We present a novel methodology to determine the phase of single-nucleotide polymorphisms (SNPs) on a chromosome, which we term clone-based systematic haplotyping (CSH). The CSH procedure is based on separating the allelic chromosomes of a diploid genome by fosmid/cosmid cloning, and subsequent SNP typing of 96 clone pools, each representing ∼10% of the genome. The pools are screened by PCR for the sequence of interest, followed by SNP typing on the PCR products using the GOOD assay. We demonstrate that by CSH, the haplotype of SNPs separated by more than 50 kilobases can definitely be assigned. We propose this method as being suitable for constructing maps of ancestral haplotypes, analysis of complex diseases, and for diagnosis of rare defects in which the molecular haplotype is crucial. In addition, by amplifying the initial DNA by many orders of magnitude, the original DNA resource is effectively immortalized, enabling the haplotyping of hundreds of thousands of SNPs per individual.
The catalytically coated ceramic plate heat exchanger represents a specialized microreactor offering a large surface‐to‐volume ratio and improved temperature control. Appropriate and economically viable manufacturing processes are presented together with the results of coating studies and thermal and reaction engineering investigations. The selective methanation of carbon monoxide, used as purification step for H2‐rich gas streams in stationary fuel cell applications, was chosen as a suitable test reaction because of its strongly exothermic behavior and its need for tight temperature control.
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