The rapid spread of clubroot disease, which is caused by Plasmodiophora brassicae, threatens Brassicaceae crop production worldwide. Breeding plants that have broad-spectrum disease resistance is one of the best ways to prevent clubroot. In the present study, eight Chinese cabbage germplasms were screened using published clubroot-resistant (CR) loci-/gene-linked markers. A CR gene Crr3 potential carrier “85-74” was detected which linked to marker BRSTS61; however, “85-74” shows different responses to local pathogens “LAB-19,” “LNND-2,” and “LAB-10” from “CR-73” which harbors Crr3. We used a next-generation sequencing-based bulked segregant analysis approach combined with genetic mapping to detect CR genes in an F2 segregant population generated from a cross between the Chinese cabbage inbred lines “85-74” (CR) and “BJN3-1” (clubroot susceptible). The “85-74” line showed resistance to a local pathogen “LAB-19” which was identified as race 4; a genetic analysis revealed that the resistance was conferred by a single dominant gene. The CR gene which we named CRd was mapped to a 60 kb (1 cM) region between markers yau389 and yau376 on chromosome A03. CRd is located upstream of Crr3 which was confirmed based on the physical positions of Crr3 linked markers. The identification of CRd linked markers can be applied to marker-assisted selection in the breeding of new CR cultivars of Chinese cabbage and other Brassica crops.

BackgroundDevelopmental disorders (DDs) are early onset disorders affecting 5%–10% of children worldwide. Chromosomal microarray analysis detecting CNVs is currently recommended as the first-tier test for DD diagnosis. However, this analysis omits a high percentage of disease-causing single nucleotide variations (SNVs) that warrant further sequencing. Currently, next-generation sequencing can be used in clinical scenarios detecting CNVs, and the use of exome sequencing in the DD cohort ahead of the microarray test has not been evaluated.MethodsClinical exome sequencing (CES) was performed on 1090 unrelated Chinese DD patients who were classified into five phenotype subgroups. CNVs and SNVs were both detected and analysed based on sequencing data.ResultsAn overall diagnostic rate of 41.38% was achieved with the combinational analysis of CNV and SNV. Over 12.02% of patients were diagnosed based on CNV, which was comparable with the published CMA diagnostic rate, while 0.74% were traditionally elusive cases who had dual diagnosis or apparently homozygous mutations that were clarified. The diagnostic rates among subgroups ranged from 21.82% to 50.32%. The top three recurrent cytobands with diagnostic CNVs were 15q11.2-q13.1, 22q11.21 and 7q11.23. The top three genes with diagnostic SNVs were: MECP2, SCN1A and SCN2A. Both the diagnostic rate and spectrums of CNVs and SNVs showed differences among the phenotype subgroups.ConclusionWith a higher diagnostic rate, more comprehensive observation of variations and lower cost compared with conventional strategies, simultaneous analysis of CNVs and SNVs based on CES showed potential as a new first-tier choice to diagnose DD.

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BackgroundRubinstein–Taybi syndrome (RSTS) is a rare genetic disease characterized by broad thumbs and halluces, facial dysmorphisms, short stature, and intellectual disability. RSTS is mainly caused by de novo variants in epigenetics‐associated gene, CREBBP. To date, there is no cohort study of CREBBP variants in Chinese RSTS patients.MethodsIn this study, 18 kids who meet the main criteria of RSTS were recruited. Molecular diagnoses were analyzed by clinical exome sequencing (CES), and the medical records were reviewed retrospectively.ResultsNineteen novel CREBBP variants in 18 RSTS patients were identified, including two missense, four nonsense, five frameshift, one splicing variants, and seven intragenic deletions. A higher incidence (37%, 7/19) of intragenic deletions was detected. One patient who had two de novo missense variants c.[4112T > A, 4118C > A] in cis and one patient who had a de novo frameshift variant c.5837delC in homozygous state (90%) were found in this study. Compared with the previously reported populations, seven clinical features were different, including the higher incidence of polydactyly, syndactyly, microcephaly, and micrognathia, and the lower incidence of angulated thumbs, autistic behavior, and epilepsy. One patient with obesity in the first year was diagnosed with CREBBP gene exon 2 deletion, was initially suspected of Prader–Willi syndrome.ConclusionWe reported the genetic and clinical information of 18 RSTS patients from Chinese population with novel CREBBP variants. This study provides a new insight into RSTS and illustrates the value of applying CES which increases the diagnostic yields and enhances the clinical care of RSTS patients.