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Below are descriptions of the Genetics grants that are currently active. To view a list of past grants in this area, please click on the link below.
Genetics - Past Grants |
Beth Israel Deaconess Medical Center, Boston, MA
2005-2010
Principal Investigator: Christopher Walsh, M.D., Ph.D.
Recessive Genes for Autism and Mental Retardation (Co-funded with The Simons Foundation)
Twin studies suggest that autism has a large genetic component; however, few potential autism susceptibility genes have been identified. The goal of this project is to use special genetic populations to map and identify autism spectrum disorders (ASD) genes to better understand their classification, pathogenesis, and potential treatments. Preliminary data show that the large families and patterns of consanguinity that characterize special populations such as the Arabic countries of the Middle East facilitate the recognition of recessively inherited neurological disorders. The investigator will identify appropriate pedigrees that show children with autism, and in which parents are related to one another, suggesting that recessively acting genes may be causing ASD in those families. He will then take advantage of this consanguinity to map and hopefully clone these recessive ASD genes. The investigator will focus on Arabic populations of the Middle East since these populations also show “founder mutations” which are restricted to certain groups, and which further facilitate precise gene mapping. This study may provide new insights into patterns of inheritance and genetic causes of autism spectrum disorders.
Christopher A. Walsh Laboratory
Children's
Hospital - Boston , Boston , MA
2004-2008
Principal Investigators: Michael E. Greenberg, Ph.D., Isaac Kohane, M.D, Ph.D., Louis M. Kunkel, Ph.D.
Genetic Studies of Autism Spectrum Disorders
This study will utilize genetics, bioinformatics, and neuroscience programs at Children's Hospital-Boston to address the genetic basis of autism spectrum disorders (ASD). One hypothesis of this study is that there are genetic variants that may predispose an individual to develop ASD, and that these genes can be identified by transmission disequilibrium testing (TDT) of candidate genes in pathways logically indicated based on gene expression and neuronal activity studies. Using TDT and trios (child with autism and their parents), and affected sib pairs (ASP) analysis, studies will be performed to look for association of ASD with candidate genes and for linkage peaks associated with ASD. Another hypothesis of this study is that there are differences in gene expression in the white blood cells of children with autism in comparison with normal children. Microarray analysis will be performed to study differences in gene expression in white blood cells of children with autism compared with that of normal children. Sparked by evidence that autism may be caused by defective synaptic maturation and the finding that activity-dependent gene transcription plays a role in synapse maturation, a third hypothesis of this study is that mutations of transcriptional regulators and their target genes may underlie some forms of autism.
Greenberg Laboratory
Kohane Laboratory
Kunkel Laboratory
University of Cambridge Autism
Research Centre, Cambridge , UK
2004-2008
Principal Investigator: Simon Baron-Cohen, Ph.D.
A Genetic Study of Mathematical Talent and Asperger's Syndrome
Autism spectrum disorders often involve impaired empathy and intact or talent in systemizing. Research has suggested a link between talent in systemizing and the likelihood of autism in a family. This suggests that one of the genes involved in autism may be the gene (or genes) that underlie systemizing talent. This research attempts to identify genes associated with a well-defined example of systemizing talent, mathematical giftedness. Researchers will obtain DNA from large families where there are many gifted mathematicians, and will re-test any significant regions of the DNA in detail in a sample of mathematicians vs. non-mathematicians. Researchers are also studying DNA of people with Asperger Syndrome (AS) to see if the genes for systemizing are implicated in the genes for AS. Genetic research may improve early diagnosis of autism spectrum conditions.
Autism Research Centre
Simon Baron-Cohen
University of Cambridge, Cambridge, UK
2005-2006
Principal Investigator: Lindsey Kent, MBChB., PhD. MRC Psych
Investigation of Imprinted Chromosomal Regions and Mitochondrial Haplotypes in Autism
Autism is a developmental condition that may impair social development, communication, and may be accompanied by narrow interests and repetitive activity. Twin and family studies demonstrate a genetic contribution to autistic spectrum disorders (ASD’s). Although substantial effort is aimed at identifying these susceptibility genes, there is no unequivocal evidence to implicate a particular gene. This study proposes two novel approaches to investigating possible genetic risk factors. Firstly, ASD’s are known to occur in a number of disorders which arise from individuals possessing extra genetic material such as chromosomal duplications. The overgrowth condition known as Beckwith Weidemann syndrome (BWS) can occur in individuals who inherit two copies of a part of chromosome 11 from their father. The researcher has recently found that a number of these BWS individuals also have autism, suggesting that an autism susceptibility gene may be present on chromosome 11, although may only be expressed when inherited from the father. Secondly, there is evidence from several case reports to suggest that variation in the mitochondrial genome may be associated with autism but the role of the mitochondrial genetic code has not been widely investigated in ASD’s. Mitochondria supply cells with sufficient energy for a wide range of cellular processes. Polymorphisms within mitochondrial genes may therefore have functional consequences on cellular functions. This study will investigate these mechanisms in 300 autism probands parent trios and 230+ Asperger syndrome trios, as well as a control sample in the mitochondrial studies.
Lindsey Kent
University of Oxford, Welcome
Trust Centre for Human Genetics, Oxford, UK
2006-2009
Principal
Investigators: Anthony Bailey, M.D., Anthony Monaco, M.D.,
Ph.D.
Identifying
and Understanding the Actions of Autism Susceptibility Genes
(Co-funded with the Simons Foundation)
Autism
spectrum disorders usually arise through the inheritance
of a relatively small number of susceptibility genes, but
these genes cause a very variable behavioral phenotype that
can include milder but related difficulties in relatives.
The investigators have identified several candidate susceptibility
genes within replicated regions of linkage on chromosomes
7 and 2 and will type dense genetic markers in these genes
and regions in a new set of families to identify the specific
genetic variants that predispose to autism. They have already
assessed relatives using interview measures of socio-communication
difficulties and repetitive/rigid behaviors and will administer
specific tests of social cognition and face recognition.
The investigators will be able to dimensionalize the autism
phenotype in two independent ways and use this information
to aid in gene identification. Once susceptibility genes
are identified they will investigate their molecular function.
Additionally the investigators will use magnetoencephalography
in a stratified sample of relatives to understand how the
brain basis of a typical social difficulty (face processing)
varies across the behavioral phenotype and how this relates
to changes in the way the brain processes language information.
Wellcome Trust Center for Human Genetics
Anthony Monaco
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