Location of facioscapulohumeral muscular dystrophy gene on chromosome 4.

The autosomal dominant disorder facioscapulohumeral muscular dystrophy (FSHD) is the last of the major progressive muscular dystrophies in which the gene had not been located. In linkage analysis on ten Dutch families with this disorder a lod score of 6.34 at a recombination fraction of 0.13 was obtained with the microsatellite marker Mfd 22 (D4S171). This maps the FSHD gene to chromosome 4. Only one family was uninformative for this marker. We found no evidence of genetic heterogeneity.

Absence of close linkage between maternal genes for susceptibility to pre-eclampsia/eclampsia and HLA DR beta.

To test the possibility that maternally expressed susceptibility genes for pre-eclampsia/eclampsia are closely linked to the HLA region on chromosome 6 of the human genome, members of ten pedigrees with multiple cases of these disorders were typed for HLA DR beta restriction fragment length polymorphisms by means of TaqI digests. The data were analysed by the LIPED program to calculate lod scores, by several programs to detect potential heterogeneity of recombination fraction between pedigrees, and by the affected-sibling and the affected-pedigree-member methods. The results exclude close linkage. If the putative susceptibility genes lie on chromosome 6 they must lie at least 5 centiMorgans, and probably more, from the HLA DR beta loci. No indication of linkage at higher recombination fractions was found. The main maternally expressed genes affecting susceptibility to pre-eclampsia are not in the HLA region.

Are there neuropsychologic manifestations of the gene for Huntington's disease in asymptomatic, at-risk individuals?

It has recently been reported that persons at risk for Huntington's disease who test positive for the linked restriction fragment length polymorphism on chromosome 4 display neuropsychologic impairments when compared with at-risk subjects who test negative for this marker. We have studied a substantially larger series of at-risk subjects who have been thoroughly screened for the absence of neurologic or psychiatric features of Huntington's disease and have undergone predictive DNA testing. No evidence of cognitive or emotional differences between marker-positive and marker-negative individuals was found. Consideration of the designs and findings of the two studies indicates that it is premature to conclude that there are neuropsychologic impairments in Huntington's disease that precede the clinical onset of the illness.

Genetic and environmental determinants of dental occlusal variation in twins of different nationalities.

We have compared 10 occlusal traits in 358 monozygous and dizygous twin pairs in 4 different samples and estimated genetic variances for these features. Variable and frequently nonsignificant genetic variance was noted across samples for incisal overbite and overjet, sagittal molar relationship, posterior crossbite, and rotations and displacements of anterior teeth. Heritability estimates (when appropriately calculated) were low in magnitude (0-40%) and erratic, emphasizing the importance of environmental influences on occlusal variation and the variability of apparent genetic determinants with respect to the environment or population in which they are measured.

Prenatal diagnosis of fetal hemoglobin Lepore-Boston disease on maternal peripheral blood.

Molecular diagnosis of hemoglobin (Hb) Lepore-Boston in the fetus was successfully accomplished using maternal blood as a source for fetal cells in three pregnancies at risk for beta-thalassemia/Hb Lepore disease. Taking advantage of the possibility of amplifying Lepore-specific DNA fragments by polymerase chain reaction and of families in which Hb Lepore was inherited by the paternal side, we demonstrated in two cases and excluded in one case the presence of this hemoglobinopathy in the fetus directly on maternal DNA. The diagnosis was concordant with that obtained by traditional approaches in all three cases. Our results unequivocally show that nucleated fetal cells are present in maternal blood during pregnancy, and demonstrate for the first time that prenatal diagnosis of a genetic disease may be feasible without invasive procedures.

Platelet MAO in subtypes of alcoholism.

A number of investigators have observed low platelet monoamine oxidase (MAO) activity in alcoholism. There is also preliminary evidence suggesting that low enzyme activity is principally associated with one of two putative subtypes of alcohol dependence, i.e., type II (male limited). The results of this study are consistent with two previous reports of reduced platelet MAO activity in type II male alcoholics as compared with type I male alcoholics and normal, healthy male controls. Type I (milieu-limited) alcoholics showed a smaller reduction in enzyme activity. The observed differences do not appear to be related to concurrent use of other psychoactive substances, characteristic differences in age between type I alcoholics and type II alcoholics, antisocial personality disorder, or variation in platelet size. Low platelet MAO activity in alcoholics is possibly related to both state and trait factors and may be a useful biochemical measure to assist with subtyping.

TSH response to TRH and family history of alcoholism.

The thyrotropin (TSH) response to intravenous thyrotropin-releasing hormone (TRH) was evaluated in 10 sons of alcoholic fathers (FHP group) and 10 matched controls (FHN group). No differences were observed between the two groups in basal TSH, peak TSH levels, on the incidence of TSH-blunting to TRH. Though there was a trend for a less intense TSH response over time after the TRH infusion, the difference between the family groups was not significant. These results are not consistent with some previous reports of an increased percentage of blunted TSH response to TRH for children of alcoholics. The clinical and research implications of these findings are discussed.

[Glucose-6-phosphate dehydrogenase as a marker of genetic predisposition to neoplasms]. / Dyhydrogeneza glukozo-6-fosforanowa jako marker genetycznie uwarunkowanej predyspozycji do choroby nowotworowej.

In the light of reports in the literature the data are presented on the importance of glucose-6-phosphate dehydrogenase in cell metabolism. The effect of decreased enzyme activity or its complete absence on the functions of the cell, and the clinical conditions associated with deficient enzyme activity are described. The influence is discussed of the genetic determination of the enzyme on the occurrence of phenotypic effects, and the use of the mosaicism phenomenon in the study on the pathogenesis of certain disturbances. Several reports from the literature are quoted concerning the study of the reverse relationship between a deficiency of the activity of the enzyme and the incidence of carcinoma. The necessity is stressed of including electrophoretic techniques into the studies.

[Population genetics of HLA polymorphism in blood donors of Bremen and Hannover]. / Untersuchungen zur Populationsgenetik des HLA-Polymorphismus bei Blutspendern aus Bremen und Hannover.

501 blood donors from Bremen have been typed for HLA-ABC and -DR. The results are compared with HLA data obtained on 474 blood donors from Hannover. The gene frequencies do not differ significantly between these two population samples. Comparisons with population samples from Kiel, Hamburg, Essen, Frankfurt/M., Mainz, Mannheim, Freiburg/Br., Munich and Vienna did also not reveal any remarkable differences concerning the gene frequencies. Analysis of linkage disequilibrium of two-factor and three-factor haplotypes could show that the typical Caucasoid allele combination A1/B8 is not a constituent part of three-factor haplotype combinations. Between the population samples from Bremen and Hannover no marked differences in the distribution of two-factor and three-factor haplotype frequencies could be found.

Some genetic markers among the Bodos of North Bengal, India.

Some genetic markers have been examined among the members of the Bodo tribes, North Bengal, India. Gene frequencies have been estimated and comparison has been done to evaluate differentiation with the common population. The overall intergroup heterogeneity was not significant for Rabha and Mech and also in consideration with the local population. But the Totos showed a difference from the local population and differed slightly from Meches and Rabhas.

Serum ferritin as a marker of affection for genetic hemochromatosis.

A bivariate segregation analysis of genetic hemochromatosis with serum ferritin concentration was undertaken to examine the pleiotropic effect of the hemochromatosis locus on each of the two phenotypes, in an ascertained sample of families from Brittany, France. The gene was recessive with respect to both phenotypes, and the estimated gene frequency in the general population was 0.054. Although the ferritin concentration was corrected for the linear relationship with age among controls, there was a residual correlation with age among male family members, consistent with the progressive increase in body iron stores among hemochromatosis homozygotes. This genotype-specific relationship with age illustrates the importance of incorporating interaction effects into analytic models, and suggests that even as a better indicator of progress of disease, rather than liability to disease, serum ferritin concentration serves well to distinguish hemochromatosis homozygotes from alternate genotypes in a family study.

Studies of association between some genetic systems (ABO, MN, EsD, GLO, C3 and Hp).

Using random population data on the ABO, MN, esterase D (EsD), glyoxalase I, complement (C3) and haptoglobin markers in the population of Madras City associations were studied between these genetic systems. Out of a total of fifteen comparisons one significant association (chi 2 = 11.0; d.f. 4; 0.05 greater than p greater than 0.02) was found between the EsD and C3 phenotypes.

Serum protein markers in Chinese schizophrenics--haptoglobin types and transferrin and group-specific component subtypes.

Four hundred and thirty-nine Chinese schizophrenic male patients were investigated for the distribution of haptoglobin types; transferrin and group-specific component subtypes. The allelic frequencies of these three polymorphisms in the patient group were compared with those in healthy controls from published series. An excess of Gc2 over Gc1 (chi 2(1) 4.1; P less than 0.05) as well as a lack of Gc1S (chi 2(1) 15.3; P less than 0.001) was observed in schizophrenia. The relative risks of Gc1F, Gc1S and Gc2 have been estimated as 1.12, 0.76 and 1.15, respectively. It appears from this study that the presence of Gc2 renders individuals susceptible while Gc1S offers protection for schizophrenia. No such association was found for the haptoglobin or transferrin polymorphisms.

Genetic epidemiology of bilateral breast cancer: a linkage analysis using the affected-pedigree-member method.

We used the affected-pedigree-member (APM) method to conduct linkage analyses on 19 pedigrees in which the probands had premenopausal bilateral breast cancer. This method analyzes all affected pairs of relatives, as opposed to siblings only, and incorporates into the analyses information on the frequency of marker alleles. Fourteen codominant marker systems were evaluated in two separate analyses. In the first, only premenopausal cases of breast cancer were coded as affected because we assumed that postmenopausal cases were due to a different etiology. In the second analysis, all cases of breast cancer were coded as affected, irrespective of menopausal status. In the premenopausal-cases-only analysis, we observed evidence suggestive of nonindependent segregation for C3 and ESD. In the all-cases analysis, we observed much weaker evidence for C3 and ESD and noted a suggestion of nonindependent segregation for AMY2 and PGM1.

DNA adducts as markers of exposure in hazardous waste workers.

The interaction of a chemical or physical agent with DNA, resulting in the formation of covalent adducts or other modifications, has been implicated in the carcinogenic process for certain classes of chemicals. Demonstration of modified DNA may be taken as evidence of the interaction of a genotoxic agent with DNA, which is the basis for this review of DNA adducts as markers of exposure in hazardous waste work.

[The HLA system antigens in rheumatism]. / Antigeny sistemy HLA pri revmatizme.

The authors studied the distribution of class I and II HLA antigens in 51 Georgian patients with rheumatic heart disease. Statistically significant differences were found between the study group and controls, regarding HLA-AI, Aw19 and Bw22 distribution. The relative risk ratio was, respectively, 2.94, 3.82 and 4.40.

Maternal serum markers in screening for Down syndrome.

The addition of two new markers in maternal serum, estriol and HCG, to those already known, namely the level of maternal serum alfa-fetoprotein and maternal age, considerably improves the expected results of a screening strategy for Down syndrome. The detection rate is slightly increased from 53.0% to 57.6%, but, more importantly, the false-positive rate decreases from 9.4% to 7.3%. It is our belief that, at least in women aged less than 35 years, a screening strategy based on a combination of maternal age and biochemical markers should be incorporated into antenatal care. For older women, the results of such a maternal serum test may refine counseling for genetic amniocentesis, as a much more explicit risk calculation can be performed than that based on age alone.

Platelet monoamine oxidase, plasma dopamine beta-hydroxylase activity, dementia and family history of alcoholism in chronic alcoholics.

The authors measured platelet monoamine oxidase (MAO) activity and plasma dopamine beta-hydroxylase activity in 36 male chronic alcoholics during a period of non-abstinence, and in 29 normal controls. The influence of family history, dementia, chronicity of drinking and liver injury on the enzyme activities was also examined by multiple regression analysis. Platelet MAO was significantly lower in the alcoholic group. Both enzyme activities were negatively related to the presence of dementia, while low MAO activity was associated with positive family history (parents, sibs) of alcoholism.