摘要:

We performed linkage and locus heterogeneity analyses of Waardenburg syndrome (WS) types 1 and 2 using 9 DNA markers from 2q35-q37, including two highly polymorphic microsatellites very closely linked to the PAX3 candidate gene. None of 5 WS type 2 (WS2) families showed linkage to the PAX3 candidate region. We localized the marker D2S102 to less than 1 cM from PAX3 (lod = 33.7, θ = 0), but a complete absence of crossovers prevented determining whether it maps distal or proximal to PAX3. Study of 14 WS type 1 (WS1) families yielded a maximum lod score of 27.81 at PAX3, θf = 0.010, θ = 0.007 assuming homogeneity. However, we found significant evidence of locus heterogeneity, with one family initially classified as WS1 unlinked to the PAX3 region. Reevaluation of the clinical features of this family revealed atypical morphology of inner canthi. This produced the appearance of dystopia canthorum and high W-index scores. While our one unlinked WS1 family exhibits atypical canthal morphology, our type 1 families with classic dystopia appear to be homogeneously linked to PAX3. These and other findings identify precautions that need to be addressed before using PAX3-linked markers for diagnostic purposes.

ISSN:0001-5652    

DOI:10.1159/000154307

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Biochemical characteristics were determined for four common molecular variants of glucose-6-phosphate dehydrogenase (G6PD) deficiency and 10 non-deficient Chinese males in Singapore. The variants included one Mediterranean (nt563 C → T), two Canton (G → T at nt 1376) and one each of Kaiping (1388 G→A) and Chinese-5 (1024 C→T) variants. Molecular identification was carried out by amplication of genomic DNA with specific oligonucleotide primers followed by digestion with restriction enzymes that recognize artificially created or naturally occurring restriction sites. All the variants had low enzyme activity in red cells (0.2-0.6 IU/g Hb). All but the Chinese-5 variant (nt1024) had a normal Km for NADP (7-10 µM). The Mediterranean variant had a high utilization of deamino-NADP (296%), followed by the Canton variant 1376 substitution (131 %). The Km for glucose-6-phosphate was low in the Mediterranean and 1376 variant (18-40 µM) but high in the 1024 substitution (104 µM). Electrophoretic mobility in TEB buffer (pH 8.6) was slightly faster (103%) for the 1376 mutation while 100% for all the others. All but the 1024 substitution had increased analogue utilization for galactose-6-phosphate and 2-deoxyglucose-6-phosphate (58 and 68% for the Mediterranean mutation and 14-23% for the 1376 and 1388 substitutions, respectively), and reduced heat

ISSN:0001-5652    

DOI:10.1159/000154308

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

HLA class I antigen frequencies were studied in 52 patients with kala-azar and compared with 222 unrelated healthy controls. The relative risk (RR) and etiologic or preventive fraction (EF/PF) were determined for each character, and statistical significance was evaluated with χ2 with Yates’ correction. Results showed that the only antigen with a statistically significant difference was HLA-A26 (15.38 vs. 1.35%; p = 0.004), with RR = 13.27 and EF = 0.142. This indicates a high risk of contracting the disease for HLA-A26-positive individuals and a relatively remarkable influence of this antigen on the prevalence rate of kala-az

ISSN:0001-5652    

DOI:10.1159/000154309

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Amplification of the human dopamine transporter gene (DAT1) was performed by the polymerase chain reaction, and polymorphism of the VNTR locus was analyzed in a population sample of 176 randomly selected Japanese individuals. Genomic DNAs were extracted from whole blood, and the 3’ untranslated region of the human DAT1 gene was amplified. The amplification products were distinguished by agarose gel electrophoresis, and visualized directly by ethidium bromide staining. In this way, four alleles were visualized directly and designated A, B, C, and D in decreasing order according to size. The relative frequencies of DAT1 alleles A through D were 0.0171, 0.0625, 0.9119, and 0.0085, respectively. Evidence of significant deviations from the Hardy-Weinberg equilibrium was observed from these Japanese population data. The DAT1 locus was estimated to have a heterozygosity index of 13 % and polymorphic information content of 0.1

ISSN:0001-5652    

DOI:10.1159/000154310

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

DNA polymorphism at the ABO locus was investigated using denaturing gradient gel electrophoresis of polymerase-chain-reaction-amplified DNA products from 315 healthy individuals of the Chinese population of Hong Kong. Five different alleles were identified: ABO*A1, O2, A1, A2 and B1. The ABO*A2 is a new allele not previously reported in the literature. The allele frequencies found were 0.3698 for O1, 0.2508 for O2, 0.1952 for A1, 0.0159 for A2, and 0.1683 for B1. The Chinese population being investigated was in Hardy-Weinberg equilibrium. The genotyping method identifies many more alleles in the ABO locus and thus makes it a more useful genetic marker in linkage analysis, paternity testing and individualization in forensic work than when the locus is genotyped using conventional DNA-based methods or phenotyped using serological methods.

ISSN:0001-5652    

DOI:10.1159/000154311

出版商:S. Karger AG    

年代:1995

数据来源: Karger

ISSN:0001-5652    

DOI:10.1159/000154312

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Placental alkaline phosphatase (PLAP) and germ cell alkaline phosphatase (GCAP) are controlled by closely linked genes on chromosome 2q34–q37. In previous investigations, associations have been found between PLAP types and spontaneous abortion. In this study, PLAP and GCAP RFLPs and haplotypes were found to show highly significant associations with spontaneous abortions in the Finnish and Swedish populations. However, different associations were found in the Finnish and Swedish populations. The Finnish abortions were associated with the GCAP allele PstI(b) 2 and the Swedish abortions with the PLAP allele Pstl(a) 2. A possible mechanism behind the associations may therefore be linkage disequilibria with deleterious alleles within or close to the alkaline phosphatase gene comple

ISSN:0001-5652    

DOI:10.1159/000154313

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

The β-thalassaemias are a heterogeneous group of inherited disorders caused by mutations in and around the structural gene of the β-chain of the adult haemoglobin (HbA). Studies at the gene level have identified a large number of β-thalassaemia gene variations in different populations. These findings have implications for the use of molecular diagnosis for genetic counselling and prenatal detection of the β-thalassaemias. In our unit, we initiated studies to investigate the molecular defects in β-thalassaemias in Saudi Arabia using amplification-refractory mutation systems, dot blot analysis and restriction endonuclease analysis, and identified mutations producing β+- and β°-thalassaemias. Twenty of the mutations encountered in the Asian, Mediterranean, Chinese and other Arab populations were investigated. The most commonly encountered mutations in Saudi β-thalassaemia patients were IVS-I-110, IVS-II-1, CD 39, IVS-I-5 and IVS-I 3’ end (–25), while frameshifts at CD 8/9, Cap+1 (A → C) and CD 6 mutations were identified at a low frequency. These mutations account for 84.94% of the total β -thalassaemia mutations. The remaining 15 % remain unknown. This is the first report on the type and nature of mutations in Saudi β -thalassaemia patients. It presents frequencies of twenty mutations and emphasises the need for further detailed investigations to clarify the whole spectrum of β -thalassaemia mutations in the

ISSN:0001-5652    

DOI:10.1159/000154314

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

To eliminate the need for distributional assumptions and to reduce the computational burden associated with the method of maximum likelihood, several researchers have proposed using estimating equations techniques for segregation analysis. One concern with the application of this technique has been that the first and second order moments may not carry sufficient information for identifying all of the parameters in segregation models. It is shown that in addition to the marginal means and covariances from nuclear family data, up to the third order product moments need to be used in estimating equations for identifying all of the segregation parameters in a major gene model. A polygenic component and potentially a common family environment parameter can also be identified using up to the fourth order moments. Two weighting functions are developed to improve statistical efficiency.

ISSN:0001-5652    

DOI:10.1159/000154315

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

CA repeat polymorphism in the endothelial nitric oxide synthase gene was studied by the polymerase chain reaction. The distribution of allele frequencies in the Japanese was determined, and found to differ from that in Caucasians.

ISSN:0001-5652    

DOI:10.1159/000154316

出版商:S. Karger AG    

年代:1995

数据来源: Karger