Posterior probability of linkage analysis of autism dataset identifies linkage to chromosome 16

Abstract

Objective-To apply phenotypic and statistical methods designed to account for heterogeneity to linkage analyses of the autism Collaborative Linkage Study of Autism (CLSA) affected sibling pair families.Method-The CLSA contains two sets of 57 families each; Set 1 has been analyzed previously, whereas this study presents the first analyses of Set 2. The two sets were analyzed independently, and were further split based on the degree of phrase speech delay in the siblings. Linkage analysis was carried out using the posterior probability of linkage (PPL), a Bayesian statistic that provides a mathematically rigorous mechanism for combining linkage evidence across multiple samples. Results-Two-pointPPLs from Set 1 led to the follow-up genotyping of 18 markers around linkage peaks on 1q, 13p, 13q, 16q, and 17q in both sets of families. Multipoint PPLs were then calculated for the entire CLSA sample. These analyses identified four regions with at least modest evidence in support of linkage: 1q at 173 cM, PPL = 0.12; 13p at 21 cM, PPL = 0.16; 16q at 63 cM, PPL= 0.36; Xq at 40 cM, PPL = 0.11. Conclusion-We find strengthened evidence for linkage of autism to chromosomes 1q, 13p, 16q, and Xq, and diminished evidence for linkage to 7q and 13q. The verity of these findings will be tested by continuing to update our PPL analyses with data from additional autism datasets.

Genetic testing in children with autism spectrum disorders

“…16 Similarly, inversion of chromosome 9, associated with mental retardation and dysmorphic features 17,18 is also seen in patients with ASD. 18,19 Abnormalities of chromosomes 13p, 20 variation in heterochromatin regions 9qh+ 21,22 and Yqh+ 19 are other chromosome abnormalities shown in autistic children or children having autistic features similar to our study. Yqh+ is considered as clinically nonsignificant polymorphism.…”

Gene expression profiling differentiates autism case–controls and phenotypic variants of autism spectrum disorders: evidence for circadian rhythm dysfunction in severe autism

“…In addition, there is enrichment in QTLs on chromosomes 2, 4, 7, 8, 10, 16, 17, 19, and 22 for the L subgroup ( P <0.05), chromosomes 7, 16, and 17 for the M group ( P = 0.0001), and on chromosomes 7 and 16 for the S subgroup ( P <0.0015) according to Chi square tests. It is notable that all of these chromosomes have undergone intensive genetic analyses as “hot spots” with respect to autism [Auranen et al, 2000; Balciuniene et al, 2007; Buxbaum et al, 2001; Kumar et al, 2008; McCauley et al, 2005; Santangelo et al, 2000; Schellenberg et al, 2006; Stone, Merriman, Cantor, Geschwind, & Nelson, 2007; Wassink et al, 2008]. Thus, the layering of gene expression data onto genetic data may be a useful means of prioritizing candidate genes within the candidate susceptibility loci for further functional and genetic analyses.…”

An increase in Semaphorin 3A biases the axonal direction and induces an aberrant dendritic arborization in an in vitro model of human neural progenitor differentiation

“…Similarly, high levels of Sema 3A have been reported in brain from patients with multiple sclerosis [16] or in the Schwan cells from patients with amyotrophic lateral sclerosis [17] and in the hippocampus of patients with Alzheimer's disease [18]. In addition, Sema3A levels are increased in the cerebellum and prefrontal cortex of schizophrenic or autistic subjects [19,20] where several polymorphisms in Sema 3A or in the Sema 3A receptors have been also described [15,[21][22][23][24][25][26][27]. On the contrary, a transient downregulation of Sema3A mRNA expression has been found in a rat model of temporal lobe epilepsy [27][28][29].…”