Association studies of candidate genes and cleft lip and palate taking into consideration geographical origin

Abstract

Isolated cleft lip and/or palate (CL/CLP) is a complex congenital anomaly with many contributing factors. There are several genes involved in the aetiology of CL/CLP, they are different in selected populations. In a previous study, the mitochondrial haplotypes of Latvian subjects with CL/CLP were characterized. Latvian subjects with CL/CLP have mostly mitochondrial haplogroups U4/U5 compared with the ethnic population of Latvia. The aim of this study was to stratify the results of genotyping based on European mitochondrial DNA (mtDNA) haplotypes. DNA samples from 108 patients with CL/CLP and from 182 unrelated and unaffected individuals selected randomly in Latvia (used as controls) were obtained for investigation. In this study, we analysed the data taking into consideration mitochondrial haplogroups and found that gene associations depended on the genetic origin of the population. The phenotype of patients with non-U haplotypes was associated with markers in wingless-type MMTV integration site family, member 3 (WNT3), collagen, type XI, alpha 2 (COL11A2), and fibroblast growth factor receptor 1 (FGFR1), whereas patients with U4 and U5 haplotypes showed significant association with WNT3 and COL11A2. It is unlikely that mtDNA variants play a direct role in the development of CL/CLP; rather, they may be a surrogate for population substructure and provide a tool to increase homogeneity and statistical power.

Association between Genes Involved in Craniofacial Development and Nonsyndromic Cleft Lip and/or Palate in the Brazilian Population

“…The craniofacial development involves a series of highly coordinated events, including proliferation, migration, epithelial-mesenchymal transition, and apoptosis, and polymorphic variations in genes that control these events may affect the normal development of the lips and palate, resulting in NSCL/P (Butali et al, 2011). Previous studies have shown statistical evidences of association between specific genes, including transition nuclear protein 1 ( TNP1 ; Beaty et al, 2006), muscle segment homeobox 1 ( MSX1 ; Beaty et al, 2002; Vieira et al, 2003; Suazo et al, 2004; Jagomagi et al, 2010; Nikopensius et al, 2010; Butali et al, 2011; Cardoso et al, 2013), Treacher Collins-Franceschetti syndrome 1 ( TCOF1 ; Masotti et al, 2005; Sull et al, 2008), fibroblast growth factor receptor 1 ( FGFR1 ; Menezes et al, 2008; Nikopensius et al, 2010; Lace et al, 2011), collagen type II, alpha 1 ( COL2A1 ; Nikopensius et al, 2010), wingless-type MMTV integration site family, member 3 ( WNT3 ; Chiquet et al, 2008; Nikopensius et al, 2010; Lace et al, 2011; Mostowska et al, 2012), tissue inhibitor of metallopeptidase 3 ( TIMP3 ; Nikopensius et al, 2010), and nonsyndromic oral clefts across different populations. However, the involvement of these genes in the Brazilian population remains uncertain.…”

Risk factors involved in orofacial cleft predisposition – review

“…As a result authors conclude that it is unlike that mtDNA has a direct role in cleft lip and palate predisposition [37]. Therefore all newborns and their parents should be closely evaluated, examined and had special data gathered, which might be very useful in diagnosis and prevention of orofacial clefts.…”

Skin Tissue Surface Morphology and Quality of RNA and Protein Extracted from Fresh and Stabilized Human Cleft Lip and Palate Tissue

“…Two most common types of CLP are cleft lip with or without cleft palate and a cleft palate only [1]. This condition reflects a breakdown in normal embryological facial development which 70% affects the upper lip, the alveolar ridge, tooth eruption and palate fusion [6][7]. Another 30% clefts are caused by monogenic syndromes or chromosomal aberrations [7].…”

“…This condition reflects a breakdown in normal embryological facial development which 70% affects the upper lip, the alveolar ridge, tooth eruption and palate fusion [6][7]. Another 30% clefts are caused by monogenic syndromes or chromosomal aberrations [7]. This cleft lip and palate caused major psychosocial and economic burden for families and society that usually require surgical repair [8][9].…”