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- Title
Physical mapping of autonomic/sympathetic candidate genetic loci for hypertension in the human genome: a somatic cell radiation hybrid library approach.
- Authors
Chitbangonsyn, S W; Mahboubi, P; Walker, D; Rana, B K; Diggle, K L; Timberlake, D S; Parmer, R J; O'Connor, D T
- Abstract
Allelic variation at multiple genetic loci may contribute to hypertension. Since autonomic/sympathetic dysfunction may play an early, pathogenic, heritable role in hypertension, we evaluated candidate loci likely to contribute to such dysfunction, including catechola-mine biosynthetic enzymes, catecholamine transporters, neuropeptides, and adrenergic receptors. Since chromosomal locations and physical map positions of many of these loci had not yet been identified, we used the GeneBridge4 human/hamster radiation (somatic cell) hybrid library panel (resolution ∼1 to ∼1.5 Mb), along with specifically designed oligonucleotide primers and PCR (200-400 bp products) to position these loci in the human genome. Primers were designed from sequences outside the coding regions (3′-flanking or intronicsegments) to avoid cross-species (hamster) amplification. Chromosomal positions were assigned in cR (centi-Ray) units (∼270 Kbp/Cr[SUB3000] for GeneBridge 4). A total of 13 loci were newly assigned chromosomal positions; of particular interest was a cluster of adrenergic candidate loci on chromosome 5q (including ADRB2, ADRA1A, DRD1, GPRK6, and NPY6R), a region harbouring linkage peaks for blood pressure. Such physical map positions will enable more precise selection of polymorphic microsatellite and single nucleotide polymorphism markers at these loci, to aid in linkage and association studies of autonomic/sympathetic dysfunction in human hypertension.
- Subjects
HYPERTENSION; HUMAN genome; RADIATION; PEPTIDES; BLOOD pressure
- Publication
Journal of Human Hypertension, 2003, Vol 17, Issue 5, p319
- ISSN
0950-9240
- Publication type
Article
- DOI
10.1038/sj.jhh.1001550