian cancer patients. However, only BRCA1 and BRCA2 are often analyzed also for large genomic changes. Here, we have analyzed 10 clinically relevant susceptibility genes in 95 breast or ovarian cancer patients with gene-panel sequencing including also copy number variants (CNV) analysis for genomic changes. We identified 12 different pathogenic BRCA1, BRCA2, TP53, PTEN, CHEK2, or RAD51C mutations in 18 of 95 patients (19%). BRCA1/2 mutations were observed in 8 patients (8.4%) and CHEK2 protein-truncating mutations in 7 patients (7.4%). In addition, we identified a novel duplication encompassing most of the RAD51C gene. We further genotyped the duplication in breast or ovarian cancer families (n = 1149), in unselected breast (n = 1729) and ovarian cancer cohorts (n = 553), and in population controls (n = 1273). Seven additional duplication carries were observed among cases but none among controls. The duplication associated with ovarian cancer risk (3/590 of all ovarian cancer patients, 0.5%, P = .032 compared with controls) and was found to represent a large fraction of all identified RAD51C mutations in the Finnish population. Our data emphasizes the importance of comprehensive mutation analysis including CNV detection in all the relevant genes., (© 2017 The Authors. Clinical Genetics published by John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Many variants of uncertain significance (VUS) have been identified in BRCA2 through clinical genetic testing. VUS pose a significant clinical challenge because the contribution of these variants to cancer risk has not been determined. We conducted a comprehensive assessment of VUS in the BRCA2 C-terminal DNA binding domain (DBD) by using a validated functional assay of BRCA2 homologous recombination (HR) DNA-repair activity and defined a classifier of variant pathogenicity. Among 139 variants evaluated, 54 had ?99% probability of pathogenicity, and 73 had ?95% probability of neutrality. Functional assay results were compared with predictions of variant pathogenicity from the Align-GVGD protein-sequence-based prediction algorithm, which has been used for variant classification. Relative to the HR assay, Align-GVGD significantly (p < 0.05) over-predicted pathogenic variants. We subsequently combined functional and Align-GVGD prediction results in a Bayesian hierarchical model (VarCall) to estimate the overall probability of pathogenicity for each VUS. In addition, to predict the effects of all other BRCA2 DBD variants and to prioritize variants for functional studies, we used the endoPhenotype-Optimized Sequence Ensemble (ePOSE) algorithm to train classifiers for BRCA2 variants by using data from the HR functional assay. Together, the results show that systematic functional assays in combination with in silico predictors of pathogenicity provide robust tools for clinical annotation of BRCA2 VUS., (Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Angular leaf spot (ALS) caused by Pseudocercospora griseola is among the devastating diseases of common bean (Phaseolus vulgaris L.) in the Southern Highlands of Tanzania (SHT). This study was conducted to assess the agronomic performance and economics of yield loss associated with the disease on five bean cultivars that are widely grown by farmers. The cultivars were evaluated in a split plot design with a randomized complete block arrangement during 2012/2013 and 2013/2014. The main plots were two rates of fungicide and a control whereas the subplots consisted of cultivars. Data were collected on disease severity, yield, and yield components. Analysis of variance was done and marginal rate of returns determined using partial budget. Results indicated significant decrease in yields, number of pods, seeds, and seed weight at P < 0.05 for untreated plots. Decreases in yield were associated with ALS disease severity that in turn was influenced by cultivar and rate of fungicide used. Higher grain yield losses of as much as 61% and the lowest marginal rate of returns were recorded for unsprayed plots during heavy rains. Fungicide usage at the recommended rates should be considered during heavy rains and breeding for resistance should be taken as an economical and sustainable strategy for managing the disease.

Purpose: The relevance of inherited pathogenic mutations in cancer predisposition genes in pancreatic cancer is not well understood. We aimed to assess the characteristics of patients with pancreatic cancer referred for hereditary cancer genetic testing and to estimate the risk of pancreatic cancer associated with mutations in panel-based cancer predisposition genes in this high-risk population., Methods: Patients with pancreatic cancer (N = 1,652) were identified from a 140,000-patient cohort undergoing multigene panel testing of predisposition genes between March 2012 and June 2016. Gene-level mutation frequencies relative to Exome Aggregation Consortium and Genome Aggregation Database reference controls were assessed., Results: The frequency of germline cancer predisposition gene mutations among patients with pancreatic cancer was 20.73%. Mutations in ATM, BRCA2, CDKN2A, MSH2, MSH6, PALB2, and TP53 were associated with high pancreatic cancer risk (odds ratio, > 5), and mutations in BRCA1 were associated with moderate risk (odds ratio, > 2). In a logistic regression model adjusted for age at diagnosis and family history of cancer, ATM and BRCA2 mutations were associated with personal history of breast or pancreatic cancer, whereas PALB2 mutations were associated with family history of breast or pancreatic cancer., Conclusion: These findings provide insight into the spectrum of mutations expected in patients with pancreatic cancer referred for cancer predisposition testing. Mutations in eight genes confer high or moderate risk of pancreatic cancer and may prove useful for risk assessment for pancreatic and other cancers. Family and personal histories of breast cancer are strong predictors of germline mutations., Competing Interests: AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO’s conflict of interest policy, please refer to www.asco.org/rwcorascopubs.org/po/author-center. Chunling Hu No relationship to disclose Holly LaDuca Employment: Ambry Genetics Stock and Other Ownership Interests: Ambry Genetics Hermela Shimelis No relationship to disclose Eric C. Polley Research Funding: GRAIL Jenna Lilyquist No relationship to disclose Steven N. Hart No relationship to disclose Jie Na No relationship to disclose Abigail Thomas No relationship to disclose Kun y. Lee No relationship to disclose Brigette Tippin Davis Employment: Ambry Genetics Stock and Other Ownership Interests: Ambry Genetics Research Funding: Ambry Genetics (Inst) Travel, Accommodations, Expenses: Ambry Genetics Mary Helen Black Employment: Ambry Genetics Research Funding: Ambry Genetics Travel, Accommodations, Expenses: Ambry Genetics Tina Pesaran Employment: Ambry Genetics Stock and Other Ownership Interests: Ambry Genetics Travel, Accommodations, Expenses: Ambry Genetics David E. Goldgar No relationship to disclose Jill S. Dolinsky Employment: Ambry Genetics Fergus J. Couch Consulting or Advisory Role: AstraZeneca Research Funding: GRAIL Other Relationship: Ambry Genetics

Most common breast cancer susceptibility variants have been identified through genome-wide association studies (GWAS) of predominantly estrogen receptor (ER)-positive disease. We conducted a GWAS using 21,468 ER-negative cases and 100,594 controls combined with 18,908 BRCA1 mutation carriers (9,414 with breast cancer), all of European origin. We identified independent associations at P < 5 × 10 -8 with ten variants at nine new loci. At P < 0.05, we replicated associations with 10 of 11 variants previously reported in ER-negative disease or BRCA1 mutation carrier GWAS and observed consistent associations with ER-negative disease for 105 susceptibility variants identified by other studies. These 125 variants explain approximately 16% of the familial risk of this breast cancer subtype. There was high genetic correlation (0.72) between risk of ER-negative breast cancer and breast cancer risk for BRCA1 mutation carriers. These findings may lead to improved risk prediction and inform further fine-mapping and functional work to better understand the biological basis of ER-negative breast cancer.

Objectives: Given the lack of adequate screening modalities, knowledge of ovarian cancer risks for carriers of pathogenic alterations in predisposition genes is important for decisions about risk-reduction by salpingo-oophorectomy. We sought to determine which genes assayed on multi-gene panels are associated with ovarian cancer, the magnitude of the associations, and for which clinically meaningful associations could be ruled out., Methods: 7768 adult ovarian cancer cases of European ancestry referred to a single clinical testing laboratory underwent multi-gene panel testing for detection of pathogenic alterations in known or suspected ovarian cancer susceptibility genes. A targeted capture approach was employed to assay each of 19 genes for the presence of pathogenic or likely pathogenic alterations. Mutation frequencies in ovarian cancer cases were compared to mutation frequencies in individuals from the Exome Aggregation Consortium (ExAC). Analyses stratified by family and personal history of other cancers and age at diagnosis were also performed., Results: Significant associations (p<0.001) were identified between alterations in 11 genes and ovarian cancer, with eight of these displaying ≥5-fold increased risk (BRCA1, BRCA2, BRIP1, MSH2, MSH6, RAD51C, RAD51D). Relative risks of ovarian cancer greater than two-fold were also observed for ATM, but could reliably be ruled out for RAD50 and CHEK2., Conclusions: These results will inform clinical management of women found to carry pathogenic alterations in genes tested on multi-gene panels. The knowledge that some genes are not associated with OC can reduce concerns of women found to carry pathogenic alterations in those genes., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Importance: Germline pathogenic variants in BRCA1 and BRCA2 predispose to an increased lifetime risk of breast cancer. However, the relevance of germline variants in other genes from multigene hereditary cancer testing panels is not well defined., Objective: To determine the risks of breast cancer associated with germline variants in cancer predisposition genes., Design, Setting, and Participants: A study population of 65 057 patients with breast cancer receiving germline genetic testing of cancer predisposition genes with hereditary cancer multigene panels. Associations between pathogenic variants in non-BRCA1 and non-BRCA2 predisposition genes and breast cancer risk were estimated in a case-control analysis of patients with breast cancer and Exome Aggregation Consortium reference controls. The women underwent testing between March 15, 2012, and June 30, 2016., Main Outcomes and Measures: Breast cancer risk conferred by pathogenic variants in non-BRCA1 and non-BRCA2 predisposition genes., Results: The mean (SD) age at diagnosis for the 65 057 women included in the analysis was 48.5 (11.1) years. The frequency of pathogenic variants in 21 panel genes identified in 41 611 consecutively tested white women with breast cancer was estimated at 10.2%. After exclusion of BRCA1, BRCA2, and syndromic breast cancer genes (CDH1, PTEN, and TP53), observed pathogenic variants in 5 of 16 genes were associated with high or moderately increased risks of breast cancer: ATM (OR, 2.78; 95% CI, 2.22-3.62), BARD1 (OR, 2.16; 95% CI, 1.31-3.63), CHEK2 (OR, 1.48; 95% CI, 1.31-1.67), PALB2 (OR, 7.46; 95% CI, 5.12-11.19), and RAD51D (OR, 3.07; 95% CI, 1.21-7.88). Conversely, variants in the BRIP1 and RAD51C ovarian cancer risk genes; the MRE11A, RAD50, and NBN MRN complex genes; the MLH1 and PMS2 mismatch repair genes; and NF1 were not associated with increased risks of breast cancer., Conclusions and Relevance: This study establishes several panel genes as high- and moderate-risk breast cancer genes and provides estimates of breast cancer risk associated with pathogenic variants in these genes among individuals qualifying for clinical genetic testing.

Recurrent drought and late blight disease are the major factors limiting potato productivity in the northwest Ethiopian highlands. Incorporating drought tolerance and late blight resistance in the same genotypes will enable the development of cultivars with high and stable yield potential under erratic rainfall conditions. The objectives of this study were to assess combining ability effects and gene action for tuber yield and traits related to drought tolerance in the International Potato Centre's (CIP's) advanced clones from the late blight resistant breeding population B group 'B3C2' and to identify promising parents and families for cultivar development. Sixteen advanced clones from the late blight resistant breeding population were crossed in two sets using the North Carolina Design II. The resulting 32 families were evaluated together with five checks and 12 parental clones in a 7 x 7 lattice design with two water regimes and two replications. The experiment was carried out at Adet, in northwest Ethiopia under well-watered and water stressed conditions with terminal drought imposed from the tuber bulking stage. The results showed highly significant differences between families, checks, and parents for growth, physiological, and tuber yield related traits. Traits including marketable tuber yield, marketable tuber number, average tuber weight and groundcover were positively correlated with total tuber yield under both drought stressed and well-watered conditions. Plant height was correlated with yield only under drought stressed condition. GCA was more important than SCA for total tuber yield, marketable tuber yield, average tuber weight, plant height, groundcover, and chlorophyll content under stress. This study identified the parents with best GCA and the combinations with best SCA effects, for both tuber yield and drought tolerance related traits. The new population is shown to be a valuable genetic resource for variety selection and improvement of potato's adaptation to the drought prone areas in northwest Ethiopia and similar environments.

Breast cancer risks conferred by many germline missense variants in the BRCA1 and BRCA2 genes, often referred to as variants of uncertain significance (VUS), have not been established. In this study, associations between 19 BRCA1 and 33 BRCA2 missense substitution variants and breast cancer risk were investigated through a breast cancer case-control study using genotyping data from 38 studies of predominantly European ancestry (41,890 cases and 41,607 controls) and nine studies of Asian ancestry (6,269 cases and 6,624 controls). The BRCA2 c.9104A>C, p.Tyr3035Ser (OR = 2.52; P = 0.04), and BRCA1 c.5096G>A, p.Arg1699Gln (OR = 4.29; P = 0.009) variant were associated with moderately increased risks of breast cancer among Europeans, whereas BRCA2 c.7522G>A, p.Gly2508Ser (OR = 2.68; P = 0.004), and c.8187G>T, p.Lys2729Asn (OR = 1.4; P = 0.004) were associated with moderate and low risks of breast cancer among Asians. Functional characterization of the BRCA2 variants using four quantitative assays showed reduced BRCA2 activity for p.Tyr3035Ser compared with wild-type. Overall, our results show how BRCA2 missense variants that influence protein function can confer clinically relevant, moderately increased risks of breast cancer, with potential implications for risk management guidelines in women with these specific variants. Cancer Res; 77(11); 2789-99. ©2017 AACR ., (©2017 American Association for Cancer Research.)

This study determined the population structure and genome-wide marker-trait association of agronomic traits of wheat for drought-tolerance breeding. Ninety-three diverse bread wheat genotypes were genotyped using the Diversity Arrays Technology sequencing (DArTseq) protocol. The number of days-to-heading (DTH), number of days-to-maturity (DTM), plant height (PHT), spike length (SPL), number of kernels per spike (KPS), thousand kernel weight (TKW) and grain yield (GYLD), assessed under drought-stressed and non-stressed conditions, were considered for the study. Population structure analysis and genome-wide association mapping were undertaken based on 16,383 silico DArTs loci with < 10% missing data. The population evaluated was grouped into nine distinct genetic structures. Inter-chromosomal linkage disequilibrium showed the existence of linkage decay as physical distance increased. A total of 62 significant (P < 0.001) marker-trait associations (MTAs) were detected explaining more than 20% of the phenotypic variation observed under both drought-stressed and non-stressed conditions. Significant (P < 0.001) MTA event(s) were observed for DTH, PHT, SPL, SPS, and KPS; under both stressed and non-stressed conditions, while additional significant (P < 0.05) associations were observed for TKW, DTM and GYLD under non-stressed condition. The MTAs reported in this population could be useful to initiate marker-assisted selection (MAS) and targeted trait introgression of wheat under drought-stressed and non-stressed conditions, and for fine mapping and cloning of the underlying genes and QTL.

Lentil is a poor competitor of weeds and its sensitivity to herbicides is a major hurdle for large scale production. The present study was conducted to select herbicide resistant lentil genotypes through seed mutagenesis. Seeds of three advanced lentil genotypes (LPP 11001, LPP 11100 and LPP 11116) were treated with two different concentrations of ethyl methanesulfonate (EMS; 0.1 and 0.2%), hydrazine hydrate (HH; 0.02 and 0.03%) and sodium azide (SA; 0.01 and 0.02%) to develop M1 seed. The M2 was screened against two herbicides including Ally Max 28.6% SG (X = 34.58 g/ha and 1.5X = 51.87 g/ha) and Atlantis 3.6% WG (X = 395.2 g/ha and 1.5X = 592.8 g/ha) using the following three screening methods: post plant emergence (PPE), pre-plant incorporation (PPI) and seed priming (SP). Data were recorded on survival index and survival percentage from each experimental unit of every population. Plants in all populations were categorized following their reaction to herbicides. The newly developed populations showed greater variation for herbicide resistance when compared to their progenitors. Phenotypic traits were significantly reduced in all the screening environments. Overall, 671 herbicide resistant mutants were selected from all testing environments. The seeds from selected plants were re-mutagenized at 150 Gy of gamma radiation and evaluated against higher dose of herbicides. This allowed selection of 134 herbicide resistant mutants. The selected mutants are useful germplasm for herbicide resistance breeding of lentil., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Genetic predisposition to male breast cancer (MBC) is not well understood. The aim of this study was to better define the predisposition genes contributing to MBC and the utility of germline multi-gene panel testing (MGPT) for explaining the etiology of MBCs., Methods: Clinical histories and molecular results were retrospectively reviewed for 715 MBC patients who underwent MGPT from March 2012 to June 2016., Results: The detection rate of MGPT was 18.1% for patients tested for variants in 16 breast cancer susceptibility genes and with no prior BRCA1/2 testing. BRCA2 and CHEK2 were the most frequently mutated genes (11.0 and 4.1% of patients with no prior BRCA1/2 testing, respectively). Pathogenic variants in BRCA2 [odds ratio (OR) = 13.9; p = 1.92 × 10 -16 ], CHEK2 (OR = 3.7; p = 6.24 × 10 -24 ), and PALB2 (OR = 6.6, p = 0.01) were associated with significantly increased risks of MBC. The average age at diagnosis of MBC was similar for patients with (64 years) and without (62 years) pathogenic variants. CHEK2 1100delC carriers had a significantly lower average age of diagnosis (n = 7; 54 years) than all others with pathogenic variants (p = 0.03). No significant differences were observed between history of additional primary cancers (non-breast) and family history of male breast cancer for patients with and without pathogenic variants. However, patients with pathogenic variants in BRCA2 were more likely to have a history of multiple primary breast cancers., Conclusion: These data suggest that all MBC patients regardless of age of diagnosis, history of multiple primary cancers, or family history of MBC should be offered MGPT., Competing Interests: Mary Pritzlaff, Pia Summerour, Shuwei Li, Patrick Reineke, Jill S. Dolinsky, Rachel McFarland, and Holly LaDuca are employees of Ambry Genetics. Jill S. Dolinsky and Elizabeth Chao are stock holders of Ambry Genetics. The other authors have nothing to disclose. Ethical Approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study formal consent is not required. The research presented here complies with the current laws of the United States of America. Research involving human and animal rights This article does not contain any studies with animals performed by any of the authors.

Knowledge on gene action and trait expression are important for effective breeding. The objective of this study was to determine the general combining ability (GCA), specific combining ability (SCA), maternal effects and heritability of drought tolerance, yield and yield components of candidate sweetpotato clones. Twelve genotypes selected for their high yield, dry matter content or drought tolerance were crossed using a full diallel mating design. Families were field evaluated at Masoro, Karama, and Rubona Research Stations of Rwanda Agriculture Board. Success rate of crosses varied from 1.8 to 62.5% with a mean of 18.8%. Family by site interaction had significant effect ( P < 0.01) on storage root and vine yields, total biomass and dry matter content of storage roots. The family effects were significant ( P < 0.01) for all parameters measured. Broad sense heritability estimates were 0.95, 0.84, 0.68, 0.47, 0.74, 0.75, 0.50, and 0.58 for canopy temperature (CT), canopy wilting (CW), root yield, skin color, flesh color, dry matter content, vine yield and total biomass, respectively. The GCA effects of parents and SCA effects of crosses were significant ( P < 0.01) for CT, CW, storage root, vine and biomass yields, and dry matter content of storage root. The ratio of GCA/SCA effects for CT, CW, yield of storage roots and dry matter content of storage roots were higher than 50%, suggesting the preponderance of additive over non-additive gene action in the expression of these traits. Maternal effects were significant ( P < 0.05) among families for CT, CW, flesh color and dry matter content, vine yield and total biomass. Across sites, the best five selected families with significant SCA effects for storage root yield were, Nsasagatebo × Otada 24, Otada 24 × Ukerewe, 4-160 × Nsasagatebo, K513261 × 2005-034 and Ukerewe × K513261 with 11.0, 9.7, 9.3, 9.2, 8.6 t/ha, respectively. The selected families are valuable genetic resources for sweetpotato breeding for drought tolerance, yield and yield components in Rwanda or similar environments.