Screening the monoamine oxidase B gene in 100 male patients with schizophrenia: a cluster of polymorphisms in African-Americans but lack of functionally significant sequence changes.
The monoamine oxidase B (MAO-B) gene was examined in 100 alleles derived from 80 Caucasian, 10 African-American, 5 Asian, and 5 Native American male patients with schizophrenia to identify sequence changes that might be associated with the disease. Approximately 235 kb of genomic sequence, primarily in coding regions, were screened by dideoxy fingerprinting, a modification of single-strand conformational polymorphism (SSCP) analysis that detects virtually 100% of sequence changes [Sarkar et al. (1992): Genomics 13:441-443; Liu and Sommer (1994): PCR Methods Appl 4:97-108]. No sequence changes of likely functional significance were identified, suggesting that mutations affecting the structure of the MAO-B protein are uncommon in the general population and are unlikely to contribute significantly to the genetic predisposition to schizophrenia. Eight polymorphisms were identified in African-Americans and Native Americans, but none were identified among Caucasians. Of the eight observed polymorphisms, a set of five transitions and one microdeletion was identified within approximately 17 kb of genomic sequence in the same 3 African-American individuals, while the remaining 7 African-Americans had a sequence identical to that in Caucasians. The presence of two such haplotypes, without intermediates, is compatible with the hypothesis that germline mutations can occur in clusters, as also suggested by other recent findings.
Sobell
J L
JL
Department of Psychiatry and Psychology, Mayo Clinic/Foundation, Rochester, Minnesota, USA.
Lind
T J
TJ
Hebrink
D D
DD
Heston
L L
LL
Sommer
S S
SS
D044383:Black People / Q000235:genetics*; D017931:DNA Primers / Q000737:chemistry; D008040:Genetic Linkage; D005819:Genetic Markers; D006801:Humans; D007198:Indians, North American / Q000235:genetics; D008297:Male; D008995:Monoamine Oxidase / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D012559:Schizophrenia / Q000201:enzymology / Q000235:genetics*; D017421:Sequence Analysis; D012730:Sex Chromosomes; D044465:White People / Q000235:genetics; D001741:Black or African American
D017931:DNA Primers; D005819:Genetic Markers; D008995:Monoamine Oxidase