RESUMO
Risk genes for Mendelian (single-gene) disorders (SGDs) are consistent across populations, but pathogenic risk variants that cause SGDs are typically population-private. The goal was to develop "QChip1," an inexpensive genotyping microarray to comprehensively screen newborns, couples, and patients for SGD risk variants in Qatar, a small nation on the Arabian Peninsula with a high degree of consanguinity. Over 108 variants in 8445 Qatari were identified for inclusion in a genotyping array containing 165,695 probes for 83,542 known and potentially pathogenic variants in 3438 SGDs. QChip1 had a concordance with whole-genome sequencing of 99.1%. Testing of QChip1 with 2707 Qatari genomes identified 32,674 risk variants, an average of 134 pathogenic alleles per Qatari genome. The most common pathogenic variants were those causing homocystinuria (1.12% risk allele frequency), and Stargardt disease (2.07%). The majority (85%) of Qatari SGD pathogenic variants were not present in Western populations such as European American, South Asian American, and African American in New York City and European and Afro-Caribbean in Puerto Rico; and only 50% were observed in a broad collection of data across the Greater Middle East including Kuwait, Iran, and United Arab Emirates. This study demonstrates the feasibility of developing accurate screening tools to identify SGD risk variants in understudied populations, and the need for ancestry-specific SGD screening tools.
RESUMO
The incidence rate of inflammatory bowel disease (IBD) is becoming a global health problem that could be caused by changes in environmental and lifestyle habits. The study aimed to identify the association between the quality of drinking water, i.e., physiochemical and biological aspects of the phenotype and activity of IBD in Eastern Croatia. The study included 312 patients (63.4% ulcerative colitis, UC, and 36.6% Crohn's disease, CD) from the area of Eastern Croatia. The data were collected by questionnaires and the analysis of the water safety, based on 65 samples of drinking water by the patient's water supply method (public supply, rural water supply, and private well). IBD was active in 38.0% patients (34.0% CD and 40.0% UC). Significant differences (p = 0.001) were observed in the distribution of patients, according to counties in which they lived in. The largest deviation was noted in coliform bacteria, Escherichia coli, and enterococci bacteria, Fe, Al, and nitrate in rural water supply and private wells, although, without significant impact on IBD phenotype and activity. The hazard quotient (HQ) simulations showed that children are a sensitive group, regarding exposure to nitrates in drinking water over a long period of time, so there is a need for further monitoring and analysis of this issue.
