Reelin Associated With Restricted and Stereotyped Behavior Based on Principal Component Analysis on Autism Diagnostic Interview-Revised

Tämä artikkeli ei ole avattavissa lehden sivuilta, koska linkit ja DOI vievät väärään artikkeliin samoin PDF sen ohessa. Kustantajalle ilmoitettu ja pyydetty korjausta.Abstract Background: Twin and family studies have indicated a strong genetic component in autism spectrum disorders, and genetic studies have revealed highly heterogeneous risk factors. The range and severity of the symptom presentation also vary in the spectrum. Thus, symptom-based phenotypes are putatively more closely related to the underlying biology of autism than the end-state diagnosis. Methods: We performed principal component analysis on Autism Diagnostic Interview-Revised algorithm for 117 Finnish families and 594 families from the Autism Genetic Research Exchange (AGRE). The resulting continuous component scores were used as quantitative phenotypes in family-based association analysis. In addition, K-means clustering was performed to cluster and visualize the results of the PCA. Unaffected siblings were included in the study. Results: The components were interpreted as Social Component (SC), communication component and Restricted and Stereotyped Behavior Component (RSBC). K-means clustering showed that, especially in SC, the range of the symptom severity was increased by the siblings. The association of neuroligin 1 with SC was increased, compared to a previous study where only the end-state diagnosis was used. In RSBC, the range of the symptom severity of siblings overlapped greatly with that of patients, which could explain why no association of reelin was found in previous studies in which only the end-state diagnosis was used, but a significant association of reelin with RSBC was now found in the Finnish families (Bonferroni-corrected p=0.029 for rs362644). Although, the Finnish sample is isolated and genetically very homogeneous, compared to the heterogeneous background of AGRE families, many single-nucleotide polymorphisms in reelin, showed modest association with RSBC in the AGRE sample, too. Conclusions: This study demonstrates how the quantitative phenotypes can affect the association analyses, and yields further support to the use of siblings in the study of complex neuropsychiatric disorders.Peer reviewe

Chromosome Evolution In Neotropical Danainae And Ithomiinae (lepidoptera).

Chromosome numbers are given for 1011 populations of 242 species, representing the full range of taxa (49 of the about 52 presently recognized genera) in the Neotropical Nymphalid butterfly subfamily Ithomiinae (prime movers for mimicry rings), including many additional geographical subspecies from 47 regions from Mexico and the Caribbean islands throughout all tropical South American countries to southern Brazil. Twelve Neotropical Danainae (in 3 genera), all but one with n=29-31, and the Australian Tellervo (n=32) served as sister groups for comparison. The numbers range near-continuously from n=5 to n=120 with modal values (33-84 counts) at n=12-18, and only 16 and 26 counts at the usual modal number of all butterfly groups, n=30-31. Superimposition of these changes in karyotype on a cladistic phylogeny of the subfamily indicates possible early halving of the complement to n about 14-15, followed by much variation in each genus and tribe. While at least 17 species in 15 genera show stable karyotypes over much of the Neotropics, at least 40 species show large geographical variation in number of chromosomes, rarely accompanied by any evidence for reduction in fertility or incipient speciation. The evolutionary opportunism of the members of this subfamily probably accompanies their known population biology and community ecology: they are common, shade-loving, highly gregarious (occurring in small multispecies pockets in deep forest) and often migratory as a community when the environment becomes unfavorable (too hot or dry).141216-3