Schizophrenia-associated chromosome 11q21 translocation : identification of flanking markers and development of chromosome 11q fragment hybrids as cloning and mapping resources

• Published in: American journal of human genetics 1993-03, Vol.52 (3), p.478-490
• Main Authors: FLETCHER, J. M, EVANS, K, SAINT CLAIR, D, VAN HEYNINGEN, V, BAILLIE, D, BYRD, P, HANRATTY, D, LEACH, S, JULIER, C, GOSDEN, J. R, MUIR, W, PORTEOUS, D. J
• Format: Article
• Language: English
• Subjects: Adult and adolescent clinical studies; Animals; Base Sequence; BASIC BIOLOGICAL SCIENCES; Biological and medical sciences; BIOLOGICAL MARKERS; Cell Fusion; Cell Line, Transformed; Cells, Cultured; CHROMOSOMAL ABERRATIONS; chromosome 11; Chromosome Banding; CHROMOSOME SORTING; CHROMOSOMES; Chromosomes, Human, Pair 1; Chromosomes, Human, Pair 11; Cloning, Molecular - methods; DETECTION; DNA - blood; DNA - genetics; DNA - isolation & purification; GENES; Genetic Linkage; Genetic Markers; Herpesvirus 4, Human - genetics; HUMAN CHROMOSOMES; Humans; Hybrid Cells - radiation effects; hybrids; Karyotyping; Lymphocytes - physiology; man; MAPPING; Medical sciences; MENTAL DISORDERS; Mice; Molecular Sequence Data; MUTATIONS 550400 > Genetics; Oligodeoxyribonucleotides; Original; Polymerase Chain Reaction - methods; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychoses; Restriction Mapping; schizophrenia; Schizophrenia - genetics; translocation; Translocation, Genetic; x radiation
• ISSN: 0002-9297; 1537-6605

Genetic linkage, molecular analysis, and in situ hybridization have identified TYR and D11S388 as markers flanking the chromosome 11 breakpoint in a large pedigree where a balanced translocation, t(1;11)(q43;q21), segregates with schizophrenia and related affective disorders. Somatic cell hybrids, separating the two translocation chromosomes from each other and from the normal homologues, have been produced with the aid of immunomagnetic sorting for chromosome 1- and chromosome 11-encoded cell-surface antigens. The genes for two of these antigens map on either side of the 11q breakpoint. Immunomagnetic bead sorting was also used to isolate two stable X-irradiation hybrids for each cell-surface antigen. Each hybrid carries only chromosome 11 fragments. Translocation and X-irradiation hybrids were analyzed, mainly by PCR, for the presence of 19 chromosome 11 and 4 chromosome 1 markers. Ten newly designed primers are reported. The X-irradiation hybrids were also studied cytogenetically, for human DNA content, by in situ Cot1 DNA hybridization and by painting the Alu-PCR products from these four lines back onto normal human metaphases. The generation of the translocation hybrids and of the chromosome 11q fragment hybrids is a necessary preliminary to determining whether a schizophrenia-predisposition gene SCZD2 is encoded at this site.