Genetics

Microcephaly and macrocephaly are overrepresented in individuals with autism and are thought to be disease-related risk factors or endophenotypes. Analysis of DNA microarray results from a family with a low functioning autistic child determined that the proband and two additional unaffected family members who carry a rare inherited 760 kb duplication of unknown clinical significance at 19p13.12 are macrocephalic. Consideration alongside overlapping deletion and duplication events in the literature provides support for a strong relationship between gene dosage at this locus and head size, with losses and gains associated with microcephaly (p=1.11x10-11) and macrocephaly (p=2.47x10-11), respectively. Data support A kinase anchor protein 8 and 8-like (AKAP8 and AKAP8L) as candidate genes involved in regulation of head growth, an interesting finding given previous work implicating the AKAP gene family in autism. Towards determination of which of AKAP8 and AKAP8L may be involved in the modulation of head size and risk for disease, we analyzed exome sequencing data for 693 autism families (2591 individuals) where head circumference data were available. No predicted loss of function variants were observed, precluding insights into relationship to head size, but highlighting strong evolutionary conservation. Taken together, findings support the idea that gene dosage at 19p13.12, and AKAP8 and/or AKAP8L in particular, play an important role in modulation of head size and may contribute to autism risk. Exome sequencing of the family also identified a rare inherited variant predicted to disrupt splicing of TPTE / PTEN2, a PTEN homologue, which may likewise contribute to both macrocephaly and autism risk.

Background With the increasing number of genomic sequencing studies, hundreds of genes have been implicated in neurodevelopmental disorders (NDDs). The rate of gene discovery far outpaces our understanding of genotype–phenotype correlations, with clinical characterization remaining a bottleneck for understanding NDDs. Most disease-associated Mendelian genes are members of gene families, and we hypothesize that those with related molecular function share clinical presentations. Methods We tested our hypothesis by considering gene families that have multiple members with an enrichment of de novo variants among NDDs, as determined by previous meta-analyses. One of these gene families is the heterogeneous nuclear ribonucleoproteins (hnRNPs), which has 33 members, five of which have been recently identified as NDD genes (HNRNPK, HNRNPU, HNRNPH1, HNRNPH2, and HNRNPR) and two of which have significant enrichment in our previous meta-analysis of probands with NDDs (HNRNPU and SYNCRIP). Util...

ABSTRACT A method for targeted variation of the radiation properties of quantum dots (QDs) to control the efficiency of resonance energy transfer in nanocrystal assemblies and nano-bio hybrid materials has been developed. The method is based on strong ultraviolet (UV) laser irradiation of QDs and allows the extinction and luminescence spectra to be controlled and the luminescence quantum yield and decay kinetics to be varied. Water-soluble QDs have been synthesized and used for analyzing the effect of energy transfer from semiconductor nanocrystals on the photocycle of the photosensitive protein bacteriorhodopsin (bR) in bR–QD complexes. The UV irradiation mode has been selected in a way permitting the modulation of QD optical parameters without modification of their structure or physico-chemical properties. It is concluded that the QD interaction with bR accelerates its photocycle, but this acceleration is determined by electrostatic interactions, rather than Förster resonance energy transfer from QDs to bR. The method of UV laser irradiation of fluorescent semiconductor QDs has proven to be an efficient technique for variation of nanocrystal optical properties without affecting their structure, as well as for fine modulation of the energy transfer processes in the nanocrystal assemblies and nano-bio hybrid materials.