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Objective:To identify the epidemic types of Group A Streptococcus (GAS)causing scarlet fever, to compare the gene structure and variability of GAS with different emm types, and to elucidate the epidemiological pattern of scarlet fever pathogens in Shenzhen. Methods:Pharyngeal swab samples were collected and analyzed retrospectively from children diagnosed with scarlet fever in Shenzhen Children′s Hospital from January 1, 2016 to May 31, 2018.The GAS strains were preserved for emm genotyping analysis.The strains of representative emm types were selected for whole-genome sequencing.The genomic polymorphism of GAS strains was described by comparative genomic analysis.Moreover, a phylogenetic tree was constructed based on the whole genome core-gene single nucleotide polymorphisms(SNPs) to clarify the evolutionary relationship between strains.Data between groups were compared by Rank sum test. Results:Among 176 GAS isolates that caused scarlet fever in children, 8 emm types were detected.The most common genotype was emm12.0 and its subtype(108/176 strains, 61.4%), followed by emm1.0 and its subtype(53/176 strains, 30.1%). These two genotypes accounted for 91.5% of all isolates collected.Comparative genome analysis was made taking GCA-900984775 as a reference sequence, and the results showed that the genomes of GAS strains had high levels of SNP and insertion or deletion (InDel) polymorphisms.There were more SNPs in emm12.0 strains[183(163, 213)] than those in emm1.0 strains[63 (54, 75)], and the difference was statistically significant ( P<0.05). As for InDel, more insertions and deletions [4(3, 6), 8(6, 10)] were observed in emm12.0 strains than those [1(0, 2), 5(3, 7)] in emm1.0 strains.According to the phylogenetic tree built by taking MGAS5005 as the reference sequence based on the whole genome core-gene SNPs, 18 strains and reference strains formed two clades. Conclusions:The emm12.0 and emm1.0 types are the most common GAS strains leading to scarlet fever in children.There are differences in the genome composition of different GAS strains.The emm12.0 strains have higher genetic diversity.
RESUMO
In spite of its strong familiality, gene identification for coronary artery disease (CAD) has not yielded a consistent picture. One major reason for this is that families or cases and controls were not recruited from a homogeneous population. We, therefore, attempted to map genes underlying 10 quantitative traits (QTs) that are known precursors of CAD in a homogeneous population (Marwari) of India. The QTs are apolipoprotein B (ApoB), C-reactive protein (CRP), fibrinogen (FBG), homocysteine (HCY), lipoprotein (a) (LPA), cholesterol – total (CHOL-T), cholesterol – HDL (CHOL-H), cholesterol – LDL (CHOL-L), cholesterol – VLDL (CHOL-V) and triglyceride (TG). We assayed 209 SNPs in 31 genes among members of Marwari families. After log-transformation and covariate-adjustment of the QTs, a two-step analysis was performed. In Step-1, data on unrelated individuals were analysed for association with the SNPs. In Step-2, for validation of Step-1 results, a quantitative transmission-disequilibrium test on parent– offspring data was performed for each SNP found to be significantly associated with a QT in Step-1 on an independent sample set drawn from the same population. Statistically significant results found for the various QTs and SNPs were: rs3774933, rs230528, rs230521, rs1005819 and rs1609798 (intronic, NFKB1) with APOB; rs5361 (Missense, R>S, SELE) and rs4648004 (Intronic, NFKB1) with FBG; rs4220 (Missense, K>R, FGB) with HCY; and rs3025035 (Intronic, VEGFA) with CHOL-H. SNPs in SELE, VEGFA, FGB and NFKB1 genes impact significantly on levels of quantitative precursors of CAD in Marwaris.