The Yale Neurogenetics Program

Co-Directors:

Matthew State, MD, PhD		Murat Gunel, MD

The Yale Neurogenetics program is a multidisciplinary effort aimed at the identification and characterization of genes important to human CNS and neurovascular development through the study of disorders affecting both the structure of the brain and its vasculature, including neuronal migration, organization and proliferation diseases and vascular malformations including intracranial aneurysms, and function of the brain, including Tourette syndrome, Autism Spectrum Disorders, Mental Retardation, epilepsy and other developmental neuropsychiatric disorders.

In addition to gene discovery, the primary aims of the program are:

• To pursue detailed studies of the biological pathways implicated by molecular genetic discoveries;
• To exploit findings to identify additional genetic, epigenetic and environmental factors essential to normal and pathological brain development and function;
• To strengthen the bedside to bench continuum in developmental brain disorders at Yale with a particular focus on developmental disabilities.
• To translate new genetic and neurobiological knowledge into clinically meaningful interventions.

Program Members:

Additional Yale Collaborators:

Richard Lifton, Tian Xu, Pietro De Camilli, Robert King, Lawrence Scahill, Ami Klin, Kasia Chawarska, Elena Grigorenko, Flora Vaccarino, William Sessa, Dennis Spencer,Christopher Pittenger.

Current Research: The following projects are ongoing within the PNG:

• Molecular cytogenetic studies of families with Autism, Tourette syndrome and Mental Retardation
• Parametric linkage analysis in rare families with Tourette syndrome
• Developmental neurobiological studies of the Tourette syndrome-associated gene SLITRK1
• A large scale, multi-site study of copy number variation followed by deep resequencing in the Simons Simplex Autism Collection
• Biochemical, genetic and developmental neurobiological studies of Contactin and Contactin Associated Proteins implicated in Autism and Specific Language Impairment
• Homozygosity mapping and identification of Copy Number Variation among consanguineous probands with structural brain and neurovascular abnormalities, autism, epilepsy and mental retardation
• Molecular genetic pathway analysis of cavernous malformation
• Rare and common variant analysis of intracranial aneurysm

Selected Recent Publications:

Bilguvar K, Yasuno K, Niemela M, Ruigrok YM, von und zu Fraunberg M, van Duijn CM, van den Berg LH, Mane S, Mason CE, Choi M, Gaa?l E, Bayri Y, Kolb L, Arlier Z, Ravuri S, Ronkainen A, Tajima A, Laakso A, Hata A, Kasuya H, Koivisto T, Rinne J, Ohman J, Breteler MMB, Wijmenga C, State MW, Rinkel GJE, Hernesniemi J, Jaaskelainen JE, Palotie A, Inoue I, Lifton RP & Gunel M (in press).Susceptibility loci for intracranial aneurysm in European and Japanese populations. Nature Genetics, 2008.

Bakkaloglu B*, O'Roak BJ*, Louvi A, Gupta AR, Abelson JF, Morgan TM, Chawarska K, Klin A, Ercan-Sencicek, AG, Stillman AA, Tanriover G, Abrahams BS, Duvall JA, Robbins EM, Geschwind DH, Biederer T Gunel M, Lifton RP, State MW (2008). Molecular Cytogenetic analysis and resequencing of Contactin Associated Protein-Like 2 (CNTNAP2) in Autism Spectrum Disorders. American Journal of Human Genetics 82:165-173.

Bayrakli F, Bilguvar K, Mason CE, Diluna ML, Bayri Y, Gungor L, Terzi M., Mane SM, Lifton RP, State MW, Gunel M (2007). Rapid identification of disease-causing mutations using copy number analysis within linkage intervals. Human Mutation 28(12):1236-1240.

Abelson JF, Kwan K, O'Roak B, Baek D, Stillman A, Morgan TM, Mathews CA, Pauls DL, Mladen-Roko R, Gunel M, Davs NR, Ercan-Sencicek AG, Guez DH, Spertus JA, Leckman JF, Dure LS, Kurlan R, SInger HS, Gilbert DL, Farhi A, Louvi A, Lifton RP, Sestan N, State MW (2005) Sequence variants in SLITRK1 are associated with Tourette syndrome. Science 310:317-320.