摘要:

One thousand children ranging from newborns to 13 years of age with a variety of clinical disorders were referred to us to investigate the possible presence of chromosomal abnormalities. Various types of chromosomal anomalies were found in 166 children (16.6%), which is significantly (p < 0.01) higher than in an unselected (control) population (0.48–0.55%). The male:female ratio was 3:2 for the total population. Furthermore, in our survey population, the sex ratio of Down’s syndrome cases of males to females was

ISSN:0001-5652    

DOI:10.1159/000154168

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

The presence of circulating autoantibodies (Abs) to the thyroid antigens thyroid peroxidase (TPO) and thyroglobulin (Tg) is a marker for autoimmune thyroid disease. Recent studies have suggested that the tendency to produce these Abs is inherited as an autosomal dominant characteristic. In order to confirm or refute these observations, we have carried out a complex segregation analysis using POINTER on Ab data in 86 unselected pedigrees (172 nuclear families). The overall prevalence of TPO Ab was 9.9% in men and 24.1% in women. Tg Ab was found in 11.0% of men and 23.5% of women. There was a marked tendency for both TPO Ab and Tg Ab to cluster in families and complex segregation analysis provided strong evidence for vertical transmission. However, it was not possible to distinguish between a single locus and a multifactorial model for either Ab. In the absence of strong evidence for a single locus, genetic linkage strategies are unlikely to be successful.

ISSN:0001-5652    

DOI:10.1159/000154169

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

The population of northern Sweden shows a marked ethnic heterogeneity and a unique distribution of disorders with a monogenic or polygenic background, among them cardiovascular diseases. We have studied variations between 23 North Swedish subpopulations (regions) with respect to hypercholesterolemia and its possible determinants including dietary factors, obesity and the degree of Finnish genetic influence. A significant regional heterogeneity was found concerning hypercholesterolemia, obesity and high consumption of ‘boiled’ coffee. Hypercholesterolemia showed significant geographical covariations with Finnish genetic influence and consumption of ‘boiled’ coffee. The results are consistent with the hypothesis that in addition to environmental factors Finnish genetic influence contributes to the development of hypercholesterolemia and thereby to the increased rate of cardiovascular disease found in northern

ISSN:0001-5652    

DOI:10.1159/000154170

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

The polymerase chain reaction and nucleotide sequencing have been used to characterise a single base substitution (CAG → TAG) at nucleotide 16842 in the C1-inhibitor gene in the affected members of a single family with type I C1-inhibitor deficiency. This mutation creates the TAG translation termination codon, thereby truncating the C1-inhibitor C-terminus by 17 amino acids. The effects of the mutation are discusse

ISSN:0001-5652    

DOI:10.1159/000154171

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Apolipoprotein E (Apo E) is a component of VLDL and HDL and plays a significant role in the regulation of cholesterol concentration. An improvement in isoelectric focusing for Apo E phenotyping is presented: the plasma Apo E was dissociated from lipoproteins by the use of Tween 20; the optimal concentration of type V neuraminidase was determined (1 U/ml); up to 48 samples were analyzed per plate and revealed by immunoblotting. Using this method, we have determined Apo E phenotypes and estimated their association with total cholesterol and Apo B levels in 498 healthy blood donors in Paris (France). The relative frequencies of Apo E alleles ε2, ε3 and ε4 in this population were 0.079, 0.801 and 0.120, respectively. The association between Apo E phenotypes and concentration of Apo B-containing lipoproteins was confirmed (Apo B (g/l): E4/E3 subjects, 1.10 ± 0.29; E3/E2 subjects, 0.93 ± 0.22; both significantly different from E3/E3 subjects, 0.99 ± 0.28). Total cholesterol (mmol/l): E4/E3 subjects, 5.43 ± 1.15; E3/E2 subjects, 4.79 ± 0.83; both significantly different from E3/E3 subjects, 5.03 ±

ISSN:0001-5652    

DOI:10.1159/000154172

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

A Task Force was assembled to address three data problems in genetic linkage analyses: (1) a secular trend, e.g. cohort effect; (2) positive assortative mating, and (3) bilineal pedigrees. All are cited as reasons for failure to replicate genetic linkage reports. However, we knew of no work demonstrating that these factors could invalidate or bias linkage analyses, nor that they were complications (e.g., variable age of onset). The Task Force concluded that these factors can reduce the power of linkage analyses and result in bias in the estimate of the recombination frequency due to the fact that they represent ‘noise’ in the system. There was little evidence that the three factors would invalidate a linkage analysis or be directly responsible for negating a linkage find

ISSN:0001-5652    

DOI:10.1159/000154173

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Multipoint linkage analysis can be extremely demanding in terms of computer time and memory, and these requirements rise exponentially with the number of markers used. A method is described for producing a rapid approximation to a multipoint analysis from the supplied results of two-point analyses with each marker. The method depends on regarding the lod scores as if they were obtained from a number of independent phase-known meioses, and making estimates concerning the proportion of all meioses which are likely to be informative for each marker. It then becomes possible to estimate the amount of information from each marker or pair of markers which is independent of information from other markers. The lod scores arising from independent contributions may then be summed to approximate the true multipoint lod score. The method has been implemented in a computer program called FASTMAP which is freely available. It has been tested on a variety of simulated and real data. In most circumstances it performs well, with a high correlation between the estimated and true multipoint lod score and little bias. However occasionally the results of the estimate deviate markedly from the multipoint lod score, especially at map positions very close to the markers. The overall usefulness of the method will therefore need to be further evaluated, but it does seem adequate at least for building exclusion maps and carrying out preliminary and exploratory analyses.

ISSN:0001-5652    

DOI:10.1159/000154174

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

The genetic structure of the human population in a random sample of 238 unrelated individuals from Garfagnana (Tuscany, Italy) was studied for five highly polymorphic serum proteins (GC, TF, PI, AHSG, ORM1) and three red cell isozymes (ACP, PGM1, ESD) by isoelectric focusing. Comparison with the gene frequencies from other districts of Tuscany has shown no significant deviation in seven out of eight polymorphic protein systems. Subtype allele frequencies of orosomucoid 1 (ORM1), which were not yet determined in Italian populations, are as follow: ORM1*F1 = 0.586, ORM1*F2 = 0.021, and ORMl*S = 0.393. The most striking features of this unique sample were the relatively high frequencies of PGM1*2B (0.093) and PI*I (0.013) alleles.

ISSN:0001-5652    

DOI:10.1159/000154175

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Seventy Italian families affected by 21-hydroxylase deficiency were studied in order to evaluate the distribution of mutations. The coding P450c21B gene, the highly homologous P450c21A pseudogene and the linked C4A, C4B and DRB genes, mapping within the major histocompatibility complex region, were studied by multiple restriction analysis and in vitro amplification. In the affected individuals, 21.4% of the chromosomes were found to carry either gene deletions or large and small gene conversions. Our findings, consistent with previous reports in other ethnic groups, provide further evidence for the genetic heterogeneity of the disease.

ISSN:0001-5652    

DOI:10.1159/000154176

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

The genes for spinal muscular atrophy (SMA) and a possible subtype of schizophrenia (SCZD1) have been mapped to chromosome 5q11.2-q13.3. DNA markers have been mapped to 5q11.2–q13.3 using a hybrid cell line deleted for this region [Gilliam et al., Genomics 0.7. New polymorphic microsatelhtes were sequenced for D5S76, D5S125, D5S39, D5S127 and HEX-B. Two-point and multipoint analysis in non-CEPH pedigrees confirmed that the microsatelhtes were in tight linkage with each other. These new microsatelhtes will increase the efficiency of linkage analysis for these disor

ISSN:0001-5652    

DOI:10.1159/000154177

出版商:S. Karger AG    

年代:1993

数据来源: Karger