A. Cravchik - Academia.edu (original) (raw)

Papers by A. Cravchik

Research paper thumbnail of The Genome Sequence of the Malaria Mosquito Anopheles gambiae

Science, 2002

Anopheles gambiae is the principal vector of malaria, a disease that afflicts more than 500 milli... more Anopheles gambiae is the principal vector of malaria, a disease that afflicts more than 500 million people and causes more than 1 million deaths each year. Tenfold shotgun sequence coverage was obtained from the PEST strain of A. gambiae and assembled into scaffolds that span 278 million base pairs. A total of 91% of the genome was organized in 303 scaffolds; the largest scaffold was 23.1 million base pairs. There was substantial genetic variation within this strain, and the apparent existence of two haplotypes of approximately equal frequency (“dual haplotypes”) in a substantial fraction of the genome likely reflects the outbred nature of the PEST strain. The sequence produced a conservative inference of more than 400,000 single-nucleotide polymorphisms that showed a markedly bimodal density distribution. Analysis of the genome sequence revealed strong evidence for about 14,000 protein-encoding transcripts. Prominent expansions in specific families of proteins likely involved in ce...

Research paper thumbnail of Identification of a novel microtubule-binding domain in microtubule-associated protein 1A (MAP1A)

Journal of Cell Science, 1994

Several microtubule-associated proteins (MAPs) have been shown to bind to microtubules via short ... more Several microtubule-associated proteins (MAPs) have been shown to bind to microtubules via short sequences with repeated amino acids motifs. A microtubule-binding domain has hitherto not been defined for the adult brain microtubule-associated protein 1A (MAP1A). We have searched for a microtubule-binding domain by expressing different protein regions of MAP1A in cultured cell lines using cDNA constructs. One construct included an area with homology to the microtubule-binding domain of MAP1B (Noble et al. (1989) J. Cell Biol. 109, 437-448), but this did not bind to microtubules in transfected cells. Further investigation of other areas of MAP1A revealed a protein domain, capable of autonomously binding to microtubules, which bears no homology to any previously described microtubule-binding sequence. This MAP1A domain is rich in charged amino acids, as are other mammalian microtubule-binding domains, but unlike them has no identifiable sequence repeats. Whereas all previously describe...

Research paper thumbnail of The Sequence of the Human Genome

Research paper thumbnail of Identification of a novel microtubule-binding domain in microtubule-associated protein 1A (MAP1A)

Several microtubule-associated proteins (MAPs) have been shown to bind to microtubules via short ... more Several microtubule-associated proteins (MAPs) have been shown to bind to microtubules via short sequences with repeated amino acids motifs. A microtubule-binding domain has hitherto not been defined for the adult brain microtubule-associated protein 1A (MAP1A). We have searched for a microtubule-binding domain by expressing different protein regions of MAP1A in cultured cell lines using cDNA constructs. One construct included an area with homology to the microtubule-binding domain of MAP1B (Noble et al. (1989) J. Cell Biol. 109, 437-448), but this did not bind to microtubules in transfected cells. Further investigation of other areas of MAP1A revealed a protein domain, capable of autonomously binding to microtubules, which bears no homology to any previously described microtubule-binding sequence. This MAP1A domain is rich in charged amino acids, as are other mammalian microtubule-binding domains, but unlike them has no identifiable sequence repeats. Whereas all previously describe...

Research paper thumbnail of Functional analysis of the human D5 dopamine receptor missense and nonsense variants: differences in dopamine binding affinities

Pharmacogenetics, 1999

The functional analysis of expressed human gene variants is important in the study of genetic sus... more The functional analysis of expressed human gene variants is important in the study of genetic susceptibility to diseases, pharmacogenetic traits and for the investigation of the human genetic diversity at the molecular level. We have performed the analysis of sequence polymorphisms in the human D5 dopamine receptor gene (DRD5) predicting missense and nonsense amino acid changes in the receptor protein. The amino acid substitutions in the human D5 dopamine receptor are: Leu88 to Phe in the putative second transmembrane domain, Ala269 to Val in the third intracellular and Pro330 to Gln in the third extracellular loops, Asn351 to Asp in the seventh transmembrane and Ser453 to Cys in the C-terminal domains and Cys335 to Stop in the third extracellular loop. The two amino acid substitutions in the transmembrane domains had an effect on agonist binding to the human D5 dopamine receptor. Asn351 to Asp resulted in an approximately 10-fold decrease in dopamine and threefold decrease in R(+)-...

Research paper thumbnail of Identification of a novel microtubule-binding domain in microtubule-associated protein 1A (MAP1A)

Journal of cell science, 1994

Several microtubule-associated proteins (MAPs) have been shown to bind to microtubules via short ... more Several microtubule-associated proteins (MAPs) have been shown to bind to microtubules via short sequences with repeated amino acids motifs. A microtubule-binding domain has hitherto not been defined for the adult brain microtubule-associated protein 1A (MAP1A). We have searched for a microtubule-binding domain by expressing different protein regions of MAP1A in cultured cell lines using cDNA constructs. One construct included an area with homology to the microtubule-binding domain of MAP1B (Noble et al. (1989) J. Cell Biol. 109, 437-448), but this did not bind to microtubules in transfected cells. Further investigation of other areas of MAP1A revealed a protein domain, capable of autonomously binding to microtubules, which bears no homology to any previously described microtubule-binding sequence. This MAP1A domain is rich in charged amino acids, as are other mammalian microtubule-binding domains, but unlike them has no identifiable sequence repeats. Whereas all previously describe...

Research paper thumbnail of A novel strategy for the immunological tagging of cDNA constructs

Gene, 1993

We describe the construction of pBact-myc, an expression vector that incorporates an immunologica... more We describe the construction of pBact-myc, an expression vector that incorporates an immunological 'tag' into the produced polypeptide. When transfected into recipient cell lines, tagged protein fragments derived from any source can be visualised using a single monoclonal antibody (mAb). The neuronal-associated protein 2c (MAP2c) was tagged with a sequence encoding a peptide from the human c-myc gene. The preservation of normal function of the tagged protein was shown by transfecting it into cultured cell lines. No difference in binding ability to cellular microtubules could be observed between the myc-tagged MAP2c and the wild-type forms, and both produced the same characteristic changes in microtubule organisation. This approach is being used to study the biological function of selected fragments of MAP2c and other MAP-encoding genes. The pBact-myc expression vector represents a fast and convenient way to produce tagged polypeptides of selected sequences encoding whole proteins or fragments, for the analysis of their function in living cells.

Research paper thumbnail of A novel strategy for the immunological tagging of cDNA constructs

Gene, 1993

We describe the construction of pBact-myc, an expression vector that incorporates an immunologica... more We describe the construction of pBact-myc, an expression vector that incorporates an immunological 'tag' into the produced polypeptide. When transfected into recipient cell lines, tagged protein fragments derived from any source can be visualised using a single monoclonal antibody (mAb). The neuronal-associated protein 2c (MAP2c) was tagged with a sequence encoding a peptide from the human c-myc gene. The preservation of normal function of the tagged protein was shown by transfecting it into cultured cell lines. No difference in binding ability to cellular microtubules could be observed between the myc-tagged MAP2c and the wild-type forms, and both produced the same characteristic changes in microtubule organisation. This approach is being used to study the biological function of selected fragments of MAP2c and other MAP-encoding genes. The pBact-myc expression vector represents a fast and convenient way to produce tagged polypeptides of selected sequences encoding whole proteins or fragments, for the analysis of their function in living cells.

Research paper thumbnail of Sequence Analysis of the Human Genome

Archives of Neurology, 2001

Research paper thumbnail of Major Depressive Disorder With Subthreshold Bipolarity: Exploring and Managing New Diagnoses

American Journal of Psychiatry, 2010

Objectives-There is growing clinical and epidemiologic evidence indicating that major mood disord... more Objectives-There is growing clinical and epidemiologic evidence indicating that major mood disorders form a spectrum from Major Depressive Disorder (MDD) to pure mania. The present investigation examined the prevalence and clinical correlates of MDD with sub-threshold bipolarity vs. pure MDD in the National Comorbidity Survey Replication (NCS-R).

Research paper thumbnail of Functional analysis of the human D5 dopamine receptor missense and nonsense variants: differences in dopamine binding affinities

Pharmacogenetics, 1999

The functional analysis of expressed human gene variants is important in the study of genetic sus... more The functional analysis of expressed human gene variants is important in the study of genetic susceptibility to diseases, pharmacogenetic traits and for the investigation of the human genetic diversity at the molecular level. We have performed the analysis of sequence polymorphisms in the human D5 dopamine receptor gene (DRD5) predicting missense and nonsense amino acid changes in the receptor protein. The amino acid substitutions in the human D5 dopamine receptor are: Leu88 to Phe in the putative second transmembrane domain, Ala269 to Val in the third intracellular and Pro330 to Gln in the third extracellular loops, Asn351 to Asp in the seventh transmembrane and Ser453 to Cys in the C-terminal domains and Cys335 to Stop in the third extracellular loop. The two amino acid substitutions in the transmembrane domains had an effect on agonist binding to the human D5 dopamine receptor. Asn351 to Asp resulted in an approximately 10-fold decrease in dopamine and threefold decrease in R(+)-...

Research paper thumbnail of Polymorphisms in known genes associated with inflammatory autoimmune disease, methods of detection and uses thereof

Research paper thumbnail of Polymorphisms in known genes associated with human disease, methods of detection and uses thereof

Research paper thumbnail of Analysis of neuroleptic binding affinities and potencies for the different human D2 dopamine receptor missense variants

Pharmacogenetics, 1999

Neuroleptics, or antipsychotics, are widely used for the treatment of psychotic symptoms such as ... more Neuroleptics, or antipsychotics, are widely used for the treatment of psychotic symptoms such as hallucinations and delusions in schizophrenia and other psychiatric disorders. Pharmacotherapy of these diseases is frequently complicated by a great variability in the clinical response to neuroleptics and by the development of serious and potentially life-threatening side-effects. Brain D2 dopamine receptors are one of the major targets of neuroleptic treatment. The human D2 dopamine receptor (DRD2) gene has three variants predicting the amino acid substitutions Ser311Cys, Pro310Ser and Val96Ala in the receptor protein. We show that several typical and atypical neuroleptics commonly used in the treatment of psychotic disorders have differences in binding affinities and potencies for the D2 dopamine receptor variants. Functional differences between dopamine receptor variants might be related to genetically determined differences in response to neuroleptic treatment.

Research paper thumbnail of Functional Analysis of the Human D2 Dopamine Receptor Missense Variants

Journal of Biological Chemistry, 1996

The human dopamine D2 receptor gene (DRD2) has three polymorphic variants that predict the amino ... more The human dopamine D2 receptor gene (DRD2) has three polymorphic variants that predict the amino acid substitutions Val96 --> Ala, Pro310 --> Ser, and Ser311 --> Cys in the receptor protein. We have investigated the ligand binding and signal transduction properties of these human D2 receptor variants by stably expressing them in cultured mammalian cells. The Cys311 and Ser310 variants of the human D2 receptor, which involve substitutions located in the third cytoplasmic loop, were markedly less effective in inhibiting cAMP synthesis than the most prevalent form (Pro310, Ser311). Despite this difference, the Cys311 and Ser310 variants couple to G proteins in CHO-K1 (Chinese hamster ovary) cells. The impairment of the Cys311 and Ser310 variants to inhibit cAMP levels thus appears to result from a reduced ability of those variant receptors to activate the appropriate Gi-like protein. The demonstration of substantial functional differences between DRD2 gene variants found in the human population might have important pharmacological implications given the widespread use of D2 receptor blocking drugs in the treatment of schizophrenia and other psychiatric disorders.

Research paper thumbnail of A Chemosensory Gene Family Encoding Candidate Gustatory and Olfactory Receptors in Drosophila

Research paper thumbnail of 386. Genetic variation in dopamine and serotonin function

Biological Psychiatry, 2000

maturation of certain neuronal circuits in the neocortex and/or striatum could, at least in part,... more maturation of certain neuronal circuits in the neocortex and/or striatum could, at least in part, be involved in the development of the behavioral responses to these drugs. To further explore certain genes that play a crucial role in the maturation of these behavioral responses, we have studied differences in MAP-or PCP-induced gene expression in the discrete brain regions between neonatal and adult period using a RNA arbitrarily primed PCR technique.

Research paper thumbnail of Antagonist Binding Characteristics of the Ser311→Cys Variant of Human Dopamine D2Receptorin Vivoandin Vitro

Biochemical and Biophysical Research Communications, 1997

tor changes has extensively been explored (2-6). Three We report in vivo and in vitro antagonist ... more tor changes has extensively been explored (2-6). Three We report in vivo and in vitro antagonist binding relatively rare naturally occurring nucleotide variants characteristics of the naturally occurring Ser 311 rCys predicting an altered amino acid sequence have been variant of the human D 2 dopamine receptor. Striatal identified in the D 2 receptor gene (5,6). The allelic frereceptor binding characteristics in vivo were meaquencies of the amino acid substitutions in Caucasians sured with positron emission tomography and the D 2 are 0.014 for Ser 311 rCys and 0.001 for Pro 310 rSer subantagonist [ 11 C]raclopride. The in vitro affinity of stitutions, respectively. Additionally, one subject heterraclopride for the Ser 311 rCys variant and the wild type otsygous for Val 96 rAla substitution has been detected receptor was studied in membrane binding assays in a sample of 380 Caucasians (5).

Research paper thumbnail of Neurochemical Individuality

Archives of General Psychiatry, 2000

Research paper thumbnail of No association detected between a Dâ receptor gene-expressed variant and schizophrenia

American Journal of Medical Genetics, 1996

A missense polymorphism (glycine to serine) in the first exon of the dopamine Dâ (DRD3) gene was ... more A missense polymorphism (glycine to serine) in the first exon of the dopamine Dâ (DRD3) gene was examined in a sib-pairs schizophrenia collection by the transmission test for linkage disequilibrium (TDT). No association due to linkage disequilibrium was detected using TDT. Additionally, no evidence for excess homozygosity was found. 26 refs., 3 tabs.

Research paper thumbnail of The Genome Sequence of the Malaria Mosquito Anopheles gambiae

Science, 2002

Anopheles gambiae is the principal vector of malaria, a disease that afflicts more than 500 milli... more Anopheles gambiae is the principal vector of malaria, a disease that afflicts more than 500 million people and causes more than 1 million deaths each year. Tenfold shotgun sequence coverage was obtained from the PEST strain of A. gambiae and assembled into scaffolds that span 278 million base pairs. A total of 91% of the genome was organized in 303 scaffolds; the largest scaffold was 23.1 million base pairs. There was substantial genetic variation within this strain, and the apparent existence of two haplotypes of approximately equal frequency (“dual haplotypes”) in a substantial fraction of the genome likely reflects the outbred nature of the PEST strain. The sequence produced a conservative inference of more than 400,000 single-nucleotide polymorphisms that showed a markedly bimodal density distribution. Analysis of the genome sequence revealed strong evidence for about 14,000 protein-encoding transcripts. Prominent expansions in specific families of proteins likely involved in ce...

Research paper thumbnail of Identification of a novel microtubule-binding domain in microtubule-associated protein 1A (MAP1A)

Journal of Cell Science, 1994

Several microtubule-associated proteins (MAPs) have been shown to bind to microtubules via short ... more Several microtubule-associated proteins (MAPs) have been shown to bind to microtubules via short sequences with repeated amino acids motifs. A microtubule-binding domain has hitherto not been defined for the adult brain microtubule-associated protein 1A (MAP1A). We have searched for a microtubule-binding domain by expressing different protein regions of MAP1A in cultured cell lines using cDNA constructs. One construct included an area with homology to the microtubule-binding domain of MAP1B (Noble et al. (1989) J. Cell Biol. 109, 437-448), but this did not bind to microtubules in transfected cells. Further investigation of other areas of MAP1A revealed a protein domain, capable of autonomously binding to microtubules, which bears no homology to any previously described microtubule-binding sequence. This MAP1A domain is rich in charged amino acids, as are other mammalian microtubule-binding domains, but unlike them has no identifiable sequence repeats. Whereas all previously describe...

Research paper thumbnail of The Sequence of the Human Genome

Research paper thumbnail of Identification of a novel microtubule-binding domain in microtubule-associated protein 1A (MAP1A)

Several microtubule-associated proteins (MAPs) have been shown to bind to microtubules via short ... more Several microtubule-associated proteins (MAPs) have been shown to bind to microtubules via short sequences with repeated amino acids motifs. A microtubule-binding domain has hitherto not been defined for the adult brain microtubule-associated protein 1A (MAP1A). We have searched for a microtubule-binding domain by expressing different protein regions of MAP1A in cultured cell lines using cDNA constructs. One construct included an area with homology to the microtubule-binding domain of MAP1B (Noble et al. (1989) J. Cell Biol. 109, 437-448), but this did not bind to microtubules in transfected cells. Further investigation of other areas of MAP1A revealed a protein domain, capable of autonomously binding to microtubules, which bears no homology to any previously described microtubule-binding sequence. This MAP1A domain is rich in charged amino acids, as are other mammalian microtubule-binding domains, but unlike them has no identifiable sequence repeats. Whereas all previously describe...

Research paper thumbnail of Functional analysis of the human D5 dopamine receptor missense and nonsense variants: differences in dopamine binding affinities

Pharmacogenetics, 1999

The functional analysis of expressed human gene variants is important in the study of genetic sus... more The functional analysis of expressed human gene variants is important in the study of genetic susceptibility to diseases, pharmacogenetic traits and for the investigation of the human genetic diversity at the molecular level. We have performed the analysis of sequence polymorphisms in the human D5 dopamine receptor gene (DRD5) predicting missense and nonsense amino acid changes in the receptor protein. The amino acid substitutions in the human D5 dopamine receptor are: Leu88 to Phe in the putative second transmembrane domain, Ala269 to Val in the third intracellular and Pro330 to Gln in the third extracellular loops, Asn351 to Asp in the seventh transmembrane and Ser453 to Cys in the C-terminal domains and Cys335 to Stop in the third extracellular loop. The two amino acid substitutions in the transmembrane domains had an effect on agonist binding to the human D5 dopamine receptor. Asn351 to Asp resulted in an approximately 10-fold decrease in dopamine and threefold decrease in R(+)-...

Research paper thumbnail of Identification of a novel microtubule-binding domain in microtubule-associated protein 1A (MAP1A)

Journal of cell science, 1994

Several microtubule-associated proteins (MAPs) have been shown to bind to microtubules via short ... more Several microtubule-associated proteins (MAPs) have been shown to bind to microtubules via short sequences with repeated amino acids motifs. A microtubule-binding domain has hitherto not been defined for the adult brain microtubule-associated protein 1A (MAP1A). We have searched for a microtubule-binding domain by expressing different protein regions of MAP1A in cultured cell lines using cDNA constructs. One construct included an area with homology to the microtubule-binding domain of MAP1B (Noble et al. (1989) J. Cell Biol. 109, 437-448), but this did not bind to microtubules in transfected cells. Further investigation of other areas of MAP1A revealed a protein domain, capable of autonomously binding to microtubules, which bears no homology to any previously described microtubule-binding sequence. This MAP1A domain is rich in charged amino acids, as are other mammalian microtubule-binding domains, but unlike them has no identifiable sequence repeats. Whereas all previously describe...

Research paper thumbnail of A novel strategy for the immunological tagging of cDNA constructs

Gene, 1993

We describe the construction of pBact-myc, an expression vector that incorporates an immunologica... more We describe the construction of pBact-myc, an expression vector that incorporates an immunological 'tag' into the produced polypeptide. When transfected into recipient cell lines, tagged protein fragments derived from any source can be visualised using a single monoclonal antibody (mAb). The neuronal-associated protein 2c (MAP2c) was tagged with a sequence encoding a peptide from the human c-myc gene. The preservation of normal function of the tagged protein was shown by transfecting it into cultured cell lines. No difference in binding ability to cellular microtubules could be observed between the myc-tagged MAP2c and the wild-type forms, and both produced the same characteristic changes in microtubule organisation. This approach is being used to study the biological function of selected fragments of MAP2c and other MAP-encoding genes. The pBact-myc expression vector represents a fast and convenient way to produce tagged polypeptides of selected sequences encoding whole proteins or fragments, for the analysis of their function in living cells.

Research paper thumbnail of A novel strategy for the immunological tagging of cDNA constructs

Gene, 1993

We describe the construction of pBact-myc, an expression vector that incorporates an immunologica... more We describe the construction of pBact-myc, an expression vector that incorporates an immunological 'tag' into the produced polypeptide. When transfected into recipient cell lines, tagged protein fragments derived from any source can be visualised using a single monoclonal antibody (mAb). The neuronal-associated protein 2c (MAP2c) was tagged with a sequence encoding a peptide from the human c-myc gene. The preservation of normal function of the tagged protein was shown by transfecting it into cultured cell lines. No difference in binding ability to cellular microtubules could be observed between the myc-tagged MAP2c and the wild-type forms, and both produced the same characteristic changes in microtubule organisation. This approach is being used to study the biological function of selected fragments of MAP2c and other MAP-encoding genes. The pBact-myc expression vector represents a fast and convenient way to produce tagged polypeptides of selected sequences encoding whole proteins or fragments, for the analysis of their function in living cells.

Research paper thumbnail of Sequence Analysis of the Human Genome

Archives of Neurology, 2001

Research paper thumbnail of Major Depressive Disorder With Subthreshold Bipolarity: Exploring and Managing New Diagnoses

American Journal of Psychiatry, 2010

Objectives-There is growing clinical and epidemiologic evidence indicating that major mood disord... more Objectives-There is growing clinical and epidemiologic evidence indicating that major mood disorders form a spectrum from Major Depressive Disorder (MDD) to pure mania. The present investigation examined the prevalence and clinical correlates of MDD with sub-threshold bipolarity vs. pure MDD in the National Comorbidity Survey Replication (NCS-R).

Research paper thumbnail of Functional analysis of the human D5 dopamine receptor missense and nonsense variants: differences in dopamine binding affinities

Pharmacogenetics, 1999

The functional analysis of expressed human gene variants is important in the study of genetic sus... more The functional analysis of expressed human gene variants is important in the study of genetic susceptibility to diseases, pharmacogenetic traits and for the investigation of the human genetic diversity at the molecular level. We have performed the analysis of sequence polymorphisms in the human D5 dopamine receptor gene (DRD5) predicting missense and nonsense amino acid changes in the receptor protein. The amino acid substitutions in the human D5 dopamine receptor are: Leu88 to Phe in the putative second transmembrane domain, Ala269 to Val in the third intracellular and Pro330 to Gln in the third extracellular loops, Asn351 to Asp in the seventh transmembrane and Ser453 to Cys in the C-terminal domains and Cys335 to Stop in the third extracellular loop. The two amino acid substitutions in the transmembrane domains had an effect on agonist binding to the human D5 dopamine receptor. Asn351 to Asp resulted in an approximately 10-fold decrease in dopamine and threefold decrease in R(+)-...

Research paper thumbnail of Polymorphisms in known genes associated with inflammatory autoimmune disease, methods of detection and uses thereof

Research paper thumbnail of Polymorphisms in known genes associated with human disease, methods of detection and uses thereof

Research paper thumbnail of Analysis of neuroleptic binding affinities and potencies for the different human D2 dopamine receptor missense variants

Pharmacogenetics, 1999

Neuroleptics, or antipsychotics, are widely used for the treatment of psychotic symptoms such as ... more Neuroleptics, or antipsychotics, are widely used for the treatment of psychotic symptoms such as hallucinations and delusions in schizophrenia and other psychiatric disorders. Pharmacotherapy of these diseases is frequently complicated by a great variability in the clinical response to neuroleptics and by the development of serious and potentially life-threatening side-effects. Brain D2 dopamine receptors are one of the major targets of neuroleptic treatment. The human D2 dopamine receptor (DRD2) gene has three variants predicting the amino acid substitutions Ser311Cys, Pro310Ser and Val96Ala in the receptor protein. We show that several typical and atypical neuroleptics commonly used in the treatment of psychotic disorders have differences in binding affinities and potencies for the D2 dopamine receptor variants. Functional differences between dopamine receptor variants might be related to genetically determined differences in response to neuroleptic treatment.

Research paper thumbnail of Functional Analysis of the Human D2 Dopamine Receptor Missense Variants

Journal of Biological Chemistry, 1996

The human dopamine D2 receptor gene (DRD2) has three polymorphic variants that predict the amino ... more The human dopamine D2 receptor gene (DRD2) has three polymorphic variants that predict the amino acid substitutions Val96 --> Ala, Pro310 --> Ser, and Ser311 --> Cys in the receptor protein. We have investigated the ligand binding and signal transduction properties of these human D2 receptor variants by stably expressing them in cultured mammalian cells. The Cys311 and Ser310 variants of the human D2 receptor, which involve substitutions located in the third cytoplasmic loop, were markedly less effective in inhibiting cAMP synthesis than the most prevalent form (Pro310, Ser311). Despite this difference, the Cys311 and Ser310 variants couple to G proteins in CHO-K1 (Chinese hamster ovary) cells. The impairment of the Cys311 and Ser310 variants to inhibit cAMP levels thus appears to result from a reduced ability of those variant receptors to activate the appropriate Gi-like protein. The demonstration of substantial functional differences between DRD2 gene variants found in the human population might have important pharmacological implications given the widespread use of D2 receptor blocking drugs in the treatment of schizophrenia and other psychiatric disorders.

Research paper thumbnail of A Chemosensory Gene Family Encoding Candidate Gustatory and Olfactory Receptors in Drosophila

Research paper thumbnail of 386. Genetic variation in dopamine and serotonin function

Biological Psychiatry, 2000

maturation of certain neuronal circuits in the neocortex and/or striatum could, at least in part,... more maturation of certain neuronal circuits in the neocortex and/or striatum could, at least in part, be involved in the development of the behavioral responses to these drugs. To further explore certain genes that play a crucial role in the maturation of these behavioral responses, we have studied differences in MAP-or PCP-induced gene expression in the discrete brain regions between neonatal and adult period using a RNA arbitrarily primed PCR technique.

Research paper thumbnail of Antagonist Binding Characteristics of the Ser311→Cys Variant of Human Dopamine D2Receptorin Vivoandin Vitro

Biochemical and Biophysical Research Communications, 1997

tor changes has extensively been explored (2-6). Three We report in vivo and in vitro antagonist ... more tor changes has extensively been explored (2-6). Three We report in vivo and in vitro antagonist binding relatively rare naturally occurring nucleotide variants characteristics of the naturally occurring Ser 311 rCys predicting an altered amino acid sequence have been variant of the human D 2 dopamine receptor. Striatal identified in the D 2 receptor gene (5,6). The allelic frereceptor binding characteristics in vivo were meaquencies of the amino acid substitutions in Caucasians sured with positron emission tomography and the D 2 are 0.014 for Ser 311 rCys and 0.001 for Pro 310 rSer subantagonist [ 11 C]raclopride. The in vitro affinity of stitutions, respectively. Additionally, one subject heterraclopride for the Ser 311 rCys variant and the wild type otsygous for Val 96 rAla substitution has been detected receptor was studied in membrane binding assays in a sample of 380 Caucasians (5).

Research paper thumbnail of Neurochemical Individuality

Archives of General Psychiatry, 2000

Research paper thumbnail of No association detected between a Dâ receptor gene-expressed variant and schizophrenia

American Journal of Medical Genetics, 1996

A missense polymorphism (glycine to serine) in the first exon of the dopamine Dâ (DRD3) gene was ... more A missense polymorphism (glycine to serine) in the first exon of the dopamine Dâ (DRD3) gene was examined in a sib-pairs schizophrenia collection by the transmission test for linkage disequilibrium (TDT). No association due to linkage disequilibrium was detected using TDT. Additionally, no evidence for excess homozygosity was found. 26 refs., 3 tabs.