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BackgroundPathogenic variants (PV) of CTNNA1 are found in families fulfilling criteria for hereditary diffuse gastric cancer (HDGC) but no risk estimates were available until now. The aim of this study is to evaluate diffuse gastric cancer (DGC) risks for carriers of germline CTNNA1 PV.MethodsData from published CTNNA1 families were updated and new families were identified through international collaborations. The cumulative risk of DGC by age for PV carriers was estimated with the genotype restricted likelihood (GRL) method, taking into account non-genotyped individuals and conditioning on all observed phenotypes and genotypes of the index case to obtain unbiased estimates. A non-parametric (NP) and the Weibull functions were used to model the shape of penetrance function with the GRL. Kaplan-Meier incidence curve and standardised incidence ratios were also computed. A ‘leave-one-out’ strategy was used to evaluate estimate uncertainty.ResultsThirteen families with 46 carriers of PV were included. The cumulative risks of DGC at 80 years for carriers of CTNNA1 PV are 49% and 57%, respectively with the Weibull GRL and NP GRL methods. Risk ratios to population incidence reach particularly high values at early ages and decrease with age. At 40 years, they are equal to 65 and 833, respectively with the Weibull GRL and NP GRL.ConclusionThis is the largest series of CTNNA1 families that provides the first risk estimates of GC. These data will help to improve management and surveillance for these patients and support inclusion of CTNNA1 in germline testing panels.

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Background: Developing high yielding varieties is a major challenge for breeders tackling the challenges of climate change in agriculture. The panicle (inflorescence) architecture of rice is one of the key components of yield potential and displays high inter- and intra-specific variability. The genus Oryza features two different crop species: Asian rice Oryza sativa L.) and the African rice O. Glaberrima Steud). One of the main morphological differences between the two independently domesticated species is the structure (or complexity) of the panicle, with O. sativa displaying a highly branched panicle, which in turn produces a larger number of grains than that of O. Glaberrima. The genetic interactions that govern the diversity of panicle complexity within and between the two species are still poorly understood. Results: To identify genetic factors linked to panicle architecture diversity in the two species, we used a set of 60 Chromosome Segment Substitution Lines (CSSLs) issued from third generation backcross (BC3DH) and carrying genomic segments from O. Glaberrima cv. MG12 in the genetic background of O. sativa Tropical Japonica cv. Caiapo. Phenotypic data were collected for rachis and primary branch length, primary, secondary and tertiary branch number and spikelet number. A total of 15 QTLs were localized on chromosomes 1, 2, 3, 7, 11 and 12 and QTLs associated with enhanced secondary and tertiary branch numbers were detected in two CSSLs. Furthermore, BC4F3:5 lines carrying different combinations of substituted segments were produced to decipher the effects of the identified QTL regions on variations in panicle architecture. A detailed analysis of phenotypes versus genotypes was carried out between the two parental genomes within these regions in order to understand how O. Glaberrima introgression events may lead to alterations in panicle traits. Conclusion: Our analysis led to the detection of genomic variations between O. Sativa cv. Caiapo and O. Glaberrima cv. MG12 in regions associated with enhanced panicle traits in specific CSSLs. These regions contain a number of key genes that regulate panicle development in O. Sativa and their interspecific genomic variations may explain the phenotypic effects observed.