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Recent studies have identified normal cellular DNA sequences which are lost in the development of embryonal and adult tumours. These tumours are thought to arise after a primary mutation in one allele of such a sequence is followed by loss of its normal homologue. In familial cases, the primary mutation is transmitted in the germ line. The secondary mutation may involve a substantial loss of chromosomal material and thus lead to identification of the site of the inherited mutation. We have examined constitutional and tumour genotypes of medullary thyroid carcinomas and phaeochromocytomas which develop in the dominantly inherited cancer syndrome multiple endocrine neoplasia type 2 (MEN2) to locate the predisposing gene in this syndrome. We observed deletion of a hypervariable region of DNA on the short arm of chromosome 1 in seven out of fourteen tumours. Analysis of the parental origin of the deleted allele in two families showed that it was derived from the affected parent in one case, which suggests that the deletion does not reflect the site of the inherited mutation in MEN2. The deleted region is distal to the breakpoint commonly detected in neuroblastomas, which share with the tumours of MEN2 embryological origin from neuroectoderm.

Minisatellite variant repeat unit mapping by PCR (MVR-PCR) assays the interspersion pattern of variant repeat units along minisatellite alleles. Mapping such internal variation in the highly polymorphic minisatellite MS31A (locus D7S21), reveals extreme levels of allelic variability, far in excess of that detectable by allele length analysis. Flanking base substitutional polymorphisms have enabled the 5' structure of large numbers of MS31A alleles to be derived from genomic DNA by allele-specific MVR-PCR. More than 100 alleles have now been mapped and all are different. Several alleles show related internal structures and some of these provide evidence of polarity in allelic variation reminiscent of that seen at two other hypervariable minisatellites, D1S8 (MS32) and D16S309 (MS205). We also describe the diploid digital coding of MS31A, including the simultaneous coding of MS31A and a second locus, MS32, by duplex MVR-PCR, which greatly enhances the potential forensic applications of this technique.

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The Waldrapp ibis (Geronticus eremita) is one of the most endangered birds in the wild. The only real hope for its survival seems to rest with captive propagation, which has fortunately proved straightforward. Preservation of genetic diversity for maintaining viable populations is a major goal in any species conservation programme. Therefore sensitive tools have to be developed for the detection and regular monitoring of population variability. Individual identity has to be verified and each individual's pedigree defined in order to enable effective selective breeding. In this study, extensive DNA fingerprinting technology was applied to a group of 39 captive Waldrapp ibises. Five minisatellite probes were used. Despite the fact that the colony was founded by only six birds and that some of the founders were apparently related, highly polymorphic banding patterns were obtained. The human- and pig-derived probes MS1, MS31, p lambda g3 and pCMS12 each detected multiple distinct loci suitable for individual identification and resolution of parentage. Probe MS51 was locus-specific and revealed six different alleles. In addition, MS31 and p lambda g3 co-detected a band present in all females but none of the males and thus could be used for sex determination. For all but four individuals both parents could be identified unambiguously. The exceptions were offspring derived from a full sib mating in which DNA results allowed no distinction between the parents and the grandparents. Comparison of the parentage assigned by DNA analysis and by observation of breeding behaviour, respectively, showed agreement in all but five instances. Here, DNA data uncovered interchange of individuals in the stud book. Application of these minisatellite probes therefore offers an extremely sensitive means for individual identification and verification and completion of pedigree records.