AIM: To develop a risk model for Crohn’s disease (CD) based on homogeneous population.METHODS: In our study were included 160 CD patients and 209 healthy individuals from Slovenia. The association study wa...AIM: To develop a risk model for Crohn’s disease (CD) based on homogeneous population.METHODS: In our study were included 160 CD patients and 209 healthy individuals from Slovenia. The association study was performed for 112 single nucleotide polymorphisms (SNPs). We generated genetic risk scores (GRS) based on the number of risk alleles using weighted additive model. Discriminatory accuracy was measured by area under ROC curve (AUC). For risk evaluation, we divided individuals according to positive and negative likelihood ratios (LR) of a test, with LR > 5 for high risk group and LR < 0.20 for low risk group.RESULTS: The highest accuracy, AUC of 0.78 was achieved with GRS combining 33 SNPs with optimal sensitivity and specificity of 75.0% and 72.7%, respectively. Individuals with the highest risk (GRS > 5.54) showed significantly increased odds of developing CD (OR = 26.65, 95%CI: 11.25-63.15) compared to the individuals with the lowest risk (GRS < 4.57) which is a considerably greater risk captured than in one SNP with the highest effect size (OR = 3.24). When more than 33 SNPs were included in GRS, discriminatory ability was not improved significantly; AUC of all 74 SNPs was 0.76.CONCLUSION: The authors proved the possibility of building accurate genetic risk score based on 33 risk variants on Slovenian CD patients which may serve as a screening tool in the targeted population.展开更多
The first seedling or all-stage resistance （R） R gene against stripe rust isolated from Moro wheat （Triticum aes- tivum L.） using a map-based cloning approach was identified as Yr10. Clone 4B of this gene encodes ...The first seedling or all-stage resistance （R） R gene against stripe rust isolated from Moro wheat （Triticum aes- tivum L.） using a map-based cloning approach was identified as Yr10. Clone 4B of this gene encodes a highly evolutionary- conserved and unique CC-NBS-LRR sequence. Clone 4E, a homolog of Yr10, but lacking transcription start site （TSS） and putative TATA-box and CAAT-box, is likely a non-expressed pseudogene. Clones 4B and 4E are 84% identical and divergent in the intron and the LRR domain. Gene silencing and transgenesis were used in conjunction with inoculation with differen- tially avirulent and virulent stripe rust strains to demonstrate Yr10 functionality. The Yr10 CC-NBS-LRR sequence is unique among known CC-NBS-LRR R genes in wheat but highly conserved homologs （E = 0.0） were identified in Aegilops tauschii and other monocots including Hordeum vulgare and Brachypodium distachyon. Related sequences were also identified in genomic databases of maize, rice, and in sorghum. This is the first report of a CC-NBS-LRR resistance gene in plants with limited homologies in its native host, but with numerous homologous R genes in related monocots that are either host or non-hosts for stripe rust. These results represent a unique example of gene evolution and dispersion across species.展开更多
文摘AIM: To develop a risk model for Crohn’s disease (CD) based on homogeneous population.METHODS: In our study were included 160 CD patients and 209 healthy individuals from Slovenia. The association study was performed for 112 single nucleotide polymorphisms (SNPs). We generated genetic risk scores (GRS) based on the number of risk alleles using weighted additive model. Discriminatory accuracy was measured by area under ROC curve (AUC). For risk evaluation, we divided individuals according to positive and negative likelihood ratios (LR) of a test, with LR > 5 for high risk group and LR < 0.20 for low risk group.RESULTS: The highest accuracy, AUC of 0.78 was achieved with GRS combining 33 SNPs with optimal sensitivity and specificity of 75.0% and 72.7%, respectively. Individuals with the highest risk (GRS > 5.54) showed significantly increased odds of developing CD (OR = 26.65, 95%CI: 11.25-63.15) compared to the individuals with the lowest risk (GRS < 4.57) which is a considerably greater risk captured than in one SNP with the highest effect size (OR = 3.24). When more than 33 SNPs were included in GRS, discriminatory ability was not improved significantly; AUC of all 74 SNPs was 0.76.CONCLUSION: The authors proved the possibility of building accurate genetic risk score based on 33 risk variants on Slovenian CD patients which may serve as a screening tool in the targeted population.
文摘The first seedling or all-stage resistance （R） R gene against stripe rust isolated from Moro wheat （Triticum aes- tivum L.） using a map-based cloning approach was identified as Yr10. Clone 4B of this gene encodes a highly evolutionary- conserved and unique CC-NBS-LRR sequence. Clone 4E, a homolog of Yr10, but lacking transcription start site （TSS） and putative TATA-box and CAAT-box, is likely a non-expressed pseudogene. Clones 4B and 4E are 84% identical and divergent in the intron and the LRR domain. Gene silencing and transgenesis were used in conjunction with inoculation with differen- tially avirulent and virulent stripe rust strains to demonstrate Yr10 functionality. The Yr10 CC-NBS-LRR sequence is unique among known CC-NBS-LRR R genes in wheat but highly conserved homologs （E = 0.0） were identified in Aegilops tauschii and other monocots including Hordeum vulgare and Brachypodium distachyon. Related sequences were also identified in genomic databases of maize, rice, and in sorghum. This is the first report of a CC-NBS-LRR resistance gene in plants with limited homologies in its native host, but with numerous homologous R genes in related monocots that are either host or non-hosts for stripe rust. These results represent a unique example of gene evolution and dispersion across species.
