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1.
J Cell Biol ; 35(3): 699-708, 1967 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-6064370

RESUMO

It has frequently been proposed that a variation in the relative content of lysine-rich, moderately lysine-rich, and arginine-rich histones might provide a mechanism by which specific portions of the genome may be genetically regulated. This possibility was investigated by comparing the electrophoretic pattern of these three fractions in cells differing markedly in their content of genetically active and genetically inactive chromatin. Three models were used: heterochromatin versus euchromatin; metaphase cells versus interphase cells, and mature lymphocytes versus phytohemagglutinin-stimulated lymphocytes. In no case was there a significant difference in the histone patterns of these contrasting models. It is concluded that, although histones may act as a generalized repressor and structural component of chromatin, factors other than a variation in histone pattern may be responsible for repression or derepression of specific segments of the genome.


Assuntos
Cromossomos/fisiologia , Histonas/análise , Animais , Arginina , Núcleo Celular , Citoplasma , Eletroforese , Feminino , Géis , Humanos , Linfócitos , Lisina , Masculino , Mitose , Modelos Biológicos , Trítio
2.
J Cell Biol ; 28(3): 437-41, 1966 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-5960806

RESUMO

To obtain an estimate of the rate of RNA synthesis by the heterochromatic sex chromatin body, human female fibroblasts were labeled with uridine-5-H(3) and radioautographed. The number of grains over the sex chromatin body was compared with the number of grains over a comparable area of euchromatin. The ratio was 0.37. When corrected for the higher content of DNA per unit area in heterochromatin, the maximum rate of RNA synthesis by the DNA of the sex chromatin body was approximately 18% of the rate of RNA synthesis by a comparable amount of euchromatin DNA. The rate of RNA synthesis by the sex chromatin body did not increase significantly with partial despiralization of this chromatin at prophase.


Assuntos
RNA/biossíntese , Cromatina Sexual/análise , Adolescente , Autorradiografia , DNA/metabolismo , Feminino , Fibroblastos/análise , Humanos , Trítio , Uridina/metabolismo
3.
J Cell Biol ; 70(2 pt 1): 440-52, 1976 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-939784

RESUMO

High resolution SDS slab gel electrophoresis has been used to examine the distribution of nonhistone proteins (NHP) in the saline-EDTA, Tris, and 0.35 M NaCl washes of isolated mouse liver nuclei. These studies led to the following conclusions: (a) all the prominent NHP which remain bound to DNA are also present in somewhat similar proportions in the saline-EDTA, Tris, and 0.35 M NaCl washes of nuclei; (b) a protein comigrating with actin is prominent in the first saline-EDTA wash of nuclei, but present as only a minor band in the subsequent washes and on washed chromatin; (c) the presence of nuclear matrix proteins in all the nuclear washes and cytosol indicates that these proteins are distributed throughout the cell; (d) a histone-binding protein (J2) analogous to the HMG1 protein of K. V. Shooter, G.H. Goodwin, and E.W. Johns (Eur J. Biochem. 47:236-270) is a prominent nucleoplasmic protein; (e) quantitation of the major NHP indicates that they are present in a range of 2.2 X 10(5)-5.2 X 10(6) copies per diploid nucleus. Most of the electrophoretically visible NHP are probably structural rather than regulatory proteins; (f) actin, myosin, tubulin, and tropomyosin, if present at all, constitute a very minor fraction of the nuclear NHP. Contractile proteins constitute a major portion of the NHP only when the chromatin is prepared from crude cell lysates instead of from purified nuclei. These studies support the conclusion that there are no clear differences between many nucleoplasmic and chromatin-bound nonhistone proteins. Except for the histones, many of the intranuclear proteins appear to be in equilibrium between DNA, HnRNA, and the nucleoplasm.


Assuntos
Núcleo Celular/análise , Cromatina/análise , Fígado/ultraestrutura , Nucleoproteínas/análise , Actinas/análise , Animais , Cromatina/isolamento & purificação , Citoplasma/análise , Eletroforese em Gel de Poliacrilamida , Histonas/análise , Camundongos , Miosinas/análise , Proteínas/análise , Tropomiosina/análise
4.
Science ; 154(3755): 1463-4, 1966 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-5921612

RESUMO

Cultures of human fibroblasts were labeled briefly with tritiated thymidine and fixed; autoradiographs were made and exposed for 3(1/2) months. No labeling was noted over the centromere of metaphase or anaphase chromosomes. The technique was sensitive to replication at the centromere of a DNA helix only 2.5 microns long, considerably shorter than the estimated length of a replicon in humans. This suggests that chromatid separation during mitosis is not associated with delayed replication of a short segment of chromosomal DNA.


Assuntos
Divisão Celular , DNA/biossíntese , Fibroblastos , Timidina/metabolismo , Autorradiografia , Feminino , Humanos , Técnicas In Vitro , Pele , Trítio
5.
Science ; 193(4253): 599-602, 1976 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-959822

RESUMO

Polylysine, polyarginine, and histones H1, H2A, H2B, and H3 inhibit Giemsa staining and chromosome banding by binding to DNA and preventing side stacking of the positively charged thiazine dyes to the negatively charged phosphate groups on DNA. This is a nonspecific effect and does not of itself provide evidence for a role of histones in G banding. The question of whether histones are involved in chromosome banding is reviewed.


Assuntos
Corantes Azur , Cromossomos/ultraestrutura , Histonas/metabolismo , Fenotiazinas , Arginina/metabolismo , Linhagem Celular , Ponto Isoelétrico , Lisina/metabolismo , Peptídeos/metabolismo
6.
Biochim Biophys Acta ; 532(1): 122-36, 1978 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-620049

RESUMO

We examined four extracts of mouse liver for histone-binding proteins using histone affinity chromatography and positively charged resins. The extracts used were cytoplasm and washes from isolated nuclei with buffers containing 0.05 M Tris, 0.15 M NaCl or 0.35 M NaCl. Proteins from the nuclear washes showed greater binding to the columns than proteins from the cytoplasm. The binding fractions were heterogeneous in gel electrophoresis systems. Proteins bound to affinity columns of individual histones were similar to those bound to columns of whole histone, polylysine and DEAE. A 25,000 dalton polypeptide (J2), found only in nuclear washes was a prominent histone-binding protein. It could be competitively eluted from DEAE with histones, suggesting polypeptide J2 may show a specific affinity for histones. Polypeptide J2 has an acidic to basic amino acid ratio of 1.58, and its amino acid composition is not similar to that of the high mobility group 1 protein. Polypeptide J2 binds to hydrophobic columns and may play a role in modifying histone-histone and histone-DNA interactions.


Assuntos
Proteínas de Transporte , Histonas , Fígado/metabolismo , Aminoácidos/análise , Animais , Proteínas de Transporte/isolamento & purificação , Proteínas de Transporte/metabolismo , Núcleo Celular/metabolismo , Cromatografia de Afinidade , Histonas/metabolismo , Camundongos , Peso Molecular
7.
Biochim Biophys Acta ; 521(1): 117-25, 1978 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-363155

RESUMO

The binding of mouse liver chromosomal proteins to DNA has been investigated using the nitrocellulose filter binding technique. Careful purification of the DNA involving nuclease S1 digestion and prefiltration through a nitrocellulose filter is used to reduce background binding in the absence of protein to less than 1%. Procedures involving direct binding of protein to labeled DNA, competition of binding of labeled DNA by unlabeled DNA, and dissociation of DNA . protein complexes with time do not indicate significant preference for binding to mouse DNA relative to Escherichia coli DNA. This specificity is demonstrated much more clearly by a novel type of procedure, which we call a sequential binding procedure. In this procedure non-specific binding proteins are sequestered by incubation with an excess of unlabeled E. coli DNA prior to addition of labeled DNA. Under these conditions, labeled mouse DNA is bound to filters to a 3- to 4-fold greater extent than labeled E. coli DNA.


Assuntos
Proteínas Cromossômicas não Histona , DNA , Animais , Carcinoma de Ehrlich/metabolismo , DNA Bacteriano/metabolismo , Escherichia coli , Cinética , Camundongos , Peso Molecular , Ligação Proteica
8.
Biochim Biophys Acta ; 578(1): 61-7, 1979 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-454672

RESUMO

Human fibroblasts were labeled by the 125I-lactoperoxidase technique and the sodium dodecyl sulfate soluble proteins examined by two-dimensional gel electrophoresis to determine the charge heterogeneity of the surface proteins and test for differences in surface proteins in several hereditary disorders. Approximately 80 polypeptides were observed. Those below 65 000 daltons tended to occur as single spots, while those of higher molecular weight were often present as a series of polypeptides of similar molecular weight (charge isomers). The possible role of these proteins in cell-cell recognition is discussed.


Assuntos
Iodoproteínas/análise , Proteínas de Membrana/análise , Linhagem Celular , Eletroforese em Gel de Poliacrilamida/métodos , Fibroblastos/análise , Humanos , Focalização Isoelétrica , Peso Molecular
9.
Biochim Biophys Acta ; 563(1): 253-60, 1979 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-497213

RESUMO

Mouse liver non-histone proteins, isolated by hydroxyapatite chromatography, were fractionated by hydrophobic chromatography using omega-amino-decyl-agarose omega-amino butyl-agarose, decyl-agarose, butyl-agarose, phenyl-Sepharose, and CPAD-Sepharose. Two column loading techniques were used. In the 0.35 M NaCl technique, the proteins were dialized into 0.35 M NaCl, applied to the column and initially eluted with 0.35 M NaCl. In the 40% (NH4)2SO4 technique, the non-histone proteins were mixed with the hydrophobic agarose, dialized against 40% (NH4)2SO4, and initially eluted with 40% (NH4)2SO4. In both cases the columns were subsequently eluted with 10 mM Tris-HCl, pH 7.5, 0.35, 1.0 and 5.0 M LiBr, and finally with 1% sodium dodecyl sulfate. The 0.35 M NaCl technique, using decyl-agarose and phenyl-Sepharose, resulted in a single step marked enrichment of the major hnRNA proteins (1 M LiBr fraction). The 40% (NH4)2SO4 technique resulted in a single step isolation of a pair of 15-20 000 dalton polypeptides.


Assuntos
Proteínas Cromossômicas não Histona/isolamento & purificação , Animais , Núcleo Celular/análise , Cromatografia de Afinidade/métodos , DNA/metabolismo , Fígado/análise , Camundongos , Ligação Proteica , Frações Subcelulares/análise
10.
Pharmacogenetics ; 6(1): 73-9, 1996 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-8845863

RESUMO

Of a group of 312 non-Hispanic Caucasians who smoked at least one pack per day, had unsuccessfully attempted to stop smoking, and were free of alcohol or other drug dependence, 48.7% carried the A1 allele of the DRD2 gene. This was significantly greater than the 25.9% prevalence in the 714 known non-Hispanic Caucasian controls without alcohol or drug abuse, p < 10(-8), and significantly greater than in a smaller set of our study controls. There was a significant, inverse relationship between the prevalence of the D2A1 allele and the age of onset of smoking, p = 0.02, and the maximum duration of time the smokers had been able to quit smoking on their own, p = 0.02. These results suggest the DRD2 gene is one of a multifactorial set of risk factors associated with smoking.


Assuntos
Receptores de Dopamina D2/genética , Fumar/genética , Adulto , Alelos , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Estados Unidos , População Branca/genética
11.
Pharmacogenetics ; 5(3): 121-41, 1995 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-7550364

RESUMO

Drug and alcohol seeking behaviour has become a great global problem affecting millions of inhabitants with a cost to society in the billions. Dopaminergic reward pathways have frequently been implicated in the etiology of addictive behaviour. While other neurotransmitters have also been implicated, to date the only molecular genetic defect which has been found to associate with alcoholism, drug dependency, obesity, smoking, pathological gambling, attention-deficit-hyperactivity disorder (ADHD), Tourette syndrome, as well as other related compulsive behaviours, are the variants of the dopamine D2 receptor gene (DRD2). In this review of the available data on the subject, we report a number of independent meta-analyses that confirm an association of DRD2 polymorphisms and impulsive-additive-compulsive behaviour (IACB), which we have termed "Reward Deficiency Syndrome". While we agree that Meta-analyses of all exant studies support an association of variants of DRD2 and IACB, correct negative findings with alcoholism may be due to differences in assessing controls and inclusion/exclusion criteria for selection of diseased probands.


Assuntos
Ligação Genética , Transtornos Mentais/genética , Receptores de Dopamina D2/genética , Comportamento Aditivo/genética , Comportamento Compulsivo/genética , Variação Genética , Humanos , Comportamento Impulsivo/genética , Transtornos Mentais/etnologia , Obesidade/genética
12.
Pharmacogenetics ; 6(3): 223-34, 1996 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-8807661

RESUMO

Pathological gambling has been termed both the 'pure' and the 'hidden' addiction. 'Pure' because it is not associated with the intake of any addicting substance, and 'hidden' because it is an extension of a common, socially accepted behaviour. The Taq A1 variant of the human DRD2 gene has been associated with drug addiction, some forms of severe alcoholism, and other impulsive, addictive behaviours. We have sought to determine if there is a similar association with pathological gambling. A total of 222 non-Hispanic Caucasian pathological gamblers from multiple sites across the US participated in the study. Of these 171 donated a sample of blood, 127 filled out several questionnaires, and 102 did both. Of the 171 pathological gamblers 50.9% carried the D2A1 allele versus 25.9% of the 714 known non-Hispanic Caucasian controls screened to exclude drug and alcohol abuse, p < 0.00000001, odds ratio (OR) = 2.96. For the 102 gamblers who filled out the questionnaires, 63.8% of those in the upper half of the Pathological Gambling Score (more severe) carried the D2A1 allele (OR versus controls = 5.03), compared to 40.9% in the lower half (less severe). Of those who had no comorbid substance abuse, 44.1% carried the D2A1 allele, compared to 60.5% of those who had comorbid substance abuse. Forty-eight controls and 102 gamblers completed a shorter version of the Pathological Gambling Score. Of the 45 controls with a score of zero, 17.8% carried the D2A1 allele. Of the 99 gamblers with a score of 5 or more, 52.5% carried the D2A1 allele (chi 2 = 15.36, p = 0.00009). These results suggest that genetic variants at the DRD2 gene play a role in pathological gambling, and support the concept that variants of this gene are a risk factor for impulsive and addictive behaviours.


Assuntos
Jogo de Azar , Motivação , Receptores de Dopamina D2/genética , Adulto , Idade de Início , Consumo de Bebidas Alcoólicas/genética , Alelos , Depressão/complicações , Depressão/genética , Humanos , Pessoa de Meia-Idade , Receptores de Dopamina D3 , Religião , Transtornos Relacionados ao Uso de Substâncias/complicações , Transtornos Relacionados ao Uso de Substâncias/genética
13.
Pharmacogenetics ; 6(4): 307-18, 1996 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-8873217

RESUMO

Defects in serotonin metabolism, and abnormalities in both blood serotonin and tryptophan levels, have been reported in many psychiatric disorders. Tryptophan 2,3-dioxygenase (TDO2) is the rate limiting enzyme for the breakdown of tryptophan to N-formyl kenurenine. Functional variants of this gene could account for the observed simultaneous increases or decreases of both serotonin and tryptophan in various disorders. We have identified four different polymorphisms of the human TDO2 gene. Association studies show a significant association of one or more of these polymorphisms and Tourette syndrome (TS), attention deficit hyperactivity disorder (ADHD) and drug dependence. The intron 6G-->T variant was significantly associated with platelet serotonin levels. Only the association with TS was significant with a Bonferroni correction (p = 0.005). Our purpose here is not to claim these associations are proven, but rather to report preliminary results and show that easily testable polymorphisms are available. We hope to encourage additional research into the potential role the TDO2 gene in these and other psychiatric disorders.


Assuntos
Polimorfismo Genético , Transtornos Relacionados ao Uso de Substâncias/genética , Síndrome de Tourette/genética , Triptofano Oxigenase/genética , Eletroforese em Gel de Poliacrilamida , Éxons , Humanos , Íntrons , Serotonina/sangue , Transtornos Relacionados ao Uso de Substâncias/sangue , Transtornos Relacionados ao Uso de Substâncias/enzimologia , Síndrome de Tourette/sangue , Síndrome de Tourette/enzimologia , Triptofano/sangue
14.
Biol Psychiatry ; 40(5): 368-72, 1996 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-8874837

RESUMO

Subjects on an addiction treatment unit who had been exposed to severe combat conditions in Vietnam were screened for posttraumatic stress disorder (PTSD). Of 24 with PTSD, 58.3% carried the D2A1 allele. Of the remaining eight who did not meet PTSD criteria, 12.5% carried the D2A1 allele (p = 0.04). In a replication study of 13 with PTSD, 61.5% carried the D2A1 allele. Of the remaining 11 who did not meet criteria for PTSD, 0% carried the D2A1 allele (p = 0.002). For the combined group 59.5% of those with PTSD carried the D2A1 allele versus 5.3% of those who did not have PTSD (p = 0.0001). These results suggest that a DRD2 variant in linkage disequilibrium with the D2A1 allele confers an increased risk to PTSD, and the absence of the variant confers a relative resistance to PTSD.


Assuntos
Receptores de Dopamina D2/genética , Transtornos de Estresse Pós-Traumáticos/genética , Adulto , Idoso , Alcoolismo/genética , Alcoolismo/psicologia , Alelos , Análise por Conglomerados , Distúrbios de Guerra/psicologia , Triagem de Portadores Genéticos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Receptores de Dopamina D2/metabolismo , Fatores de Risco , Transtornos de Estresse Pós-Traumáticos/metabolismo , Transtornos Relacionados ao Uso de Substâncias/genética , Transtornos Relacionados ao Uso de Substâncias/psicologia , Estados Unidos , Veteranos
15.
Biol Psychiatry ; 37(11): 798-805, 1995 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-7647164

RESUMO

The defence style questionnaire (DSQ) was administered to Caucasian males consisting of 123 subjects from a V.A. addiction treatment unit (ATU), 42 Tourette syndrome (TS) subjects, and 49 controls. For the ATU and TS subjects, there was a significant decrease in the mean score for mature defenses and a significant increase in mean score for immature defenses compared to controls. Many of the individual subscores showed the same significant differences. Dopamine D2 receptor (DRD2) gene haplotypes, identified by allele specific polymerase chain reaction of two mutations (G/T and C/T) 241 base pairs apart, were determined in 57 of the ATU subjects and 42 of the controls. Subjects with the 1 haplotype tended to show a decrease in mature and an increase in neurotic and immature defense styles compared to those without the 1 haplotype. Of the eight times that the subscale scores were significant for haplotype 1 versus non-1, they were always in this direction. There results suggest that the DRD2 locus is one factors controlling defense styles. The difference in the mean scores between controls and substance abuse subjects indicates that other genes and environmental factors also play a role.


Assuntos
Mecanismos de Defesa , Haplótipos , Drogas Ilícitas , Psicotrópicos , Receptores de Dopamina D2/genética , Transtornos Relacionados ao Uso de Substâncias/genética , Síndrome de Tourette/genética , Alcoolismo/genética , Alcoolismo/psicologia , Mapeamento Cromossômico , Análise Mutacional de DNA , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Neuróticos/genética , Transtornos Neuróticos/psicologia , Determinação da Personalidade , Inventário de Personalidade , Polimorfismo Genético , Transtornos Relacionados ao Uso de Substâncias/psicologia , Síndrome de Tourette/psicologia
16.
Am J Psychiatry ; 139(7): 913-5, 1982 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-6953768

RESUMO

The authors describe a 32-year-old man with Gilles de la Tourette's syndrome whose most severe symptom was exhibitionism. Treatment with low doses of haloperidol eliminated all exhibitionistic urges. This patient's oldest son has multiple tics and his nephew has Tourette's syndrome with mild exhibitionism. The major implications of this case are that 1) all patients with compulsive-type exhibitionism should be carefully questioned about symptoms of Tourette's syndrome and, if positive, be given a trial regimen of haloperidol; 2) some patients with compulsive exhibitionism and no symptoms of Tourette's syndrome have a genetic, neurochemical disorder and respond to haloperidol.


Assuntos
Exibicionismo/genética , Haloperidol/uso terapêutico , Transtornos Parafílicos/genética , Síndrome de Tourette/genética , Adulto , Criança , Exibicionismo/tratamento farmacológico , Humanos , Masculino , Linhagem , Síndrome de Tourette/tratamento farmacológico
17.
Arch Neurol ; 55(4): 513-6, 1998 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-9561979

RESUMO

BACKGROUND: In a prior study we observed an association between the dopamine D2 receptor gene (DRD2) and the age of onset and/or diagnosis of multiple sclerosis (MS). We hypothesized that this effect was mediated through the dopaminergic control of the release of prolactin, a modulator of immune response. Since gamma-aminobutyric acid also modulates the release of prolactin, we examined the possible association between alleles of the GABRA3 (gamma-aminobutyric acid A3 receptor) gene and MS. DESIGN: We examined the GABRA3 alleles of 189 subjects with MS who died of their disease. They were divided into test group 1 (n=64) and retest group 2 (n=56). Each group had a separate set of controls (group 1, n=109; group 2, n=430). All subjects were white. All were tested at a dinucleotide cytosine-adenosine repeat polymorphism with 6 alleles representing 11 to 16 repeats. RESULTS: In the first group there was a significant difference in the frequency of the GABRA3 alleles (P<.002), with the most notable difference being an increase in the frequency of the 16-repeat allele in subjects with MS and a relative decrease in the other alleles. In the replication group there was again a significant difference in the distribution of the GABRA3 alleles (P<.001), and again the greatest difference was an increase in the frequency of the 16-repeat allele in subjects with MS. For both groups combined, a significant difference in the frequency of the 16-repeat allele was noted (chi2=46.30; P<.001). CONCLUSIONS: These results suggest the GABRA3 gene may be a risk factor for MS. As with the DRD2 gene, the effect may be mediated through its regulation of prolactin release.


Assuntos
Esclerose Múltipla/genética , Prolactina/fisiologia , Receptores de GABA-A/genética , Ácido gama-Aminobutírico/fisiologia , Alelos , Distribuição de Qui-Quadrado , Citocinas/metabolismo , Feminino , Ligação Genética , Glutamato Descarboxilase/metabolismo , Humanos , Linfócitos/metabolismo , Masculino , Fatores de Risco , Estudos em Gêmeos como Assunto , Cromossomo X
18.
Am J Med Genet ; 60(2): 111-21, 1995 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-7485244

RESUMO

Tourette syndrome (TS) is a common, neuropsychiatric disorder which has many similarities to attention deficit hyperactivity disorder (ADHD). TS probands have a high frequency of a variety of behavioral disorders including depression. The depression may be due to a pleiotrophic effect of the Gts genes, proband ascertainment bias, or a result of coping with the chronic tics. To distinguish between these hypotheses we examined the responses to 17 Diagnostic Interview Schedule questions to evaluate the 9 DSM-III-R criteria for major depressive episode in 1,080 adults consisting of TS and ADHD probands, their relatives and controls. Using a Bonferonni corrected p there was a significant progressive increase in 16 of 17 depressive symptoms and for a life time history of a major depressive episode in groups with increased genetic loading for Gts genes. Similar trends were seen in the small number of ADHD probands and their relatives. There was also a significant increase for these variables in non-proband TS relatives versus non-TS relatives, indicating the association of depression with Gts genes was not due to ascertainment bias or the inappropriate choice of controls. Multiple linear regression analysis indicated that obsessive-compulsive behaviors, sex, ADHD, drug abuse, and age all showed a more significant effect on depressive symptoms than the number of tics. The presence or absence of TS in the relatives had a much greater effect on risk for depression than the presence or absence of an episode of major depression in the proband. These results are consistent with the hypothesis that Gts and ADHD genes play a major role in depression.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/genética , Depressão/genética , Síndrome de Tourette/genética , Adolescente , Adulto , Transtorno do Deficit de Atenção com Hiperatividade/complicações , Estudos de Casos e Controles , Depressão/complicações , Transtorno Depressivo/complicações , Transtorno Depressivo/genética , Síndrome de Fadiga Crônica/complicações , Síndrome de Fadiga Crônica/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Genéticos , Transtorno Obsessivo-Compulsivo/complicações , Transtorno Obsessivo-Compulsivo/genética , Análise de Regressão , Síndrome de Tourette/complicações
19.
Am J Med Genet ; 54(3): 227-41, 1994 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-7810580

RESUMO

Most significant variations in the expression of human sexuality are considered to be the result of learned behavior or psychological problems. Tourette syndrome (TS) is a common, hereditary tic and disinhibition disorder sometimes associated with compulsive use of obscene words (coprolalia) and previously reported to be occasionally associated with exhibitionism. To further explore the relationship between the Gts genes and sexual behavior, questions concerning a wide range of such behaviors were administered to 1,040 subjects, 14 years of age or older, consisting of 358 TS probands, 101 non-proband relatives with TS, 359 non-TS first degree relatives, 79 attention deficit hyperactivity disorder (ADHD) probands, 70 unaffected relatives of the ADHD probands, and 73 controls. The behaviors included magnitude of sex drive, sex orientation, exhibitionism, transvestitism, transsexualism, sadism, masochism, pedophilia, fetishism, aversion to being touched, and aversion to sex. While most of these behaviors occurred in a distinct minority of TS subjects, there was a significant positive correlation between each behavior examined and the degree of genetic loading for the Gts gene(s). The nature of these behaviors and their association with TS suggests many are variants of obsessive-compulsive disorder. Studies in animals indicate that changes in serotonin and dopamine play a significant role in the sexual behavior and many lines of evidence are consistent with the hypothesis that TS is due to genetic changes in serotonin and dopamine metabolism. These studies suggest that genetic factors play a much greater role in a wide range of forms of sexual expression than previously thought.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/genética , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Comportamento Sexual , Síndrome de Tourette/genética , Síndrome de Tourette/psicologia , Adolescente , Adulto , Análise de Variância , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Regressão
20.
Am J Med Genet ; 36(4): 418-30, 1990 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-2389798

RESUMO

Blood serotonin and tryptophan levels were studied in 1,440 individuals. These included patients with Tourette syndrome (TS), attention deficit hyperactivity disorder (ADHA), or ADHD with a family history of TS (ADHD 2 degrees TS); relatives (parents, sibs) of these patients; other patients with TS-like disorders; and controls. There were significant decreases in the serotonin/platelet ratio (P = 0.0001) and in tryptophan (P less than 0.0001) in unmedicated patients with TS. Parents of TS patients showed a comparable, significant decrease in serotonin/platelet ratio (P less than 0.0001) and in tryptophan (P less than 0.0001), and there was no difference between parents with and without symptoms. This suggested that these were trait markers for the Gts gene and agrees with the proposal that TS patients are homozygous for Gts gene and that both parents are Gts gene carriers. Although there was no decrease in the serotonin/platelet ratio in ADHD patients, tryptophan levels were significantly decreased and there was a significant decrease in both the serotonin/platelet ratio and in tryptophan in the parents of patients with ADHD including those without a family history of TS. This is consistent with a close link between TS and ADHD. The basic defect may be a dysregulation of serotonin metabolism. The low blood serotonin and tryptophan levels in TS are consistent with the wide range of behavioral disorders seen in TS and suggest tryptophan oxygenase as a possible candidate gene.


Assuntos
Serotonina/sangue , Síndrome de Tourette/sangue , Triptofano/sangue , Adulto , Envelhecimento/metabolismo , Transtorno do Deficit de Atenção com Hiperatividade/sangue , Transtorno do Deficit de Atenção com Hiperatividade/genética , Criança , Clonagem Molecular , Jejum , Feminino , Homozigoto , Humanos , Intestinos/enzimologia , Fígado/enzimologia , Masculino , Transtornos Mentais/genética , Contagem de Plaquetas , Fatores Sexuais , Síndrome de Tourette/genética , Triptofano Oxigenase/genética , Triptofano Oxigenase/metabolismo
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