Discovery of a novel CHD7 CHARGE syndrome variant by integrated omics analyses

Chromodomain helicase DNA-binding protein 7 (CHD7) pathogenic variants are identified in more than 90% of infants and children with CHARGE (Coloboma of the iris, retina, and/or optic disk; congenital Heart defects, choanal Atresia, Retardation of growth and development, Genital hypoplasia, and characteristic outer and inner Ear anomalies and deafness) syndrome. Approximately, 10% of cases have no known genetic cause identified. We report a male child with clinical features of CHARGE syndrome and nondiagnostic genetic testing that included chromosomal microarray, CHD7 sequencing and deletion/duplication analysis, SEMA3E sequencing, and trio exome and whole-genome sequencing (WGS). We used a comprehensive clinical assessment, genome-wide methylation analysis (GMA), reanalysis of WGS data, and CHD7 RNA studies to discover a novel variant that causes CHD7 haploinsufficiency. The 7-year-old Hispanic male proband has typical phenotypic features of CHARGE syndrome. GMA revealed a CHD7-associated epigenetic signature. Reanalysis of the WGS data with focused bioinformatic analysis of CHD7 detected a novel, de novo 15 base pair deletion in Intron 4 of CHD7 (c.2239-20_2239-6delGTCTTGGGTTTTTGT [NM_017780.3]). Using proband RNA, we confirmed that this novel deletion causes CHD7 haploinsufficiency by disrupting the canonical 3′ splice site and introducing a premature stop codon. Integrated genomic, epigenomic, and transcriptome analyses discovered a novel CHD7 variant that causes CHARGE syndrome

A supramolecular helix that disregards chirality

The functions of complex crystalline systems derived from supramolecular biological and non-biological assemblies typically emerge from homochiral programmed primary structures via first principles involving secondary, tertiary and quaternary structures. In contrast, heterochiral and racemic compounds yield disordered crystals, amorphous solids or liquids. Here, we report the self-assembly of perylene bisimide derivatives in a supramolecular helix that in turn self-organizes in columnar hexagonal crystalline domains regardless of the enantiomeric purity of the perylene bisimide. We show that both homochiral and racemic perylene bisimide compounds, including a mixture of 21 diastereomers that cannot be deracemized at the molecular level, self-organize to form single-handed helical assemblies with identical single-crystal-like order. We propose that this high crystalline order is generated via a cogwheel mechanism that disregards the chirality of the self-assembling building blocks. We anticipate that this mechanism will facilitate access to previously inaccessible complex crystalline systems from racemic and homochiral building blocks

Cryogenic Orbital Test Bed 3 (CRYOTE3) Overview and Status

CRYOTE3 is a grassroots CFM test effort with contributing government and industry partners focused on developing and testing hardware to produce needed data for model validation and implementation into flight systems

Castanea dentata

"Macon #3" tree used in Bill Carey's thesis. 28 Sep 2001

Castanea dentata

[Leaves collected by Dr. Paul Sisco. No locality or date given.

Castanea dentata

NC: Macon Co. Wayah Ranger District, Pisgah NF. GPS: N35 10.782, W83 33.672. Wayah Bald Tree C

Castanea dentata

Macon #2 Tree. Bill Carey thesis subject

Castanea dentata

NC: Macon Co. Wayah Bald Tree A. GPS: N 35 10.217, W 83 34.898. 'Joe James Tree.

Castanea dentata

NC: Yancey Co. Hancy creek. Off Rt. 197, south of Murchison, NC. Rick Wilson Tree. June 2000

Castanea dentata

NC: Buncombe Co. Highway 197. GPS: N35 46.212, W82 31.118. Jack Webb Tree