De Novo and Rare Inherited Copy-Number Variations in the Hemiplegic Form of Cerebral Palsy

PurposeHemiplegia is a subtype of cerebral palsy (CP) in which one side of the body is affected. Our earlier study of unselected children with CP demonstrated de novo and clinically relevant rare inherited genomic copy-number variations (CNVs) in 9.6% of participants. Here, we examined the prevalence and types of CNVs specifically in hemiplegic CP.MethodsWe genotyped 97 unrelated probands with hemiplegic CP and their parents. We compared their CNVs to those of 10,851 population controls, in order to identify rare CNVs

The molecular genetics of autism

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Candidate-Gene Screening and Association Analysis at the Autism-Susceptibility Locus on Chromosome 16p: Evidence of Association at GRIN2A and ABAT

Autism is a highly heritable neurodevelopmental disorder whose underlying genetic causes have yet to be identified. To date, there have been eight genome screens for autism, two of which identified a putative susceptibility locus on chromosome 16p. In the present study, 10 positional candidate genes that map to 16p11-13 were examined for coding variants: A2BP1, ABAT, BFAR, CREBBP, EMP2, GRIN2A, MRTF-B, SSTR5, TBX6, and UBN1. Screening of all coding and regulatory regions by denaturing high-performance liquid chromatography identified seven nonsynonymous changes. Five of these mutations were found to cosegregate with autism, but the mutations are not predicted to have deleterious effects on protein structure and are unlikely to represent significant etiological variants. Selected variants from candidate genes were genotyped in the entire International Molecular Genetics Study of Autism Consortium collection of 239 multiplex families and were tested for association with autism by use of the pedigree disequilibrium test. Additionally, genotype frequencies were compared between 239 unrelated affected individuals and 192 controls. Patterns of linkage disequilibrium were investigated, and the transmission of haplotypes across candidate genes was tested for association. Evidence of single-marker association was found for variants in ABAT, CREBBP, and GRIN2A. Within these genes, 12 single-nucleotide polymorphisms (SNPs) were subsequently genotyped in 91 autism trios (one affected individual and two unaffected parents), and the association was replicated within GRIN2A (Fisher's exact test, P<.0001). Logistic regression analysis of SNP data across GRIN2A and ABAT showed a trend toward haplotypic differences between cases and controls

Linkage and candidate gene studies of autism spectrum disorders in European populations

Over the past decade, research on the genetic variants underlying susceptibility to autism and autism spectrum disorders (ASDs) has focused on linkage and candidate gene studies. This research has implicated various chromosomal loci and genes. Candidate gene studies have proven to be particularly intractable, with many studies failing to replicate previously reported associations. In this paper, we investigate previously implicated genomic regions for a role in ASD susceptibility, using four cohorts of European ancestry. Initially, a 384 SNP Illumina GoldenGate array was used to examine linkage at six previously implicated loci. We identify linkage approaching genome-wide suggestive levels on chromosome 2 (rs2885116, MLOD=1.89). Association analysis showed significant associations in MKL2 with ASD (rs756472, P=4.31 × 10−5) and between SND1 and strict autism (rs1881084, P=7.76 × 10−5) in the Finnish and Northern Dutch populations, respectively. Subsequently, we used a second 384 SNP Illumina GoldenGate array to examine the association in seven candidate genes, and evidence for association was found in RELN (rs362780, P=0.00165). Further increasing the sample size strengthened the association with RELN (rs362780, P=0.001) and produced a second significant result in GRIK2 (rs2518261, P=0.008). Our results strengthen the case for a more detailed study of the role of RELN and GRIK2 in autism susceptibility, as well as identifying two new potential candidate genes, MKL2 and SND1

Studying the interaction between charm and light-flavor mesons

International audienceThe two-particle momentum correlation functions between charm mesons ($\mathrm{D^{*\pm}}$ and $\mathrm{D}^\pm$) and charged light-flavor mesons ($\pi^{\pm}$ and K$^{\pm}$) in all charge-combinations are measured for the first time by the ALICE Collaboration in high-multiplicity proton-proton collisions at a center-of-mass energy of $\sqrt{s} =13$ TeV. For $\mathrm{DK}$ and $\mathrm{D^*K}$ pairs, the experimental results are in agreement with theoretical predictions of the residual strong interaction based on quantum chromodynamics calculations on the lattice and chiral effective field theory. In the case of $\mathrm{D}\pi$ and $\mathrm{D^*}\pi$ pairs, tension between the calculations including strong interactions and the measurement is observed. For all particle pairs, the data can be adequately described by Coulomb interaction only, indicating a shallow interaction between charm and light-flavor mesons. Finally, the scattering lengths governing the residual strong interaction of the $\mathrm{D}\pi$ and $\mathrm{D^*}\pi$ systems are determined by fitting the experimental correlation functions with a model that employs a Gaussian potential. The extracted values are small and compatible with zero