title: Parent-of-origin effects for MSX1 in a Chilean population with nonsyndromic cleft lip/palate.
abstract: Based on association and sequencing studies, investigators have postulated muscle segment homeobox 1 (MSX1) as a strong candidate gene involved in the causation of nonsyndromic cleft lip with or without cleft palate (NSCLP). Parent-of-origin effects have been suggested for some NSCLP candidate genes but not for MSX1. The aims of the present study were to test for allele/haplotype associations applying the transmission disequilibrium test (TDT) and the transmission asymmetry test (TAT) to evaluate the possible parent-of-origin effects of MSX1 in Chilean patients with NSCLP. We analyzed five SNPs (rs6446693/c.-425G>T/c.-35G>A/rs3775261/rs12532) located from 6.3 kb upstream to 3' UTR in a sample of 150 unrelated NSCLP case-parent trios. Four haplotypes showed overtransmission from parents to affected progeny, but individual SNPs did not. Two haplotypes presented allele combination C-G-A-G (P = 0.035) and two T-G-C-A (P = 0.044) (SNP order rs6446693/c.-35G>A/rs3775261/rs12532). The rs12532 A allele had a 2.08-fold increase in the risk of NSCLP when inherited from the father (95% CI: 1.10-4.02; P = 0.025), but not from the mother. These results could indicate epigenetic control by imprinting in the role of MSX1 in NSCLP. Different authors have proposed that some genes that play a role in NSCLP depend on parental origin. Our findings and those previously reported by our group show that a variety of factors appears to be involved in the association between MSX1 and NSCLP. The full mechanism of MSX1 in the development of NSCLP has not been fully understood.
authors.affiliation: Programa de Genética Humana, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
authors.forename: José
authors.initials: J
authors.lastname: Suazo
authors.forename: José Luis
authors.initials: JL
authors.lastname: Santos
authors.forename: Lilian
authors.initials: L
authors.lastname: Jara
authors.forename: Rafael
authors.initials: R
authors.lastname: Blanco
mesh_terms: D002677:Chile / Q000453:epidemiology; D002971:Cleft Lip / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D002972:Cleft Palate / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D005260:Female; D005819:Genetic Markers; D018392:Genomic Imprinting; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics*; D051957:MSX1 Transcription Factor / Q000235:genetics*; D008297:Male; D010290:Parents; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D005819:Genetic Markers; D051957:MSX1 Transcription Factor; C484083:MSX1 protein, human