ABSTRACT
Many candidate gene association studies have evaluated incomplete, unrepresentative sets of single nucleotide polymorphisms (SNPs), producing non-significant results that are difficult to interpret. Using a rapid, efficient strategy designed to investigate all common SNPs, we tested associations between schizophrenia and two positional candidate genes: ACSL6 (Acyl-Coenzyme A synthetase long-chain family member 6) and SIRT5 (silent mating type information regulation 2 homologue 5). We initially evaluated the utility of DNA sequencing traces to estimate SNP allele frequencies in pooled DNA samples. The mean variances for the DNA sequencing estimates were acceptable and were comparable to other published methods (mean variance: 0.0008, range 0-0.0119). Using pooled DNA samples from cases with schizophrenia/schizoaffective disorder (Diagnostic and Statistical Manual of Mental Disorders edition IV criteria) and controls (n=200, each group), we next sequenced all exons, introns and flanking upstream/downstream sequences for ACSL6 and SIRT5. Among 69 identified SNPs, case-control allele frequency comparisons revealed nine suggestive associations (P<0.2). Each of these SNPs was next genotyped in the individual samples composing the pools. A suggestive association with rs 11743803 at ACSL6 remained (allele-wise P=0.02), with diminished evidence in an extended sample (448 cases, 554 controls, P=0.062). In conclusion, we propose a multi-stage method for comprehensive, rapid, efficient and economical genetic association analysis that enables simultaneous SNP detection and allele frequency estimation in large samples. This strategy may be particularly useful for research groups lacking access to high throughput genotyping facilities. Our analyses did not yield convincing evidence for associations of schizophrenia with ACSL6 or SIRT5.
Subject(s)
Coenzyme A Ligases/genetics , DNA/genetics , Gene Frequency , Polymorphism, Single Nucleotide/genetics , Schizophrenia/genetics , Sirtuins/genetics , Case-Control Studies , DNA Mutational Analysis/methods , Gene Pool , Genetic Predisposition to Disease , Genetic Testing/methods , Humans , Reference ValuesABSTRACT
In the absence of a formal nutritional support team, a group of physicians, pharmacists, dietitians, and nurses at the authors' institution organized to devise alternative ways to facilitate nutritional support. The efforts of this group led to the redesign of the Pharmacy Department's parenteral nutrition order form into a clinical tool for the prescribing physician, and the development of a system for daily patient monitoring by dietitians and pharmacists for patients receiving specialized nutritional products. The delivery of parenteral nutrition was also streamlined to coordinate with the daily patient monitoring. A future goal is to increase three-way communication and teamwork among the physicians, dietitians, and pharmacists. These methods may be practical alternatives to facilitating nutritional support without the benefit of a support team.
