Congener-specific transfer of PCDD/Fs from air to cows milk : an evaluation of current modelling approaches.

Three different approaches have been used to model the transfer of individual PCDD/F congeners from the air to cows' milk. These are: (1) an ‘Equilibrium Partitioning’ approach, (2) a ‘Deposition Velocity’ approach and (3) a ‘Scavenging’ approach. Air-leaf transfers and livestock feed-milk transfers, the two most critical components of the food chain exposure model, are discussed. A representative database for measured PCDD/Fs in UK air, herbage and milk is presented and the performance of each predicted model concentration against this measured dataset is assessed. Weaknesses and uncertainties associated with modelling the complex transfer processes involved are highlighte

A point mutation in the pre-ZRS disrupts sonic hedgehog expression in the limb bud and results in triphalangeal thumb-polysyndactyly syndrome

Item does not contain fulltextPURPOSE: The zone of polarizing activity regulatory sequence (ZRS) is an enhancer that regulates sonic hedgehog during embryonic limb development. Recently, mutations in a noncoding evolutionary conserved sequence 500 bp upstream of the ZRS, termed the pre-ZRS (pZRS), have been associated with polydactyly in dogs and humans. Here, we report the first case of triphalangeal thumb-polysyndactyly syndrome (TPT-PS) to be associated with mutations in this region and show via mouse enhancer assays how this mutation leads to ectopic expression throughout the developing limb bud. METHODS: We used linkage analysis, whole-exome sequencing, Sanger sequencing, fluorescence in situ hybridization, multiplex ligation-dependent probe amplification, single-nucleotide polymorphism array, and a mouse transgenic enhancer assay. RESULTS: Ten members of a TPT-PS family were included in this study. The mutation was linked to chromosome 7q36 (LOD score 3.0). No aberrations in the ZRS could be identified. A point mutation in the pZRS (chr7:156585476G>C; GRCh37/hg19) was detected in all affected family members. Functional characterization using a mouse transgenic enhancer essay showed extended ectopic expression dispersed throughout the entire limb bud (E11.5). CONCLUSION: Our work describes the first mutation in the pZRS to be associated with TPT-PS and provides functional evidence that this mutation leads to ectopic expression of this enhancer within the developing limb