Gj Temeerman

IDENTIFICATION OF CROSSOVERS IN WILSON DISEASE FAMILIES AS REFERENCE POINTS FOR A GENETIC LOCALIZATION OF THE GENE

SummaryWilson disease (WD) is an autosomal recessive disorder of copper metabolism. A minimum recombinant analysis using D13S22, ESD, RB1, D13S31, D13S55, D13S26, D13S39, and D13S12, all localized at 13q14-q22, has been carried out in 20WD families of Northwest-European origin. No inconsistencies have been observed with respect to locus order or location of the WD locus (WND) compared with previous linkage studies. D13S31 was mapped as the closest marker proximal to WND, whereas D13S55 and D13S26 were mapped as the closest markers distal to WND. We have identified a crossover between WND and D13S31 in one family and a crossover between WND and D13S55 in another. These crossover sites can be used as reference points for new chromosome 13q14-q21 markers, and are therefore important for a more accurate mapping of the WD locus.

Close linkage of the Wilsons's disease locus to D13S12 in the chromosomal region 13q21 and not to ESD in 13q14

SummaryWilsons disease (WD) is an autosomal recessive disorder resulting in copper accumulation notably in liver and brain tissue. Linkage of the WD locus (WND) to ESD at 13q14 was first shown by studies in families of Middle Eastern origin using the isozymic polymorphism of esterase D. Using RFLPs detected by the ESD cDNA we could not confirm this reported close linkage in an analysis of 17 WD families of northwest European origin. A tight linkage was detected, however, to the marker D13S12, located more distally at 13q21. No obligate cross-overs were detected in 63 gametes informative for this marker. Our data confirm an assignment of WND to 13q14-21. Its localization, however, seems to be more distal to ESD than previously reported. Although genetic heterogeneity cannot be excluded, the observed differences between the two populations are probably due to random variation.

Remarks on the article "Use of Linkage Equilibrium Data in Prenatal Diagnosis of Cystic Fibrosis" by L. Strain et al.

The contribution of Strain et al. (1988) has the merit of being the first to draw attention to the linkage disequilibrium between cystic fibrosis (CF) and KM19/XV-2c in connection with prenatal diagnosis. Clinically however, the relevance of this linkage disequilibrium is different from that reported by Strain et al. They compute a posteriori probabilities of the linkage phase with CF on the basis of KM19/XV-2c phenotypes, combined with microvillar enzyme tests, for use in subsequent first trimester prenatal diagnosis. There are two objections to their approach. The first is their use of European data concerning the linkage disequilibrium. On theoretical grounds, the population cannot be considered to display the same linkage disequilibrium throughout Europe because of founder effects and different possible mutations. Recent investigations show significant differences in linkage disequilibrium between the north and south of Europe, and between the west and east of the continent. It is therefore preferable to use data from the area where the parents were born, to ensure that such data are applicable. The disadvantage of this approach is that there are fewer data on the linkage disequilibrium; however, given the numbers of CF families present, enough families should be obtained. The second objection is a major one. Strain et al. do not take into account the information available from parental KM19/XV-2c phenotypes. This information is however vital for a correct assessment of the probability of being affected with CF. The most striking difference between the figures presented by Strain et al. and an approach taking into account data from the parents (and even grandparents) exists when the marker phenotype of the fetus can be explained by two different sets of haplotypes. For this case, Strain et al. compute probabilities of about 0.5 being affected (Table 2, case BC/ AD). This case is considerably more subtle than one would expect. In the first place, a [+ ,+] [ , ] (AD) or [ + , ] [ , + ] (BC) phenotype can often be interpreted as the genotype because of information from the parents. Three possible cases can be distinguished, although they are lumped together by Strain et al.; they can be used as an example. For comparison, the data for the linkage disequilibrium are the same as those given by Strain et al. Table 1 gives the relevant probabilities.

Raster images and measurement with a Vickers M86 scanning microdensitometer and interferometer by computer control

A simple and easily adaptable interface between a Vickers M86 scanning microdensitometer and microinterferometer and a Z80 CP/M based microcomputer (Zenith Z89) is described. The hardware is supplemented by a software package written in Fortran‐66, linked with an assembly routine for two‐dimensional spot control and measurement. Facilities are provided for background correction, image processing, calibration of the spot movement, correction for glare, diffraction and finite spotsize and computer‐aided focusing. Results can be plotted on a matrix printer and on a graphical unit as ruled surface plot, as isophase or isodensity contour diagram or in three‐dimensional projection with hidden line removal.