Linkage mapping of the spinal muscular atrophy gene

Spinal muscular atrophy (SMA) is a common autosomal recessive disorder resulting in loss of motor neurons. We have performed linkage analysis on a panel of families using nine markers that are closely linked to the SMA gene. The highest lod score was obtained with the marker D5S351 (Z_max = 10.04 at = 0 excluding two unlinked families, and Z_max = 8.77 at = 0.007 with all families). One type III family did not show linkage to the 5q13 markers, and in one type I consanguineous family the affected individual did not show homozygosity except for the marker D5S435. Three recombinants were identified with the closest centromeric marker, D5S435, which position the gene telomeric of this marker. These recombinants will facilitate finer mapping of the location of the SMA gene. Lastly, two families provide strong evidence for a remarkable variability in presentation of the SMA phenotype, with the age at onset in one family varying from 17 months to 13 years.     

A third gene locus for tuberous sclerosis is closely linked to the phenylalanine hydroxylase gene locus

Summary Following the observation of a patient suffering from tuberous sclerosis (TSC) with a de novo reciprocal translocation t(3;12)(p26.3;q23.3), we have undertaken a linkage study in 15 TSC families using polymorphic DNA markers neighbouring the chromosome breakpoints. Significant lod scores have been obtained for markers D12S7 (z _max=2.34, =0.14) and PAH (phenylalanine hydroxylase) (z _max=4.34, =0.0). In multipoint linkage analysis, the peak lod score was 4.56 at the PAH gene locus. These data suggest the existence of a third gene locus for TSC (TSC3) on chromosome 12q22-24.1. The regions that have been found to be linked to TSC in different families map to the positions of three enzymes, phenylalanine hydroxylase (12q22-24), tyrosinase (11q14-22), and dopamine-beta-hydroxylase (9q34), all of which are involved in the conversion of phenylalanine to catecholamine neurotransmitters or melanin. Disorders of these biochemical pathways might be involved in the pathogenesis of TSC.     

Assignment of congenital cataract Volkmann type (CCV) to chromosome 1p36

Congenital cataract, type Volkmann (McKusick no 115665, gene symbol CCV) is an autosomal dominant eye disease. The disease is characterized by a progressive, central and zonular cataract, with opacities both in the embryonic, fetal and juvenile nucleus and around the anterior and posterior Y-suture. We examined blood samples from 91 members of a Danish pedigree comprising 426 members, by using highly informative short tandem repeat polymorphisms and found the closest linkage of the disease gene (CCV) to a (CA) _n dinucleotide repeat polymorphism at locus D1S243 (Zmax = 14.04 at _M = 0.025 _F = 0.000), at a penetrance of 0.90. Using two additional chromosome 1 markers, we were able to map the CCV gene in the sequence 1pter-(CCV, D1S243)-D1S468-D1S214. The (enolase 1) gene has been mapped to this area; however, a mutation described in this gene did not give eye disease.     

Hydraulic model of a gas-lift bioreactor with flocculating yeast

The hydraulic model of a gas lift bioreactor, during a continuous alcoholic fermentation by using a strongly flocculating yeast, is analysed. Sucrose at two different concentrations (50 and 100 g/l) was used as substrate and the dilution rate for all the experiments was 1 h^–1. The biomass concentrations were between 85 and 110 g dry weight/1. A stimulus response technique was used to obtain the Residence Time Distribution curves, a pulse of a lactose solution being used as the tracer. Mixing time was determined by means of the response to a pulse of an acid tracer. These experiments were carried out by using an on-line data-acquisition system. The bioreactor behaviour is completely homogeneous, except for high substrate and biomass concentrations. A two parameters combined model is necessary, in this case, to fit the experimental data. Mixing times are very low, in the order of 10 seconds.List of Symbols C _T1 Tracer concentration of the tank 1 (g/l) - C _T10 Reference tracer concentration (g/l) - C Normalized tracer concentration (dimensionless) - Q ₀ Feed flowrate (l/h) - Q ₁ Flow exchanged between tank 1 and 2 (l/h) - [S] Substrate concentration (g/l) - t Time (s) - t _mix Mixing time (s) - t _c Circulation time (s) - V Reactor total volume (l) - X Biomass concentration expressed as dry weigh (g d.w./l) - Fraction of the total volume occupied by the highly agitated region - Fraction of the total flow which is exchanged between reactor 1 and 2 - Mean residence time (s), = V/Q ₀ - Dimensionless time, = t/ The stay of E. Roca at the ISIM in Montpellier (France) was supported by a grant from the CICYT (project BIO92 0568) of the Spanish Government.     

Use of the crossflow-microscreen technique for SCP production from dilute substrates

Summary A crossflow-microscreen cultivation technique was successfully used to select and maintain an easily harvestable microbial culture with a limited number of species under non-aseptic conditions in diluted cheese whey. The microbial selective pressure exerted by the system could be manipulated by varying the hydraulic () and mean cell () residence times. The optimum system parameters were =1 h and =10 h, resulting in a selected microbial population comprising three species only, namely Geotrichum candidum, Streptococcus cremoris and Leuconostoc lactophilum. The amino acid profile of the SCP produced compared favourably with other types of protein. The crossflow-microscreen technique makes SCP production possible from dilute, waste organic effluents.     

3′ creatine kinase (M-type) polymorphisms linked to myotonic dystrophy in Italian and Spanish populations

Summary Linkage analysis and haplotype characterization for the allelic system detected at the 3 creatine kinase muscle type (CKMM) locus were carried out in 59 myotonic dystrophy (DM) families from Italy and Spain. A maximum lod score (z _max) of 21.26 at a recombination frequency () of 0.00 was found. No statistically significant linkage disequilibrium was observed between DM and the RFLPs examined. However, a substantial linkage disequilibrium was found between CKMM-TaqI and CKMM-NcoI sites in these two populations.     

A method for the investigation of those transformations under which the visual recognition of a given object is invariant

An experiment is described which shows in operation the program set out in Foster (1972a) for the investigation of the invariance transformations of visual recognition. The concern in the present study is with the Lie group of rotations SO(2), and a certain centrally located foveal Landolt ring. By presenting to the visual system this Landolt ring and a rotated image in rapid succession, one attempted to induce a specified rotation-type phi-motion. Two subjects were employed. Both reported the existence of the required type of phi-motion for rotations ₀ of the Landolt ring about the visual axis with -2/72/7. By appealing to the basic Proposition 2 of Foster (1972 a), the conclusion is reached that the visual system appears capable of effecting upon a certain centrally located foveal annulus the local 1-parameter group of rotations about the visual axis ₀, [–2/7,2/7].     

Three DNA markers for hypophosphataemic rickets

Summary This paper presents three markers, 16D/E, pHMAI (DXS208), and CRI-L1391 (DXS274), that show close linkage for X-linked hypophosphataemic rickets (HYP). DXS274 is closely linked to HYP ( _max= 0.00, Z_max = 4.20), and DXS41 (99.6), ( _max= 0.00, Z_max = 5.20). Marker 16D/E maps distal to the disease locus ( _max= 0.05, Z_max = 3.11). The pHMAI probe recognises the same restriction fragment length polymorphism (RFLP) as 99.6. Multipoint analysis suggests that the most probable order of loci is Xpter-(DXS43, 16D/E)-HYP-DXS274-(DXS208, DXS41)-Xcen. The location of DXS274 distal to HYP cannot be excluded, as no recombinants were observed between DXS274 and HYP, or between DXS274 and DXS41/DXS208. One of the families contains a large number of recombinants, four of which are double recombinants. This most probably means that the disease in this family maps elsewhere on the X chromosome or on an autosome, indicating locus heterogeneity.     

Phosphorus depletion in the rhizosphere as influenced by soil moisture

To study the influence of soil moisture on phosphorus (P) depletion in the rhizosphere, maize (Zea mays cv. Trak) was pre-grown in vermiculite filled-PVC tubes for 9 days and then the plants with the tubes were transplanted into soil columns maintained at two soil moisture levels () of 0.14 and 0.20 cm³ cm^–3 for 10 days. The soil columns were separated at 1 cm depth by a nylon screen of 53 m inner mesh size, into 1 cm soil layer above and 3 cm soil column below screen. A root mat developed over the screen, but root hairs only could penetrate it. Regardless of the soil moisture level in the columns, and adequate and equal water and nutrients supply was maintained via wicks from an external nutrient solution to the plant roots in vermiculite. After 10 days, the soil columns were separated from the root mats, quickly frozen in liquid nitrogen and sliced into thin layers (0.2mm) using a refrigerated microtome to give soil samples at defined distances from the root mats for analyses. Lower soil moisture (=0.14) resulted in narrower and steeper depletion profile of 0.5 M NaHCO₃ extractable P (NaHCO₃-P_i) as compared to higher soil moisture (=0.20). Depletion of P in soil solution in the immediate vicinity of root mats did not differ much but the extension of the depletion zones was 0.10 cm at =0.14 and 0.20 cm at =0.20. The depletion up to 0.05cm with =0.14 and up to 0.07 cm with =0.20 was uniform, and may be attributed to the depletion in the root hair zone. Beyond the root hair zones, the theory of diffusion and mass flow was able to explain the observed differences in shape and extent of the P depletion profiles at the two soil moisture levels.     

Modulation of natural killer activity by thymosin alpha 1 and interferon

Summary A single injection of -interferon (-IFN) (30 000 units/mouse), a major biological modifier of natural killer (NK) cytolytic activity, strongly stimulated NK activity in normal mice, as expected, while the same treatment did not statistically alter the NK response in cyclophosphamide (CY)-suppressed animals.We investigated the possibility of thymosin ₁ cooperating with -IFN in boosting NK activity in CY-suppressed animals.The results show that treatment with thymosin ₁ (200 g/kg) for 4 days, followed by a single injection of -IFN 24 h before testing, strongly restored NK activity in CY-suppressed mice. Thymosin ₁ was, moreover, able to accelerate the recovery rate of NK activity in bone marrow reconstituted murine chimeras.Taken together the data support the concept that the synergic effect between thymosin ₁ and -IFN could be the result of effects on differentiation of the NK lineage at different levels.     

Multipoint linkage analysis in X-linked Alport syndrome

Summary In order to localize the gene for the X-linked form of Alport syndrome (ATS) more precisely, we performed restriction fragment length polymorphism analysis with nine different X-chromosomal DNA markers in 107 members of twelve Danish families segregating for classic ATS or progressive hereditary nephritis without deafness. Two-point linkage analysis confirmed close linkage to the markers DXS17(S21) (Z _max = 4.44 at = 0.04), DXS94(pXG-12) (Z _max=8.07 at =0.04), and DXS101(cX52.5) (Z _max=6.04 at =0.00), and revealed close linkage to two other markers: DXS88(pG3-1) (Z _max =6.36 at =0.00) and DXS11(p22–33) (z _max=3.45 at =0.00). Multipoint linkage analysis has mapped the gene to the region between the markers DXS17 and DXS94, closely linked to DXS101. By taking into account the consensus map and results from other studies, the most probable order of the loci is: DXYS1(pDP34)-DXS3(p19-2)-DXS17-(ATS, DXS101)-DXS94-DXS11-DXS42(p43-15)-DXS51(52A). DXS88 was found to be located between DXS17 and DXS42, but the order in relation to the ATS locus and the other markers used in this study could not be determined.     

Genetic fine localization of the arrestin (S-antigen) gene 4 cM distal from D2S172

Arrestin is a component of the light transduction cascade that takes place in the outer segment of retinal rods. In situ hybridization and linkage analysis have localized the arrestin gene to a region of 50 cM between CRYG and D2S23/D2S55 on chromosome 2q24–37. We have performed pairwise and multipoint linkage analysis between arrestin and four highly polymorphic markers from this region. The results indicate tight linkage between the gene and the microsatellite D2S172 (Z _max = 9.25 at =0.038). This fine localization of the gene should provide a useful tool for cosegregation analyses involving the arrestin gene.     

Linkage analysis for 18 enzyme loci in Pinus rigida Mill.

Summary Estimates of recombination frequency among enzyme loci of pitch pine revealed two new linkages, Mdh3:Pgm2 (=0.01) and Pep1:Mdh4 (=0.38), and confirmed two previously established linkages. Tighter linkage (=0.30) was ruled out for nearly all gene pairs examined. In general, the Bayesian approach used in this study to test for linkage performed better than alternative methods.This work was supported by the School of Natural Resources, College of Agricultural and Life Sciences, University of Wisconsin, Madison, WI, and by McIntyre-Stennis, project no. 142-C385     

Comparative Analysis of the Mechanisms Underlying Nifedipine-Induced Blockade of Three Subtypes of T-Type Ca2+ Channels

We analyzed the effects of nifedipine on a family of recombinant low-threshold Ca²⁺ channels functionally expressed in Xenopus oocytes and formed by three different subunits (1G, 1H, and 1I). The 1G and 1I channels demonstrated a low sensitivity to nifedipine even in high concentrations (IC₅₀ = 98 and 243 M, maximum blocking intensity A_max = 25 and 47%, respectively). At the same time, the above agent effectively blocked channels formed by the 1H-subunit (IC₅₀ = 5 M and A_max = 41%). The nifedipine-caused effects were voltage-dependent, and their changes depended on the initial state of the channel. In the case of 1G-subunits, the blockade was determined mostly by binding of nifedipine with closed channels, whereas in the cases of 1H- and 1I-subunits this resulted from binding of nifedipine with channels in the activated and inactivated states. The obtained data allow us to obtain estimates of the pharmacological properties of the above three subtypes of recombinant channels and, in the future, to compare these characteristics with the properties of low-threshold Ca²⁺ channels in native cells.     

Changes in the Central Regulation of the Respiratory Function after a Single Session of Intermittent Normobaric Hypoxia

Correlations between EEG findings and external respiration and gas exchange indices recorded prior to and after a single session of intermittent normobaric hypoxia were calculated by means of the Neirokartograf (MBN) program. Changes in the central regulation of respiration were observed for a period of more than one hour. The hypoxia caused a decline in EEG coherence in the left hemisphere and a decrease in the statistically significant correlations between the bioelectric rhythms of the , , and ranges and the external respiration and gas exchange indices.     

Changes in Cortical Activity in Altered States of Consciousness: The Study of Meditation by High-Resolution EEG

The specific features of the topology of spectral powers and coherent interregional interrelationships in the narrow, individually determined -, -, ₁-, ₂-, and ₃-frequency bands were studied by means of high-resolution EEG (62 channels) in novice and experienced meditators (NMs and EMs) at rest and under the conditions of generation of an altered state of consciousness characterized by inactivation of cognitive activity and the occurrence of a positive emotional experience of happiness. EMs in the meditation-free state were found to be characterized by a shift in the values of the individual frequency to a lower-frequency region of the spectrum, along with higher, compared to NMs, -, ₁-, ₂-, and ₃-band power values, which probably reflects the cumulative character of the influence of long-term meditative practice. The effective achievement of altered states of consciousness in EMs was associated with an increase in the local - and ₁ powers in the anterior cortical areas, as well as long-distance coherence between the prefrontal and posterior associative cortex with the formation of a center of gravity in the left prefrontal region (lead AF ₃). According to the data of the correlation analysis of the EEG power values and the data of subjective scaling of the meditation state, the -power values were positively associated with positive emotional experiences and negatively associated with the level of mental activity. The results of this study are consistent with current concepts that the and activities in narrow frequency bands reflect the activity of multifunctional neuronal networks selectively associated with processes of cognitive and affective activity.     

An assessment of the production and performance of F1 hybrid wheats based on Triticum timopheevi cytoplasm

Summary This work reports on the production and yield assessment of F₁ wheat hybrids from crosses between cytoplasmic male sterile lines, with Triticum timopheevi cytoplasm, and cultivars with fertility restoring genes.In four years of trials conducted between 1974 and 1977, only three F₁ hybrids out of a total of 168 yielded significantly more than the control variety Maris Huntsman, which currently occupies a substantial proportion of the area planted with winter wheat in the UK. Because of the rapid increase in yield of conventional wheat varieties, which has already led to varieties which outyielded Maris Huntsman, the yield advantage of these F₁ hybrids is insufficient for them to be developed as commercial varieties.The efficient production of uncontaminated male sterile and F₁ seed presents problems of isolation and a difficult biological problem in increasing the cross breeding potential of maintainer and restorer lines. These together with selection for other parental characters such as restoration, short straw and resistance to sprouting make the development of F₁ hybrids more difficult and expensive than that of conventional varieties.     

Marfan syndrome: exclusion of genetic linkage to five genes coding for connective tissue components in the long arm of chromosome 2

Summary Marfan syndrome represents a heterogeneous connective tissue disease, the symptoms arising in several tissues and organs. The defective gene(s) behind this autosomal dominant condition has not been found despite considerable research. The main targets of the research have been the genes coding for connective tissue components. Several of the candidate genes suspected to be defective in Marfan syndrome are located on the long arm of chromosome 2. These genes include a cluster of two genes coding for fibrillar collagens COL3A1 and COL5A2, and a third member of the collagen gene family: COL6A3. Furthermore, genes for elastin (ELN) and fibronectin (FN) are also located in this area of chromosome 2. We studied this chromosomal area using restriction fragment length polymorphism (RFLP) linkage analysis in five Finnish Marfan families with affected members in three generations. In two point linkage analyses, Lod scores of –3.192 ( = 0.1) to COL3A1, –1.683 ( = 0) to COL6A3 and –2.664 ( = 0.01) to FN were obtained, whereas the linkage analysis between elastin and the disease was non-informative (Lod score 0.444, = 0). With the multipoint linkage analysis that permits simultaneous examination of several loci and more efficient use of family data, we obtained an exclusion of all these loci as the site of the mutation leading to Marfan syndrome in these families.     

Further evidence against linkage between christ-siemens-touraine (CST) and XG loci

Summary A Brazilian informative pedigree for the CST:XG linkage relationship is analysed. The present lods, together with those from previously published data, provide evidence for the exclusion of linkage until a value of around 0.34.     

Parametric and jackknife confidence interval estimators for two-factor mating design genetic variance ratios

Summary Confidence interval estimators have not been defined for dominance to additive genetic variance () and average degree of dominance () for the nested, factorial, and backcross mating designs. The objective of this paper was to describe interval estimators for these parameters. Approximate F random variables were defined for expected mean square (EMS) ratios for linear models with one environmental effect. Approximate 1– parametric interval estimators were defined for and using these random variables. Random variables defined for linear models with no environmental effects are not approximately distributed as F random variables because common EMS are involved in the numerators and denominators of the EMS ratios. Delete-one jackknife (jackknife) interval estimators were defined for and for linear models with zero or one environmental effect(s); In transformed analysis of variance point estimates were used in pseudovalue estimators.Oregon Agricultural Experiment Station Technical Paper No. 8067