Laboratory of Behavioral Genetics
Using genetic linkage analysis, a number of genes responsible for Mendelian inherited defects have been mapped and, subsequently, cloned. Unfortunately the search for markers linked to major psychiatric disorders, such as schizophrenia, bipolar disorders, and substance abuse has been disappointing. One method that may hold promise as an adjunct to linkage analysis in schizophrenia is to search for chromosomal alterations that may be associated with the development of the illness.
We are interested in broadening the search for chromosomal defects in schizophrenia by applying a new strategy, representational difference analysis (RDA). This is a PCR-based hybridization technique that can be used to identify unique sequences within a population of DNA molecules when compared to control DNA. The resulting resolution allows for the detection of submicroscopic chromosomal alterations of virtually any size. Current work in our lab includes:
- Identification of probands with apparent sporadic schizophrenia, and use RDA to compare the DNA of these patients the DNA of their parents.
- perform high resolution G-banding chromosome analysis on probands with sporadic schizophrenia as a method of complementing RDA analysis.
- Characterize an RDA generated fragment by DNA sequence, Southeren blotting, RNA analysis and pulse field gel electrophoresis, and determine chromosomal assignment.
- Use RDA generated fragment as a probe for human cDNA and cosmid genomic libraries to identify schizophrenia candidate loci.
- Apply RDA using post mortem schizophrenia brain as tester and non-brain tissue from same individual as driver in order to identify unique viral sequences tha may be present in brain.
Nolan KA. Bilder RM. Lachman HM. Volavka J. Catechol o-methyltransferase val(158)met polymorphism in schizophrenia: differential effects of val and met alleles on cognitive stability and flexibility. Am J Psychiatry. 161: 359-61, 2004 View Text via PubMed
Strous RD. Nolan KA. Lapidus R. Diaz L. Saito T. Lachman HM. Aggressive behavior in schizophrenia is associated with the low enzyme activity COMT polymorphism: a replication study. Am J Med Genet. 120B: 29-34, 2003 View Text via PubMed
Stopkova P. Saito T. Fann CS. Papolos DF. Vevera J. Paclt I. Zukov I. Stryjer R. Strous RD. Lachman HM. Polymorphism screening of PIP5K2A: a candidate gene for chromosome 10p-linked psychiatric disorders. Am J Med Genet. 123B: 50-8, 2003 View Text via PubMed
Saito T. Stopkova P. Diaz L. Papolos DF. Boussemart L. Lachman HM. Polymorphism screening of PIK4CA: possible candidate gene for chromosome 22q11-linked psychiatric disorders. Am J Med Genet. 116B: 77-83, 2003 View Text via PubMed
Saito T. Lachman HM. Diaz L. Hallikainen T. Kauhanen J. Salonen JT. Ryynanen OP. Karvonen MK. Syvalahti E. Pohjalainen T. Hietala J. Tiihonen J. Analysis of monoamine oxidase A (MAOA) promoter polymorphism in Finnish male alcoholics. Psychiatry Res. 109: 113-9, 2002 View Text via PubMed
Saito T. Guan F. Papolos DF. Rajouria N. Fann CS. Lachman HM. Polymorphism in SNAP29 gene promoter region associated with schizophrenia. Mol Psychiatry. 6: 193-201, 2001 View Text via PubMed
Saito T. Guan F. Papolos DF. Lau S. Klein M. Fann CS. Lachman HM. Mutation analysis of SYNJ1: a possible candidate gene for chromosome 21q22-linked bipolar disorder. Mol Psychiatry. 6: 387-95, 2001 View Text via PubMed
Yan L. Szumlanski CL. Rice SR. Sobell JL. Lachman HM. Weinshilboum RM. Histamine N-methyltransferase functional polymorphism: lack of association with schizophrenia. Am J Med Genet. 96: 404-6, 2000 View Text via PubMed
Vandenbergh DJ. Rodriguez LA. Hivert E. Schiller JH. Villareal G. Pugh EW. Lachman H. Uhl GR. Long forms of the dopamine receptor (DRD4) gene VNTR are more prevalent in substance abusers: no interaction with functional alleles of the catechol-o-methyltransferase (COMT) gene. Am J Med Genet. 96: 678-83, 2000 View Text via PubMed
Saito T. Parsia S. Papolos DF. Lachman HM. Analysis of the pseudoautosomal X-linked gene SYBL1in bipolar affective disorder: description of a new candidate allele for psychiatric disorders. Am J Med Genet. 96: 317-23, 2000 View Text via PubMed
Russ MJ. Lachman HM. Kashdan T. Saito T. Bajmakovic-Kacila S. Analysis of catechol-O-methyltransferase and 5-hydroxytryptamine transporter polymorphisms in patients at risk for suicide. Psychiatry Res. 93: 73-8, 2000 View Text via PubMed
Nolan KA. Volavka J. Lachman HM. Saito T. An association between a polymorphism of the tryptophan hydroxylase gene and aggression in schizophrenia and schizoaffective disorder. Psychiatr Genet. 10: 109-15, 2000 View Text via PubMed
Nolan KA. Volavka J. Czobor P. Cseh A. Lachman H. Saito T. Tiihonen J. Putkonen A. Hallikainen T. Kotilainen I. Rasanen P. Isohanni M. Jarvelin MR. Karvonen MK. Suicidal behavior in patients with schizophrenia is related to COMT polymorphism. Psychiatr Genet. 10: 117-24, 2000 View Text via PubMed
Russ MJ, Lachman HM, Kashdan T, Saito T, Bajmakovic-Kacila S. Related Articles Analysis of catechol-O-methyltransferase and 5-hydroxytryptamine transporter polymorphisms in patients at risk for suicide. Psychiatry Res. 2000 Feb 14;93(1):73-8.
Hallikainen T, Saito T, Lachman HM, Volavka J, Pohjalainen T, Ryynanen OP, Kauhanen J, Syvalahti E, Hietala J, Tiihonen J. Association between low activity serotonin transporter promoter genotype and early onset alcoholism with habitual impulsive violent behavior. Mol Psychiatry. 1999 Jul;4(4):385-8.
Saito T. Papolos DF. Chernak D. Rapaport MH. Kelsoe JR. Lachman HM. Analysis of GNAZ gene polymorphism in bipolar affective disorder [In Process Citation]. Am.J.Med.Genet. 88:324-328, 1999 Aug. Full TextPDF Format - Requires Acrobat - Educational Use Only
Kalcheva N. Lachman HM. Shafit-Zagardo B. Survey for CAG repeat polymorphisms in the human MAP-2 gene. Psychiatr.Genet. 9:43-46, 1999 Mar.
Lachman HM. Papolos DF. Chromosome 22q11 deletions and aggressive behaviour [letter] [see comments]. Br.J.Psychiatry. 172:540, 1998 June
Papolos DF. Veit S. Faedda GL. Saito T. Lachman HM. Ultra-ultra rapid cycling bipolar disorder is associated with the low activity catecholamine-O-methyltransferase allele. Mol.Psychiatry. 3:346-349, 1998 July
Lachman HM. Nolan KA. Mohr P. Saito T. Volavka J. Association between catechol O-methyltransferase genotype and violence in schizophrenia and schizoaffective disorder. Am.J.Psychiatry. 155:835-837, 1998 June Full TextPDF Format - Requires Acrobat - Educational Use Only
Vandenbergh DJ. Rodriguez LA. Miller IT. Uhl GR. Lachman HM. High-activity catechol-O-methyltransferase allele is more prevalent in polysubstance abusers. Am.J.Med.Genet. 74:439-442, 1997 July Full TextPDF Format - Requires Acrobat - Educational Use Only
Lachman HM. Kelsoe JR. Remick RA. Sadovnick AD. Rapaport MH. Lin M. Pazur BA. Roe AM. Saito T. Papolos DF. Linkage studies suggest a possible locus for bipolar disorder near the velo-cardio-facial syndrome region on chromosome 22. Am.J.Med.Genet. 74:121-128, 1997 Apr. Full TextPDF Format - Requires Acrobat - Educational Use Only
Lachman HM. Kelsoe J. Moreno L. Katz S. Papolos DF. Lack of association of catechol-O-methyltransferase (COMT) functional polymorphism in bipolar affective disorder. Psychiatr.Genet. 7:13-17, 1997
Strous RD. Bark N. Parsia SS. Volavka J. Lachman HM. Analysis of a functional catechol-O-methyltransferase gene polymorphism in schizophrenia: evidence for association with aggressive and antisocial behavior. Psychiatry Res. 69[2-3]:71-77, 1997 Mar. Full TextPDF Format - Requires Acrobat - Educational Use Only
Strous RD. Bark N. Woerner M. Lachman HM. Lack of association of a functional catechol-O-methyltransferase gene polymorphism in schizophrenia. Biol.Psychiatry. 41:493-495, 1997 Feb. Full TextPDF Format - Requires Acrobat - Educational Use Only
Lachman HM. Morrow B. Shprintzen R. Veit S. Parsia SS. Faedda G. Goldberg R. Kucherlapati R. Papolos DF. Association of codon 108/158 catechol-O-methyltransferase gene polymorphism with the psychiatric manifestations of velo-cardio-facial syndrome. American Journal of Medical Genetics. 67(5): 468-472, 1996 Sept.
Lachman HM. Papolos DF. Saito T. Yu YM. Szumlanski CL. Weinshilboum RM. Human catechol-O-methyltransferase pharmacogenetics: description of a functional polymorphism and its potential application to neuropsychiatric disorders. Pharmacogenetics. 6(3): 243-250, 1996 June
Papolos DF. Yu YM. Rosenbaum E. Lachman HM. Modulation of learned helplessness by 5-hydroxytryptamine2A receptor antisense oligodeoxynucleotides. Psychiatry Research. 63(2-3): 197-203, 1996 July
Lachman HM. Papolos DF. A molecular model for bipolar affective disorder. Medical Hypotheses. 45(3): 255-264, 1995 Sept.
Lin MJ. Parsia SS. Papolos DF. Lachman HM. Highly polymorphic sequence variation in calcineurin B coding region (PPP3R1). Human Molecular Genetics. 3(3): 520, 1994 Mar.
Papolos DF. Edwards E. Marmur R. Lachman HM. Henn FA. Effects of the antiglucocorticoid RU 38486 on the induction of learned helpless behavior in Sprague-Dawley rats. Brain Research. 615(2): 304-309, 1993 July
Lachman HM. Papolos DF. Boyle A. Sheftel G. Juthani M. Edwards E. Henn FA. Alterations in glucocorticoid inducible RNAs in the limbic system of learned helpless rats. Brain Research. 609(1-2): 110-116, 1993 Apr.
Lachman HM. Papolos DF. Weiner ED. Ramazankhana R. Hartnick C. Edwards E. Henn FA. Hippocampal neuropeptide Y mRNA is reduced in a strain of learned helpless resistant rats. Brain Research.Molecular Brain Research. 14(1-2): 94-100, 1992 June
Weiner ED. Mallat AM. Papolos DF. Lachman HM. Acute lithium treatment enhances neuropeptide Y gene expression in rat hippocampus. Brain Research.Molecular Brain Research. 12(1-3): 209-214, 1992 Jan.
Nagel RL. Erlingsson S. Fabry ME. Croizat H. Susuka SM. Lachman H. Sutton M. Driscoll C. Bouhassira E. Billett HH. The Senegal DNA haplotype is associated with the amelioration of anemia in African-American sickle cell anemia patients. Blood. 77(6): 1371-1375, 1991 Mar.
Weiner ED. Kalasapudi VD. Papolos DF. Lachman HM. Lithium augments pilocarpine-induced fos gene expression in rat brain. Brain Research. 553(1): 117-122, 1991 July
Zeff RA. Zhao YF. Tatake R. Lachman H. Borriello F. Nathenson SG. Cis- and trans-repression of class I major histocompatibility gene expression in Abelson virus-transformed murine leukemia. Blood. 78(2): 524-532, 1991 July
Divish MM. Sheftel G. Boyle A. Kalasapudi VD. Papolos DF. Lachman HM. Differential effect of lithium on fos protooncogene expression mediated by receptor and postreceptor activators of protein kinase C and cyclic adenosine monophosphate: model for its antimanic action. Journal of Neuroscience Research. 28(1): 40-48, 1991 Jan.
Kalasapudi VD. Sheftel G. Divish MM. Papolos DF. Lachman HM. Lithium augments fos protoonocogene expression in PC12 pheochromocytoma cells: implications for therapeutic action of lithium. Brain Research. 521(1-2): 47-54, 1990 June
de CF. Lachman H. Transfection of a T-cell line with neo increases dexamethasone cytotoxicity. Leukemia Research. 14(7): 623-627, 1990
Brion LP. Schwartz JH. Lachman HM. Zavilowitz BJ. Schwartz GJ. Development of H secretion by cultured renal inner medullary collecting duct cells. American Journal of Physiology. 257(3 Pt 2): F486-F501, 1989 Sept.
Lachman HM. c-myc protooncogene expression in mouse erythroleukemia cells. [Review] [93 refs]. Environmental Health Perspectives. 80161-172, 1989 Mar.
Bouhassira EE. Lachman H. Krishnamoorthy R. Labie D. Nagel RL. A gene conversion located 5' to the A gamma gene in linkage disequilibrium with the Bantu haplotype in sickle cell anemia. Journal of Clinical Investigation. 83(6): 2070-2073, 1989 June
Lachman HM. Papolos DF. Abnormal signal transduction: a hypothetical model for bipolar affective disorder. Life Sciences. 45(16): 1413-1426, 1989
Nepveu A. Marcu KB. Skoultchi AI. Lachman HM. Contributions of transcriptional and post-transcriptional mechanisms to the regulation of c-myc expression in mouse erythroleukemia cells. Genes & Development. 1(9): 938-945, 1987 Nov.
Lachman HM. Cheng GH. Skoultchi AI. Transfection of mouse erythroleukemia cells with myc sequences changes the rate of induced commitment to differentiate. Proceedings of the National Academy of Sciences of the United States of America. 83(17): 6480-6484, 1986 Sept.
Lachman HM. Hatton KS. Skoultchi AI. Schildkraut CL. c-myc mRNA levels in the cell cycle change in mouse erythroleukemia cells following inducer treatment. Proceedings of the National Academy of Sciences of the United States of America. 82(16): 5323-5327, 1985 Aug.
Lachman HM. Skoultchi AI. Expression of c-myc changes during differentiation of mouse erythroleukaemia cells. Nature. 310(5978): 592-594, 1984 Aug.
Lachman HM. Mears JG. DNase I hypersensitivity in the gamma globin gene locus of K562 cells. Nucleic Acids Research. 11(17): 6065-6077, 1983 Sept.
Mears JG. Lachman HM. Labie D. Nagel RL. Alpha-thalassemia is related to prolonged survival in sickle cell anemia. Blood. 62(2): 286-290, 1983 Aug.
Mears JG. Lachman HM. Cabannes R. Amegnizin KP. Labie D. Nagel RL. Sickle gene. Its origin and diffusion from West Africa. Journal of Clinical Investigation. 68(3): 606-610, 1981 Sept.