Molecular study of parental origin of extra chromosome 21 in regular and de novo translocation trisomies.

The parental origin of the extra chromosome 21 (or extra 21q) was determined in seven informative families with a Down syndrome (DS) child by using molecular polymorphisms. Five DS patients had regular trisomy, one a de novo 14/21 translocation and another a de novo 21/21 translocation or isochromosome 21q. In four families with regular trisomy, the extra chromosome was of maternal origin, and in one family it was paternally derived.

Potential gene sequence isolation and regional mapping in human chromosome 21.

The transcription start sites of many genes are associated with CpG-rich DNA regions (CpG islands) containing clusters of rare cutting, methylation-sensitive restriction enzyme sites [Bird, 1986]. To detect gene sequences from human chromosome 21, we have screened cloned DNA fragments from a chromosome 21-specific cosmid library for the presence of such restriction sites. Several DNA fragments containing rare cutter sites, including Sac II, were isolated and five of them partially characterized.

Pericentric inversion of chromosome 9: prevalence in 300 Down syndrome families and molecular studies of nondisjunction.

The incidence of Down syndrome (DS) families where one of the parents is an heterozygous carrier of pericentric inversion of the heterochromatic region of chromosome 9-inv(9) (qh) - was determined in 3 independent groups of 100 families each. The total number of 17 such families found in the sample is significantly greater than the expected number of 5.73 for a sample of non-DS families of equal size.

Coincident maternal meiotic nondisjunction of chromosomes X and 21 without evidence of autosomal asynapsis.

A family in which the proband showed phenotypic signs of both the Turner and Down syndromes was studied cytogenetically and with restriction fragment length polymorphisms. The proband's karyotype was 46,X,+21, showing double aneuploidy without any signs of mosaicism. The single X and one chromosome 21 were of paternal origin while two chromosome 21 were of maternal origin.

Use of restriction fragment length polymorphic probes in the analysis of Down's syndrome trisomy.

Restriction fragment length polymorphic probes are being used more frequently in the molecular analysis of Down's syndrome and in the origin of nondisjunction in the syndrome. The type of information gained from RFLPs overlaps but differs from the information from cytogenetic heteromorphisms. From the allele frequencies of commonly available probes we have derived the expected frequencies of all matings in the population.

On the origin of recurrent trisomy 21: determination using chromosomal and DNA polymorphisms.

A family is described in which two cases of trisomy 21 occurred in, respectively, a newborn infant and a prenatally diagnosed fetus. Using fluorescent chromosomal polymorphisms, it was established that in both cases the extra chromosome resulted from a first meiotic division error in the mother and that the father contributed the same centromeric region to both children. RFLP-associated probes were used to examine the genetic content of the chromosomes.

The X chromosome shows less genetic variation at restriction sites than the autosomes.

Using a standard technique, 122 single-copy probes were screened for their ability to detect restriction fragment length polymorphisms (RFLPs) in the human genome. The use of a standardized RFLP screening enables the introduction of statistical methods in the analysis of differences in RFLP content between chromosomes and enzymes. RFLPs were detected from panels containing at least 17 unrelated chromosomes, digested with TaqI, MspI, BglII, HindIII, EcoRI, and PstI.

Construction and analysis of an EMBL-3 phage library containing partially digested human chromosome 21-specific DNA inserts (15-20 kb).

In the mouse-human hybrid cell line SCC 16-5, chromosome 21 is the only human chromosome present. Fractions highly enriched for this chromosome were obtained by applying the chromosome velocity sedimentation technique to this cell line. DNA prepared from these chromosomal fractions was partially digested with Mbo I, size fractionated on an NaCl gradient, and cloned in the EMBL-3 phage vector.

Bifunctionality and polarized infidelity at the hisB locus of Aspergillus nidulans.

The histidine (hisB) locus of Aspergillus nidulans is unusual in two ways. Firstly, it is bifunctional; besides coding for imidazole glycerol phosphate (IGP) dehydrase, it is required for the production of ascospores (fertility). It appears, therefore, to be partly homologous to the hisB locus of Salmonella typhimurium, which codes for IGP dehydrase and histidinol phosphate phosphatase.