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Content archived on 2024-04-16

Upgrading of RC-link family bank


Research has been carried out with respect to the immortalization of lymphocytes from, ideally, all the approximately 6000 individuals in the bank and the complete typing of all the 6000 individuals in the bank for each of a large number of highly polymorphic deoxyribonucleic acid (DNA) marker systems well spread over the genome.

The bank can be used as an instrument for analysis of such complex traits and disease dispositions that are sufficiently frequent for segregating in a number of families within the bank.^M This is being accomplished through genetic linkage analysis, testing the trait or the disease disposition against the full array of markers. Laboratory facilities and methodological routines are being established for marker testing in material collected from families with certain Mendelian and chromosomal conditions. Some 100 families have been immortalized, the transformation being effected by exposure of lymphocytes to Epstein-Barr virus. Testing of a considerable number of polymerase chain reaction (PCR) based marker systems is being carried out.

With respect to exploiting techniques, certain complicated features like hair colour, hair curling, and eye colour have been considered. Following an indication of linkage between a category of green eye colour and the Luther-Secretor marker complex apparent linkage/nonassociation relationships have been between brown hair colour and green eye colour, as well as between hair curling and red hair. A linkage study of smell sensitivity to various substances has been initiated. Linkage studies have been pursued with Mendelian diseases (MD). Linkage of Groenouw's disease with markers on chromosome region 5q was discovered. Further, in a large Danish kindred with an apparently Mendelian distribution of maniodepressive disease, a suggestion of linkage was found with the enzyme marker PGP resulting in tentative assignment of a locus for this kind of MD to chromosome 16. In a study of Marner's cataract (CAM) it was shown that CAM is localized between the markers D16S4 and the haptoglobin locus on the long arm of chromosome 16. In further mapping with PCR based markers a more precise map of the CAM region is being developed.
Upgrading of family bank:

Eventually the total family bank, comprising material from nearly 1000 families with a total of approximately 6000 individuals, will be upgraded. Lymphocytes from each individual will be transformed into immortal cell strains. Eventually, all these families will be equipped with a grid of up to two hundred DNA marker systems, evenly spread over the full genome, and additional to the 70 classical marker systems (blood types and enzyme systems, etc.) for which the total bank has previously been tested.

The very large number of normal families is necessary to make the bank useful as an instrument for the genetic analysis of a number of normal physiological and other traits. In some methodological pilot studies such traits have included: total ridge count of finger prints, smell sensitivity to androsterone, various aspects of eye colour and hair colour.

During the 24 months of this project, a set of approximately 140 families with a total of about 1500 individuals within the family bank will be immortalized by exposure to Epstein-Barr virus. The cells will be grown in sufficient quantity to extract at least about 250ug DNA for each person. DNA will be extracted immediately from part of the material, while the rest of the immortalized cells will be stored in liquid nitrogen. Aliquots of these cells will be stored for future further culturing and for direct distribution to interested scientists.


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Københavns Universitet
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2200 København N

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