Human mitochondrial DNA types in Finland

Summary Variation in mitochondrial DNA (mtDNA) in a sample of 110 Finns was analyzed with six restriction enzymes, AvaII, BamHI, HaeII, HinII, HpaI, and MspI, by using total blood cell DNA probed with mouse mtDNA. Two new enzyme morphs were observed, one for HaeII and one for HindII. Double-digestion experiments indicated that the BamHI morphs 2 and 3 result from base changes leading to AvaII morphs 3 and 9, respectively. Of the ten different mtDNA types observed, defined by restriction fragment patterns, seven have been previously described in Caucasoid populations. The three new Finnish mtDNA types can be derived from Caucasoid lineages by single restriction site changes. The results were used to reconstruct a phylogenetic tree for Caucasoid mtDNA types defined by the enzymes used. The frequencies of mtDNA types were used to compute genetic distances between Finns, Italians, and Israeli Jews. The frequencies of both enzyme morphs and mtDNA types show that the Finnish population is highly homogeneous.     

Physical fine mapping of genes underlying X-linked deafness and non fra(X)-X-linked mental retardation at Xq21

Summary Linkage studies and cytogenetically visible deletions associated with nonspecific X-linked mental retardation (XLMR) and a specific form of deafness (DFN3) have indicated that the genes responsible for these disorders are located at Xq21. Using DNA probes from this region, we have studied several overlapping deletions spanning different parts of Xq21. This has enabled us to assign the DFN3 gene and a gene for nonspecific XLMR to an interval that encompasses the locus DXS232 and that is flanked by DXS26 and DXS121.     

TAP1 and TAP2 transporter genes and predisposition to insulin dependent diabetes mellitus.

Genetic control of insulin dependent diabetes mellitus (IDDM) is mainly dependent on HLA genes in the major histocompatibility complex (MHC). The participation of TAP1 and TAP2 genes, located in the MHC region and coding for antigenic peptide transporters, was investigated in 116 IDDM patients and 98 normal controls using oligotyping after DNA amplification. The TAP2-B allele had a dominant protective effect, additive to that of the DR2 haplotype but antagonist to the susceptibility associated with the DR3 and/or DR4 haplotypes. The TAP2-A allele, in the homozygous state, had a predisposing effect. TAP1 allelic distribution did not differ among IDDM patients and controls. These data argue in favour of the role of peptide transporter gene in diabetogenesis.     

Confirmation of the chromosomal localization of human lamp genes and their exclusion as candidate genes for Salla disease

Summary Salla disease is an inherited lysosomal storage disorder caused by accumulation of free sialic acid in the lysosomes. Lamp genes, lamp A and lamp B (lysosome associated membrane proteins), are the first known genes encoding for human lysosomal membrane proteins. Absence of linkage in a large group of families shows that lamp genes are not involved in Salla disease. The lamp genes were localized, using Southern hybridization in hamster — human hybrid cell panels, to chromosomes 13 (lamp A) and X (lamp B).     

Hunter syndrome in Jews in Israel: further evidence for prenatal selection favoring the Hunter allele

Summary Among all the Jewish families with Hunter patients in Israel, 10 were Ashkenazi or Moroccan in origin. In those families, there was a paucity of new mutations. In addition, a significant deviation of the segregation ratio between the Hunter gene and the normal allele was demonstrated among the offspring of heterozygous mothers or siblings of affected children in these families. These results confirm and extend our previous observations suggesting selection in favor of the X chromosome carrying the Hunter allele among Ashkenazi and Moroccan Jews.     

Thymic hormone-containing cells. VII. Adrenals and gonads control the in vivo secretion of thymulin and its plasmatic inhibitor

The influence of adrenals and gonads on the intrathymic production and the circulating level of thymulin was evaluated in young adult mice. Adrenalectomy (Adx) and gonadectomy (Cx) induce a temporary decrease of thymulin serum level. One simultaneously notes, as a compensatory phenomenon, an increase in the thymic content of the hormone-producing cells. The decrease of serum thymulin levels after Adx and Cx is at least partially due to the appearance of low m.w. thymulin-inhibitory molecules. The fact that thymectomy prevents the appearance of these inhibitors suggests that the effects of Adx and Cx could be explained by a negative control by sex hormones of the synthesis or activity of thymulin inhibitors produced or controlled by the thymus. Specific hormone replacement therapy of castrated/adrenalectomized animals normalized thymulin serum level and thymic content. Such correction was also spontaneously observed after 4 mo, suggesting that other mechanisms (e.g., an influence of the hypothalamus-hypophysis axis) might be involved in the endocrine control of thymic hormone secretion.     

The wasted mutant mouse. I. An animal model of secretory IgA deficiency with normal serum IgA

The wasted (wst) mutation was recently described as a spontaneous, recessive mutation leading to pathologic changes affecting both the neurologic and the immune systems of wst/wst homozygotes, which presented symptoms analogous to those observed in patients with ataxia-telangiectasia (A.T.). We studied the IgA system of wst/wst mutants and their normal littermates to determine whether IgA deficiency commonly found in A.T. patients was also affecting these mutants. Interestingly, although IgA plasma cells were totally absent from their entire (small and large) intestine, their serum contained a normal level of IgA with a normal ratio of monomeric vs polymeric IgA. The absence of gut IgA plasma cells was not due to malnutrition and was not compensated by the appearance of cells secreting any other isotypes. Studies at the precursor cell level showed the absence of IgA-specific B cell precursors in the Peyer's patches, whereas sIgA B cells and IgA plasma cells were found in normal numbers in the spleen of wasted mice. These data suggest that secretory and serum IgA may comprise distinct systems and that the wasted mutant mouse is a potential model for the study of the physiology and regulation of IgA production.     

Energy partitioning in three species of nematode from polysaprobic environments

Summary The partitioning of energy in three species of nematode, Paroigolaimella bernensis, Diplogasteritus nudicapitatus and Rhabditis curvicaudata, from a polysaprobic environment is considered. Temperature was shown to have a profound impact on the rate at which these organisms obtained food resources and on the partitioning of energy into growth, reproduction and maintenance. Declining temperature resulted in a reduction in energy consumption and in production and maintenance costs. Absorption efficiencies were relatively low, rarely exceeding 20% and lying on average between 5–15%. Net production efficiencies varied throughout the life-cycle, but attained maximum levels of 70–80%. Females achieved higher net production efficiency than males. The physiology and ecological implications are discussed.     

Exogenous glutathione induces sister chromatid exchanges,clastogenicity and endoreduplication in V79-E Chinese hamster cells

Glutathione (GSH) dissolved in Eagle's MEM and added to cultures o of V79-E cells in concentrations between 2.5 × 10^–4 and 10^–3 moles/l for 1 h induces a dose-dependent cell cycle delay, sister chromatid exchanges and clastogenic damage. 7–8% of the metaphases showed endoreduplication at a recovery phase of 25 and 30 h after treatment with 10^–3 molesll GSH. Higher concentrations were lethal. The highest tolerated dose corresponds to the intracellular GSH level in V79-E cells. In the same range of concentrations, glutathione disulfide was inactive. Endoreduplication induction by GSH is G2-phase specific and endoreduplication metaphases show a reduced occurrence of single SCEs when extrapolated to the diploid complement. The adverse effects of GSH are independent of the presence of serum in the culture fluid but completely abolished when the treatment is performed in Hank's solution instead of MEM. The mechanism of genotoxicity of exogenous GSH is discussed but, at present, no pertinent explanation can be given.Abbreviations BUdR 5-bromodeoxyuridine - GSH glutathione - GSSG glutathione disulfide - SCE sister chromatid exchange