email hatchwel@cshl.edu, phone (516) 422-4121, fax (516) 422-4109

Despite recent success in the elucidation of the genetic basis of Mendelian disorders, relatively little progress has been made in the area of sporadic human genetic disease. For those conditions associated with de novo mutations, linkage analysis (the main starting point for positional cloning of genes implicated in Mendelian disorders) is not applicable. Even after exhaustive cytogenetic and/or biochemical analysis, the genetic basis in the majority of patients with sporadic disease remains unknown. A number of sporadic disorders, however, are now known to be associated with submicroscopic rearrangements (by definition not detectable by conventional cytogenetic analysis). For such conditions, the location of the relevant genomic pathology has been uncovered as a result of serendipity (i.e., the observation of rare individuals class that harbor easily detectable rearrangements associated with a particular class of disease).

With increasing convergence of phenotype and genotype, approaches will be required that allow for a more routine and sensitive interrogation of the human genome. Our main focus has been to attempt to detect subtle (i.e., 2:1) genomic copy number differences in selected individuals with phenotypes reminiscent of known microdeletion syndromes. We have recently identified one such deletion in a patient with a complex syndrome whose karyotype was reported as normal. Our work will focus on characterizing this recently uncovered microdeletion and on continuing to develop and refine the tools used to detect genomic copy number alterations.

Selected Publications

Hatchwell E., F. Long, J. Wilde, J. Crolla, and K. Temple. 1998. Molecular confirmation of germ line mosaicism for a submicroscopic deletion of chromosome 22q11. Am. J. Med. Genet. 78: 103–106.

Webber, S.A., E. Hatchwell, J.C.K. Barber, P.E.F. Daubeney, J.A. Crolla, A.P. Salmon, B.R. Keeton, I.K. Temple, and N.R. Dennis. 1996. Importance of microdeletions of chromosomal region 22q11 as a cause of selected malformations of the ventricular outflow tracts and aortic arch: a three-year prospective study. J. Pediatr. 129: 26–32.

Hatchwell, E., D. Robinson, J.A. Crolla, and A.E. Cockwell. 1996, X inactivation analysis in a female with hypomelanosis of Ito associated with a balanced X;17 translocation: evidence for funtional disomy of Xp. J.Med.Genet. 33: 216-220.

Hatchwell, E. 1996. Hypomelanosis of Ito and X; autosome translocations: a unifying hypothesis. J.Med.Genet. 33: 177-183.