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Parent‐of‐origin effects for MSX1 in a Chilean population with nonsyndromic cleft lip/palate
Author(s) -
Suazo José,
Santos José Luis,
Jara Lilian,
Blanco Rafael
Publication year - 2010
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.33528
Subject(s) - genetics , haplotype , biology , single nucleotide polymorphism , allele , transmission disequilibrium test , linkage disequilibrium , snp , candidate gene , allele frequency , population , gene , genotype , medicine , environmental health
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. © 2010 Wiley‐Liss, Inc.