Author Correction: Refining polyploid breeding in sweet potato through allele dosage enhancement
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Origin and de novo domestication of sweet orange
Sweet orange is cultivated worldwide but suffers from various devastating diseases because of its monogenetic background. The elucidation of the origin of a crop facilitates the domestication of new crops that may better cope with new challenges. Here we collected and sequenced 226 citrus accessions and assembled telomere-to-telomere phased diploid genomes of sweet orange and sour orange. On the basis of a high-resolution haplotype-resolved genome analysis, we inferred that sweet orange originated from a sour orange × mandarin cross and confirmed this model using artificial hybridization experiments. We identified defense-related metabolites that potently inhibited the growth of multiple industrially important pathogenic bacteria. We introduced diversity to sweet orange, which showed wide segregation in fruit flavor and disease resistance and produced canker-resistant sweet orange by selecting defense-related metabolites. Our findings elucidate the origin of sweet orange and de novo domesticated disease-resistant sweet oranges, illuminating a strategy for the rapid domestication of perennial crops.
Multiomic quantification of the KRAS mutation dosage improves the preoperative prediction of survival and recurrence in patients with pancreatic ductal adenocarcinoma
Most cancer mutation profiling studies are laboratory-based and lack direct clinical application. For clinical use, it is necessary to focus on key genes and integrate them with relevant clinical variables. We aimed to evaluate the prognostic value of the dosage of the KRAS G12 mutation, a key pancreatic ductal adenocarcinoma (PDAC) variant and to investigate the biological mechanism of the prognosis associated with the dosage of the KRAS G12 mutation. In this retrospective cohort study, we analyzed 193 surgically treated patients with PDAC between 2009 and 2016. RNA, whole-exome, and KRAS-targeted sequencing data were used to estimate the dosage of the KRAS G12 mutant. Our prognostic scoring system included the mutation dosage from targeted sequencing ( > 0.195, 1 point), maximal tumor diameter at preoperative imaging ( > 20 mm, 1 point), and carbohydrate antigen 19-9 levels ( > 150 U/mL, 1 point). The KRAS mutation dosage exhibited comparable performance with clinical variables for survival prediction. High KRAS mutation dosages activated the cell cycle, leading to high mutation rates and poor prognosis. According to prognostic scoring systems that integrate mutation dosage with clinical factors, patients with 0 points had superior median overall survival of 97.0 months and 1-year, 3-year, and 5-year overall survival rates of 95.8%, 70.8%, and 66.4%, respectively. In contrast, patients with 3 points had worse median overall survival of only 16.0 months and 1-year, 3-year, and 5-year overall survival rates of 65.2%, 8.7%, and 8.7%, respectively. The incorporation of the KRAS G12 mutation dosage variable into prognostic scoring systems can improve clinical variable-based survival prediction, highlighting the feasibility of an integrated scoring system with clinical significance.
Atlas of imprinted and allele-specific DNA methylation in the human body
Allele-specific DNA methylation reflects genetic variation and parentally-inherited changes, and is involved in gene regulation and pathologies. Yet, our knowledge of this phenomenon is largely limited to blood. Here we present a comprehensive atlas of allele-specific DNA methylation using deep whole-genome sequencing across 39 normal human cell types. We identified 325k regions, covering 6% of the genome and 11% of CpGs, that show a bimodal distribution of methylated and unmethylated molecules. In 34k of these regions, genetic variations at individual alleles segregate with methylation patterns, validating allele-specific methylation. We also identified 460 regions showing parental allele-specific methylation, the majority of which are novel, as well as 78 regions associated with known imprinted genes. Surprisingly, sequence-dependent and parental allele-dependent methylation is often restricted to specific cell types, revealing unappreciated variation of allele-specific methylation across the human body. Finally, we validate tissue-specific, maternal allele-specific methylation of CHD7, offering a potential mechanism for the paternal bias in the inheritance mode of CHARGE syndrome associated with this gene. The atlas provides a resource for studying allele-specific methylation and regulatory mechanisms underlying imprinted expression in specific human cell types.
Multi-population GWAS detects robust marker associations in a newly established six-rowed winter barley breeding program
Genome-wide association study (GWAS) is a powerful tool for identifying marker-trait associations that can accelerate breeding progress. Yet, its power is typically constrained in newly established breeding programs where large phenotypic and genotypic datasets have not yet accumulated. Expanding the dataset by inclusion of data from well-established breeding programs with many years of phenotyping and genotyping can potentially address this problem. In this study we performed single- and multi-population GWAS on heading date and lodging in four barley breeding populations with varying combinations of row-type and growth habit. Focusing on a recently established 6-rowed winter (6RW) barley population, single-population GWAS hardly resulted in any significant associations. Nevertheless, the combination of the 6RW target population with other populations in multi-population GWAS detected four and five robust candidate quantitative trait loci for heading date and lodging, respectively. Of these, three remained undetected when analysing the combined populations individually. Further, multi-population GWAS detected markers capturing a larger proportion of genetic variance in 6RW. For multi-population GWAS, we compared the findings of a univariate model (MP1) with a multivariate model (MP2). While both models surpassed single-population GWAS in power, MP2 offered a significant advantage by having more realistic assumptions while pointing towards robust marker-trait associations across populations. Additionally, comparisons of GWAS findings for MP2 and single-population GWAS allowed identification of population-specific loci. In conclusion, our study presents a promising approach to kick-start genomics-based breeding in newly established breeding populations.
Analysing the pedigree to identify undesirable losses of genetic diversity and to prioritize management decisions in captive breeding: a case study
When prevention of species extinction is the priority, captive breeding is a key component in conservation programmes, allowing the recording of pedigree information in studbooks. The genealogical information registered in Cuvier’s gazelle studbook between 1975 and 2023 was analysed to (a) assess if the implemented mating policy was successful in preserving the genetic background of the founders (1 male:3 females) in the present population, and b) improve future management and breeding decisions. Although the maternal contribution of one founder female was lost and the mean inbreeding of the total live population was high (0.305 ± 0.095), the breeding policy applied produced better results than expected from a population starting from four founders. It was successful in keeping the individual increase in inbreeding low (0.047 ± 0.021), and, notably, the inbreeding tended to decrease during the last three decades of the breeding programme, ensuring the viability of this highly inbred population. Historical dissemination of individuals among the zoos of Europe and North America caused population structuring and genetic differentiation of the live North American population. However, it did not risk the viability of the captive population. The average relatedness coefficients allowed the identification of individuals with underrepresented genotypes, which is relevant to plan future mating guidelines to keep the founders’ representation balanced in the next generations. This study highlights the importance of keeping long-term pedigree information to monitor changes in the genetic diversity of captive populations, which is crucial to implement optimal mating decisions and assuring their long-term viability within an ex situ conservation programme.
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