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Polymorphism

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A linkage study of affective disorder with DNA markers for the ABO-AK1-ORM linkage group near the dopamine beta hydroxylase gene.

Biol Psychiatry 1994 Oct 1;36(7):434-442 Sherrington R, Curtis D, Brynjolfsson J, Moloney E, Rifkin L, Petursson H, Gurling H Academic Department of Psychiatry, University College, London, U.K.

Combining data from a number of studies has provided evidence for a susceptibility allele for affective disorder near to the ABO-AK1-ORM region on chromosome 9q34. The dopamine beta hydroxylase gene locus is also at 9q34. Five multigenerational families with bipolar and unipolar affective disorder were analyzed for linkage with highly polymorphic microsatellite markers from the candidate region. The segregation of the illness in these families was compatible with an autosomal dominant susceptibility allele.

Localization of the human dopamine beta hydroxylase (DBH) gene to chromosome 9q34.

Cytogenet Cell Genet 1988;48(1):48-50 Craig SP, Buckle VJ, Lamouroux A, Mallet J, Craig IW Department of Biochemistry, University of Oxford, UK.

A human cDNA clone for dopamine beta hydroxylase (DBH) has been isolated from a phaeochromocytoma library. In situ hybridization of this probe to replication-banded chromosomes has localized the gene to chromosome 9q34. The structural gene for the enzyme is therefore close to the ABO blood group locus. This suggests that the previously described activity variation in levels of serum DBH may reflect alterations in either the structure or regulation of the DBH coding sequences. Both biochemical and genetic evidence therefore indicate independence of DBH from the pterin-dependent aromatic amino acid hydroxylases of the neurotransmitter pathways.

Linkage of a gene regulating dopamine-beta-hydroxylase activity and the ABO blood group locus.

Am J Hum Genet 1988 Jan;42(1):160-166 Wilson AF, Elston RC, Siervogel RM, Tran LD Department of Biometry and Genetics, Louisiana State University Medical Center, New Orleans 70112.

Previous studies have presented evidence suggesting that levels of dopamine beta hydroxylase (DBH) activity are controlled by a gene linked to the ABO blood group locus. In this study, linkage analyses in four large families of whites and one family of blacks were performed on the untransformed and on the square root--and natural log--transformed DBH activity. In the families of white individuals, the results of both the sib-pair and lod-score linkage analyses strongly indicate that a gene regulating DBH activity is linked to the ABO blood group locus on chromosome 9q (i.e., lod score 5.88 at a recombination fraction of .0). The transformation used has a large effect on the maximum lod score and estimated recombination fraction. This putative gene does not appear to be polymorphic in the family of blacks.

Segregation and linkage studies of plasma dopamine-beta-hydroxylase (DBH), erythrocyte catechol-O-methyltransferase (COMT), and platelet monoamine oxidase (MAO): possible linkage between the ABO locus and a gene controlling DBH activity.

Goldin LR, Gershon ES, Lake CR, Murphy DL, McGinniss M, Sparkes RS

Am J Hum Genet 1982 Mar;34(2):250-262 Measurements of dopamine-beta-hydroxylase (DBH), catechol-O-methyltransferase (COMT), and monoamine oxidase (MAO) along with 27 polymorphic marker phenotypes were available for 162 patients with major affective disorders and 1,125 of their relatives. COMT in 30 families with 351 individuals, and MAO in 50 families with 309 individuals. The familial distribution of both DBH and COMT are consistent with two codominant alleles at the same locus that account for 56% and 59% of the total variance, respectively. MAO activity cannot be shown to be segregating as a single major gene, but a purely nongenetic hypothesis is also rejected. A possible linkage of a locus for DBH to the ABO locus is indicated by a maximum lod score of 1.82 at 0% and 10% recombination fractions for males and females, respectively. A lod score of 0.61 at 0% recombination for a similar analysis in a single large pedigree was reported by Elston et al., making the combined lod score for the two studies equal to 2.32 at 0% recombination.

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