The amyloid beta protein has been identified as an important component of both cerebrovascular amyloid and amyloid plaques of Alzheimer9s disease and Down syndrome. A complementary DNA for the beta protein suggests that it derives from a larger protein expressed in a variety of tissues. Overexpression of the gene in brain tissue from fetuses with Down syndrome (trisomy 21) can be explained by dosage since the locus encoding the beta protein maps to chromosome 21. Regional localization of this gene by both physical and genetic mapping places it in the vicinity of the genetic defect causing the inherited form of Alzheimer9s disease.

https://science.sciencemag.org/content/sci/235/4791/880.full.pdf

Amyloid beta protein gene: cDNA, mRNA distribution, and genetic linkage near the Alzheimer locus

Alzheimer's disease is a leading cause of morbidity and mortality among the elderly. Several families have been described in which Alzheimer's disease is caused by an autosomal dominant gene defect. The chromosomal location of this defective gene has been discovered by using genetic linkage to DNA markers on chromosome 21. The localization on chromosome 21 provides an explanation for the occurrence of Alzheimer's disease-like pathology in Down syndrome. Isolation and characterization of the gene at this locus may yield new insights into the nature of the defect causing familial Alzheimer's disease and possibly, into the etiology of all forms of Alzheimer's disease.

http://science.sciencemag.org/content/sci/235/4791/885.full.pdf

The genetic defect causing familial Alzheimer's disease maps on chromosome 21

https://deepblue.lib.umich.edu/bitstream/handle/2027.42/28319/0000075.pdf;sequence=1

ELAM-1--dependent cell adhesion to vascular endothelium determined by a transfected human fucosyltransferase cDNA.

Radiation hybrid (RH) mapping, a somatic cell genetic technique, was developed as a general approach for constructing long-range maps of mammalian chromosomes. This statistical method depends on x-ray breakage of chromosomes to determine the distances between DNA markers, as well as their order on the chromosome. In addition, the method allows the relative likelihoods of alternative marker orders to be determined. The RH procedure was used to map 14 DNA probes from a region of human chromosome 21 spanning 20 megabase pairs. The map was confirmed by pulsed-field gel electrophoretic analysis. The results demonstrate the effectiveness of RH mapping for constructing high-resolution, contiguous maps of mammalian chromosomes.

https://science.sciencemag.org/content/sci/250/4978/245.full.pdf

Radiation hybrid mapping: a somatic cell genetic method for constructing high-resolution maps of mammalian chromosomes

Adhesion of circulating leukocytes to the vascular endothelium during inflammation is mediated in part by their interaction with the endothelial-leukocyte adhesion molecule ELAM-1. ELAM-1, a member of the LEC-CAM family of cell adhesion molecules, expresses an N-terminal carbohydrate recognition domain (CRD) homologous to various calcium-dependent mammalian lectins. However, the contribution of the CRD to cell adhesion and its carbohydrate binding specificity have not been elucidated. This study demonstrates that transfection of a human fucosyltransferase cDNA into nonmyeloid cell lines confers ELAM-1--dependent endothelial adhesion. Binding activity correlates with de novo cell surface expression of the sialylated Lewis x tetrasaccharide, whose biosynthesis is determined by the transfected fucosyltransferase cDNA. We propose that specific alpha(1,3)fucosyltransferases regulate cell adhesion to ELAM-1 by modulating cell surface expression of one or more alpha(2,3)sialylated, alpha(1,3)fucosylated lactosaminoglycans represented by the sialyl Lewis x carbohydrate determinant.

Cell Adhesion to Vascular Endothelium Determined by a Transfected Human Fucosyltransferase cDNA

We have used a panel of Chinese hamster X human somatic cell hybrids, each containing various portions of chromosome 21 as the only detectable human chromosome component, for regional mapping of cloned, chromosome 21-derived DNA sequences. Thirty unique and very low-repeat sequences were mapped to the short arm and three sections of the long arm. Three unique sequences map to the proximal part of the terminal band 21q22.3, and five to the distal part of this band. Some of these may represent parts of gene sequences that may be relevant to the pathogenesis of Down syndrome, as 21q22 is the area required to be present in triplicate for the full clinical picture.

Regional localization of DNA sequences on chromosome 21 using somatic cell hybrids.

Using a series of human-hamster hybrid cell lines, a gene coding for glycinamide ribonucleotide transformylase was mapped to human chromosome 21. The availability of hybrids containing only portions of chromosome 21 allowed the gene to be assigned to the region between the q11.2 and the q22.2 bands, inclusive. Differentiation of human and hamster glycinamide ribonucleotide transformylase was accomplished via an immunoprecipitation assay that employed a polyclonal antibody raised against the human enzyme.

M L Van Keuren

Papers

Regional localization of DNA sequences on chromosome 21 using somatic cell hybrids.

Assignment of a third purine biosynthetic gene (glycinamide ribonucleotide transformylase) to human chromosome 21.