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Dorothy Warburton
Dorothy Warburton
Professor of Clinical Genetics and Development


Address: Children's Hospital South 3959 Broadway, Room CHC 406 New York NY 10032
Phone: 212-305-7143
Fax: 212-305-7436
E-mail:

 dw9@columbia.edu
Education and Training:
 Ph.D. 1961, McGill University
Research Associate in Obstetrics and Gynecology 1964-1967, College of Physicians & Surgeons, Columbia University
Director, Genetics Services 1967-1968, St. Luke's Hospital
Instructor in Obstetrics and Gynecology 1968-1969, College of Physicians and Surgeons, Columbia University
Affiliations:
 bullet  Department of Genetics and Development
bullet  Herbert Irving Comprehensive Cancer Center
bullet  Department of Pathology
bullet  Columbia Genome Center
Training Activities:
 bullet  Graduate Program in Genetics and Development
bullet  Course Director: G 6211: Genetic Approaches to Biological Problems (spring)
bullet  Participant in Pediatric Endocrine, Genetics and Development, Statistical Genetics and Genetic Epidemiology, and Dermatology Training Grants
bullet  Graduate student mentor ( Division of Environmental Sciences, School of Public Health)
bullet  Lecturer in courses for Medical and Dental students, Graduate Students, Graduate Nurses, Residents, Public Health students
Research Summary:
 (800 words, max)
 Human cytogenetics.
Current Research:
 My principal research interest concerns the causes and the consequences of human aneuploidy due to meiotic error. Chromosomal abnormalities large enough to be visible under the light microscope account for about 50% of early miscarriages and 25% of congenital anomalies and mental retardation in humans. They are also associated with most tumors. Current molecular techniques such as fluorescence in situ hybridization (FISH) have expanded the ability to detect microdeletions and analyze the origin of structural and numerical abnormalities. For example, several malformation syndromes of previously undetermined origin have been shown to result from microdeletions or duplications, or from previously unrecognizable meiotic and mitotic errors resulting in uniparental disomy.

Increasing maternal age is the only known factor associated with the frequency of aneuploidy at conception. The reason for this association is unknown, but we have proposed the hypothesis that it is directly related to the decline in the size of the number of functional oocytes in an aging ovary.

Our current research is focused on two areas, one epidemiological, and the other experimental. First, epidemiological studies are being carried out to test this hypothesis and explore other factors associated with recurrent spontaneous abortion. We have completed an analysis showing that women with trisomic conceptions have an earlier age at menopause than women with no history of trisomy, consistent with the hypothesis. In the current phase of the study, counts of maturing follicles by USG and hormonal measures of aging are being compared between women with trisomic conceptions and controls. Further analysis of this data will explore environmental variables associated with ovarian aging. We are currently undertaking a new study of women with pregnancy loss to examine the reported increased prevalence of highly skewed X-inactivation in this population and relate it to the chromosomal status of the conception. Women with highly skewed X inactivation will be examined with molecular cytogenetic methods to determine if an X chromosome structural aberration is responsible for the skewing, and to identify regions of the X involved in ovarian maintenance.

Secondly, FISH and immunohistochemical analysis of proteins involved in recombination, are being used to examine timing and patterns of pairing in human fetal oocytes, the stage where meiotic prophase beings in the human female. Chromosome pairs appear to differ in their timing of initiation of pairing, and their patterns of recombination sites. Such differences may shed light on the variation among chromosomes in their frequency of nondisjunction and the relationship of meiotic errors to maternal age and patterns of recombination.
Publications:
(6 max)
 1. Bocskay KA, Orjuela MA, Tang D, Liu X, Warburton D, Perera FP: (2007) Fluorescence in situ hybridization is necessary to detect an association between chromosome aberrations and polycyclic aromatic hydrocarbon exposure in utero and reveals nonrandom chromosome involvement.  Environ Mol Mutagen  48(2): 114-23

2. Brown L, Abigania M, Warburton D, Brown S: (2006) Validation of QF-PCR for prenatal aneuploidy screening in the United States.  Prenat Diagn   26(11): 1068-74

3. Kline J, Kinney A, Levin B, Kelly A, Yu CY, Brown S, Warburton D: (2006) X-chromosome inactivation and ovarian age during the reproductive years.  Fertil Steril  85(5): 1488-95

4. Li CM, Guo M, Salas M, Schupf N, Silverman W, Zigman WB, Husain S, Warburton D, Thaker H, Tycko B: (2005) Cell type-specific over-expression of chromosome 21 genes in fibroblasts and fetal hearts with trisomy 21.  BMC Med Genet.   7: 24

5. Warburton D.: (2005) Biological aging and the etiology of aneuploidy.  Cytogenet Genome Res   111(3-4): 266-272

6. Jobanputra V, Chung WK, Hacker AM, Emanuel BS, Warburton D: (2005) A unique case of der(11)t(11;22),-22 arising from 3:1 segregation of a maternal t(11;22) in a family with co-segregation of the translocation and breast cancer.  Prenat Diagn  25(8): 683-686

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