摘要:

When a disease is controlled by two or more mendelian loci acting epistatically, it can be modeled in a linkage analysis as a single-locus mendelian disease with reduced penetrance. Previous work has demonstrated the reliability of such approximation for nuclear families, but not for extended pedigrees. We simulated extended pedigrees under two-locus models, in which one of the two disease loci was linked to a marker, and analyzed them both under the correct two-locus models and under single-locus approximations. The single-locus approximations provided results that were very close to the correct two-locus results. This held true, whether we ascertained pedigrees based on the presence of at least one affected individual, or based on the presence of at least five affected individuals. While a simulation study cannot guarantee that extrapolation of the results to models other than those examined is justified, our findings strongly suggest that single-locus linkage analysis can be reliably used in analyzing two-locus disorders in extended pedigrees. We also found striking confirmation of the importance of performing linkage analyses under both dominant and recessive models when the mode of inheritance is unknown, for extended pedigrees ascertained through multiple affected individuals.

ISSN:0001-5652    

DOI:10.1159/000154155

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Increased body iron stores and transferrin (TF) variants have been found to be associated with adverse health effects believed to be caused by oxygen free radicals. Previous attempts to establish a relationship between TF types, serum TF concentrations and iron-binding have been inconclusive. We have studied serum iron, total iron-binding capacity (TIBC), TF saturation and serum ferritin in relation to genetic TF types in a population sample (691 females and 639 males) from northern Sweden in an attempt to elucidate whether individuals with TF variants associated with adverse somatic and reproductive effects (TFC2 and C3) have increased body iron stores. As expected there was a highly significant sex difference, males manifesting increased body iron stores viz. increased levels of serum iron, TF saturation and serum ferritin, and a lower TIBC. There was no consistent and statistically significant association between the TFC2 variant and the parameters that indicate iron binding and storage. Thus the associations between TFC2 and somatic and reproductive damage appear to be independent of iron binding and body iron stores. TIBC (and TF levels) showed significant differences between TF types in females (p = 0.0015) but not in males. In females the TFC3 variant was associated with a significantly lower (p = 0.002) TIBC value. This decreased TIBC value was, however, not accompanied by an increased ferritin value, thus there was no unequivocal evidence for an association between TFC3 and increased body iron stores.

ISSN:0001-5652    

DOI:10.1159/000154156

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Medium-chain acyl CoA dehydrogenase (MCAD) deficiency is a potentially fatal inherited defect of fatty acid β-oxidation. Approximately 90% of the disease-causing alleles in diagnosed patients are due to a single base mutation, an A (adenine) to G (guanine) transition at position 985 of MCAD cDNA (G985). In a limited number of cases it was found that this mutation was always associated with a particular haplotype, defined by three intragenic restriction fragment length polymorphisms, indicating a founder effect [Kølvraa et al.; Hum Genet 1991;87:425–429]. In addition, recent studies of American patients and their ancestors suggested the existence of a founder from northern Europe [Yokota et al.; Am J Hum Genet 1991;49:1280–1291]. In the present study we document (1) that the G985 heterozygous frequency in the Caucasian population of North Carolina in the USA is 1/84, which is 5- to 10-fold higher than in non-Caucasian Americans; (2) that there exists a 100% association of the G985 mutation in 17 families with MCAD-deficient patients to a certain haplotype, defined by the restriction endonucleases BanII, PstI and TaqI; (3) that MCAD deficiency due to the G985 mutation is more frequent in the Netherlands, Ireland, England, Belgium and Denmark than in other western European countries, and (4) that the frequency distribution of G985 mutation carriers is 1/68–1/101 in newborns in the United Kingdom and Denmark, and 1/333 in Italy. These results support the notion of a founder effect in northwestern

ISSN:0001-5652    

DOI:10.1159/000154157

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Glutamate dehydrogenase (GLUD) is an important mitochondrial enzyme that participates in neuronal transmission by catalyzing the deamination of L-glutamate, which serves as a potent excitatory neurotransmitter. The direct involvement of GLUD in the pathogenesis of certain human neurodegenerative disorders has been suggested recently. To investigate its possible role in the induction and progression of these disorders, we have initiated studies focusing on the chromosomal organization of the several members of the GLUD family and their functional status. In the present study using a panel of human × rodent somatic cell hybrids and in situ hybridization to metaphase chromosomes, we documented that the members of the GLUD gene family are dispersed in the human genome. The functional GLUD1 gene was mapped to chromosome 10q22.3-q23, and an intronless processed gene (GLUDP1) to chromosome Xq22-q23, while the truncated intron-containing GLUD pseudogene GLUDP2 was also assigned on chromosome 10, but not closely linked to the GLUD1 gene. These results provide novel information concerning the chromosomal organization of the human GLUD gene family

ISSN:0001-5652    

DOI:10.1159/000154158

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Four probes that recognize D2S44, D17S79, D4S163 and Df 8S27 loci, were used to produce DNA profiles of 8- to 10-week-old chorionic villus samples and from blood samples of their respective parents. A total of 30 pedigrees were analyzed. The results showed strict Mendelian inheritance. The cumulative paternity index (PI) and probability of paternity (W) obtained with D2S44, D17S79 and D4S163 loci were sufficient to exceed the required standard (PI > 369, W > 99.73) for assertion of paternity for all predigrees tested. Therefore, these three loci are likely to satisfy the paternity test requirements in the majority of paternity cases, involving unrelated individuals, in the Chinese Han population. The other combinations of three loci did not produce high enough values for all cases, but all W values were > 98%. The results show that, using DNA from chorionic villi, these polymorphic loci can resolve cases of disputed paternity during early pregnancy.

ISSN:0001-5652    

DOI:10.1159/000154159

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Serum complement (C3, BF, C4) types were examined in Swedish Saamis (Lapps). In agreement with previous studies, a very low frequency of the C3*F allele (0.033) was found. Compared to Swedes and other Caucasian populations, Swedish Saamis showed a significantly increased frequency of the BFS, C4A4 and C4B2 variants, and a lower frequency of C4 deficiency. BFS, C4A4 and C4B2 show haplotype associations and thus the frequency of the S-A4-B2 complotype is significantly increased among the Saamis. Although the serum complement constitution of the Saamis shows some similarity with that of Asiatic Mongoloid populations it is unlikely to be due to Asiatic ethnic influence. The marked genetic deviations of the Saamis from all other populations has often been interpreted as a result of the founder effect and genetic drift. In this particular case, however, immunogenetic adaptation appears to be a plausible alternative explanation for the deviations in genetic complement factors.

ISSN:0001-5652    

DOI:10.1159/000154160

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Interview and medical-record data of 11,659 nondiabetic, non-asthmatic women were analyzed to evaluate the relationship between ABO and Rh blood groups and adverse outcomes of pregnancy. No statistically significant associations were found in logistic regression analyses that controlled for age, race, smoking and parity. The results of our study demonstrate the importance of controlling for confounding variables, and do not support a relationship between maternal blood group and adverse pregnancy outcomes including malformations.

ISSN:0001-5652    

DOI:10.1159/000154161

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

A 5-year-old girl with Klippel-Feil anomaly and bimanual polydactyly of triphalangeal thumb is described. The main findings include – in addition to the classical congenital fusion of cervical vertebrae and the clinical triad of short neck, limitation of head and neck movement and low-set posterior hairline – several associated abnormalities: scoliosis, spina bifida occulta, absence of ribs, conductive hearing loss, mirror movements, unilateral renal ectopia with dilation of the collecting system, and microtia. The hand malformation appears to represent a previously unreported defect associated with Klippel-Feil anom

ISSN:0001-5652    

DOI:10.1159/000154162

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

The genetic polymorphism of two salivary enzymes (esterase and α-amylase) was studied in individuals from eight districts of Greece. The pooled gene frequencies were: SetS = 0.63, SetF = 0.37, AMY1 = 0.87, AMY2 = 0.10, AMY3 = 0.02, and AMY4 = 0.01. There was no intrapopulation heterogeneity, while there was a significant difference between the Greeks and the few other European populations studied

ISSN:0001-5652    

DOI:10.1159/000154163

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

We have previously reported the mapping of the chronic (type II/intermediate and type III/mild/Kugelberg-Welander) form of the childhood-onset spinal muscular atrophies (SMA) to chromosome 5q11.2–13.3, with evidence for nonallelic genetic heterogeneity within a small sample of seven families [Brzustowicz et al., Nature 1990;344:540–541]. We now report the results of linkage analysis and heterogeneity testing on a set of 38 families with chronic SMA. Significant evidence for nonallelic heterogeneity was detected among these families, with the predominant locus for chronic SMA mapping to a 0.51-cM region on 5q, between the loci D5S6 and MAP1B. The estimated proportion of linked families, α, was 0.91, with a 2.3-unit support interval of 0.75 to 0.98. The indication that some families diagnosed with chronic SMA are not linked to chromosome 5q must be considered in strategies to map the SMA locus. The relevance of these findings to acute SMA (SMA type I, severe, Werdnig-Hoffmann disease) is still unk

ISSN:0001-5652    

DOI:10.1159/000154164

出版商:S. Karger AG    

年代:1993

数据来源: Karger