The Dopamine Transporter Protein Gene (SLC6A3): Primary Linkage Mapping and Linkage Studies in Tourette Syndrome

Joel Gelernter, David Vandenbergh, Susan D. Kruger, David L. Pauls, Roger Kurlan, Andrew J. Pakstis, Kenneth K. Kidd, George Uhl

Research output: Contribution to journalArticle

Abstract

The dopamine transporter, the molecule responsible for presynaptic reuptake of dopamine and a major site of action of psychostimulant drugs, including cocaine, is encoded by locus SLC6A3 (alias DAT1). The protein's actions and DAT's specific localization to dopaminergic neurons make it a candidate gene for several psychiatric illnesses. Alleles at this locus have been reported to be associated with cocaine-induced paranoia and attention deficit disorder. SLC6A3 has been mapped to distal chromosome 5p, using physical methods. Our goal was to place SLC6A3 in the genetic linkage map and to test for linkage to Tourette syndrome. Genetic linkage methods were used to place SLC6A3 in the genetic linkage map. Four extended pedigrees (one of which overlaps with CEPH) were typed. Linkage with Tourette syndrome (TS) was also examined. SLC6A3 showed close linkage with several markers previously mapped to distal chromosome 5p, including D5S11 (Zmax = 16.0, θM = θF = 0.03, results from four families) and D5S678 (Zmax = 7.84, θM = θF = 0, results from two families). Observed crossovers established that SLC6A3 is a distal marker close to D5S10 and D5S678, but these three distal markers could not be ordered. Linkage between TS and SLC6A3 could be excluded independently in two branches of a large kindred segregating TS; the lod score in a third family was also negative, but not significant. Cumulative results show a lod score of -6.2 at θ = 0 and of -3.9 at θ = 0.05 (dominant model, narrow disease definition). SLC6A3 thus maps to distal chromosome 5p by linkage analysis, in agreement with previous physical mapping data. A mutation at SLC6A3 is not causative for TS in the two large families that generated significant negative lod scores (if the parameters of our analyses were correct) and is unlikely to be causative in the family that generated a negative lod score that did not reach significance. These results do not exclude a role for the dopamine transporter in influencing risk for TS in combination with other loci.

Original languageEnglish (US)
Pages (from-to)459-463
Number of pages5
JournalGenomics
Volume30
Issue number3
DOIs
StatePublished - Dec 10 1995
Externally publishedYes

Fingerprint

Tourette Syndrome
Dopamine Plasma Membrane Transport Proteins
Chromosome Mapping
Lod Score
Genetic Linkage
Genes
Chromosomes
Cocaine
Paranoid Disorders
Dopaminergic Neurons
Attention Deficit Disorder with Hyperactivity
Pedigree
Psychiatry
Dopamine
Alleles
Mutation
Pharmaceutical Preparations
Proteins

ASJC Scopus subject areas

  • Genetics

Cite this

Gelernter, J., Vandenbergh, D., Kruger, S. D., Pauls, D. L., Kurlan, R., Pakstis, A. J., ... Uhl, G. (1995). The Dopamine Transporter Protein Gene (SLC6A3): Primary Linkage Mapping and Linkage Studies in Tourette Syndrome. Genomics, 30(3), 459-463. https://doi.org/10.1006/geno.1995.1265

The Dopamine Transporter Protein Gene (SLC6A3) : Primary Linkage Mapping and Linkage Studies in Tourette Syndrome. / Gelernter, Joel; Vandenbergh, David; Kruger, Susan D.; Pauls, David L.; Kurlan, Roger; Pakstis, Andrew J.; Kidd, Kenneth K.; Uhl, George.

In: Genomics, Vol. 30, No. 3, 10.12.1995, p. 459-463.

Research output: Contribution to journalArticle

Gelernter, J, Vandenbergh, D, Kruger, SD, Pauls, DL, Kurlan, R, Pakstis, AJ, Kidd, KK & Uhl, G 1995, 'The Dopamine Transporter Protein Gene (SLC6A3): Primary Linkage Mapping and Linkage Studies in Tourette Syndrome', Genomics, vol. 30, no. 3, pp. 459-463. https://doi.org/10.1006/geno.1995.1265
Gelernter J, Vandenbergh D, Kruger SD, Pauls DL, Kurlan R, Pakstis AJ et al. The Dopamine Transporter Protein Gene (SLC6A3): Primary Linkage Mapping and Linkage Studies in Tourette Syndrome. Genomics. 1995 Dec 10;30(3):459-463. https://doi.org/10.1006/geno.1995.1265
Gelernter, Joel ; Vandenbergh, David ; Kruger, Susan D. ; Pauls, David L. ; Kurlan, Roger ; Pakstis, Andrew J. ; Kidd, Kenneth K. ; Uhl, George. / The Dopamine Transporter Protein Gene (SLC6A3) : Primary Linkage Mapping and Linkage Studies in Tourette Syndrome. In: Genomics. 1995 ; Vol. 30, No. 3. pp. 459-463.
@article{e4880a20af1c460787a2cb74849d577a,
title = "The Dopamine Transporter Protein Gene (SLC6A3): Primary Linkage Mapping and Linkage Studies in Tourette Syndrome",
abstract = "The dopamine transporter, the molecule responsible for presynaptic reuptake of dopamine and a major site of action of psychostimulant drugs, including cocaine, is encoded by locus SLC6A3 (alias DAT1). The protein's actions and DAT's specific localization to dopaminergic neurons make it a candidate gene for several psychiatric illnesses. Alleles at this locus have been reported to be associated with cocaine-induced paranoia and attention deficit disorder. SLC6A3 has been mapped to distal chromosome 5p, using physical methods. Our goal was to place SLC6A3 in the genetic linkage map and to test for linkage to Tourette syndrome. Genetic linkage methods were used to place SLC6A3 in the genetic linkage map. Four extended pedigrees (one of which overlaps with CEPH) were typed. Linkage with Tourette syndrome (TS) was also examined. SLC6A3 showed close linkage with several markers previously mapped to distal chromosome 5p, including D5S11 (Zmax = 16.0, θM = θF = 0.03, results from four families) and D5S678 (Zmax = 7.84, θM = θF = 0, results from two families). Observed crossovers established that SLC6A3 is a distal marker close to D5S10 and D5S678, but these three distal markers could not be ordered. Linkage between TS and SLC6A3 could be excluded independently in two branches of a large kindred segregating TS; the lod score in a third family was also negative, but not significant. Cumulative results show a lod score of -6.2 at θ = 0 and of -3.9 at θ = 0.05 (dominant model, narrow disease definition). SLC6A3 thus maps to distal chromosome 5p by linkage analysis, in agreement with previous physical mapping data. A mutation at SLC6A3 is not causative for TS in the two large families that generated significant negative lod scores (if the parameters of our analyses were correct) and is unlikely to be causative in the family that generated a negative lod score that did not reach significance. These results do not exclude a role for the dopamine transporter in influencing risk for TS in combination with other loci.",
author = "Joel Gelernter and David Vandenbergh and Kruger, {Susan D.} and Pauls, {David L.} and Roger Kurlan and Pakstis, {Andrew J.} and Kidd, {Kenneth K.} and George Uhl",
year = "1995",
month = "12",
day = "10",
doi = "10.1006/geno.1995.1265",
language = "English (US)",
volume = "30",
pages = "459--463",
journal = "Genomics",
issn = "0888-7543",
publisher = "Academic Press Inc.",
number = "3",

}

TY - JOUR

T1 - The Dopamine Transporter Protein Gene (SLC6A3)

T2 - Primary Linkage Mapping and Linkage Studies in Tourette Syndrome

AU - Gelernter, Joel

AU - Vandenbergh, David

AU - Kruger, Susan D.

AU - Pauls, David L.

AU - Kurlan, Roger

AU - Pakstis, Andrew J.

AU - Kidd, Kenneth K.

AU - Uhl, George

PY - 1995/12/10

Y1 - 1995/12/10

N2 - The dopamine transporter, the molecule responsible for presynaptic reuptake of dopamine and a major site of action of psychostimulant drugs, including cocaine, is encoded by locus SLC6A3 (alias DAT1). The protein's actions and DAT's specific localization to dopaminergic neurons make it a candidate gene for several psychiatric illnesses. Alleles at this locus have been reported to be associated with cocaine-induced paranoia and attention deficit disorder. SLC6A3 has been mapped to distal chromosome 5p, using physical methods. Our goal was to place SLC6A3 in the genetic linkage map and to test for linkage to Tourette syndrome. Genetic linkage methods were used to place SLC6A3 in the genetic linkage map. Four extended pedigrees (one of which overlaps with CEPH) were typed. Linkage with Tourette syndrome (TS) was also examined. SLC6A3 showed close linkage with several markers previously mapped to distal chromosome 5p, including D5S11 (Zmax = 16.0, θM = θF = 0.03, results from four families) and D5S678 (Zmax = 7.84, θM = θF = 0, results from two families). Observed crossovers established that SLC6A3 is a distal marker close to D5S10 and D5S678, but these three distal markers could not be ordered. Linkage between TS and SLC6A3 could be excluded independently in two branches of a large kindred segregating TS; the lod score in a third family was also negative, but not significant. Cumulative results show a lod score of -6.2 at θ = 0 and of -3.9 at θ = 0.05 (dominant model, narrow disease definition). SLC6A3 thus maps to distal chromosome 5p by linkage analysis, in agreement with previous physical mapping data. A mutation at SLC6A3 is not causative for TS in the two large families that generated significant negative lod scores (if the parameters of our analyses were correct) and is unlikely to be causative in the family that generated a negative lod score that did not reach significance. These results do not exclude a role for the dopamine transporter in influencing risk for TS in combination with other loci.

AB - The dopamine transporter, the molecule responsible for presynaptic reuptake of dopamine and a major site of action of psychostimulant drugs, including cocaine, is encoded by locus SLC6A3 (alias DAT1). The protein's actions and DAT's specific localization to dopaminergic neurons make it a candidate gene for several psychiatric illnesses. Alleles at this locus have been reported to be associated with cocaine-induced paranoia and attention deficit disorder. SLC6A3 has been mapped to distal chromosome 5p, using physical methods. Our goal was to place SLC6A3 in the genetic linkage map and to test for linkage to Tourette syndrome. Genetic linkage methods were used to place SLC6A3 in the genetic linkage map. Four extended pedigrees (one of which overlaps with CEPH) were typed. Linkage with Tourette syndrome (TS) was also examined. SLC6A3 showed close linkage with several markers previously mapped to distal chromosome 5p, including D5S11 (Zmax = 16.0, θM = θF = 0.03, results from four families) and D5S678 (Zmax = 7.84, θM = θF = 0, results from two families). Observed crossovers established that SLC6A3 is a distal marker close to D5S10 and D5S678, but these three distal markers could not be ordered. Linkage between TS and SLC6A3 could be excluded independently in two branches of a large kindred segregating TS; the lod score in a third family was also negative, but not significant. Cumulative results show a lod score of -6.2 at θ = 0 and of -3.9 at θ = 0.05 (dominant model, narrow disease definition). SLC6A3 thus maps to distal chromosome 5p by linkage analysis, in agreement with previous physical mapping data. A mutation at SLC6A3 is not causative for TS in the two large families that generated significant negative lod scores (if the parameters of our analyses were correct) and is unlikely to be causative in the family that generated a negative lod score that did not reach significance. These results do not exclude a role for the dopamine transporter in influencing risk for TS in combination with other loci.

UR - http://www.scopus.com/inward/record.url?scp=0029563012&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029563012&partnerID=8YFLogxK

U2 - 10.1006/geno.1995.1265

DO - 10.1006/geno.1995.1265

M3 - Article

C2 - 8825631

AN - SCOPUS:0029563012

VL - 30

SP - 459

EP - 463

JO - Genomics

JF - Genomics

SN - 0888-7543

IS - 3

ER -