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Titolo:
Single nucleotide polymorphisms distinguish multiple dopamine transporter alleles in primates: implications for association with attention deficit hyperactivity disorder and other neuropsychiatric disorders
Autore:
Miller, GM; De la Garza, R; Novak, MA; Madras, BK;
Indirizzi:
Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Div Neurochem, Southborough, MA 01772 USA Harvard Univ Southborough MA USA 01772 rochem, Southborough, MA 01772 USA Univ Massachusetts, Dept Psychol, Amherst, MA 01003 USA Univ Massachusetts Amherst MA USA 01003 pt Psychol, Amherst, MA 01003 USA
Titolo Testata:
MOLECULAR PSYCHIATRY
fascicolo: 1, volume: 6, anno: 2001,
pagine: 50 - 58
SICI:
1359-4184(200101)6:1<50:SNPDMD>2.0.ZU;2-8
Fonte:
ISI
Lingua:
ENG
Soggetto:
GENE POLYMORPHISM; DEFICIT/HYPERACTIVITY DISORDER; PARKINSONS-DISEASE; LOCUS-COERULEUS; CAUDATE-PUTAMEN; VARIABLE NUMBER; ANIMAL-MODEL; RECEPTOR; DAT1; METHYLPHENIDATE;
Keywords:
tandem repeat; rhesus monkey; VNTR; FNTR; 3 ' untranslated region; PCR; cloning;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
51
Recensione:
Indirizzi per estratti:
Indirizzo: Madras, BK Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Div Neurochem, 1 Pine Hill Dr, Southborough, MA 01772 USA Harvard Univ 1 Pine HillDr Southborough MA USA 01772 01772 USA
Citazione:
G.M. Miller et al., "Single nucleotide polymorphisms distinguish multiple dopamine transporter alleles in primates: implications for association with attention deficit hyperactivity disorder and other neuropsychiatric disorders", MOL PSYCHI, 6(1), 2001, pp. 50-58

Abstract

The human dopamine transporter (DAT) gene contains a variable number tandem repeat (VNTR; 40 bases/3 to >11 repeats) in the 3'-untranslated region (3'-UTR), resulting in multiple alleles categorized by length. The 10-copy allele has been associated with attention deficit hyperactivity disorder (ADHD), yet it accounts for only a small proportion of symptom variance. We investigated whether the rhesus monkey DAT gene contains a repeat sequence similar to the human and whether this region differs in the five most hyperactive and the five most sedate animals selected from a behaviorally characterized cohort (n = 22). A fixed number tandem repeat (FNTR; 39 bases/12 repeats) was observed in all animals. Accordingly, this FNTR is unbefitting an association of DAT transcript length with hyperactivity. However, sequence analysis revealed potential single nucleotide polymorphisms (SNPs), one of which affects a Bst1107l restriction site. We screened the entire cohort, confirmed that all the rhesus monkeys had repeat regions of the same length, and demonstrated that digestion with Bst1107l was sufficient to distinguishtwo distinct FNTR alleles. Bst1107l genotype was suggestive but not predictive of hyperactive behavior. Based on these data, we speculated that SNPs may exist in human DAT VNTR alleles. To support this hypothesis, we cloned a portion of a novel 10-repeat allele from the human gene containing an SNPthat abolishes a Dral restriction site. We conclude that SNPs create a diversity of DAT alleles between individuals that may be greater than previously identified based solely on the length of the VNTR region, and that alleles of specific sequence may contribute to dopamine-related disorders.

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Documento generato il 19/01/20 alle ore 07:01:46