Genome scan, fine-mapping, and candidate gene analysis of non-syndromic cleft lip with or without cleft palate reveals phenotype-specific differences in linkage and association results

Human Heredity
Mary L MarazitaMauricio Arcos-Burgos

Abstract

Non-syndromic orofacial clefts, i.e. cleft lip (CL) and cleft palate (CP), are among the most common birth defects. The goal of this study was to identify genomic regions and genes for CL with or without CP (CL/P). We performed linkage analyses of a 10 cM genome scan in 820 multiplex CL/P families (6,565 individuals). Significant linkage results were followed by association analyses of 1,476 SNPs in candidate genes and regions, utilizing a weighted false discovery rate (wFDR) approach to control for multiple testing and incorporate the genome scan results. Significant (multipoint HLOD >or=3.2) or genome-wide-significant (HLOD >or=4.02) linkage results were found for regions 1q32, 2p13, 3q27-28, 9q21, 12p11, 14q21-24 and 16q24. SNPs in IRF6 (1q32) and in or near FOXE1 (9q21) reached formal genome-wide wFDR-adjusted significance. Further, results were phenotype dependent in that the IRF6 region results were most significant for families in which affected individuals have CL alone, and the FOXE1 region results were most significant in families in which some or all of the affected individuals have CL with CP. These results highlight the importance of careful phenotypic delineation in large samples of families for genetic analyses o...Continue Reading

References

Jan 21, 2010·European Journal of Human Genetics : EJHG·Roxann G IngersollTerri H Beaty
Feb 19, 2011·Nature Reviews. Genetics·Michael J DixonJeffrey C Murray
Dec 30, 2010·DNA and Cell Biology·Zhong-Lin JiaXiang-Li Kong
Feb 27, 2013·DNA and Cell Biology·Marcella Rosa FilézioLívia Máris Ribeiro Paranaiba
Apr 20, 2012·PloS One·Qianqian ChenTerri H Beaty
Mar 23, 2012·Journal of Applied Oral Science : Revista FOB·José Alberto de Souza FreitasJoão Henrique Nogueira Pinto
May 27, 2010·The Cleft Palate-craniofacial Journal : Official Publication of the American Cleft Palate-Craniofacial Association·Wei LiEric T Everett
Sep 8, 2010·The Cleft Palate-craniofacial Journal : Official Publication of the American Cleft Palate-Craniofacial Association·Ariadne LetraMary L Marazita
May 7, 2011·The Cleft Palate-craniofacial Journal : Official Publication of the American Cleft Palate-Craniofacial Association·Fedik RahimovJeffrey C Murray
Oct 11, 2011·The Cleft Palate-craniofacial Journal : Official Publication of the American Cleft Palate-Craniofacial Association·Masanori HikidaKoh-Ichiro Yoshiura
Nov 15, 2011·The Cleft Palate-craniofacial Journal : Official Publication of the American Cleft Palate-Craniofacial Association·Hong WangTerri H Beaty
Nov 21, 2013·Genetics Research·Chalurmpon SrichomthongVorasuk Shotelersuk
Jun 19, 2012·Annual Review of Genomics and Human Genetics·Mary L Marazita
Dec 10, 2015·Birth Defects Research. Part A, Clinical and Molecular Teratology·Francesca CuraElisabeth Mangold
Feb 19, 2016·Birth Defects Research. Part A, Clinical and Molecular Teratology·Juan Antonio GiliJorge Santiago López-Camelo
Jul 4, 2012·European Journal of Medical Genetics·Mauricio CamargoMauricio Arcos-Burgos
Sep 3, 2011·Trends in Molecular Medicine·Elisabeth MangoldMarkus M Nöthen
Jul 23, 2015·American Journal of Medical Genetics. Part a·Andrea do Rego BorgesSilvia R A Reis
Jul 9, 2009·Oral Diseases·Astanand JugessurN Kilpatrick
Oct 15, 2013·American Journal of Medical Genetics. Part C, Seminars in Medical Genetics·Elizabeth J Leslie, Mary L Marazita
Mar 9, 2011·Birth Defects Research. Part A, Clinical and Molecular Teratology·Jenna A PlamondonDiana M Juriloff
Mar 16, 2012·American Journal of Medical Genetics. Part a·Min ShiTerri H Beaty
Apr 5, 2011·Birth Defects Research. Part A, Clinical and Molecular Teratology·Tiit NikopensiusAndres Metspalu
Mar 19, 2014·Birth Defects Research. Part A, Clinical and Molecular Teratology·Khalid A AldhoraeElisabeth Mangold
Jun 29, 2010·American Journal of Medical Genetics. Part a·Ariadne LetraAlexandre R Vieira
Nov 26, 2009·Birth Defects Research. Part A, Clinical and Molecular Teratology·Tonia C CarterJames L Mills
Jun 5, 2015·Birth Defects Research. Part A, Clinical and Molecular Teratology·Adrianna MostowskaPaweł P Jagodziński
Oct 2, 2015·Indian Journal of Plastic Surgery : Official Publication of the Association of Plastic Surgeons of India·Sathyaprasad SavithaR Rekha
Aug 11, 2015·Journal of Oral Biology and Craniofacial Research·D Mehrotra

Citations

Sep 1, 1976·Plastic and Reconstructive Surgery·J A Lehman, J S Artz
Jan 1, 1986·American Journal of Medical Genetics. Supplement·M MelnickD N Hu
Sep 1, 1984·American Journal of Medical Genetics·Mary L MarazitaM Melnick
Jan 1, 1994·Genetic Epidemiology·Susan E Hodge, R C Elston
Aug 15, 1993·American Journal of Medical Genetics·E W McPhersonD J Salsburey
Jun 23, 1998·American Journal of Human Genetics·J R O'Connell, D E Weeks
Aug 11, 1998·Nature Genetics·M De FeliceRoberto Di Lauro
Mar 30, 2000·Annals of Human Genetics·Lesley H WiseCathryn M Lewis
Oct 31, 2000·Genetic Epidemiology·N M LairdX Xu
Feb 13, 2001·Human Molecular Genetics·J A McGrathH van Bokhoven
Apr 21, 2001·European Journal of Human Genetics : EJHG·S HorvathN M Laird
Jan 16, 2002·American Journal of Human Genetics·Susan E HodgeDavid A Greenberg
Mar 7, 2002·The Cleft Palate-craniofacial Journal : Official Publication of the American Cleft Palate-Craniofacial Association·Mary L MarazitaYou-e Liu
May 31, 2002·American Journal of Human Genetics·H van Bokhoven, Han G Brunner
Jun 28, 2002·American Journal of Human Genetics·Mary L MarazitaYou-e Liu
Aug 27, 2002·Orthodontics & Craniofacial Research·K NeiswangerMary L Marazita
Aug 31, 2002·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Nina DathanRoberto Di Lauro
Sep 10, 2002·Nature Genetics·Shinji KondoJeffrey C Murray
Oct 18, 2002·American Journal of Ophthalmology·Elias I TraboulsiDavid M Meisler
Nov 28, 2002·American Journal of Human Genetics·Paul Schliekelman, Montgomery Slatkin
Dec 18, 2002·Clinical Genetics·M BahuauM-P Vazquez
May 20, 2003·Development, Growth & Differentiation·Nathan L BrownJonathan R Sandy
Jun 13, 2003·American Journal of Human Genetics·Cathryn M LewisTomas Helgason
Jun 13, 2003·American Journal of Human Genetics·Douglas F LevinsonCathryn M Lewis
Aug 6, 2003·Proceedings of the National Academy of Sciences of the United States of America·Paola SebastianiMarco F Ramoni
Aug 14, 2003·Human Molecular Genetics·David R FitzPatrickDavid T Bonthron
Aug 27, 2003·European Journal of Human Genetics : EJHG·Gaëlle BougeardThierry Frébourg
Oct 23, 2003·European Journal of Human Genetics : EJHG·Joanna S ZeigerIain McIntosh
Nov 5, 2003·American Journal of Medical Genetics. Part a·Diego F WyszynskiJoan E Bailey-Wilson
Apr 2, 2004·American Journal of Medical Genetics. Part a·Mary L MarazitaK Gürler Gürsu
Jun 17, 2004·The Journal of Clinical Investigation·Jeffrey C Murray, Brian C Schutte
Aug 7, 2004·Bioinformatics·J C BarrettM J Daly
Aug 25, 2004·Clinical Genetics·A K RayL L Field
Sep 2, 2004·Cold Spring Harbor Symposia on Quantitative Biology·P Y Kwok, M Xiao

Related Concepts

Genome-Wide Association Study
Study
14q21.3
Genome
Genes
Candidate Disease Gene
Cleft Palate, Isolated
Properdin Deficiency, X-LINKED
Candidate Gene Analysis
Chromosomes, Human

Related Feeds

Birth Defects

Birth defects encompass structural and functional alterations that occur during embryonic or fetal development and are present since birth. The cause may be genetic, environmental or unknown and can result in physical and/or mental impairment. Here is the latest research on birth defects.