Comprehensive population screening in the Ashkenazi Jewish population for recurrent disease-causing variants.

The Ashkenazi Jewish (AJ) population has an increased risk for a variety of recessive diseases due to historical founder effects and genetic drift. For some, the disease-causing founder mutations have been identified and well-characterized, but for others, further study is necessary. The purpose of this study is to assess the carrier frequencies of 85 pathogenic variants causative of 29 recessive conditions in the AJ population. Up to 3000 AJ individuals were genotyped by Luminex MagPlex® -TAG™ bead array or Agena Bioscience™ MassARRAY assays. We identified seven conditions with carrier frequencies higher than 1 in 100, nine between 1 in 100 and 1 in 200, and four between 1 in 200 and 1 in 500. Variants in nine conditions had a detected carrier rate of less than 1 in 500 or were not identified in approximately 2000 AJ individuals. We assessed the combined AJ carrier frequency for 18 relatively prevalent diseases to be 1 in 6, and the risk of AJ individuals to be a carrier couple for one of these 18 diseases as 1 in 441. We note additional recessive genetic conditions should be considered for AJ carrier screening panels.

A founder mutation in COL4A3 causes autosomal recessive Alport syndrome in the Ashkenazi Jewish population.

Alport syndrome is an inherited progressive nephropathy arising from mutations in the type IV collagen genes, COL4A3, COL4A4, and COL4A5. Symptoms also include sensorineural hearing loss and ocular lesions. We determined the molecular basis of Alport syndrome in a non-consanguineous Ashkenazi Jewish family with multiple affected females using linkage analysis and next generation sequencing. We identified a homozygous COL4A3 mutation, c.40_63del, in affected individuals with mutant alleles inherited from each parent on partially conserved haplotypes. Large-scale population screening of 2017 unrelated Ashkenazi Jewish samples revealed a carrier frequency of 1 in 183 indicating that COL4A3 c.40_63del is a founder mutation which may be a common cause of Alport syndrome in this population. Additionally, we determined that heterozygous mutation carriers in this family do not meet criteria for a diagnosis of Thin Basement Membrane Nephropathy and concluded that carriers of c.40_63del are not likely to develop benign familial hematuria.

Fate of malathion and chlorpyrifos methyl in rough rice and milling fractions before and after parboiling and cooking.

Long-grain rough rice treated with malathion (14 ppm) or chlorpyrifos methyl (Reldan) (6 ppm or 12 ppm) was sampled after 1,6, and 12 wk. Samples from each treatment were processed raw or were parboiled with fresh steeping water, once-used, and twice-used steeping water. Three replicates of rough rice and of each milling fraction were preserved, and three of milled rice were cooked. Chemical residues were measured on rough rice, hulls, brown rice, bran, milled rice, and cooked rice. Parboiling reduced residues on rough rice and hulls but tended to increase residues in the other fractions. Residues of Reldan in bran were substantially increased by parboiling. Doubling the amount of Reldan applied to rough rice approximately doubled the residues found in the milling fractions. Small amounts of the protectants survived all processing including cooking. Residues of malathion in cooked rice averaged about 0.016 ppm in nonparboiled and 0.013 ppm in parboiled rice. Residue of Reldan in cooked rice was commensurate with the amount applied to rough rice. When applied to rough rice at 6 ppm, residues of Reldan in cooked rice averaged 0.05 ppm in nonparboiled rice and 0l.065 ppm in parboiled rice. When applied to rough rice at 12 ppm, residues in cooked rice averaged .053 ppm in nonparboiled rice and 0.15 ppm in parboiled rice. Legal tolerances were not exceeded in any milling fraction. Reuse of the steeping water had little or no effect on residues.