Exclusion of close linkage of tourette's syndrome to D1 dopamine receptor

Joel Gelernter, James L. Kennedy, David Grandy, Qun Yong Zhou, Olivier Civelli, David L. Pauls, Andrew Pakstis, Roger Kurlan, Roger K. Sunahara, Hyman B. Niznik, Brian O'Dowd, Philip Seeman, Kenneth K. Kidd

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Objective: The authors' goal was to establish if a mutation in D1 dopamine receptor locus (DRD1), or one genetically close to it, could cause Gilles de la Tourette's syndrome. Method: DRD1 and linked markers (D5S36, D5S61, and D5S62) were studied in a large Mennonite Tourette's syndrome kindred. Only individuals with the full Tourette's syndrome were considered to be affected in one series of analyses; in another series the diagnostic spectrum was broadened to include chronic multiple tics. Liability classes were defined to take into account age at onset and sex differences; dominant inheritance was assumed. The authors' version of the LINKMAP program of the LINKAGE package modified to run under distributed parallel processing (Linda LINKMAP) was used for the multipoint linkage analysis. Results: Complete (θ=0.0) linkage of Tourette's syndrome with DRD1 was ruled out (lod score of -10.1) when the disease was defined narrowly. The area of exclusion of linkage (lod score between -2 and -10.5) extended from map position -0.10 to map position 0.50. The authors conducted an additional (centromeric) multipoint analysis with D5S36 as well as glucocorticoid receptor (GRL) and D5S22, resulting in an overlapping area of exclusion to map position -0.30 when the disease was defined narrowly. Conclusions: This result provides strong evidence against linkage of the DRD1 D1 dopamine receptor locus with Tourette's syndrome. This exclusion extends the authors' earlier work with the dopamine system in Tourette's syndrome to exclude the two best characterized dopamine receptors from linkage with Tourette's syndrome.

Original languageEnglish (US)
Pages (from-to)449-453
Number of pages5
JournalAmerican Journal of Psychiatry
Volume150
Issue number3
StatePublished - 1993
Externally publishedYes

Fingerprint

Tourette Syndrome
Dopamine D1 Receptors
Lod Score
Tics
Glucocorticoid Receptors
Dopamine Receptors
Age of Onset
Sex Characteristics
Dopamine
Mutation

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

Gelernter, J., Kennedy, J. L., Grandy, D., Zhou, Q. Y., Civelli, O., Pauls, D. L., ... Kidd, K. K. (1993). Exclusion of close linkage of tourette's syndrome to D1 dopamine receptor. American Journal of Psychiatry, 150(3), 449-453.

Exclusion of close linkage of tourette's syndrome to D1 dopamine receptor. / Gelernter, Joel; Kennedy, James L.; Grandy, David; Zhou, Qun Yong; Civelli, Olivier; Pauls, David L.; Pakstis, Andrew; Kurlan, Roger; Sunahara, Roger K.; Niznik, Hyman B.; O'Dowd, Brian; Seeman, Philip; Kidd, Kenneth K.

In: American Journal of Psychiatry, Vol. 150, No. 3, 1993, p. 449-453.

Research output: Contribution to journalArticle

Gelernter, J, Kennedy, JL, Grandy, D, Zhou, QY, Civelli, O, Pauls, DL, Pakstis, A, Kurlan, R, Sunahara, RK, Niznik, HB, O'Dowd, B, Seeman, P & Kidd, KK 1993, 'Exclusion of close linkage of tourette's syndrome to D1 dopamine receptor', American Journal of Psychiatry, vol. 150, no. 3, pp. 449-453.
Gelernter J, Kennedy JL, Grandy D, Zhou QY, Civelli O, Pauls DL et al. Exclusion of close linkage of tourette's syndrome to D1 dopamine receptor. American Journal of Psychiatry. 1993;150(3):449-453.
Gelernter, Joel ; Kennedy, James L. ; Grandy, David ; Zhou, Qun Yong ; Civelli, Olivier ; Pauls, David L. ; Pakstis, Andrew ; Kurlan, Roger ; Sunahara, Roger K. ; Niznik, Hyman B. ; O'Dowd, Brian ; Seeman, Philip ; Kidd, Kenneth K. / Exclusion of close linkage of tourette's syndrome to D1 dopamine receptor. In: American Journal of Psychiatry. 1993 ; Vol. 150, No. 3. pp. 449-453.
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abstract = "Objective: The authors' goal was to establish if a mutation in D1 dopamine receptor locus (DRD1), or one genetically close to it, could cause Gilles de la Tourette's syndrome. Method: DRD1 and linked markers (D5S36, D5S61, and D5S62) were studied in a large Mennonite Tourette's syndrome kindred. Only individuals with the full Tourette's syndrome were considered to be affected in one series of analyses; in another series the diagnostic spectrum was broadened to include chronic multiple tics. Liability classes were defined to take into account age at onset and sex differences; dominant inheritance was assumed. The authors' version of the LINKMAP program of the LINKAGE package modified to run under distributed parallel processing (Linda LINKMAP) was used for the multipoint linkage analysis. Results: Complete (θ=0.0) linkage of Tourette's syndrome with DRD1 was ruled out (lod score of -10.1) when the disease was defined narrowly. The area of exclusion of linkage (lod score between -2 and -10.5) extended from map position -0.10 to map position 0.50. The authors conducted an additional (centromeric) multipoint analysis with D5S36 as well as glucocorticoid receptor (GRL) and D5S22, resulting in an overlapping area of exclusion to map position -0.30 when the disease was defined narrowly. Conclusions: This result provides strong evidence against linkage of the DRD1 D1 dopamine receptor locus with Tourette's syndrome. This exclusion extends the authors' earlier work with the dopamine system in Tourette's syndrome to exclude the two best characterized dopamine receptors from linkage with Tourette's syndrome.",
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T1 - Exclusion of close linkage of tourette's syndrome to D1 dopamine receptor

AU - Gelernter, Joel

AU - Kennedy, James L.

AU - Grandy, David

AU - Zhou, Qun Yong

AU - Civelli, Olivier

AU - Pauls, David L.

AU - Pakstis, Andrew

AU - Kurlan, Roger

AU - Sunahara, Roger K.

AU - Niznik, Hyman B.

AU - O'Dowd, Brian

AU - Seeman, Philip

AU - Kidd, Kenneth K.

PY - 1993

Y1 - 1993

N2 - Objective: The authors' goal was to establish if a mutation in D1 dopamine receptor locus (DRD1), or one genetically close to it, could cause Gilles de la Tourette's syndrome. Method: DRD1 and linked markers (D5S36, D5S61, and D5S62) were studied in a large Mennonite Tourette's syndrome kindred. Only individuals with the full Tourette's syndrome were considered to be affected in one series of analyses; in another series the diagnostic spectrum was broadened to include chronic multiple tics. Liability classes were defined to take into account age at onset and sex differences; dominant inheritance was assumed. The authors' version of the LINKMAP program of the LINKAGE package modified to run under distributed parallel processing (Linda LINKMAP) was used for the multipoint linkage analysis. Results: Complete (θ=0.0) linkage of Tourette's syndrome with DRD1 was ruled out (lod score of -10.1) when the disease was defined narrowly. The area of exclusion of linkage (lod score between -2 and -10.5) extended from map position -0.10 to map position 0.50. The authors conducted an additional (centromeric) multipoint analysis with D5S36 as well as glucocorticoid receptor (GRL) and D5S22, resulting in an overlapping area of exclusion to map position -0.30 when the disease was defined narrowly. Conclusions: This result provides strong evidence against linkage of the DRD1 D1 dopamine receptor locus with Tourette's syndrome. This exclusion extends the authors' earlier work with the dopamine system in Tourette's syndrome to exclude the two best characterized dopamine receptors from linkage with Tourette's syndrome.

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