Naturally occurring variations in the human cholinesterase genes: heritability and association with cardiovascular and metabolic traits.

Cholinergic neurotransmission in the central and autonomic nervous systems regulates immediate variations in and longer-term maintenance of cardiovascular function with acetylcholinesterase (AChE) activity that is critical to temporal responsiveness. Butyrylcholinesterase (BChE), largely confined to the liver and plasma, subserves metabolic functions. AChE and BChE are found in hematopoietic cells and plasma, enabling one to correlate enzyme levels in whole blood with hereditary traits in twins.

Autonomic function in hypertension; role of genetic variation at the catecholamine storage vesicle protein chromogranin B.

Rationale: Hypertension is a complex trait with deranged autonomic control of the circulation. Chromogranin B () is the most abundant core protein in human catecholamine secretory vesicles, playing an important role in their biogenesis. Does common inter-individual variation at the locus contribute to phenotypic variation in CHGB and catecholamine secretion, autonomic stability of the circulation, or blood pressure in the population?

Methods And Results: To probe inter-individual variability in , we systematically studied polymorphism across the locus by re-sequencing (~6 kbp footprint spanning the promoter, 5 exons, exon/intron borders, UTRs) in n=160 subjects (2n=320 chromosomes) of diverse biogeographic ancestries.

Natural variation within the neuronal nicotinic acetylcholine receptor cluster on human chromosome 15q24: influence on heritable autonomic traits in twin pairs.

Nicotinic acetylcholine receptors (nAChRs) are combinations of subunits arranged as pentamers encircling a central cation channel. At least nine alpha and four beta subunits are expressed in the central and peripheral nervous systems; their presence in autonomic ganglia, the adrenal medulla, and central nervous system, with accompanying responses elicited by nicotinic agonists, point to their involvement in cardiovascular homeostasis. nAChRs formed by alpha3, alpha5, and beta4 subunits may regulate blood pressure (BP) by mediating release of catestatin, the endogenous nicotinic antagonist fragment of chromogranin A (CHGA) and potent inhibitor of catecholamine secretion.

Assessment of multiple displacement amplification for polymorphism discovery and haplotype determination at a highly polymorphic locus, MC1R.

The identification of common genetic variants such as single nucleotide polymorphisms (SNPs) in the human genome has become central in human population genetics and evolution studies, as well as in the study of the genetic basis of complex traits and diseases. Crucial for the accurate identification of genetic variants is the availability of high quality genomic DNA (gDNA). Since popular sources of gDNA (buccal cells, lymphocytes, hair bulb) often do not yield sufficient quantities of DNA for molecular genetic applications, whole genome amplification methods have recently been introduced to generate a renewable source of double-stranded linear DNA.