Scientist:
Research Projects: SNP Discovery and Analysis in Craniofacial Birth Defects
The challenge in finding genes involved in the etiology of human
malformations is to identify markers rapidly and efficiently, genotype
these markers on samples of families ascertained through an affected
child, and conduct appropriate statistical tests for linkage and/or
linkage disequilibrium. Frequently, in studies of human malformations
a number of candidate genes are identified, but available markers
may be located well outside the gene itself and even modest genetic
distances can raise the possibility that a true susceptibility gene
will be overlooked because known markers are not sufficiently close
to detect linkage.
Until now such candidate gene studies have been restricted by the
high costs of genotyping, the lack of genomic sequence from which
to design primers and the paucity of known polymorphisms. We are
now entering a watershed era in human genetics that should make
the identification of genes underlying complex disorders and gene-environment
interactions more fruitful. The current effort to complete the human
genome, identify all of our genes and build a database of common
polymorphisms is nearly complete. These resources along with an
ongoing technological revolution in DNA analysis will have a major
impact on the search for genes that produce genetically complex
disease.
We are using the new genomic tools to identify the genetic basis
of two craniofacial disorders; isolated cleft lip and palate and
isolated craniosynostosis. In our study, we are collecting DNAs
from parents and affected children with these disorders, sequencing
candidate genes identified from the human genome sequence by virtue
of their chromosomal locations, their known or inferred biology
and by their expression in tissues affected in these disorders.
The coding and promoter regions of these genes are sequenced from
a selected number of probands to find SNPs (single nucleotide polymorphisms)
which can then be screened in all of the parents and affected children.
Currently we have selected over 150 candidate genes and are in the
process of sequencing them to find SNPs. As of the fall of 2001
we are finding about one SNP per day. In parallel with SNP discovery
we have been actively testing methods to allow high throughput and
accurate SNP scoring and plan to shortly begin this portion of the
study. Lastly, a series of laboratory databases have been built
to manage all of the protocols and data generated in this study.
Access to that data is currently available to collaborators in the
project and will be released publicly as data is completed on particular
loci.
This project is funded by the NIH grant RO1 HD 39082. The Principal
Investigator is Allan Scott, Ph.D. Other scientists involved are
Ethylin Wang Jabs, MD, Ian McIntosh, Ph.D., Terry L. Beaty, Ph.D.,
Kung-Lee Liang, Ph.D., Sonya Rasmussen, MD, Larry D. Edmonds, M.S.P.H.
Last Updated:
6/28/02
|
