Leland Allen

Localization of the fibrillin (FBN) gene to chromosome 15, band q21.1

Fibrillin (FBN), a large extracellular matrix glycoprotein, is an important component of structures called microfibrils. Because fibrillin microfibrils appear to be abnormal in patients with the Marfan syndrome, fibrillin is a candidate for the gene defect in the Marfan syndrome. Derived clones from fibrillin cDNA were used as probes in isotopic and nonisotopic in situ hybridization studies to map the chromosomal location of the fibrillin gene. Fluorescent signals were found on chromosome 15 band q21.1; an excess of silver grains was noted over a similar region of chromosome 15 following in situ hybridization with a tritium-labeled probe. These results are consistent with linkage studies that localize the Marfan gene to chromosome 15.

Turner syndrome resulting from partial deletion of Y chromosome short arm." Localization of male determinants

Chromosome studies performed because of the possibility of Turner syndrome in an infant girl with pedal edema and mild neck webbing revealed an XY karyotype. Subsequent exploratory laparotomy showed dysplastic ovaries with nests of germ cells with the morphologic features of gonadoblastoma. Repeat chromosome studies from peripheral blood using high-resolution techniques, and also from skin and ovarian fibroblasts, showed an XY karyotype but with a partial deletion of the Y short arm, which was not detected with standard techniques. These findings indicate that testis determining factors are located in this deleted region of the Y chromosome but that other gene(s) remain that induce gonadoblastoma.

Intrachromosomal location of the telomeric repeat (TTAGGG)n

Eukaryotic telomeres are specialized DNA-protein structures that are thought to ensure chromosomal stability and complete replication of the chromosome ends. All telomeres which have been studied consist of a tandem array of G-rich repeats which seem to be sufficient for telomere function. Originally, the human telomeric repeat (TTAGGG)n was assumed to be exclusively located at the very end of all human chromosomes. More recent evidence, however, suggests an extension into proterminal regions. Very little is known about the interstitial distribution of telomeric repeats. Here we present evidence for the presence of (TTAGGG)n repeats in internal loci on the long and short arms of different human chromosomes. In addition, we studied the genomic organization of these repeats in more detail and discuss possible functions of interstitial telomeric repeats in the human genome.

Localization of a human brain sodium channel gene (SCN2A) to chromosome 2.

A DNA probe derived from a human genomic library has been used to localize on human chromosomes a gene coding for the alpha-subunit of the brain type II sodium channel (SCN2A). Hybridization of the probe to Southern blots made with DNAs from a rodent-human somatic cell hybrid panel indicates localization to the long arm of human chromosome 2. In situ hybridization to metaphase chromosomes confirms this assignment and indicates regional localization to 2q21-q33. The probe also reveals a frequent two-allele HaeIII RFLP.

A low-copy repeat located in subtelomeric regions of 14 different human chromosomal termini

Two cosmid clones, cG1A3 and cG1A6, containing large blocks of a telomeric repeat sequence, (TTAGGG)n, were isolated independently. Restriction mapping and fingerprinting studies suggested that cosmid cG1A6 is entirely contained within cG1A3. Competitive in situ hybridization localized cG1A3 to 14 different human telomeres and one internal site at 2q14----q21, indicating the presence of a subtelomeric low-copy repeat within this cosmid.