Maria Karayiorgou

Genetic and physical map of the interferon region on chromosome 9p

A region of chromosome 9, surrounding the interferon-beta (IFNB1) locus and the interferon-alpha (IFNA) gene cluster on 9p13-p22, has been shown to be frequently deleted or rearranged in a number of human cancers, including leukemia, glioma, non-small-cell lung carcinoma, and melanoma. To assist in better defining the precise region(s) of 9p implicated in each of these malignancies, a combined genetic and physical map of this region was generated using the available 9p markers IFNB1, IFNA, D9S3, and D9S19, along with a newly described locus, D9S126. The relative order and distances between these loci were determined by multipoint linkage analysis of CEPH (Centre dEtude du Polymorphisme Humain) pedigree DNAs, pulsed-field gel electrophoresis, and fluorescence in situ hybridization. All three mapping approaches gave concordant results and, in the case of multipoint linkage analysis, the following gene order was supported for these and other closely linked chromosome 9 markers present in the CEPH database: pter-D9S33-IFNB1/IFNA-D9S126-D9S3-D9S19 -D9S9/D9S15-ASSP3-qter. This map serves to extend preexisting chromosome 9 maps (which focus primarily on 9q) and also reassigns D9S3 and D9S19 to more proximal locations on 9p.

The human mitochondrial citrate transporter gene (SLC20A3) maps to chromosome band 22q11 within a region implicated in DiGeorge syndrome, velo-cardio-facial syndrome and schizophrenia

Abstract The gene encoding the human mitochondrial citrate transporter designated SLC20A3 was mapped to chromosome 22 by analyzing its segregation in a panel of human-hamster somatic cell hybrids. This assignment was confirmed by fluorescence in situ hybridization to metaphase chromosomes, and the gene was further localized to band 22q11.21. The gene is located in a critical region associated with allelic losses in a variety of clinical syndromes, including DiGeorge syndrome, velo-cardio-facial syndrome and a subtype of schizophrenia.

Genetic Mouse Models of Psychiatric Disorders

The mental well-being of humans depends on the discovery of the causes of mental illnesses and the use of this knowledge to direct the generation of new treatments and the development of preventive measures. In this context, defining how we can exploit the power of animal models in investigative strategies designed to understand and manipulate candidate causal factors remains a critical challenge. The fact that mental illnesses are uniquely human disorders does not negate the feasibility of developing and using relevant animal models, but only defines the challenge and sets the limitations of an animal model. Because the field is still in its infancy, addressing the roles and targets of animal models of mental illnesses effectively and responsibly will require additional empirical data, as well as critical thinking from scientists, journal editors, and funding agencies. In this chapter, we discuss some general guidelines for the development of genetic mouse models of psychiatric disorders and offer a theoretical framework for the interpretation of their analysis. At the end, we discuss some results and practical issues emerging from our ongoing work on a genetic mouse model of schizophrenia.