Exclusion of two candidate pigment loci,c and b,part of chromosome 11p,and 33 random polymorphic markers as the locus for tyrosinase-positive oculocutaneous albinism

The locus for Tyrosinase-Positive Oculocutaneous Albinism (ty-pos OCA) has not yet been localised. The search for the ty-pos OCA locus has included a search for linkage to candidate pigment loci and a candidate chromosomal region, as well as a random search using highly polymorphic markers in 42 families, including 271 individuals of whom 79 are affected. The lod scores for the tyrosinase (TYR) locus (11q14–q21), homologous to the albino locus, c, in the mouse and the CAS2/TRP1 locus (9p22-pter), homologous to the brown locus, b, in the mouse were -5.89 and -7.22, respectively, at a recombination fraction of =0.01, thus excluding them from being the ty-pos OCA locus. In the candidate chromosomal region, 11p, four loci (probes) were tested, SAA (pSAA82), CALC (pHC36), HBB (Gamma-globin haplotype) and an AC repeat polymorphism at the Wilm's Tumour locus (WT1). A portion of 11p was excluded with the following lod scores: pSAA82 lod=-2.05 at =0.10; pHC36 lod=-3.87 at =0.05; gamma-globin haplotype lod=-2.80 at =0.10; and WT1 lod=-2.34 at =0.10. Thirty-three polymorphic markers randomly distributed on 13 different chromosomes were all excluded from close linkage to ty-pos OCA.     

The Duffy blood group is linked to the α-spectrin locus in a large pedigree with autosomal dominant inheritance of Charcot-Marie-Tooth disease type 1

Summary The -spectrin locus (SPTA) on chromsome 1 maps to 1q22–q25 and -spectrin specific probes detect restriction fragment length polymorphisms (RFLPs) with the endonucleases MspI and PvuII. The Duffy blood group (FY) has been mapped to the 1p21–q23 region. We found positive linkage between the -spectrin and the Duffy loci with a maximal Lod score of 3.81 at =0.0 using the computer program MLINK. This indicates that both loci are very closely linked and probably localized to 1q22–q23.     

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.     

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.     

PKU locus: Genetic linkage with human amylase (Amy) loci and assignment to linkage group I

Summary The linked alpha-amylase loci Amy 1 and Amy 2 were evaluated for their linkage relationship to the PKU locus using data collected from two (one Czech and one Polish) groups of families. The five sibships informative for Amy 1: PKU give a score of 1.505 at =0.00 and the eight sibships informative for Amy 2: PKU give a score of 2.709 at =0.00. Due to the tandem position of Amy 1 and Amy 2 loci, these data could be combined, and linkage between Amy and PKU loci established with a score 4.214 at =0.00. The practical significance of the linkage, especially for identifying PKU allele carriers, is emphasized.     

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.     

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.     

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.     

No evidence for linkage between the loci for coagulation factor XIII-A and HLA

Summary The linkage analysis between the locus for coagulation factor XIII-A (F13A) and HLA region genes (HLA-A,-C,-B) was performed. In males, the maximum of lod scores between F13A and HLA was 0.33 at =0.30, and in females lod scores were negative at all values of . The results provided no evidence for close linkage between F13A and HLA genes.     

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     

Genetic mapping of anhidrotic ectodermal dysplasia: DXS159, a closely linked proximal marker

Summary Three families with anhidrotic ectodermal dysplasia (AED) have been studied by linkage analysis with seven polymorphic DNA markers from the Xp11-q21 region. Previously reported linkage to DXYS1 (Xq13-q21) has been confirmed (z()=4.08 at =0.05) and we have also established linkage to another polymorphic locus, DXS159, located in Xq11-q12 (z()=4.28 at =0.05). Physical mapping places DSX159 proximal to the Xq12 breakpoint of an X autosome translocation found in a female with clinical signs of ectodermal dysplasia. Of all markers that have been used in linkage analysis of AED, DXS159 would appear the closest on the proximal side of the disease locus.     

Mapping dominant markers using F2 matings

The development of efficient methods for amplifying random DNA sequences by the polymerase chain reaction has created the basis for mapping virtually unlimited numbers of mixed-phase dominant DNA markers in one population. Although dominant markers can be efficiently mapped using many different kinds of matings, recombination frequencies and locus orders are often mis-estimated from repulsion F₂ matings. The major problem with these matings, apart from excessive sampling errors of recombination frequency () estimates, is the bias of the maximum-likelihood estimator (MLE) of ( _ML). when the observed frequency of double-recessive phenotypes is 0 and the observed frequency of double-dominant phenotypes is less than 2/3 — the bias for those samples is — . We used simulation to estimate the mean bias of _ML. Mean bias is a function of n and and decreases as n increases. Valid maps of dominant markers can be built by using sub-sets of markers linked in coupling, thereby creating male and feamle coupling maps, as long as the maps are fairly dense (about 5 cM) — the sampling errors of increase as increases for coupling linkages and are equal to those for backcross matings when =0. The use of F₂ matings for mapping dominant markers is not necessarily proscribed because they yield twice as many useful markers as a backcross population, albeit in two maps, for the same number of DNA extractions and PCR assays; however, dominant markers can be more effeciently exploited by using doubled-haploid, recombinant-inbred, or other inbred populations.     

Autosomal dominant cerebellar ataxia type I in Martinique (French West Indies): Genetic analysis of three unrelated SCA2 families

Autosomal dominant cerebellar ataxias (ADCAs) are a group of neurodegenerative disorders that are clinically and genetically heterogeneous. We report here a genetic linkage study, with five chromosome 12q markers, of three Martinican families with ADCA type I, for which the spinocerebellar ataxia 1 (SCA1) locus was excluded. Linkage to the SCA2 locus was demonstrated with a maximal lod score of 6.64 at = 0.00 with marker D12S354. Recombinational events observed by haplotype reconstruction demonstrated that the SCA2 locus is located in an approximately 7-cM interval flanked by D 12S 105 and D12S79. Using thez _max-l method, multipoint analysis further reduced the candidate interval for SCA2 to a region of 5 cM. Two families shared a common haplotype at loci spanning 7 cM, which suggests a founder effect, whereas a different haplotype segregated with the disease in the third family. Finally, a mean anticipation of 12 ± 14 years was found in parent-child couples, with no parental sex effect, suggesting that the disease might be caused by an expanded and unstable triplet repeat.     

The gene encoding human transmembrane secretory component (locus PIGR) is linked to D1S58 on chromosome 1

The human transmembrane secretory component (SC or poly-Ig receptor, PIGR) is expressed basolaterally on glandular epithelial cells and is responsible for the external translocation of polymeric IgA and IgM. SC is hence a key molecule in antibody protection of mucosal surfaces. The human SC gene (locus PIGR) is located on chromosome 1 (1q31–q41). Here we present the first genetic linkage study of PIGR versus syntenic markers, including D1S58 and F13B, which have been previously regionalized to 1q31–q32 and 1q31–q32.1, respectively. We found that PIGR is closely linked to D1S58 (lods + 5.06 at _max = 0.06, without sex difference). PIGR versus F13B showed + 1.46 at _max = 0.25 for both sexes combined. A recombination of 0.06 between F13B and D1S58 (lods + 2.24) was in contrast to a previously published study giving _max = 0.22 (lods + 3.9), the combined lods being 5.6 at _max = 0.20. The progeny of a triply heterozygotic female indicated that PIGR is the flanking locus, therefore suggesting a cen-F13B-D1S58-PIGR-qter gene sequence on human chromosome 1. Only negative lod scores to RH, C8@, and PGM1 on 1p, and FY on proximal 1q, were found. Current combined Norwegian allele frequencies were estimated for PIGR to be A1 = 0.63, A2 = 0.37 (370 chromosomes), and for D1S58 to be A1 = 0.44, A2 = 0.56 (218 chromosomes).     

Reactivity of θ and α EEG Frequency Bands in Voluntary Attention in Junior Schoolchildren

Spatiotemporal organization of rhythmic and EEG components was studied by means of spectral-correlation analysis in seven- to eight-year-old children (n = 18) during anticipatory selective attention to sensory tactile and auditory stimuli. The topography of changes in coherence of the oscillations suggests that functional assemblies formed on the basis of the rhythm are modality-specific. Their centers are localized in respective sensory-specific cortical regions (central areas of both hemispheres during tactile attention and temporal areas during auditory attention). The functional integration on the basis of the rhythm is represented in both hemispheres by functional associations of the temporal, frontal, and (to a lesser extent) posterior associative areas independently of the modality of a relevant signal. Both types of the functional integration are significant for a correct solution of a perceptive task. The proposition that the cooperation of the - and systems in neuronal organization of voluntary attention ensure, respectively, its informational and motivational aspects.     

Linkage studies of the Wiskott-Aldrich syndrome: polymorphisms at TIMP and the X chromosome centromere are informative markers for genetic prediction

Summary Eleven families segregating for the X-linked recessive immune deficiency disorder, Wiskott-Aldrich syndrome (WAS), were studied by linkage analysis with an alpha satellite DNA probe, pBamX-7, which detects polymorphism at the X chromosome centromere, locus DXZ1, as well as three other polymorphic markers defining loci on the proximal short arm of the X chromosome. Linkage has been established between WAS and DXZ1 ( ()=7.08 at =0.03) and WAS and the TIMP gene locus ( ()=5.09 at =0.0). We have also confirmed close linkage between DXZ1 and two marker loci, DXS14 and DXS7, previously shown to be linked to the WAS locus. The probe pBamX-7 detected allelic variation in all females tested, reflecting the high frequency of polymorphism at the centromere. One WAS carrier revealed a recombination between WAS and both marker loci DXZ1 and DXS14, indicating that WAS does not map between these loci. In conjunction with previous data from genetic mapping studies of WAS, these results confirm the pericentromerix Xp localization of WAS and demonstrate the usefulness of alpha satelite DNA probes as tools for genetic prediction in WAS as well as other pericentric X-linked diseases.     

Mapping of the gene for X-chromosomal split-hand/split-foot anomaly to Xq26–q26.1

A large inbred kindred from Pakistan in which an isolated type of split-hand/split-foot anomaly is transmitted as an X-chromosomal trait has previously been described. An X/autosomal translocation and an X-chromosomal rearrangement have been excluded by cytogenetic studies. In order to map the gene responsible for this disorder, linkage analysis has been performed by using 14 highly polymorphic DNA markers distributed over the whole X chromosome. Two-point linkage analysis between the disease locus and X-chromosomal marker loci gives maximal lod scores at = 0.00 with the loci DXS294 (Z _max= 5.13) and HPRT (Z _max= 4.43), respectively, suggesting that the gene for the X-chromosomal split-hand/split-foot anomaly is localized at Xq26–q26.1.     

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.     

No evidence for linkage of familial hypertrophic cardiomyopathy and chromosome 14q1 locus D14S26 in a chinese family: evidence for genetic heterogeneity

Summary To understand the molecular basis of familial hypertrophic cardiomyopathy (FHC) in the Chinese population, a family with FHC was investigated. Nineteen family members who were 16 years of age or older were examined by M-mode or two-dimensional echocardiography. Eight members were diagnosed to be affected echocardiographically or clinically. Lymphocytes isolated from 20 family members were successfully transformed into permanent lymphoblastoid cell lines by Epstein-Barr virus. Three genomic DNA probes (CRI-L436, CRI-L329, and pSC14) that were derived from chromosome 14q1 loci and demonstrated to be linked closely to FHC were used to probe this family. Using the techniques of restriction fragment length polymorphism (RFLP) and linkage analysis, the probe CRI-L436, which recognized locus D14S26, was found informative in this family. The lod scores were -2.0 at = 0.025 and -1.49 at = 0.05. Thus, there was no evidence of linkage between the locus D14S26 and the gene for FHC in the pedigree studied. In addition, polymerase chain reaction (PCR) amplification did not indicate a mutation on exon 13 of the cardiac myosin heavy chain gene as previously reported. Our data suggest that FHC is a genetically heterogeneous disease.