RESUMEN
APOBEC mutational signatures SBS2 and SBS13 are common in many human cancer types. However, there is an incomplete understanding of its stimulus, when it occurs in the progression from normal to cancer cell and the APOBEC enzymes responsible. Here we whole-genome sequenced 342 microdissected normal epithelial crypts from the small intestines of 39 individuals and found that SBS2/SBS13 mutations were present in 17% of crypts, more frequent than most other normal tissues. Crypts with SBS2/SBS13 often had immediate crypt neighbors without SBS2/SBS13, suggesting that the underlying cause of SBS2/SBS13 is cell-intrinsic. APOBEC mutagenesis occurred in an episodic manner throughout the human lifespan, including in young children. APOBEC1 mRNA levels were very high in the small intestine epithelium, but low in the large intestine epithelium and other tissues. The results suggest that the high levels of SBS2/SBS13 in the small intestine are collateral damage from APOBEC1 fulfilling its physiological function of editing APOB mRNA.
Asunto(s)
Apolipoproteínas B , Citidina Desaminasa , Niño , Humanos , Preescolar , Apolipoproteínas B/genética , Citidina Desaminasa/genética , Mutagénesis/genética , ARN Mensajero/genética , Desaminasas APOBEC-1/genética , Intestino DelgadoRESUMEN
Previous studies have suggested that girls with Turner syndrome (TS) exhibit symptoms of social anxiety during interactions with others. However, few studies have quantified these behaviors during naturalistic face-to-face social encounters. In this study, we coded observational markers of social anxiety in prepubertal girls with TS and age-matched controls during a 10-min social encounter with an unfamiliar examiner. Results showed that girls with TS exhibited significantly higher levels of gaze avoidance compared to controls. Impairments in social gaze were particularly increased in girls with a maternally retained X chromosome (Xm), suggesting a genomic imprinting effect. These data indicate that social gaze avoidance may be a critical behavioral marker for identifying early social dysfunction in young girls with TS.