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Mission

One of the main focuses of our laboratory is the identification and characterization of chromosomal imbalances involved in mental retardation and autism. We are also interested in elucidating the underlying mechanisms that cause these rearrangements.  

Background

Our laboratory is actively involved in identifying and characterizing cryptic telomere and other genomic rearrangements in patients with unexplained mental retardation and autism. We are interested in:

(1) determining the frequency of rearrangements in these populations,

(2) studying the mechanism of abnormal chromosome formation and

(3) correlating genotype changes with phenotypic consequences.

The delineation of genotype/phenotype correlations is important for clinical diagnosis and prognosis and will help in determining which regions of the genome are tolerant to dosage imbalance versus those that are pathogenic.

We are specifically interested in characterizing rearrangements involving the telomeric regions of human chromosomes. As a postdoctoral fellow in Dr. David Ledbetter’s lab, the PI was involved in developing a unique set of telomeric clones corresponding to the most distal unique DNA for each telomere region (Knight and Lese et al., 2000).

Subsequent to this probe set, the PI and Dr. Ledbetter have continued their collaboration and have developed a “molecular ruler” strategy, which consists of clones equally spaced from the telomere of each chromosome up to 5 Mb, which we use to delineate the sizes of telomere rearrangements. In addition, Dr. Ledbetter’s lab has also developed molecular ruler clones for the pericentromeric regions of each chromosome arm. By comparing the size of the deletion or duplication with the corresponding phenotype from multiple cases involving the same chromosome, we are developing clinical correlations for specific telomere and centromere rearrangements. We are also studying the mechanism by which these rearrangements occur – including those that are causative of a phenotype and those that are “benign variants” which have been inherited from a phenotypically normal parent.

Another interest of our laboratory is the development of new technologies for more efficient identification of genomic imbalances. Towards this goal, we are in the process of validating the use of Comparative Genomic Hybridization with arrays containing genomic clones (BACs, PACs,…) and oligonucleotides.