BRCA1 frameshift variants leading to extended incorrect protein C termini.

Carriers of BRCA1 germline pathogenic variants are at substantially higher risk of developing breast and ovarian cancer than the general population. Accurate identification of at-risk individuals is crucial for risk stratification and the implementation of targeted preventive and therapeutic interventions. Despite significant progress in variant classification efforts, a sizable portion of reported BRCA1 variants remain as variants of uncertain clinical significance (VUSs). Variants leading to premature protein termination and loss of essential functional domains are typically classified as pathogenic. However, the impact of frameshift variants that result in an extended incorrect terminus is not clear. Using validated functional assays, we conducted a systematic functional assessment of 17 previously reported BRCA1 extended incorrect terminus variants (EITs) and concluded that 16 constitute loss-of-function variants. This suggests that most EITs are likely to be pathogenic. However, one variant, c.5578dup, displayed a protein expression level, affinity to known binding partners, and activity in transcription and homologous recombination assays comparable to the wild-type BRCA1 protein. Twenty-three additional carriers of c.5578dup were identified at a US clinical diagnostic lab and assessed using a family history likelihood model providing, in combination with the functional data, a likely benign interpretation. These results, consistent with family history data in the current study and available data from ClinVar, indicate that most, but not all, BRCA1 variants leading to an extended incorrect terminus constitute loss-of-function variants and underscore the need for comprehensive assessment of individual variants.

Performance of super hybrid rice cultivars grown under no-tillage and direct seeding

Good progress has been made in the super hybrid rice (Oryza sativa L.) breeding in China. However, rice yield not only depends on the genetic characteristics but also on the agronomic practices. No-tillage and direct seeding (NTDS) is a simplified cultivation technology that greatly simplifies both land preparation and crop establishment. Aiming to determine the grain yield performance of super hybrid rice under NTDS and to identify critical factors that determine grain yield, field experiments were conducted in Nanxian, Hunan Province, China in 2009 and 2010. Two super hybrid cultivars, Liangyoupeijiu and Y-liangyou 1, were grown under conventional tillage and transplanting (CTTP) and NTDS. Grain yield, yield components, biomass production, crop growth rate and biomass accumulation during sowing to heading (HD) and HD to maturity were measured for each cultivar. There was no difference in grain yield under NTDS and CTTP. However, grain yield differed with cultivar and year. Y-liangyou 1 produced 4 % higher grain yield than Liangyoupeijiu in 2009, whereas in 2010 both cultivars yielded similarly. Grain yields of both cultivars were higher in 2009 than in 2010. Higher grain yield of Y-liangyou 1 in 2009 was associated with higher spikelet filling (spikelet filling percentage and grain weight), which resulted from higher biomass production. Crop growth rate after HD was critical for biomass production by the super hybrid rice. We suggest that increasing the crop growth rate after HD is an effective approach to increase grain yield of super hybrid rice under NTDS.

Performance of super hybrid rice cultivars grown under no-tillage and direct seeding

Good progress has been made in the super hybrid rice (Oryza sativa L.) breeding in China. However, rice yield not only depends on the genetic characteristics but also on the agronomic practices. No-tillage and direct seeding (NTDS) is a simplified cultivation technology that greatly simplifies both land preparation and crop establishment. Aiming to determine the grain yield performance of super hybrid rice under NTDS and to identify critical factors that determine grain yield, field experiments were conducted in Nanxian, Hunan Province, China in 2009 and 2010. Two super hybrid cultivars, Liangyoupeijiu and Y-liangyou 1, were grown under conventional tillage and transplanting (CTTP) and NTDS. Grain yield, yield components, biomass production, crop growth rate and biomass accumulation during sowing to heading (HD) and HD to maturity were measured for each cultivar. There was no difference in grain yield under NTDS and CTTP. However, grain yield differed with cultivar and year. Y-liangyou 1 produced 4 % higher grain yield than Liangyoupeijiu in 2009, whereas in 2010 both cultivars yielded similarly. Grain yields of both cultivars were higher in 2009 than in 2010. Higher grain yield of Y-liangyou 1 in 2009 was associated with higher spikelet filling (spikelet filling percentage and grain weight), which resulted from higher biomass production. Crop growth rate after HD was critical for biomass production by the super hybrid rice. We suggest that increasing the crop growth rate after HD is an effective approach to increase grain yield of super hybrid rice under NTDS.