Patients with biallelic GGC repeat expansions in NOTCH2NLC exhibiting a typical neuronal intranuclear inclusion disease phenotype.

We report two patients with autosomal dominant neuronal intranuclear inclusion disease (NIID) harboring the biallelic GGC repeat expansion in NOTCH2NLC to uncover the impact of repeat expansion zygosity on the clinical phenotype. The zygosity of the entire NOTCH2NLC GGC repeat expansion and DNA methylation were comprehensively evaluated using fluorescent amplicon length PCR (AL-PCR), Southern blotting and targeted long-read sequencing, and detailed genetic/epigenetic and clinical features were described. In AL-PCR, we could not recognize the wild-type allele in both patients. Targeted long-read sequencing revealed that one patient harbored a homozygous repeat expansion. The other patient harbored compound heterozygous repeat expansions. The GGC repeats and the nearest CpG island were hypomethylated in all expanded alleles in both patients. Both patients harboring the biallelic GGC repeat expansion showed a typical dementia-dominant NIID phenotype. In conclusion, the biallelic GGC repeat expansion in two typical NIID patients indicated that NOTCH2NLC-related diseases could be completely dominant.

Rapid identification of candidate genes controlling male-sterility in Foxtail millet (Setaria italica).

Photo-(thermo-) sensitive genic male-sterile line is the key component of two-line hybridization system in foxtail millet (Setaria italica), but the genetic basis of male sterility in most male-sterile lines is still unclear. In the present study, a large F2 population was developed derived from a cross between the photo-(thermo-) sensitive male-sterile line A2 and the fertile-line 1484-5. Thirty plants with extreme high and extreme low fertility were selected from the population to construct a sterile DNA pool and a fertile DNA pool, respectively. Sequencing both DNA pools and data analysis revealed that two QTLs conferred male-sterility, qSiMS6.1 with a major effect and qSiMS6.2 with a minor effect, on chromosome 6. Both QTLs exhibited complete dominance. The major QTL, qSiMS6.1, was delimited to a 186-kb interval between the markers SiM20 and SiM9 by the joint analysis of QTL-seq and QTL mapping with SSR and structure variation markers. Millet_GLEAN_10020454 in this region is the most likely candidate gene for qSiMS6.1 since it is predicted to encode a male-sterile 5 like protein. These results lay a solid foundation for qSiMS6.1 cloning and provided gene resources for breeding new male-sterile lines. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-021-01269-2.