1. ¹Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA
2. ²School of Medicine, Johns Hopkins University, Baltimore, MD, USA
3. ³Boston University, School of Medicine, Boston, MA, USA
4. ⁴National Human Genome Research Institute, National Institutes of Health, Baltimore, MD, USA
5. ⁵Hospital Infantil de Mexico "Federico Gomez", Mexico City, Mexico
6. ⁶Centro Nacional de Genetica Medica, Buenos Aires, Argentina
7. ⁷Asociacion Piel, Buenos Aires, Argentina
8. ⁸University of the Pacific School of Dentistry, San Francisco, CA, USA
9. ⁹1st Medical School Charles University, Prague, Czech Republic

Correspondence: Dr Joanna S Zeiger, Department of Epidemiology, Room 6513, 615 N. Wolfe Street, Baltimore, MD 21205, USA. Tel: +1 410-955 7961; Fax: +1 410 955-0863; E-mail: jzeiger@jhmi.edu

Received 26 September 2002; Revised 19 May 2003; Accepted 21 May 2003.

Abstract

Results from a genome-wide screen of 10 multiplex families ascertained through probands with nonsyndromic cleft lip with or without cleft palate (CL/P) in Mexico, Argentina, and the United States yielded suggestive evidence of linkage to chromosomes 2, 6, 17 and 18. Fine mapping excluded all regions except chromosome 2. Subsequent analysis was performed on the original 10 families plus an additional 16 families using 31 markers on chromosome 2. This analysis showed intriguing evidence of linkage to 2q (Zlr=2.26, empirical P-value=0.028 in a chromosome-wide analysis). Transmission disequilibrium tests also revealed evidence of linkage and disequilibrium for two markers in this region (D2S168 and D2S1400 with P-values=0.022 and 0.006, respectively). A subset of these 26 families provided additional evidence for a susceptibility gene for CL/P on 2q, suggesting that further studies of genes in this region are warranted.