Cloning a balanced t(9;11)(p24;q23.1) chromosomal translocation breakpoint segregating with bipolar affective disorder in a small pedigree
- Univ. of Pittsburgh, PA (United States); and others
A small multigenerational pedigree was previously identified in which a balanced 9;11 chromosomal translocation was cosegregating with bipolar affective disorder. We hypothesize that genes or gene regulatory sequences disrupted by the translocation are contributing to bipolar affective disorder in a dominant fashion. The general strategy involves (1) using somatic cell hybrids containing the derivative 9 or 11 chromosomes to identify the closest chromosome 9 and 11 flanking markers, (2) using the nearest markers as PCR and hybridization probes to isolate both normal DNA (YAC) and patient DNA (cosmid) adjacent to and incorporating the translocation breakpoint, and (3) identifying expressed sequences in the genomic DNA that may be disrupted by the translocation. From a fusion of the translocation patient cell line and a recipient hamster cell line, somatic cell hybrids were isolated which contain either the human derivative 9 or derivative 11 chromosome. Using PCR-based STS assays with these hybrids, the location of the translocation breakpoint was localized to an estimated 500 kb region at chromosome 11 band q23.1 and a 1 cM region in 9 band p24 (more telomeric than originally reported). From a large set of CEPH and Roswell Park yeast artificial chromosomes (YACs), six chromosome 11 YACs spanning the 11q23.1 breakpoint have now been identified. A combination of pulsed field gel eletrophoresis and YAC mapping has narrowed the chromosome 11 region to less than 430 kb. Current efforts are focused on generating new chromosome 11 probes within the flanking markers, mapping these probes back to the der(9) and der(11) containing hybrids and the chromosome 11 YAC mapping panel. As the region is physically narrowed, we will identify candidate genes whose expression may be altered by this t(9:11) translocation.
- OSTI ID:
- 133395
- Report Number(s):
- CONF-941009-; ISSN 0002-9297; TRN: 95:005313-0123
- Journal Information:
- American Journal of Human Genetics, Vol. 55, Issue Suppl.3; Conference: 44. annual meeting of the American Society of Human Genetics, Montreal (Canada), 18-22 Oct 1994; Other Information: PBD: Sep 1994
- Country of Publication:
- United States
- Language:
- English
Similar Records
Progress towards mapping the constitutional t(11:22) breakpoint
Isolation of a yeast artificial chromosome spanning the 8; 21 translocation breakpoint t(8; 21)(q22; q22. 3) in acute myelogenous leukemia
Related Subjects
BASIC STUDIES
HUMAN CHROMOSOME 9
GENETIC MAPPING
CHROMOSOMAL ABERRATIONS
HUMAN CHROMOSOMES
PATIENTS
HEREDITARY DISEASES
MENTAL DISORDERS
DNA-CLONING
SOMATIC CELLS
DNA HYBRIDIZATION
GENES
DOMINANT MUTATIONS
BIOLOGICAL MARKERS
YEASTS
PROBES
POLYMERASE CHAIN REACTION
ELECTROPHORESIS