摘要:

AbstractThe D14S43 marker is closely linked to the major gene for early onset autosomal dominant Alzheimer's disease on chromosome 14. Allelic frequencies at the D14S43 locus were compared in 113 familial and isolated cases of early onset Alzheimer's disease (<60 years of age at onset) (EOAD) and 109 unaffected individuals of the same geographic origin. Allele 7 was significantly (P= 0.033) more frequent in type 1 EOAD patients (13.2%), defined by the presence of at least another first degree relative with EOAD, than in controls (4.1%). Since an autosomal dominant gene is probably responsible for type 1 patients, allelic association may reflect linkage disequilibrium at the D14S43 locus. This would mean that some patients share a common ancestral mutation. However, since multiple tests were carried out, this result must be interpreted with caution, and needs confirmation in an independent sample. © 1995 Wiley‐Liss, I

ISSN:0148-7299    

DOI:10.1002/ajmg.1320600202

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractWe have recently described a family in which there is cosegregation of major affective disorder with Darier's disease and have mapped this autosomal dominant skin disorder to 12q23‐q24.1. This has provided an interesting candidate region for genetic studies of bipolar disorder. We have studied the segregation of seven markers spanning the Darier's disease locus in 45 bipolar disorder pedigrees and found modest evidence in support of linkage under heterogeneity for 5 of these markers. Nonparametric analyses were suggestive of linkage with a marker at the gene encoding a secretory form of phospholipase A2. Our sample has relatively low power to detect linkage under heterogeneity and independent researchers should examine markers from this region in further samples of bipolar pedigrees. © 1995 Wiley‐Liss,

ISSN:0148-7299    

DOI:10.1002/ajmg.1320600203

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractIt is generally agreed that there is a genetic component in the etiology of schizophrenia which may be tested by the application of linkage analysis to multiply‐affected families. One genetic region of interest is the long arm of chromosome 11 because of previously reported associations of genetic variation in this region with schizophrenia, and because of the fact that it contains the locus for the dopamine D2 receptor gene. In this study we have examined the segregation of schizophrenia with microsatellite dinucleotide repeat DNA markers along chromosome 11q in 5 Israeli families multiply‐affected for schizophrenia. The hypothesis of linkage under genetic homogeneity of causation was tested under a number of genetic models. Linkage analysis provided no evidence for significant causal mutations within the region bounded by INT and D11S420 on chromosome 11q. It is still possible, however, that a gene of major effect exists in this region, either with low penetrance or with heterogeneity. © 1995 Wiley‐Lis

ISSN:0148-7299    

DOI:10.1002/ajmg.1320600204

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractThe clinical features of Parkinson's disease, particularly rigidity and bradykinesia and occasionally tremor, are seen in juvenile‐onset Huntington's disease. Therefore, the CAG and CCG repeats in the Huntington's disease gene were investigated in 45 Parkinson's disease patients and compared to 40 control individuals. All of the Parkinson's disease chromosomes fell within the normal size ranges. In addition, the distributions of the two repeats in the Parkinson's disease patients did not differ significantly from those of the control population. Therefore, abnormalities of these trinucleotide repeats in the Huntington's disease gene are not likely to contribute to the pathogenesis of Parkinson's disease. © 1995 Wiley‐Liss,

ISSN:0148-7299    

DOI:10.1002/ajmg.1320600205

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractTourette 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 theGtsgenes, 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 forGtsgenes. 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 withGtsgenes 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 thatGtsandADHDgenes play a major role in depression. © 1995 Wiley

ISSN:0148-7299    

DOI:10.1002/ajmg.1320600206

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractAn association between the liability to early onset alcoholism/substance abuse and a recently discovered dinucleotide repeat length polymorphism at the MAOA gene (MAOCA‐1) was examined using polymerase chain reaction (PCR). A significant correlation between the presence/absence of the disorder and the length of the MAOCA‐1 repeat was found in males, but not females, with “long” alleles (repeat length above 115 bp) associated with both increased risk for the disorder and lower age of onset of substance abuse. These preliminary data suggest that further exploration of the relationship between the MAOA gene and behavioral traits in an expanded sample is warranted. © 1995 Wiley

ISSN:0148-7299    

DOI:10.1002/ajmg.1320600207

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractThe intention of this controlled family study was to evaluate reasons for comorbidity of schizophrenia and panic disorder. Observed rates of psychiatric disorders in first‐degree relatives of patients and of controls were compared with rates predicted by possible hypotheses explaining comorbidity. The sample consisted of 59 patients with schizophrenia (including seven with schizophreni‐form disorder), 54 patients with panic disorder (with or without agoraphobia), 29 comorbid patients with lifetime diagnoses of panic disorder and schizophrenia (or schizo‐phreniform disorder, 2 patients) and 109 controls, and their 1068 first‐degree relatives. Information from clinical performance, clinical and structured interviews, and from family history was joined to establish DSM‐III‐R diagnoses in patients and relatives. As expected, schizophrenia and panic disorder were found to be familial. The hypothesis, that the familial load for primary panic disorders distinguished schizophrenics (4.3%) and controls (0.9%), could be verified (P0.05). The observed familial aggregation pattern of psychiatric disorders in relatives of schizophrenics, panic patients, comorbid patients, and controls refers to an etiological relation of schizophrenia and panic disorder, or at least to a relationship of subgroups of these disorders. © 1995 Wil

ISSN:0148-7299    

DOI:10.1002/ajmg.1320600208

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractCytogenetic analysis was carried out in unrelated schizophrenic patients, unrelated controls and patients and family members in multiplex families. The size distribution of chromosome 1 heterochromatic region (1qH, C‐band variants) among 21 unrelated schizophrenic patients was different from that found in a group of 46 controls. The patient group had 1qH variants of smaller size than the control group (P<0.01). Incubation of phytohemagglutinin‐treated blood lymphocytes with 5‐azacytidine (which causes decondensation and extension of the heterochromatin) led to a lesser degree of heterochromatin decondensation in a group of patients than in the controls (7 schizophrenic, 9 controls,P<0.01). The distribution of phenotypes of Duffy blood group system [whose locus is linked to the 1qH region (Donahue et al.: Proc Natl Acad Sci USA 61:949–955, 1968; Rouleau et al.: Genomics 7:313–318, 1990)] among 28 schizophrenic patients was also different from that in the general population. Cosegregation of schizophrenia with a 1qH (C‐band) variant and Duffy blood group allele was observed in one of six multiplex families. The overall results suggest that alterations within the Duffy/1qH region are involved in schizophrenia in some cases. This region contains the locus of D5 dopamine receptor pseudogene 2 (1q21.1), which is transcribed in normal lymphocytes (Takahashi et al.: FEBS Lett 314:23–25, 1992). © 1995 W

ISSN:0148-7299    

DOI:10.1002/ajmg.1320600209

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractAs part of a systematic search for a major genetic locus for schizophrenia we have examined chromosome 22 using 14 highly polymorphic markers in 23 disease pedigrees. The markers were distributed at an average distance of 6.6 cM, covering 70–80% of the chromosome. We analyzed the data by the lod score method using five plausible genetic models ranging from dominant to recessive, after testing the power of our sample under the same genetic parameters. The most positive lod score found was 1.51 under a recessive model for the marker D22S278, which is insufficient to conclude linkage. However, an excess of shared alleles in affected siblings (P<.01) was found for both D22S278 and D22S283. For D22S278, theAstatistic was equal to the lod score (1.51) and therefore did not provide additional evidence for linkage allowing for heterogeneity, but the Liang statistic was more significant (P= .002). Our results suggest the possibility that the region around D22S278 and D22S283 contains a gene which contributes to the aetiology of schizophrenia. © 1995 Wiley‐Liss,

ISSN:0148-7299    

DOI:10.1002/ajmg.1320600210

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractWe have characterized two intragenic polymorphisms in the neurofibromatosis type 1 (NF1) gene by direct sequencing of PCR products. The variants for these polymorphisms were initially detected on Hydrolink gels. One of the polymorphisms involves a G to A transition in intron 41 at the 28th base upstream of exon 42 with an observed ‘G’/‘A’ heterozygosity of 0.42. The other polymorphism is a T to C transition in intron 16 at the 16th base upstream of exon 17 with an observed ‘T’/‘C’ heterozygosity of 0.09. In combination with other documented polymorphisms in the NF1 gene, these variants should assist in genetic analysis of NF1 families. © 1995

ISSN:0148-7299    

DOI:10.1002/ajmg.1320600211

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY