Genomic architecture of autism spectrum disorder in Qatar: The BARAKA-Qatar Study.

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by impaired social and communication skills, restricted interests, and repetitive behaviors. The prevalence of ASD among children in Qatar was recently estimated to be 1.1%, though the genetic architecture underlying ASD both in Qatar and the greater Middle East has been largely unexplored. Here, we describe the first genomic data release from the BARAKA-Qatar Study-a nationwide program building a broadly consented biorepository of individuals with ASD and their families available for sample and data sharing and multi-omics research. METHODS: In this first release, we present a comprehensive analysis of whole-genome sequencing (WGS) data of the first 100 families (372 individuals), investigating the genetic architecture, including single-nucleotide variants (SNVs), copy number variants (CNVs), tandem repeat expansions (TREs), as well as mitochondrial DNA variants (mtDNA) segregating with ASD in local families. RESULTS: Overall, we identify potentially pathogenic variants in known genes or regions in 27 out of 100 families (27%), of which 11 variants (40.7%) were classified as pathogenic or likely-pathogenic based on American College of Medical Genetics (ACMG) guidelines. Dominant variants, including de novo and inherited, contributed to 15 (55.6%) of these families, consisting of SNVs/indels (66.7%), CNVs (13.3%), TREs (13.3%), and mtDNA variants (6.7%). Moreover, homozygous variants were found in 7 families (25.9%), with a sixfold increase in homozygous burden in consanguineous versus non-consanguineous families (13.6% and 1.8%, respectively). Furthermore, 28 novel ASD candidate genes were identified in 20 families, 23 of which had recurrent hits in MSSNG and SSC cohorts. CONCLUSIONS: This study illustrates the value of ASD studies in under-represented populations and the importance of WGS as a comprehensive tool for establishing a molecular diagnosis for families with ASD. Moreover, it uncovers a significant role for recessive variation in ASD architecture in consanguineous settings and provides a unique resource of Middle Eastern genomes for future research to the global ASD community.

Optical properties of methyl-substituted germanane monolayer in the presence of the external magnetic field, strain and spin-orbit coupling.

In this research, we use the tight-binding model, which includes spin-orbit coupling and an external magnetic field, to describe the optical properties of the methyl-substituted germanane (GeCH3) monolayer. We have applied the Kubo formula, linear response theory, and Green's function approach to calculate the optical absorption coefficient of the GeCH3monolayer. Here, the effects of an external magnetic field, strain, spin-orbit coupling, temperature, and electron/hole doping on the frequency dependence behavior of the optical conductivity have been investigated in detail. Our numerical results show that with increasing the external magnetic field, strain, and electron doping, the weight of the Drude increases. The optical absorption peak decreases and shifts to higher frequencies by applying an external magnetic field, strain, and electron doping. Controlling the optical and electronic properties of GeCH3is leading to use this structure it in the electronic and optoelectronic industries.

Investigating the magnetic, thermoelectric, and thermodynamic properties of the GeCH3 single-layer considering external magnetic field, doping, and strain.

Extensive research is ongoing to improve the performance of thermoelectric and thermodynamic properties of the material because preventing energy waste is vital in modern society. Herein, we study the thermoelectric and thermodynamic properties of the GeCH3 single-layer (SL) under the influence of an external magnetic field, electron doping, and tensile and compressive biaxial strain by using the tight-binding and equilibrium Green's function method. We found that the electronic heat capacity, magnetic susceptibility, and electronic thermal and electrical conductivity increase by employing an external magnetic field, electron doping, and tensile biaxial strain. However, compressive biaxial strain yields a decrease in thermoelectric and thermodynamic properties. The results of our study show that the GeCH3 SL is paramagnetic. The results presented here that the GeCH3 SL is a suitable alternative for use in thermoelectric, spintronic, and valleytronics devices.

Effect of external magnetic field and doping on electronic and thermodynamic properties of planer and buckled silicene monolayer.

In this research, the electronic and thermodynamic properties of the planer and buckled silicene monolayer under an external magnetic field and doping using the tight-binding (TB) model and the Green function approach are investigated. Also, the dependence of the electronic heat capacity and magnetic susceptibility with temperature, external magnetic field, electron, and hole doping for the planer and buckled silicene monolayer is calculated. Our numerical calculation exhibits that the planer and buckled silicene monolayer have a zero band gap. We find that the electronic heat capacity increases (decreases) by applying an external magnetic field, and electron and hole doping at lower (higher) temperatures due to the increase in the thermal energy (scattering and collision) of the charge carriers. Finally, we observe that the planer and buckled silicene monolayer is antiferromagnetic, which is changed to the ferromagnetic phase when an external magnetic field and doping are applied, which makes the silicene monolayer suitable for spintronic applications.

Genomic architecture of autism from comprehensive whole-genome sequence annotation.

Fully understanding autism spectrum disorder (ASD) genetics requires whole-genome sequencing (WGS). We present the latest release of the Autism Speaks MSSNG resource, which includes WGS data from 5,100 individuals with ASD and 6,212 non-ASD parents and siblings (total n = 11,312). Examining a wide variety of genetic variants in MSSNG and the Simons Simplex Collection (SSC; n = 9,205), we identified ASD-associated rare variants in 718/5,100 individuals with ASD from MSSNG (14.1%) and 350/2,419 from SSC (14.5%). Considering genomic architecture, 52% were nuclear sequence-level variants, 46% were nuclear structural variants (including copy-number variants, inversions, large insertions, uniparental isodisomies, and tandem repeat expansions), and 2% were mitochondrial variants. Our study provides a guidebook for exploring genotype-phenotype correlations in families who carry ASD-associated rare variants and serves as an entry point to the expanded studies required to dissect the etiology in the ∼85% of the ASD population that remain idiopathic.

Patterns of allele frequency differences among domestic cat breeds assessed by a 63K SNP array.

Cats are ubiquitous companion animals that have been keenly associated with humans for thousands of years and only recently have been intentionally bred for aesthetically appealing coat looks and body forms. The intense selection on single gene phenotypes and the various breeding histories of cat breeds have left different marks on the genomes. Using a previously published 63K Feline SNP array dataset of twenty-six cat breeds, this study utilized a genetic differentiation-based method (di) to empirically identify candidate regions under selection. Defined as three or more overlapping (500Kb) windows of high levels of population differentiation, we identified a total of 205 candidate regions under selection across cat breeds with an average of 6 candidate regions per breed and an average size of 1.5 Mb per candidate region. Using the combined size of candidate regions of each breed, we conservatively estimate that a minimum of ~ 0.1-0.7% of the autosomal genome is potentially under selection in cats. As positive controls and tests of our methodology, we explored the candidate regions of known breed-defining genes (e.g., FGF5 for longhaired breeds) and we were able to detect the genes within candidate regions, each in its corresponding breed. For breed specific exploration of candidate regions under selection, eleven representative candidate regions were found to encompass potential candidate genes for several phenotypes such as brachycephaly of Persian (DLX6, DLX5, DLX2), curled ears of American Curl (MCRIP2, PBX1), and body-form of Siamese and Oriental (ADGRD1), which encourages further molecular investigations. The current assessment of the candidate regions under selection is empiric and detailed analyses are needed to rigorously disentangle effects of demography and population structure from artificial selection.

Author Correction: Applications and efficiencies of the first cat 63 K DNA array.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Author Correction: Applications and efficiencies of the first cat 63K DNA array.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Applications and efficiencies of the first cat 63K DNA array.

The development of high throughput SNP genotyping technologies has improved the genetic dissection of simple and complex traits in many species including cats. The properties of feline 62,897 SNPs Illumina Infinium iSelect DNA array are described using a dataset of over 2,000 feline samples, the most extensive to date, representing 41 cat breeds, a random bred population, and four wild felid species. Accuracy and efficiency of the array's genotypes and its utility in performing population-based analyses were evaluated. Average marker distance across the array was 37,741 Kb, and across the dataset, only 1% (625) of the markers exhibited poor genotyping and only 0.35% (221) showed Mendelian errors. Marker polymorphism varied across cat breeds and the average minor allele frequency (MAF) of all markers across domestic cats was 0.21. Population structure analysis confirmed a Western to Eastern structural continuum of cat breeds. Genome-wide linkage disequilibrium ranged from 50-1,500 Kb for domestic cats and 750 Kb for European wildcats (Felis silvestris silvestris). Array use in trait association mapping was investigated under different modes of inheritance, selection and population sizes. The efficient array design and cat genotype dataset continues to advance the understanding of cat breeds and will support monogenic health studies across feline breeds and populations.