Professor, Departments of Molecular
and Human Genetics and Biochemistry & Molecular
Biology
B.S., Virginia Polytechnic Institute and State University,
1971
Ph.D., Massachusetts Institute of Technology, 1976
Postdoc, University of California at Santa Barbara, 1979
RESEARCH
INTERESTS:
Work
in my laboratory is directed primarily toward clinical and basic research
applications of microarray-based comparative genomic hydrization (CGH).
Array-CGH is a powerful and sensitive hybridization-based approach
to analyze the relative copy number of specific sequences of interest
in complex genomes. Our primary goal is to develop this technology
as a molecular cytogenetics approach to detect deletions and amplifications
of regions in the human genome associated with a variety of genetic
disorders. The current clinical system is based on microarrays constructed
with approximately 1000 BAC clones selected from chromosomal regions
of frequent deletions and duplications associated with greater than
40 human disorders, as well as from both the telomeric and pericentromeric
regions of all human chromosomes (see reference 1). Future arrays will
allow simultaneous analysis of many additional important regions for
both postnatal and prenatal diagnostics and will also be applied to
studies of cancer progression and classification. Similar microarray
based technology can also be used to examine important basic properties
of DNA replication, such as replication timing and, can even potentially
allow the precise mapping of active initiation sites for replication
of human chromosomes.
Our replication work is focused primarily on the study of the molecular mechanisms for establishing replication origins and for controlling the relative time of replication of specific sequences within S phase. We use both fluorescence in situ hybridization with large-insert genomic probes on interphase mammalian nuclei and microarray hybridization approaches to determine replication patterns over extended chromosomal regions of the human genome. We are particularly interested in mapping domains of coordinate replication control and analyzing the mechanisms of establishing and maintaining the boundaries of these domains, predominantly on the X chromosome around the X-inactivation center and the FRAXA-FRAXE regions. We are also using chromosome immunofluorescence and chromatin immunoprecipitation techniques at these same regions with modification specific histone antibodies to map chromatin domains associated with differentially modified histones, including acetylated histones H3 and H4 and various forms of methylated histone H3. Together these studies will allow us to determine the relationships between replication timing, gene transcription, and chromatin structure.
SELECTED PUBLICATIONS:
1. Cheung SW, Shaw CA, Yu W,
Li J, Ou Z, Patel A, Yatsenko SA, Cooper ML, Furman P, Stankiewicz P,
Lupski JR, Chinault AC, Beaudet AL (2005). Development
and validation of a CGH microarray for clinical cytogenetic diagnosis. Genet.
Med. 7: 422-432.
2. Boggs BA, Cheung P, Heard E, Spector DL, Chinault AC, Allis CD (2002). Differentially methylated forms of histone H3 show unique association patterns with inactive human X chromosomes. Nat. Genet. 30: 73-76.
3. Cabeza-Arvelaiz Y, Thompson TC, Sepulveda JL, Chinault AC (2001). LAPSER1: A novel candidate tumor suppressor gene from 10q24.3. Oncogene 20: 6707-6717.
4. Cabeza-Arvelaiz Y, Sepulveda JL, Lebovitz RM, Thompson TC, Chinault AC (2001). Functional identification of LZTS1 as a candidate prostate tumor suppressor gene on human chromosome 8p22. Oncogene 20: 4169-4179.
5. Pershouse M, Li J, Yang C, Su H, Brundage E, Di W, Biggs PJ, Bradley A, Chinault AC (2000). BAC contig from a 3-cM region of mouse chromosome 11 surrounding Brca1. Genomics 69: 139-142.
6. Bilyeu K, Chinault AC (1998). Replication timing properties across the pseudoautosomal region boundary and cytogenetic band boundaries on human distal Xp. Chromosoma 107: 105-112.
7. Boggs BA, Chinault AC (1997). Analysis of DNA replication by fluorescence in situ hybridization. Methods 13: 259-270.
8. Subramanian PS, Chinault AC (1997). Replication timing properties of the human HPRT locus on active, inactive and reactivated X chromosomes. Somat. Cell Mol. Genet. 23: 97-109.
9. Subramanian PS, Nelson DL, Chinault AC (1996). Large domains of apparent delayed replication timing associated with triplet repeat expansion at FRAXA and FRAXE. Am. J. Hum. Genet. 59: 407-416.
For more publications, see listing on Pub Med.
CONTACT INFORMATION:
A. Craig Chinault, Ph.D.
Department of Molecular and Human Genetics
Baylor College of Medicine
One Baylor Plaza
Houston, Texas 77030, U.S.A.
Telephone: 713-798-6075
Fax: 713-798-8597
E-mail: