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Fine mapping of the 5p13 locus linked to schizophrenia and schizotypal personality disorder in a Puerto Rican family

Bespalova, Irina N.a; Angelo, Gary W.a; Durner, Martinac; Smith, Christopher J.a; Siever, Larry J.a; Buxbaum, Joseph D.a b; Silverman, Jeremy M.a

Original Articles

A locus involved in schizophrenia and related disorders in a Puerto Rican family has previously been mapped to chromosome 5p. The maximum two-point log of the odds (LOD) score of 3.72 was obtained for marker D5S111, and increased to 4.37 by multipoint analysis, assuming autosomal dominant inheritance with 90% penetrance. Additional genotyping and haplotype analysis placed the novel locus on 5p13.2–p13.3 within the interval between markers D5S1993 and D5S631. In the current study, we saturated the interval between markers D5S1993 and D5S631 with densely spaced polymorphic markers, genotyped these markers in the most informative branch of the family, and narrowed the critical region to 2.8 Mb. G-protein-coupled receptor gene [somatostatin and angiotensin-like peptide receptor (SALPR)] is one of the candidate genes within the critical interval. Sequence analysis of the coding region and the putative promoter of somatostatin and angiotensin-like peptide receptor did not reveal functionally significant variants in affected family members, although several polymorphisms were detected.

aDepartment of Psychiatry

bDepartment of Neurobiology, Mount Sinai School of Medicine, One Gustave Levy Place, New York, NY 10029

cDepartment of Biostatistics, Division of Statistical Genetics, Columbia University, 1051 Riverside Drive, New York, NY 10032, USA

Sponsorship: This study was supported by the program project grant MH045212 to Kenneth L. Davis and J.M.S., an NIMH Conte Center Grant MH066392 to K.L.D and J.D.B., a Schizophrenia Research Program grant (Scottish Rite) to J.M.S., and a Merit Award to K.L.D. and J.M.S. from the Department of Veterans Affairs.

Correspondence and requests for reprints to Irina N. Bespalova, Department of Psychiatry, Mount Sinai School of Medicine, One Gustave Levy Place, Box 1230, New York, NY 10029, USA

Tel: +1 212 659 8843; fax: +1 212 659 5626;

e-mail: irina.bespalova@mssm.edu

© 2005 Lippincott Williams & Wilkins, Inc.