Baylor
College of Medicine, Houston , TX
2004
Principal
Investigator: Arthur Beaudet, M.D.
Search
for an Autism Gene on the Y Chromosome (funded through NAAR)
The
male to female ratio in autism is 4:1 in the global autistic
population. Despite this gender difference, male predisposition
to autistic disorder has not been explained. The reduced
rate at which people with autism have children makes vertical
transmission uncommon and genetic analysis confusing. Furthermore,
genome scans based on linkage analysis cannot study the
non-recombining region of the Y chromosome and the lack
of Y linkage in these studies does not rule out the possibility
of susceptibility loci for autism on this chromosome. Dr.
Beaudet proposes that a dysfunction of genes involved in
synapse function and located on the Y chromosome can cause
autism. To analyze for a Y chromosome effect in autism,
Dr. Beaudet will screen Y chromosome haplotypes in subjects
with autism and controls by using Y-polymorphic markers
looking for specific haplogroups that could be associated
with autism. Dr. Beaudet is also testing the hypothesis
that the Y-linked SYBLI and NLGN4Y genes, whose products
are molecules involved in the vesicular trafficking and
synaptogenesis, are candidate genes for involvement in autism.
Arthur
Beaudet
Broad
Institute, Massachusetts Institute of Technology, Cambridge
, MA
2005-2006
Principal
Investigators: David H. Skuse, M.D., Ph.D., Eric Lander,
Ph.D, Pamela Sklar, M.D., Ph.D.
Confirmatory
study of influence of EFHC2 genetic variant on complex phenotype
in x-monosomic females
This
research aims to identify genetic influences in the development
and function of neural systems that may be disrupted in
individuals with impaired social and cognitive functions
by studying individuals with Turners syndrome, a condition
in which one of the two X chromosomes normally found in
females is missing or incomplete. Because individuals with
Turner syndrome have similar social cognitive deficits as
many individuals with autism, and because autism is a condition
in which males outnumber females significantly, the results
of this research may shed light on genetic vulnerability
to autism. The goal is to map a genetic locus to the X-chromosome
associated with emotion-processing deficits in individuals
with Turner syndrome. Researchers intend to investigate
through a replication study, the hypothesis that the EFHC2
gene contributes to social cognitive difficulties in Turner
syndrome, and the hypothesis that specific allelic variants
in the gene contribute to vulnerability to autism.
Broad
Institute, Massachusetts Institute of Technology
Lander
Laboratory
Pamela
Sklar
Massachusetts
General Hospital, Boston, MA
2005-2007
Principal Investigator: Susan Santangelo, Sc.D.
Co-Investigators: Iain Fraser, MBCHB, D. Phil, Katherine Tsatsanis, Ph.D.
The
Establishment of a Well-Characterized Cohort for Autism
Studies at the Massachusetts General Hospital
This
project will establish a well-characterized and documented
patient sample and database that will allow investigators
to begin a multidisciplinary, comprehensive program designed
to elucidate underlying mechanisms important in the manifestation
of autism. The investigators envision the establishment
of a repository of genotypic and phenotypic information
which will serve the needs of researchers interested in
the neurobiology of the disorder. The patient sample and
database will be developed from the patient population of
the Learning and Developmental Disabilities Evaluation and
Rehabilitation Service (LADDERS) program. In one year, 75
individuals with autism and their immediate family members
who seek treatment at the LADDERS program will be recruited
and expertly phenotyped with measures that will support
a myriad of studies investigating the etiology of autism.
A comprehensive database will be created that will contain
all of the phenotypic and genetic information for these
families. Both quantitative and qualitative phenotypes will
be assessed for individuals with autism, their siblings
and parents. All of the individuals with autism will be
examined for evidence of gastrointestinal difficulties,
immune dysfunction, and medical problems that may be associated
with mitochondrial disorders. A permanent bank of cell lines
will be established from recruited families to support gene
mapping studies and DNA, RNA and protein level analyses
in the future.
Susan Santangelo
Katherine Tsatsanis
North Shore Long Island Jewish Research
Institute, Manhasset , New York
2004-2006
Principal
Investigator: Peter K. Gregersen, M.D.
Autism
and Absolute Pitch
This
project is based on the hypothesis that there are common
genetic factors involved in autism and a rare cognitive
ability in normal subjects known as absolute pitch (also
called "perfect pitch"). This research will utilize
an internet-based test which can detect absolute pitch ability
without the need to know conventional musical designations
for pitch. Using this test, individuals with autism and
their family members will be formally tested for absolute
pitch ability. Researchers will investigate whether genes
that may carry predisposition to absolute pitch are also
involved in genetic predisposition to autism. This project
may provide insight into the genetics of autism by studying
a readily measurable trait (absolute pitch) to identify
candidate genes.
North
Shore Long Island Jewish Health System
University College London , Behavioral and Brain Sciences
Unit / Institute of Child Health, London , UK
2004-2006
Principal
Investigator: David H. Skuse, M.D.
A Family Study of Genetic Susceptibility to Autistic Traits
Research
has shown that not everyone who has the genetic susceptibility
to autism will become autistic. It is believed that gene
discovery in autism could be facilitated by use of endophenotypes
in linkage and association studies. Endophenotypes are hidden
indicators of genetic susceptibility reflecting underlying
disruption to covert processes such as cognition, and they
are not directly correlated with behavioral expression of
risk. The goal of this research is to test the hypothesis
that genetic susceptibility to a social-cognitive endophenotype
in children with autism and their first degree relatives
is due to allelic variance in the same risk haplotypes that
are of relevance to Turner syndrome. The long term goal
is to discover specific genes that influence development
of social cognition in males and females and which increase
susceptibility to autism in families with a child with autism.
Institute
of Child Health
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.
University of Cambridge Autism Research
Centre, Cambridge , UK
2004-2005
Principal
Investigator: Emma Weisblatt, Ph.D.
DNA
Collection from a Cohort of Children with Asperger's Syndrome,
PDD-NOS and High-Functioning Autism and their Families
This
project involves the collection of DNA samples from 100
to 150 probands of high-functioning patients with autism
spectrum diagnoses and their parents and siblings. Researchers
will use a candidate gene approach to contribute to the
search for autism susceptibility genes. One of the major
aims of this research is to investigate phenotypic markers,
such as sensory processing differences or electrophysiological
differences, for use in genetic studies. These will help
to identify subgroups of patients with autism who may differ
in their underlying neurobiological characteristics.
Autism
Research Centre
Emma
Weisblatt
University of Oxford , Wellcome
Trust Centre for Human Genetics, Oxford , UK
2003-2005
Principal
Investigators: Anthony Bailey, M.D., Anthony Monaco, M.D.,
Ph.D.
Identifying
and Understanding the Actions of Autism Susceptibility Genes
This
research involves the search of the top two regions of peak
linkage (currently on chromosomes 2q and 7q) for Single
Nucleotide Polymorphisms (SNPs) that may be in linkage disequilibrium
with autism susceptibility alleles. Dr. Monaco's most current
analysis of linkage on chromosome 7q with regards to parent
of origin effects indicates that there may be two genes
in this region of chromosome 7q, one paternally linked and
the other maternally linked in separate areas. To pursue
this finding, the NLM Family Foundation is supporting the
search for the paternally and maternally linked regions
on chromosome 7q with high density SNPs to test for association.
Knowledge of parent of origin effects will allow Dr. Monaco
to test genes in the two regions for imprinting (expression
from only one chromosome depending on its parent of origin)
using both molecular and bioinformatics approaches, thus
speeding up his localization and identification of autism
susceptibility genes.
Wellcome
Trust Center for Human Genetics
Anthony
Monaco
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