Autism Spectrum Disorder (ASD) demonstrates high heritability and familial clustering, yet the genetic causes remain only partially understood as a result of extensive clinical and genomic heterogeneity. Whole-genome sequencing (WGS) shows promise as a tool for identifying ASD risk genes as well as unreported mutations in known loci, but an assessment of its full utility in an ASD group has not been performed. We used WGS to examine 32 families with ASD to detect de novo or rare inherited genetic variants predicted to be deleterious (loss-of-function and damaging missense mutations). Among ASD probands, we identified deleterious de novo mutations in six of 32 (19%) families and X-linked or autosomal inherited alterations in ten of 32 (31%) families (some had combinations of mutations). The proportion of families identified with such putative mutations was larger than has been previously reported; this yield was in part due to the comprehensive and uniform coverage afforded by WGS. Deleterious variants were found in four unrecognized, nine known, and eight candidate ASD risk genes. Examples include CAPRIN1 and AFF2 (both linked to FMR1, which is involved in fragile X syndrome), VIP (involved in social-cognitive deficits), and other genes such as SCN2A and KCNQ2 (linked to epilepsy), NRXN1, and CHD7, which causes ASD-associated CHARGE syndrome. Taken together, these results suggest that WGS and thorough bioinformatic analyses for de novo and rare inherited mutations will improve the detection of genetic variants likely to be associated with ASD or its accompanying clinical symptoms.

A simple one-step procedure for the preparation of columns for capillary electrochromatography is described. The nonpolar compounds (stearyl or butyl methacrylate) used for the introduction of hydrophobic ligands (C18, C4) are rendered water-soluble in the aqueous monomer mixture used for the synthesis of the matrix by the addition of a surfactant. This solution is sucked into a piece of fused silica tubing, the inner walls of which are activated by methacryl groups. Following polymerization, the continuous bed column is ready for use. Since the bed is attached covalently to the tubing wall, no frit to support the bed is required, which simplifies the preparation of the column. In addition, a frit can easily become clogged and is often a site for the generation of air bubbles. Some new approaches to increase the resolution and shorten the analysis times in electrochromatography are suggested and demonstrated experimentally, such as sharpening the starting zone, employing gradient elution, or adding SDS (below cmc) to the mobile phase. Separation of five polycyclic aromatic hydrocarbons can be achieved in 5 min in a 25-μm-i.d. column.

The effect of low concentrations of organic modifiers on the electroosmotic mobility, mueo, and electrophoretic mobility of the micelle, muep, mc, in micellar electrokinetic chromatography (MEKC) with sodium dodecyl sulfate (SDS) solutions was investigated. The results showed that mueo was mainly influenced by the viscosity of the running solution. A linear relationship between mueo and the concentration of the organic modifier was found in MEKC. A newly defined parameter, the mobility ratio, Rm, mc, which is the ratio of the electrophoretic mobility of the micelle to the electroosmotic mobility, and which characterizes the surface charge density of the micelle in MEKC system with organic modifiers, was introduced. A linear relationship between Rm, mc and the organic modifier concentration was observed. The parameter Rm, mc was found to be useful to investigate the changes in the micellar phase with the addition of organic modifier. The measured muep, mc values showed different and interesting characteristics among different organic modifiers.

Limiting mutual diffusion coefficients of aromatic compounds in acetone have been measured at 298.2 K by using the chromatographic peak-broadening method. The data of the polar and nonpolar pseudoplanar solutes are compared, and the effects of molecular association on diffusion as well as the solvation numbers are determined. It is found that the effects of hydrogen bonding are such that -OHϾ-NH 2 Ͼ-SH, and that the solvation numbers are approximately equal for solutes containing the same polar group. Using ab initio molecular orbital theory, molecular solute-acetone interaction energies have been calculated. There exists a nearly linear relationship between the interaction energy and the effect of solute-solvent association on diffusion. The applicability of the rough-hard-sphere theory to the diffusion of associated molecules is discussed. © 1997 American Institute of Physics. ͓S0021-9606͑97͒53330-7͔