Fine Mapping of Two Genetic Loci for Nonsyndromic Cleft Lip
BACKGROUND: Two previous family-based studies, (Prescott et al, 2000; Moreno et al, 2004), have yielded positive results for genetic loci at 11p12-q25 and 17q12-31 for nonsyndromic cleft lip with or without cleft palate (CL/P). OBJECTIVES: The purpose of this study is to confirm and fine map these two loci in an extended sample collection of families. METHODS: 23 multiplex families and 144 nuclear trios, consisting of an affected proband and both parents, from Iowa, Ohio and Washington and 76 multiplex families and 85 trios from Colombia. Both simple tandem repeat polymorphisms (STRPs) and single nucleotide polymorphisms (SNPs) were chosen at a 1-2cM density for these regions with a total of 20 markers for 11p12-q25 and 30 markers for 17q12-31. Multipoint parametric dominant and recessive models as well as nonparametric (SIMWALK NPL) analysis was performed. Association analyses (FBAT) were also conducted. RESULTS: The 11p12-q25 region yielded positive linkage results in the Ohio families with a MaxDomHLOD of 1.306 (D11S4958; 133cM; a=0.50 ) and a significant NPL p-value of 0.023 (D11S4464 and D11S4958, 123 cM). LD was observed in the 17q12-31 for markers rs199533 (p=0.017, 69cM) and rs70602 (p=0.024, 69cM) in 292 Colombian trios. Furthermore, significant LD was observed for the entire data set (521 triads) with the marker rs1530364 (p-val 0.014, 65cM). CONCLUSIONS: These results confirm the presence of CL/P susceptibility loci at 11q13-25 and 17q12-21. These regions contain genes involved in craniofacial development such as BARX2 (11q25) and WNT9b and WNT3 at 17q21, which is syntenic to the mouse Clf1 region. Grants: NIH R01DE14677, K02DE015291, P60DE13076; March of Dimes #6-FY01-616.
Division: IADR/AADR/CADR General Session
Meeting:2005 IADR/AADR/CADR General Session (Baltimore, Maryland) Location: Baltimore, Maryland
Year: 2005 Final Presentation ID:1279 Abstract Category|Abstract Category(s):Craniofacial Biology
Authors
Mishima, Hiroyuki
( University of Iowa, Iowa City, IA, USA
)
Jones, Marilyn
( Children’s Hospital of San Diego, San Diego, CA, USA
)
Robin, Nathanial
( University of Alabama at Birmingham, Birmingham, AL, USA
)
Busch, Tamara
( University of Iowa, Iowa City, IA, USA
)
Arcos-burgos, Mauricio
( National Institutes of Health, Bethesda, MD, USA
)
Marazita, Mary L.
( University of Pittsburgh, Pittsburgh, PA, USA
)
Lidral, Andrew C.
( University of Iowa, Iowa, IA, USA
)
Moreno, Lina M.
( University of Iowa, Iowa City, IA, USA
)
Maher, Brion S
( University of Pittsburgh, Pittsburgh, PA, USA
)
Cooper, Margaret E
( University of Pittsburgh, Pittsburgh, PA, USA
)
Goldstein, Toby
( University of Pittsburgh, Pittsburgh, PA, USA
)
Mach, Amy
( University of Iowa, Iowa City, IA, USA
)
Valencia, Consuelo
( Universidad de Anioquia - Facultad de Odontologia, Medellin, N/A, Colombia
)
Hing, Anne
( Children's Hospital and Regional Medical Center, Seattle, WA, USA
)
Lammer, Ed
( 6 Children’s Hospital of Oakland Research Institute, Oakland, CA, USA
)
SESSION INFORMATION
Poster Session
Craniofacial Biology--Sarnat Award Finalists, Poster Session II
03/10/2005