A convergent functional genomics approach identifies GRK3 as a candidate gene for bipolar disordr on 22q

Alexander Niculescu, R. L. Hauger, D. S. Segal, R. Kuczenski, T. Barrett, J. R. Kelsoe

Research output: Contribution to journalArticle

Abstract

We have previously reported evidence of genetic linkage of bipolar disorder to markers on 22q. In our genome survey of 20 families, the highest lod score was 3.8 at D22S278, though positive lod scores were obtained over 20 cM in that region. Such broad linkage peaks are characteristic of complex genetic traits and considerably confound efforts to fine map genes. We have addressed this problem using a convergent functional genomics approach to identify genes of likely pathophysiological significance. Rats were treated with amphetamine and saline as an animal model of mania and sacrificed 24 hours later. Prefrontal cortex and amygdala were dissected and RNA isolated for gene expression studies using the Affymetrix U34A GeneChip. Out of 8,000 genes examined, one of the genes with the largest change in expression was G protein receptor coupled kinase 3 (GRK3). GRK3 may mediate homologous desensitization of D1 receptors. It also maps very near a linkage peak (D22S419) in our family set and others. Preliminary western blot analyses of lymphoblastoid cell lines from bipolar subjects from families with evidence of linkage to 22q suggest a decrease in GRK3 expression. These data argue that GRK3 may be a susceptibility gene for bipolar disorder.

Original languageEnglish (US)
Pages (from-to)483
Number of pages1
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume96
Issue number4
StatePublished - Aug 7 2000
Externally publishedYes

Fingerprint

G-Protein-Coupled Receptor Kinase 3
Genomics
Bipolar Disorder
Lod Score
Genes
Genetic Linkage
Amphetamine
Amygdala
Prefrontal Cortex
Animal Models
Western Blotting
Genome
RNA
Gene Expression
Cell Line

ASJC Scopus subject areas

  • Genetics(clinical)
  • Neuropsychology and Physiological Psychology
  • Neuroscience(all)

Cite this

A convergent functional genomics approach identifies GRK3 as a candidate gene for bipolar disordr on 22q. / Niculescu, Alexander; Hauger, R. L.; Segal, D. S.; Kuczenski, R.; Barrett, T.; Kelsoe, J. R.

In: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, Vol. 96, No. 4, 07.08.2000, p. 483.

Research output: Contribution to journalArticle

@article{0d61be8c0c9c4718b3008b7d647e473e,
title = "A convergent functional genomics approach identifies GRK3 as a candidate gene for bipolar disordr on 22q",
abstract = "We have previously reported evidence of genetic linkage of bipolar disorder to markers on 22q. In our genome survey of 20 families, the highest lod score was 3.8 at D22S278, though positive lod scores were obtained over 20 cM in that region. Such broad linkage peaks are characteristic of complex genetic traits and considerably confound efforts to fine map genes. We have addressed this problem using a convergent functional genomics approach to identify genes of likely pathophysiological significance. Rats were treated with amphetamine and saline as an animal model of mania and sacrificed 24 hours later. Prefrontal cortex and amygdala were dissected and RNA isolated for gene expression studies using the Affymetrix U34A GeneChip. Out of 8,000 genes examined, one of the genes with the largest change in expression was G protein receptor coupled kinase 3 (GRK3). GRK3 may mediate homologous desensitization of D1 receptors. It also maps very near a linkage peak (D22S419) in our family set and others. Preliminary western blot analyses of lymphoblastoid cell lines from bipolar subjects from families with evidence of linkage to 22q suggest a decrease in GRK3 expression. These data argue that GRK3 may be a susceptibility gene for bipolar disorder.",
author = "Alexander Niculescu and Hauger, {R. L.} and Segal, {D. S.} and R. Kuczenski and T. Barrett and Kelsoe, {J. R.}",
year = "2000",
month = "8",
day = "7",
language = "English (US)",
volume = "96",
pages = "483",
journal = "American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics",
issn = "1552-4841",
publisher = "Wiley-Liss Inc.",
number = "4",

}

TY - JOUR

T1 - A convergent functional genomics approach identifies GRK3 as a candidate gene for bipolar disordr on 22q

AU - Niculescu, Alexander

AU - Hauger, R. L.

AU - Segal, D. S.

AU - Kuczenski, R.

AU - Barrett, T.

AU - Kelsoe, J. R.

PY - 2000/8/7

Y1 - 2000/8/7

N2 - We have previously reported evidence of genetic linkage of bipolar disorder to markers on 22q. In our genome survey of 20 families, the highest lod score was 3.8 at D22S278, though positive lod scores were obtained over 20 cM in that region. Such broad linkage peaks are characteristic of complex genetic traits and considerably confound efforts to fine map genes. We have addressed this problem using a convergent functional genomics approach to identify genes of likely pathophysiological significance. Rats were treated with amphetamine and saline as an animal model of mania and sacrificed 24 hours later. Prefrontal cortex and amygdala were dissected and RNA isolated for gene expression studies using the Affymetrix U34A GeneChip. Out of 8,000 genes examined, one of the genes with the largest change in expression was G protein receptor coupled kinase 3 (GRK3). GRK3 may mediate homologous desensitization of D1 receptors. It also maps very near a linkage peak (D22S419) in our family set and others. Preliminary western blot analyses of lymphoblastoid cell lines from bipolar subjects from families with evidence of linkage to 22q suggest a decrease in GRK3 expression. These data argue that GRK3 may be a susceptibility gene for bipolar disorder.

AB - We have previously reported evidence of genetic linkage of bipolar disorder to markers on 22q. In our genome survey of 20 families, the highest lod score was 3.8 at D22S278, though positive lod scores were obtained over 20 cM in that region. Such broad linkage peaks are characteristic of complex genetic traits and considerably confound efforts to fine map genes. We have addressed this problem using a convergent functional genomics approach to identify genes of likely pathophysiological significance. Rats were treated with amphetamine and saline as an animal model of mania and sacrificed 24 hours later. Prefrontal cortex and amygdala were dissected and RNA isolated for gene expression studies using the Affymetrix U34A GeneChip. Out of 8,000 genes examined, one of the genes with the largest change in expression was G protein receptor coupled kinase 3 (GRK3). GRK3 may mediate homologous desensitization of D1 receptors. It also maps very near a linkage peak (D22S419) in our family set and others. Preliminary western blot analyses of lymphoblastoid cell lines from bipolar subjects from families with evidence of linkage to 22q suggest a decrease in GRK3 expression. These data argue that GRK3 may be a susceptibility gene for bipolar disorder.

UR - http://www.scopus.com/inward/record.url?scp=33749100406&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33749100406&partnerID=8YFLogxK

M3 - Article

VL - 96

SP - 483

JO - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics

JF - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics

SN - 1552-4841

IS - 4

ER -