Chen Ling

Exome sequencing of 20,791 cases of type 2 diabetes and 24,440 controls Protein-coding genetic variants that strongly affect disease risk can yield relevant clues to disease pathogenesis. Here we report exome-sequencing analyses of 20,791 individuals with type 2 diabetes (T2D) and 24,440 non-diabetic control participants from 5 ancestries. We identify gene-level associations of rare variants (with minor allele frequencies of less than 0.5%) in 4 genes at exome-wide significance, including a series of more than 30 SLC30A8 alleles that conveys protection against T2D, and in 12 gene sets, including those corresponding to T2D drug targets (P = 6.1 10 -3 ) and candidate genes from knockout mice (P = 5.2 10 -3 ). Within our study, the strongest T2D gene-level signals for rare variants explain at most 25% of the heritability of the strongest common single-variant signals, and the gene-level effect sizes of the rare variants that we observed in established T2D drug targets will require 75,000-185,000 sequenced cases to achieve exome-wide significance. We propose a method to interpret these modest rare-variant associations and to incorporate these associations into future target or gene prioritization efforts.

Fusarium head blight (FHB) is a devastating wheat disease worldwide. To decipher the genetic architecture of FHB resistance in Chinese germplasm, a Wheat Association Panel for Scab Research (WAPS) consisting of 240 leading Chinese wheat cultivars and elite lines was genotyped using the 90K single nucleotide polymorphism (SNP) arrays. The FHB response was evaluated in the field nurseries at Wuhan in Hubei province over four consecutive years from 2014 to 2017. Five quantitative trait loci (QTL) were consistently identified on chromosome arms 1AS, 2DL, 5AS, 5AL, and 7DS using a mixed linear model (MLM), explaining 5.6%, 10.3%, 5.7%, 5.4%, and 5.6% of phenotypic variation, respectively. The QTL on 5AS, 5AL, and 7DS QTL are probably novel. The allelic frequency analysis indicated that cultivars from the Middle and Lower Yangtze River Valleys harbored more favorable alleles and were therefore more resistant than those from other regions. To facilitate in-house germplasm screening and marker-assisted selection, SNP-derived PCR markers were developed for the QTL regions on 1AS, 5AS, and 5AL QTL. In addition to the above five QTL, the WAPS population had a very low frequency of Fhb1, confirming that the gene is not widely used in Chinese wheat breeding programs. The resistant lines and molecular markers developed in this study are resources and information for enhancing FHB resistance in breeding populations by marker-assisted recurrent selection and gene stacking.

Two experiments were conducted to investigate the effects of exogenous catalase (CAT) in the diet of weaned piglets on growth performance, oxidative capacity, and hepatic apoptosis after challenge with lipopolysaccharide (LPS). In experiment 1, 72 weaned piglets [Duroc × Landrace × Yorkshire, 6.90 ± 0.01 kg body weight (BW), 21 d of age] were randomly assigned to be fed either a basal diet (CON group) or a basal diet supplemented with 2,000 mg/kg CAT (CAT group; dietary CAT activity, 120 U/kg) for 35 d. Blood samples were collected on day 21 and day 35. At the end of this experiment, 12 pigs were selected from each of the CON and CAT groups, and six pigs were injected with LPS (50 μg/kg BW), while the remaining six pigs were injected with an equal amount of sterile saline, resulting in a 2 × 2 factorial arrangement of treatments (experiment 2). Blood samples and rectal temperature data were collected 0 and 4 h after challenge, and liver samples were obtained after evisceration. The gain-to-feed ratio was higher (P < 0.05) in piglets in the CAT group than in those in the CON group from day 1 to 35. Catalase and total superoxide dismutase (T-SOD) activities were higher (P < 0.05), whereas malondialdehyde (MDA) concentrations were lower (P < 0.05), in piglets in the CAT group than in those in the CON group at day 35. During challenge, rectal temperature and liver MDA and H2O2 concentrations increased significantly (P < 0.05), whereas plasma CAT and glutathione peroxidase (GSH-Px) activities and liver CAT activity decreased markedly (P < 0.05), in LPS-challenged piglets 4 h post-challenge. Increased CAT activity and decreased MDA concentration were observed in the plasma and liver of piglets in the CAT group 4 h post-challenge (P < 0.05). Dietary CAT supplementation markedly suppressed the LPS-induced decrease in plasma GSH-Px activity and liver CAT activity to levels observed in the CON group (P < 0.05) as well as significantly decreasing the concentration and mRNA expression of caspase-3 and caspase-9 (P < 0.05). LPS-induced liver injury was also attenuated by dietary CAT supplementation, as demonstrated by a decrease in liver caspase-3 mRNA expression (P < 0.05). Overall, dietary supplementation with 2,000 mg/kg exogenous CAT (dietary CAT activity, 120 U/kg) improves growth performance and has a beneficial effect on antioxidant capacity in weaned piglets; alleviates oxidative stress and reduces liver damage by suppressing hepatic apoptosis in LPS-challenged piglets.

Abstract Microsatellite markers are popular for assigning parentage, but single-nucleotide polymorphisms (SNPs) have only been applied in this area recently. To evaluate these two markers which have been previously studied in golden snub-nosed monkeys, we genotyped 12 individuals using 37 microsatellite loci and 37 SNP markers. The data showed that 32 of 37 microsatellite loci were polymorphic, and most microsatellite loci were high informative (mean PIC = 0.599). Meanwhile, 24 of 37 SNP markers were polymorphic and most were low informative (mean PIC = 0.244). For microsatellites, the combined exclusion probability with one-parent-unknown/known (CE-1P/CE-2P) nearly reached 1, while for the SNP markers, CE-2P only reached 0.9582. Under the condition of one parent known/unknown, the CE-2P and CE-1P could meet the international human parental standard (0.9973) by using five or nine microsatellite loci respectively. For SNP markers, we doubled the loci (n = 48) and simulated parentage testing, and the data showed that the CE-2P was 0.998 while the CE-1P was still low. This result indicated that the SNP loci which we used here had low polymorphism and that more loci need to be developed in the future. In addition, we corrected one case of failed identification by excluding siblings and reducing the range of candidate paternities.