title: Genomic screening identifies novel linkages and provides further evidence for a role of MYH9 in nonsyndromic cleft lip and palate.
abstract: Nonsyndromic cleft lip with or without cleft palate (NSCLP) is a common birth anomaly that requires prolonged multidisciplinary rehabilitation. Although variation in several genes has been identified as contributing to NSCLP, most of the genetic susceptibility loci have yet to be defined. To identify additional contributory genes, a high-throughput genomic scan was performed using the Illumina Linkage IVb Panel platform. We genotyped 6008 SNPs in nine non-Hispanic white NSCLP multiplex families and a single large African-American NSCLP multiplex family. Fourteen chromosomal regions were identified with LOD>1.5, including six regions not previously reported. Analysis of the data from the African-American and non-Hispanic white families revealed two likely chromosomal regions: 8q21.3-24.12 and 22q12.2-12.3 with LOD scores of 2.98 and 2.66, respectively. On the basis of biological function, syndecan 2 (SDC2) and growth differentiation factor 6 (GDF6) in 8q21.3-24.12 and myosin heavy-chain 9, non-muscle (MYH9) in 22q12.2-12.3 were selected as candidate genes. Association analyses from these genes yielded marginally significant P-values for SNPs in SDC2 and GDF6 (0.01<or=P<0.05). Evidence for an altered transmission was found for four MYH9 SNPs (P<0.01). SNP rs1002246 exhibited altered transmission by all analytic methods. However, analysis of two SNP MYH9 haplotypes did not identify a single high-risk haplotype. Our results confirm a previous report that 8q21.3-24.12 may harbor a clefting gene and identify 22q12.2-12.3 as a new candidate region that contains MYH9. Most importantly, we confirm the previous report of an association with MYH9.
authors: Department of Pediatrics, University of Texas Medical School at Houston, Houston, TX 77225, USA.
authors: Brett T
authors: BT
authors: Chiquet
authors: Syed S
authors: SS
authors: Hashmi
authors: Robin
authors: R
authors: Henry
authors: Amber
authors: A
authors: Burt
authors: John B
authors: JB
authors: Mulliken
authors: Samuel
authors: S
authors: Stal
authors: Molly
authors: M
authors: Bray
authors: Susan H
authors: SH
authors: Blanton
authors: Jacqueline T
authors: JT
authors: Hecht
mesh_terms: D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D020409:Molecular Motor Proteins / Q000235:genetics*; D018995:Myosin Heavy Chains / Q000235:genetics*; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide
chemical_list: C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; D018995:Myosin Heavy Chains