title: CRISPLD2: a novel NSCLP candidate gene.
abstract: Non-syndromic cleft lip with or without cleft palate (NSCLP) results from the complex interaction between genes and environmental factors. Candidate gene analysis and genome scans have been employed to identify the genes contributing to NSCLP. In this study, we evaluated the 16q24.1 chromosomal region, which has been identified by multiple genome scans as an NSCLP region of interest. Two candidate genes were found in the region: interferon regulatory factor 8 (IRF8) and cysteine-rich secretory protein LCCL domain containing 2 (CRISPLD2). Initially, Caucasian and Hispanic NSCLP multiplex families and simplex parent-child trios were genotyped for single nucleotide polymorphisms (SNPs) in both IRF8 and CRISPLD2. CRISPLD2 was subsequently genotyped in a data set comprised of NSCLP families from Colombia, South America. Linkage disequilibrium analysis identified a significant association between CRISPLD2 and NSCLP in both our Caucasian and Hispanic NSCLP cohorts. SNP rs1546124 and haplotypes between rs1546124 and either rs4783099 or rs16974880 were significant in the Caucasian multiplex population (P=0.01, P=0.002 and P=0.001, respectively). An altered transmission of CRISPLD2 SNPs rs8061351 (P=0.02) and rs2326398 (P=0.06) was detected in the Hispanic population. No association was found between CRISPLD2 and our Colombian population or IRF8 and NSCLP. In situ hybridization showed that CRISPLD2 is expressed in the mandible, palate and nasopharynx regions during craniofacial development at E13.5-E17.5, respectively. Altogether, these data suggest that genetic variation in CRISPLD2 has a role in the etiology of NSCLP.
authors.affiliation: Department of Pediatrics, University of Texas Medical School, Houston, TX 77030, USA.
authors.forename: Brett T
authors.initials: BT
authors.lastname: Chiquet
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Lidral
authors.forename: Samuel
authors.initials: S
authors.lastname: Stal
authors.forename: John B
authors.initials: JB
authors.lastname: Mulliken
authors.forename: Lina M
authors.initials: LM
authors.lastname: Moreno
authors.forename: Mauricio
authors.initials: M
authors.lastname: Arcos-Burgos
authors.forename: Mauricio
authors.initials: M
authors.lastname: Arco-Burgos
authors.forename: Consuelo
authors.initials: C
authors.lastname: Valencia-Ramirez
authors.forename: Susan H
authors.initials: SH
authors.lastname: Blanton
authors.forename: Jacqueline T
authors.initials: JT
authors.lastname: Hecht
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics*; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D002971:Cleft Lip / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002972:Cleft Palate / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D003105:Colombia; D005190:Family; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006630:Hispanic or Latino; D006801:Humans; D050835:Interferon Regulatory Factors / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D015810:Linkage Disequilibrium; D008297:Male; D008334:Mandible / Q000196:embryology / Q000473:pathology; D051379:Mice; D020641:Polymorphism, Single Nucleotide; D044465:White People; D000099185:Interferon Regulatory Factor-8
chemical_list: D015815:Cell Adhesion Molecules; D050835:Interferon Regulatory Factors; D000099185:Interferon Regulatory Factor-8; C525599:CRISPLD2 protein, human