Amanda Barba1, Christian Urbina2, Lorena Maili2, Matthew R Greives3, Steven J Blackwell4, John B Mulliken5, Brett Chiquet1,2,6, Susan H Blanton7, Jacqueline T Hecht1,2, Ariadne Letra1,2,8. 1. Center for Craniofacial Research, School of Dentistry, University of Texas Health Science Center at Houston, Houston, Texas. 2. Department of Pediatrics, Pediatrics Research Center, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas. 3. Department of Pediatric Surgery, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas. 4. Department of Plastic Surgery, Shriners Hospital for Children, Houston, Texas. 5. Department of Plastic and Oral Surgery, Boston Children's Hospital, Boston, Massachusetts. 6. Department of Pediatric Dentistry, School of Dentistry, University of Texas Health Science Center at Houston, Houston, Texas. 7. Department of Human Genetics and John P. Hussman Institute of Human Genomics, University of Miami Miller School of Medicine, Miami, Florida. 8. Department of Diagnostic and Biomedical Sciences, School of Dentistry, University of Texas Health Science Center at Houston, Houston, Texas.
Abstract
BACKGROUND: Nonsyndromic cleft lip with or without cleft palate (NSCLP) is a common birth defect with multifactorial etiology. Genetic studies have identified numerous gene variants in association with NSCLP. IFT88 (intraflagellar transport 88) has been suggested to play a major role in craniofacial development, as Ift88 mutant mice exhibit cleft palate and mutations in IFT88 were identified in individuals with NSCLP. OBJECTIVE: To investigate the association of IFT88 single nucleotide gene variants (SNVs) with NSCLP in a large family data set consisting of non-Hispanic white (NHW) and Hispanic families. METHODS: Nine SNVs in/nearby IFT88 were genotyped in 482 NHW families and 301 Hispanic NSCLP families. Genotyping was performed using TaqMan® chemistry. Single- and pairwise-SNV association analyses were performed for all families stratified by ethnicity and family history of NSCLP using the family-based association test (FBAT), and association in the presence of linkage (APL). Bonferroni correction was used to adjust for multiple testing and p values ≤.0055 were considered statistically significant. RESULTS: Significant association was found between IFT88 rs9509311 and rs2497490 and NSCLP in NHW all families (p = .004 and .005, respectively), while nominal associations were found for rs7998361 and rs9509307 (p < .05). Pairwise association analyses also showed nominal associations between NSCLP in both NHW and Hispanic data sets (p < .05). No association was found between individual variants in IFT88 and NSCLP in Hispanics. CONCLUSIONS: Our results suggest that variation in IFT88 may contribute to NSCLP risk, particularly in multiplex families from a non-Hispanic white population.
BACKGROUND:Nonsyndromic cleft lip with or without cleft palate (NSCLP) is a common birth defect with multifactorial etiology. Genetic studies have identified numerous gene variants in association with NSCLP. IFT88 (intraflagellar transport 88) has been suggested to play a major role in craniofacial development, as Ift88 mutant mice exhibit cleft palate and mutations in IFT88 were identified in individuals with NSCLP. OBJECTIVE: To investigate the association of IFT88 single nucleotide gene variants (SNVs) with NSCLP in a large family data set consisting of non-Hispanic white (NHW) and Hispanic families. METHODS: Nine SNVs in/nearby IFT88 were genotyped in 482 NHW families and 301 Hispanic NSCLP families. Genotyping was performed using TaqMan® chemistry. Single- and pairwise-SNV association analyses were performed for all families stratified by ethnicity and family history of NSCLP using the family-based association test (FBAT), and association in the presence of linkage (APL). Bonferroni correction was used to adjust for multiple testing and p values ≤.0055 were considered statistically significant. RESULTS: Significant association was found between IFT88rs9509311 and rs2497490 and NSCLP in NHW all families (p = .004 and .005, respectively), while nominal associations were found for rs7998361 and rs9509307 (p < .05). Pairwise association analyses also showed nominal associations between NSCLP in both NHW and Hispanic data sets (p < .05). No association was found between individual variants in IFT88 and NSCLP in Hispanics. CONCLUSIONS: Our results suggest that variation in IFT88 may contribute to NSCLP risk, particularly in multiplex families from a non-Hispanic white population.
Authors: Huan Liu; Elizabeth J Leslie; Jenna C Carlson; Terri H Beaty; Mary L Marazita; Andrew C Lidral; Robert A Cornell Journal: Nat Commun Date: 2017-03-13 Impact factor: 14.919
Authors: Eric R Gamazon; Ayellet V Segrè; Martijn van de Bunt; Xiaoquan Wen; Hualin S Xi; Farhad Hormozdiari; Halit Ongen; Anuar Konkashbaev; Eske M Derks; François Aguet; Jie Quan; Dan L Nicolae; Eleazar Eskin; Manolis Kellis; Gad Getz; Mark I McCarthy; Emmanouil T Dermitzakis; Nancy J Cox; Kristin G Ardlie Journal: Nat Genet Date: 2018-06-28 Impact factor: 38.330
Authors: Vershanna E Morris; S Shahrukh Hashmi; Lisha Zhu; Lorena Maili; Christian Urbina; Steven Blackwell; Matthew R Greives; Edward P Buchanan; John B Mulliken; Susan H Blanton; W Jim Zheng; Jacqueline T Hecht; Ariadne Letra Journal: Hum Genet Date: 2020-04-21 Impact factor: 4.132