Defining the Effect of the 16p11.2 Duplication on Cognition, Behavior, and Medical Comorbidities.

IMPORTANCE: The 16p11.2 BP4-BP5 duplication is the copy number variant most frequently associated with autism spectrum disorder (ASD), schizophrenia, and comorbidities such as decreased body mass index (BMI). OBJECTIVES: To characterize the effects of the 16p11.2 duplication on cognitive, behavioral, medical, and anthropometric traits and to understand the specificity of these effects by systematically comparing results in duplication carriers and reciprocal deletion carriers, who are also at risk for ASD. DESIGN, SETTING, AND PARTICIPANTS: This international cohort study of 1006 study participants compared 270 duplication carriers with their 102 intrafamilial control individuals, 390 reciprocal deletion carriers, and 244 deletion controls from European and North American cohorts. Data were collected from August 1, 2010, to May 31, 2015 and analyzed from January 1 to August 14, 2015. Linear mixed models were used to estimate the effect of the duplication and deletion on clinical traits by comparison with noncarrier relatives. MAIN OUTCOMES AND MEASURES: Findings on the Full-Scale IQ (FSIQ), Nonverbal IQ, and Verbal IQ; the presence of ASD or other DSM-IV diagnoses; BMI; head circumference; and medical data. RESULTS: Among the 1006 study participants, the duplication was associated with a mean FSIQ score that was lower by 26.3 points between proband carriers and noncarrier relatives and a lower mean FSIQ score (16.2-11.4 points) in nonproband carriers. The mean overall effect of the deletion was similar (-22.1 points; P < .001). However, broad variation in FSIQ was found, with a 19.4- and 2.0-fold increase in the proportion of FSIQ scores that were very low (≤40) and higher than the mean (>100) compared with the deletion group (P < .001). Parental FSIQ predicted part of this variation (approximately 36.0% in hereditary probands). Although the frequency of ASD was similar in deletion and duplication proband carriers (16.0% and 20.0%, respectively), the FSIQ was significantly lower (by 26.3 points) in the duplication probands with ASD. There also were lower head circumference and BMI measurements among duplication carriers, which is consistent with the findings of previous studies. CONCLUSIONS AND RELEVANCE: The mean effect of the duplication on cognition is similar to that of the reciprocal deletion, but the variance in the duplication is significantly higher, with severe and mild subgroups not observed with the deletion. These results suggest that additional genetic and familial factors contribute to this variability. Additional studies will be necessary to characterize the predictors of cognitive deficits

Época da indução e evocação floral em Citrus sinensis (L.) Osbeck cv. Pêra Rio The flower induction and evocation period in Citrus sinensis (L.) Osbeck cv. Pêra Rio

A produção do estímulo floral (indução) e emissão das primeiras sépalas, na gema floralmente determinada (evocação floral) em Citrus sinensis (L.) Osbeck cv. Pêra Rio pôde ser acompanhada pelas variações anatômicas nos meristemas apicais e axilares. Com objetivo de determinar a época na qual ocorre a indução e evocação floral, cortes longitudinais de gemas apicais e axilares, corados com pironina Y-methylgreen foram efetuados em períodos regulares de maio a agosto. Através das mudanças no formato da gema, principalmente diâmetro, que aumentou com a indução, foi possível determinar a época do ano na qual gemas vegetativas são induzidas a florescerem. Foram detectadas variações nos diâmetros das gemas no período de início da morfogênese floral (meados até o final de julho). A medição do diâmetro das gemas mostra-se um procedimento eficiente para acompanhar os fenômenos decorrentes da indução, evocação e morfogênese florais. Gemas vegetativas apresentam diâmetro médio de 100µm, com túnica composta por três camadas, de formato cônico, recobrindo o corpo, ao passo que a reprodutiva é mais achatada, após a iniciação do primeiro primórdio de sépala, exibindo diâmetro médio de 200µm. Coloração com pironina Y-methylgreen proporciona a captação do fenômeno da evocação floral, pela detecção de regiões mais concentradas em RNA, nas zonas periféricas das gemas; alteração bioquímica esta que precede a emissão das sépalas.<br>The research aims to determine the time in which the inflorescence induction and evocation occurs. The production of inflorescence stimulus (induction) and emission of first sepals in a bud determined as a flower bud (floral evocation) in Citrus sinensis (L.) Osbeck cv. Pêra Rio could be observed through the anatomic variations of the apical and lateral meristems. Longitudinal sections, stained with pironina Y-methylgreen were done in regular periods from May to August. The time of the year in which the vegetative buds are induced to blossom was determined through the bud shape changes, chiefly considering the diameter, which has increased with the induction. Bud diameter variations were detected on the second half of July, the period of floral morphogenesis incipience. The measurement of the bud diameter is an efficient procedure to follow up the phenomena originated from the floral induction, evocation and morphogenesis. Vegetative buds bring out an average diameter of 100µm with a three-layer tunic in a conic shape, recovering its body. The reproductive bud, in turn, is flatter, after the initiation of the first sepal primordium, showing an average diameter of 200µm. The pironina Y-methylgreen stain provides the observation of the floral evocation phenomenon, through the detection of regions with a higher RNA level, in the bud external areas. This biochemical alteration precedes the sepal emission