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Genetics

We conduct molecular and behavioral genetics studies designed to localize the genes that influence normal variation in brain structure and function and to elucidate neuroimaging or neurocognitive endophenotypes for complex mental illnesses.

 

Molecular Genetics

Our primary molecular genetics collaborators are Drs. John Blangero and Laura Almasy at the Southwest Foundation for Biomedical Research.  SFBR's Department of Genetics works to advance human health through basic biomedical research with animal and human populations, specifically by characterizing the genetic components of susceptibility to common diseases of public health importance.  To this end, the SFBR team has advanced the use of lymphocyte based transcriptional profiling to aid large scale exploration of the human genome.  Drs. Almasy and Blangero developed Sequential Oligogenic Linkage Analysis Routines (SOLAR) software package. SOLAR is an extensive, flexible software package for genetic variance components analysis, including linkage analysis, quantitative genetic analysis, SNP association analysis (QTN and QTLD), and covariate screening. Operations are included for calculation of marker-specific or multipoint identity-by-descent (IBD) matrices in pedigrees of arbitrary size and complexity, and for linkage analysis of multiple quantitative traits and/or discrete traits which may involve multiple loci (oligogenic analysis), dominance effects, household effects, and interactions.

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Behavioral Genetics

Although genetic epidemiologic studies have demonstrated that most mental illnesses are substantially heritable, the molecular genetic bases of these disorders remain elusive. Given evidence that genes predisposing to schizophrenia, bipolar disorder, unipolar depression, substance abuse and dependence may be transmitted without expression of the clinical phenotype, interest has arisen in developing indicators of processes mediating between genotype and phenotype. Such allied phenotypes or endophenotypes may directly index the underlying pathology, or liability to disease, and hence can be measured in both affected and unaffected individuals. Endophenotypic markers are often quantitative, allowing for powerful analysis strategies which are not readily available for qualitative phenotypic markers such as diagnostic category.

 

Select Publications

  • Glahn DC, Almasy L, Blangero J, Burk GM, Estrada J, Peralta JM, Meyenberg N, Castro MP, Barrett J, Nicolini H, Raventós H, Escamilla MA. Adjudicating neurocognitive endophenotypes for schizophrenia. Am J Med Genet B Neuropsychiatr Genet. 2007 Mar 5;144B(2):242-9.
  • Göring HH, Curran JE, Johnson MP, Dyer TD, Charlesworth J, Cole SA, Jowett JB, Abraham LJ, Rainwater DL, Comuzzie AG, Mahaney MC, Almasy L, MacCluer JW, Kissebah AH, Collier GR, Moses EK, Blangero J. Discovery of expression QTLs using large-scale transcriptional profiling in human lymphocytes. Nat Genet. 2007 Oct;39(10):1208-16.
  • Sabb FW, Bearden CE, Glahn DC, Parker DS, Freimer N, Bilder RM. A collaborative knowledge base for cognitive phenomics. Mol Psychiatry. 2008 Apr;13(4):350-60.
  • Glahn DC, Thompson PM, Blangero J. Neuroimaging endophenotypes: strategies for finding genes influencing brain structure and function. Hum Brain Mapp. 2007 Jun;28(6):488-501.
  • Rogers J, Kochunov P, Lancaster J, Shelledy W, Glahn D, Blangero J, Fox P. Heritability of brain volume, surface area and shape: an MRI study in an extended pedigree of baboons. Hum Brain Mapp. 2007 Jun;28(6):576-83.
  • Contreras J, Hare L, Camarena B, Glahn D, Dassori A, Medina R, Contreras S, Ramirez M, Armas R, Munoz R, Mendoza R, Raventos H, Ontiveros A, Nicolini H, Palmer R, Escamilla M. The serotonin transporter 5-HTTPR polymorphism is associated with current and lifetime depression in persons with chronic psychotic disorders. Acta Psychiatr Scand. 2009 Feb;119(2):117-27.
  • Glahn, D.C., Bearden, C.E., Niendam, T.A., & Escamilla, M.A. (2004). The feasibility of neuropsychological endophenotypes in the search for genes associated with bipolar affective disorder. Bipolar Disorder, 6, 171-182.
  • Glahn DC, Therman S, Manninen M, Huttunen M, Kaprio J, Lönnqvist J, Cannon TD. Spatial working memory as an endophenotype for schizophrenia. Biol Psychiatry. 2003 Apr 1;53(7):624-6.
  • Cannon, T.D., Huttunen, M.O., Lonnqvist, J., et al. (2000). The inheritance of neuropsychological dysfunction in twins discordant for schizophrenia. Am J Hum Genet, 67, 369-382.
  • Almasy L, Blangero J. Multipoint quantitative-trait linkage analysis in general pedigrees. Am J Hum Genet. 1998 May;62(5):1198-211.
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