FAT4 identified as a potential modifier of orofacial cleft laterality

Sarah W. Curtis; Daniel Chang; Miranda R. Sun; Michael P. Epstein; Jeffrey C. Murray; Eleanor Feingold; Terri H. Beaty; Seth M. Weinberg; Mary L. Marazita; Robert J. Lipinski; Jenna C. Carlson; Elizabeth J. Leslie

doi:10.1002/gepi.22420

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FAT4 identified as a potential modifier of orofacial cleft laterality

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FAT4 identified as a potential modifier of orofacial cleft laterality

Sarah W. Curtis, Daniel Chang, Miranda R. Sun, Michael P. Epstein, Jeffrey C. Murray, Eleanor Feingold, Terri H. Beaty, Seth M. Weinberg, Mary L. Marazita, Robert J. Lipinski, …

Genetic epidemiology, Vol.45(7), pp.721-735

10/2021

DOI: 10.1002/gepi.22420

PMCID: PMC8630827

PMID: 34130359

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https://www.ncbi.nlm.nih.gov/pmc/articles/8630827View

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Abstract

Orofacial clefts (OFCs) are common (1 in 700 births) congenital malformations that include a cleft lip (CL) and cleft lip and palate (CLP). These OFC subtypes are also heterogeneous themselves, with the CL occurring on the left, right, or both sides of the upper lip. Unilateral CL and CLP have a 2:1 bias towards left-sided clefts, suggesting a nonrandom process. Here, we performed a study of left- and right-sided clefts within the CL and CLP subtypes to better understand the genetic factors controlling cleft laterality. We conducted genome-wide modifier analyses by comparing cases that had right unilateral CL (RCL; N = 130), left unilateral CL (LCL; N = 216), right unilateral CLP (RCLP; N = 416), or left unilateral CLP (LCLP; N = 638), and identified a candidate region on 4q28, 400 kb downstream from FAT4, that approached genome-wide significance for LCL versus RCL (p = 8.4 x 10(-8)). Consistent with its potential involvement as a genetic modifier of CL, we found that Fat4 exhibits a specific domain of expression in the mesenchyme of the medial nasal processes that form the median upper lip. Overall, these results suggest that the epidemiological similarities in left- to right-sided clefts in CL and CLP are not reflected in the genetic association results.

Genetics & Heredity

Life Sciences & Biomedicine

Mathematical & Computational Biology

Science & Technology

Details

Title: Subtitle: FAT4 identified as a potential modifier of orofacial cleft laterality
Creators: Sarah W. Curtis - Emory University
Daniel Chang - Emory University
Miranda R. Sun - University of Wisconsin–Madison
Michael P. Epstein - Emory University
Jeffrey C. Murray - University of Iowa
Eleanor Feingold - University of Pittsburgh
Terri H. Beaty - Johns Hopkins University
Seth M. Weinberg - University of Pittsburgh
Mary L. Marazita - University of Pittsburgh
Robert J. Lipinski - University of Wisconsin–Madison
Jenna C. Carlson - University of Pittsburgh
Elizabeth J. Leslie - Emory University
Resource Type: Journal article
Publication Details: Genetic epidemiology, Vol.45(7), pp.721-735
DOI: 10.1002/gepi.22420
PMID: 34130359
PMCID: PMC8630827
NLM abbreviation: Genet Epidemiol
ISSN: 0741-0395
eISSN: 1098-2272
Publisher: Wiley
Number of pages: 15
Grant note: HHSN268201200008I; R00-DE025060; R01-DE012472; R01-DE009886; R01DE014581; R01-DE016148; R21-DE016930; R37-DE008559; U01-DE018993; U01DE024425 / National Institute of Dental and Craniofacial Research; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Dental & Craniofacial Research (NIDCR) X01HG007485; X01-HG007821 / National Human Genome Research Institute; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI)
Language: English
Date published: 10/2021
Academic Unit: Anatomy and Cell Biology; Stead Family Department of Pediatrics; Epidemiology; Pediatric Dentistry; Craniofacial Anomalies Research Center; Dental Research
Record Identifier: 9985035876702771

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