Association of IFT88 gene variants with nonsyndromic cleft lip with or without cleft palate

Amanda Barba, Christian Urbina, Lorena Maili, Matthew R. Greives, Steven J. Blackwell, John B. Mulliken, Brett Chiquet, Susan H Blanton, Jacqueline T. Hecht, Ariadne Letra

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournalBirth Defects Research
DOIs
StatePublished - Jan 1 2019

Fingerprint

Cleft Lip
Cleft Palate
Genes
Association reactions
Hispanic Americans
Nucleotides
Defects
Mutation
Testing

Keywords

  • association
  • cleft lip/palate
  • gene
  • IFT88
  • nonsyndromic

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Embryology
  • Toxicology
  • Developmental Biology
  • Health, Toxicology and Mutagenesis

Cite this

Barba, A., Urbina, C., Maili, L., Greives, M. R., Blackwell, S. J., Mulliken, J. B., ... Letra, A. (2019). Association of IFT88 gene variants with nonsyndromic cleft lip with or without cleft palate. Birth Defects Research. https://doi.org/10.1002/bdr2.1504

Association of IFT88 gene variants with nonsyndromic cleft lip with or without cleft palate. / Barba, Amanda; Urbina, Christian; Maili, Lorena; Greives, Matthew R.; Blackwell, Steven J.; Mulliken, John B.; Chiquet, Brett; Blanton, Susan H; Hecht, Jacqueline T.; Letra, Ariadne.

In: Birth Defects Research, 01.01.2019.

Research output: Contribution to journalArticle

Barba, A, Urbina, C, Maili, L, Greives, MR, Blackwell, SJ, Mulliken, JB, Chiquet, B, Blanton, SH, Hecht, JT & Letra, A 2019, 'Association of IFT88 gene variants with nonsyndromic cleft lip with or without cleft palate', Birth Defects Research. https://doi.org/10.1002/bdr2.1504
Barba, Amanda ; Urbina, Christian ; Maili, Lorena ; Greives, Matthew R. ; Blackwell, Steven J. ; Mulliken, John B. ; Chiquet, Brett ; Blanton, Susan H ; Hecht, Jacqueline T. ; Letra, Ariadne. / Association of IFT88 gene variants with nonsyndromic cleft lip with or without cleft palate. In: Birth Defects Research. 2019.
@article{39ab3b44015c432ca8fdb62740a6e989,
title = "Association of IFT88 gene variants with nonsyndromic cleft lip with or without cleft palate",
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{\circledR} 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.",
keywords = "association, cleft lip/palate, gene, IFT88, nonsyndromic",
author = "Amanda Barba and Christian Urbina and Lorena Maili and Greives, {Matthew R.} and Blackwell, {Steven J.} and Mulliken, {John B.} and Brett Chiquet and Blanton, {Susan H} and Hecht, {Jacqueline T.} and Ariadne Letra",
year = "2019",
month = "1",
day = "1",
doi = "10.1002/bdr2.1504",
language = "English (US)",
journal = "Birth Defects Research",
issn = "2472-1727",
publisher = "John Wiley and Sons Ltd",

}

TY - JOUR

T1 - Association of IFT88 gene variants with nonsyndromic cleft lip with or without cleft palate

AU - Barba, Amanda

AU - Urbina, Christian

AU - Maili, Lorena

AU - Greives, Matthew R.

AU - Blackwell, Steven J.

AU - Mulliken, John B.

AU - Chiquet, Brett

AU - Blanton, Susan H

AU - Hecht, Jacqueline T.

AU - Letra, Ariadne

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

KW - association

KW - cleft lip/palate

KW - gene

KW - IFT88

KW - nonsyndromic

UR - http://www.scopus.com/inward/record.url?scp=85063868145&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85063868145&partnerID=8YFLogxK

U2 - 10.1002/bdr2.1504

DO - 10.1002/bdr2.1504

M3 - Article

C2 - 30953423

AN - SCOPUS:85063868145

JO - Birth Defects Research

JF - Birth Defects Research

SN - 2472-1727

ER -