High-resolution mapping of the [gamma]-aminobutyric acid receptor subunit [beta]3 and [alpha]5 gene cluster on chromosome 15q11-q13, and localization of breakpoints in two Angelman syndrome patients

Journal Article · Tue Jun 01 04:00:00 EDT 1993 · American Journal of Human Genetics; (United States)

OSTI ID:6449566

Sinnett, D; Wagstaff, J; Woolf, E ^[1]; Glatt, K ^[2]; Kirkness, E.J. Lalande, M. ^[3]

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1. Children's Hospital, Boston, MA (United States) Harvard Medical School, Boston, MA (United States)
2. Children's Hospital, Boston, MA (United States)
3. National Inst. of Alcohol Abuse and Alcoholism, Rockville, MD (United States); Children's Hospital, Boston, MA (United States) Harvard Medical School, Boston, MA (United States) Howard Hughes Medical Inst., Boston, MA (United States)

The [gamma]-aminobutyric acid (GABA[sub A]) receptors are a family of ligand-gated chloride channels constituting the major inhibitory neurotransmitter receptors in the nervous system. In order to determine the genomic organization of the GABA[sub A] receptor [beta]3 subunit gene (GABRB3) and [alpha]5 subunit gene (GABRA5) in chromosome 15q11-q13, the authors have constructed a high-resolution physical map using the combined techniques of field-inversion gel electrophoresis and phage genomic library screening. This map, which covers nearly 1.0 Mb, shows that GABRB3 and GABRA5 are separated by less than 100 kb and are arranged in a head-to-head configuration. GABRB3 encompasses approximately 250 kb, while GABRA5 is contained within 70 kb. This difference in size is due in large part to an intron of 150 kb within GABRB3. The authors have also identified seven putative CpG islands within a 600-kb interval. Chromosomal rearrangement breakpoints -- in one Angelman syndrome (AS) patient with an unbalanced translocation and in another patient with a submicroscopic deletion -- are located within the large GABRB3 intron. These findings will facilitate chromosomal walking strategies for cloning the regions disrupted by the DNA rearrangements in these AS patients and will be valuable for mapping new genes to the AS chromosomal region. 64 refs., 6 figs., 2 tabs.

• OSTI ID: 6449566
• Journal Information: American Journal of Human Genetics; (United States), Journal Name: American Journal of Human Genetics; (United States) Vol. 52:6; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

550400* -- Genetics
59 BASIC BIOLOGICAL SCIENCES
AMINO ACIDS
AMINOBUTYRIC ACID
AUTONOMIC NERVOUS SYSTEM AGENTS
CARBOXYLIC ACIDS
CHROMOSOMAL ABERRATIONS
CHROMOSOMES
CONGENITAL DISEASES
DISEASES
DRUGS
ELECTROPHORESIS
GENES
HEREDITARY DISEASES
HUMAN CHROMOSOMES
MAPPING
MEMBRANE PROTEINS
MUTATIONS
NEUROREGULATORS
ORGANIC ACIDS
ORGANIC COMPOUNDS
PROTEINS
RECEPTORS