[autismo-biologia] Rare structural variation of synapse and
neurotransmission genes in autism
daniela marianicerati
marianicerati a yahoo.it
Sab 19 Mar 2011 16:20:35 CET
Segnalo l’articolo
Rare structural variation of synapse and neurotransmission genes in autism
X Gai1, H M Xie1, J C Perin1, N Takahashi2, K Murphy1, A S Wenocur1, M D'arcy1,
R J O'Hara1, E Goldmuntz3,6, D E Grice4, T H Shaikh5, H Hakonarson6,7,8, J
D Buxbaum2, J Elia9,10 and P S White1,6,11
Molecular Psychiatryadvance online publication 1 March 2011; doi:
10.1038/mp.2011.10
L’articolo puo’ essere letto integralmente al link
http://www.nature.com/mp/journal/vaop/ncurrent/full/mp201110a.html
Gli autori hanno studiato le CNVs (genome copy-number variations) in campioni
numericamente consistenti di persone con autismo e in campioni di controllo.
Numericamente le CNV sono frequenti sia nei probandi che nei controlli. Gli
autori si sono quindi focalizzati sulle CNV presenti solo nelle persone con
autismo per risalire dai geni alla funzione da essi codificata.
Questo tipo di ricerca ha condotto alla funzione sinaptica e alla
neurotrasmissione.
Copio alcuni stralci
“In this study we show that biological processes associated with synapse
function and neurotransmission are significantly enriched, with replication, in
ASD subjects versus controls”
Gli autori hanno poi studiato dei modelli animali portatori di anomalie dei geni
contenuti nelle CNV trovando conferma di una correlazione tra genotipo e
fenotipo similautistico(abnormal (±CNS) synaptic transmission, abnormal motor
capabilities/coordination/movement, abnormal motor coordination/balance, reduced
NMDA-mediated synaptic currents, abnormal impulse conducting system conduction,
decreased startle reflex, abnormal miniature excitatory postsynaptic currentsand
abnormal spatial learning)
“Analysis of phenotypes observed for mouse models of copy-variant genes
established significant and replicated enrichment of observable phenotypes
consistent with ASD behaviors”
Gli autori pertanto concludono
“These results implicate several new variants that involve synaptic function and
glutamatergic signaling processes as important contributors of ASD
pathophysiology”
Entrando più nel particolare copio altri stralci
“A total of 395 inherited CNVs (135 duplications, 256 heterozygous deletions and
4 hemizygous deletions of the X chromosome) were identified in 286 autism
subjects that were not present in healthy controls
Many of these processes were associated with synaptic function and
neurotransmission, including cell–cell signaling (P=1.97 × 10−7), transmission
of nerve impulse (P=7.06 × 10−5), synaptic transmission (P=8.05 × 10−5), neuron
adhesion (P=2.06 × 10−3), central nervous system development (P=4.30 × 10−3),
regulation of neurotransmitter levels (P=4.88 × 10−3), neurotransmitter
secretion (P=1.30 × 10−2) and neurotransmitter transport (P=2.95 × 10−2).
Autism CNV genes frequently associated with terms related to synapse function
and neurotransmission included previous candidates CNTN4, NRXN1 and PARK2, as
well as genes CNTN6, CTNND2, GRIN2A, NCAM2, GRM7, GRM8 and RCAN1.
Le conclusioni degli autori sono le seguenti
“our results do consistently and independently implicate possible pathways,
functions and gene sets that can be readily investigated by follow-up genomic
and experimental investigation.
Our current results extend these findings and, more importantly, for the first
time provide statistical evidence that synaptic function and glutamate-mediated
neurotransmission are contributing factors in autism etiology”
Lo spostamento dai geni alle sinapsi e alla neurotrasmissione dovrebbe stimolare
la ricerca di target per nuovi farmaci.
Sappiamo che dall’ipotesi alla commercializzazione di un farmaco la strada è
lunga, ma, come dice Gianni Rodari “Chi non parte in verità in nessun posto
arriverà”
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