Haplotype-based analysis of alpha 2A, 2B, and 2C adrenergic receptor genes captures information on common functional loci at each gene.
The alpha 2-adrenergic receptors (alpha2-AR) mediate physiological effects of epinephrine and norepinephrine. Three genes encode alpha2-AR subtypes carrying common functional polymorphisms (ADRA2A Asn251Lys, ADRA2B Ins/Del301-303 and ADRA2C Ins/Del322-325). We genotyped these functional markers plus a panel of single nucleotide polymorphisms evenly spaced over the gene regions to identify gene haplotype block structure. A total of 24 markers were genotyped in 96 Caucasians and 96 African Americans. ADRA2A and ADRA2B each had a single haplotype block at least 11 and 16 kb in size, respectively, in both populations. ADRA2C had one haplotype block of 10 kb in Caucasians only. For the three genes, haplotype diversity and the number of common haplotypes were highest in African Americans, but a similar number of markers (3-6) per block was sufficient to capture maximum diversity in either population. For each of the three genes, the haplotype was capable of capturing the information content of the known functional locus even when that locus was not genotyped. The alpha2-AR haplotype maps and marker panels are useful tools for genetic linkage studies to detect effects of known and unknown alpha2-AR functional loci.
Belfer
Inna
I
Pain and Neurosensory Mechanisms Branch, National Institute of Dental and Craniofacial Research, Bethesda, 20892, MD, USA. ibelfer@mail.nih.gov.|Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, Department of Health and Human Services, National Institutes of Health, Bethesda, 20892, MD, USA. ibelfer@mail.nih.gov.|National Institutes of Health, 12420 Parklawn Drive, Suite 451, MSC 8110, Rockville, MD, 20852, USA. ibelfer@mail.nih.gov.
Buzas
Beata
B
Pain and Neurosensory Mechanisms Branch, National Institute of Dental and Craniofacial Research, Bethesda, 20892, MD, USA.|Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, Department of Health and Human Services, National Institutes of Health, Bethesda, 20892, MD, USA.
Hipp
Heather
H
Pain and Neurosensory Mechanisms Branch, National Institute of Dental and Craniofacial Research, Bethesda, 20892, MD, USA.|Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, Department of Health and Human Services, National Institutes of Health, Bethesda, 20892, MD, USA.
Phillips
Gabriel
G
Pain and Neurosensory Mechanisms Branch, National Institute of Dental and Craniofacial Research, Bethesda, 20892, MD, USA.|Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, Department of Health and Human Services, National Institutes of Health, Bethesda, 20892, MD, USA.
Taubman
Julie
J
Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, Department of Health and Human Services, National Institutes of Health, Bethesda, 20892, MD, USA.
Lorincz
Ilona
I
Pain and Neurosensory Mechanisms Branch, National Institute of Dental and Craniofacial Research, Bethesda, 20892, MD, USA.|Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, Department of Health and Human Services, National Institutes of Health, Bethesda, 20892, MD, USA.
Evans
Catherine
C
Pain and Neurosensory Mechanisms Branch, National Institute of Dental and Craniofacial Research, Bethesda, 20892, MD, USA.|Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, Department of Health and Human Services, National Institutes of Health, Bethesda, 20892, MD, USA.
Lipsky
Robert H
RH
Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, Department of Health and Human Services, National Institutes of Health, Bethesda, 20892, MD, USA.
Enoch
Mary-Anne
MA
Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, Department of Health and Human Services, National Institutes of Health, Bethesda, 20892, MD, USA.
Max
Mitchell B
MB
Pain and Neurosensory Mechanisms Branch, National Institute of Dental and Craniofacial Research, Bethesda, 20892, MD, USA.
Goldman
David
D
Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, Department of Health and Human Services, National Institutes of Health, Bethesda, 20892, MD, USA.
D001741:Black or African American / Q000235:genetics; D001483:Base Sequence; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D004247:DNA / Q000235:genetics; D005819:Genetic Markers; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide; D018341:Receptors, Adrenergic, alpha-2 / Q000145:classification / Q000235:genetics*; D044465:White People / Q000235:genetics
D005819:Genetic Markers; D018341:Receptors, Adrenergic, alpha-2; D004247:DNA