摘要:

There is general consensus that linkage with a quantitative trait locus cannot be detected with a reasonable number of sibpairs unless that trait has a very high heritability or the pairs are highly selected. However, the latter may require the screening of a very large number of pairs before a relatively small number of highly informative pairs is attained. At the same time, it is known that, for the same number of typed individuals, larger sibships tend to provide more linkage information than do independent sibpairs. We thus compared the efficiency of two sampling schemes, (1) random and (2) single ascertainment via an individual with an extreme phenotype, for sibship sizes ranging from two to five. The results demonstrate the clear trade-off between sibship size and the stringency of the ascertainment scheme.

ISSN:0001-5652    

DOI:10.1159/000154381

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Association of the dopamine D3 receptor gene (DRD3) and schizophrenia was examined in unrelated Israeli and Italian schizophrenic patients and ethnically matched normal control subjects. In the combined sample, there was a siginificant excess of DRD3 allele 2 among the schizophrenic patients (χ2 = 4.70, d.f. 1, p = 0.03). Comparison of genotype frequencies revealed an excess of the 2-2 genotype in the combined schizophrenic sample (χ2 = 8.30, d.f. 1, p = 0.01) and in the non-Ashkenazi Israeli schizophrenics alone (χ2 = 5.70, d.f. 2, p = 0.05). DRD3 2-2 genotype conferred a significantly increased risk of schizophrenia (χ2 = 8.21, d.f. 1, p = 0.004; OR = 2.87, CI 95% = 1.36-5.76) in the combined sample and in the non-Ashkenazi Israeli schizophrenics (χ2 = 7.22, d.f. 1, p = 0.04; OR = 7.22, CI 95% = 1.04-24.83). In the combined and Italian samples, allele 2 was associated with early age of onset as was the 2-2 genotype in the combined sample and non-Ash-kenazi group. The 2-2 genotype was associated with poor response to neuroleptics, particularly in the non-Ashkenazi, Israeli schizophrenics. The possibility that DRD3 or a locus in linkage disequilibrium with it may play a role in the transmission of schizophrenia, is considered in relation to previous positive and negative rep

ISSN:0001-5652    

DOI:10.1159/000154382

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Molecular characterization of glucose-6-phosphate dehydrogenase (G6PD) variants was carried out in 150 unrelated G6PD deficient blood donors from the region of Campinas, Brazil. By allele specific oligomer hybridization or digestion of exon 4 of the G6PD gene with the restriction endonuclease NlaIII, we detected the 202 G→A mutation in 146 individuals. This mutation was associated with the 376 G→A substitution and only one haplotype was observed in these individuals. Digestion of exon 6 with the restriction enzyme Mboll showed the presence of the Mediterranean variant in three individuals. Haplotype analysis showed, in all three samples, a T at nt 1311 and the C at nt 13 in intron 11 suggesting a European origin of this variant. By SSCP analysis and direct sequencing we detected the mutation nt 1003 G→A (335 Ala→Thr) in one blood donor. This mutation was previously described in a boy of Indian ancestry and the variant was denominated G6PD Chatam. The case described here has no Indian ancestry; thus, we presume that the mutations have arisen independently, although we do not know the haplotype of the Indian patient. The haplotype of our case was the most common observed in our population (Pvull, BspHl+, Pstl+, 1311C, NlaIII-). Thus, our data indicate that G6PD A- with the 202 G→A mutation is the most frequent G6PD deficiency in the population of southeastern Brazil. The remaining variants had a Mediterranean origin. These results are in agreement with the origin of the Brazilian p

ISSN:0001-5652    

DOI:10.1159/000154383

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

We have demonstrated an association between apolipoprotein E (apoE) gene polymorphisms and Alzheimer’s disease (AD) in 163 Japanese patients by means of PCR. We found a significant increase in risk of nonfamilial AD for apoE allele ε4 in these individuals; this trend decreases with the increase in onset age. In centenarians, the distribution of apoE gene alleles is similar to that in the general population. The protective effect of allele ε2 against the development of AD is not statistically significant in our analysis. This indicates that apoE polymorphism is associated with AD regardless of race and that the age of onset is related to the apoE gene in the development of A

ISSN:0001-5652    

DOI:10.1159/000154384

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Several studies have shown that major depression is accompanied by significantly increased plasma levels of positive acute-phase proteins such as haptoglobin (Hp). A significant higher frequency of the HP* 1 allele has recently been detected in patients with unipolar major depression. Pursuing the hypothesis that certain unipolar and bipolar disorders may be genetically related, this study analyzed Hp genotype and allele frequencies in bipolar patients, taking into account their family history of major affective disorders. An increase of HP* 1 allele frequency was found in the subgroup of patients with family history of exclusively unipolar disorder (70% in patients vs. 38% in controls, χ2 = 8.34, p = 0.004). The relative risk for the HP*1 carriers in this subgroup was 3.8 (χ2 = 7.29, p = 0.007). These results suggest a genetic and etiological heterogeneity in the bipolar disorde

ISSN:0001-5652    

DOI:10.1159/000154385

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

During the period between December 1988 and February 1995, a total of 279,482 newborn infants were screened in the regional neonatal screening program for congenital hypothyroidism (CH) in Riyadh province, Saudi Arabia. Eighty-one infants were confirmed to have CH giving an incidence of 1 in 3,450. Variable congenital anomalies, other than those of the thyroid gland, were present in 16 (19.8%). The anomalies most frequently encountered were congenital heart defects (7), unclassified multiple congenital anomalies (5) and Down’s syndrome (2). The results of our study confirm this association, and emphasize the need to search for such anomalies in infants born with CH. Nationwide studies, however, on birth defects in the general population and those associated with CH are still needed to help us understanding the role of local genetic and environmental factor

ISSN:0001-5652    

DOI:10.1159/000154386

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Genomic DNA from probands of various Waardenburg syndrome (WS) families were PCR-amplified using primers flanking the 8 exons of PAX3. The PCR fragments were screened for sequence variants, and subsequently cycle se-quenced. Mutations were detected in exon 6 for 3 probands of WS type 1 families. These mutations all occur in the paired homeodomain DNA-binding motif.

ISSN:0001-5652    

DOI:10.1159/000154387

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

A pyruvate kinase deficiency prevalence study and determination of the normal levels of the enzyme were performed in Antalya city, Turkey. Heparinized blood samples obtained from a representative population of the Antalya province (617 women and 573 men) were tested for pyruvate kinase deficiency by qualitative and quantitative tests between April 1992 and March 1994. The mean pyruvate kinase activity was found to be 19.8 ± 4.0 IU/g Hb whereas the enzyme activity of deficient cases varied between 7.5 and 12.2 IU/g Hb. Taking into account that pyruvate kinase deficiency is the second most common cause of nonspherocytic congenital hemolytic anemia, detection of deficient cases by genetic screening tests appears to be an informative clinical indicator of hemolytic anemia

ISSN:0001-5652    

DOI:10.1159/000154388

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Spinocerebellar ataxia type 1 is caused by the expansion of a CAG trinucleotide repeat, located at th 5’ end of the gene responsible for the disease (SCA1 gene). We propose a simple and rapid method for SCA1 diagnosis, avoiding both radioactive and Southern blotting analysis. The method allows an accurate allele sizing by visualization of polymerase chain reaction products through a silver nitrate-stained polyacrylamide ge

ISSN:0001-5652    

DOI:10.1159/000154389

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Polymorphisms in the tumor suppressor gene p53 were identified by Southern blots of denaturing gradient gels (melting polymorphisms). Five polymorphisms were identified in white blood cell DNA, with the frequency of heterozygotes varying from 4 to 27%. The strategy of hybridizing the same blots with different probes suggests that two of the polymorphisms are located in the region of exons 5-6 and one is in the region of exons 7-9. This study illustrates the use of this method for analysis of tumor suppressor genes and suggests future applications, such as for the assay of loss of heterozygosity. That assay is used to detect gene deletions in tumors, an important event in human tumorigenesis.

ISSN:0001-5652    

DOI:10.1159/000154390

出版商:S. Karger AG    

年代:1997

数据来源: Karger