Details

Autor(en) / Beteiligte

• Camargo, Mauricio
• Rivera, Dora
• Moreno, Lina
• Lidral, Andrew C
• Harper, Ursula
• Jones, Marypat
• Solomon, Benjamin D
• Roessler, Erich
• Vélez, Jorge I
• Martinez, Ariel F
• Chandrasekharappa, Settara C
• Arcos-Burgos, Mauricio

Titel

GWAS reveals new recessive loci associated with non-syndromic facial clefting

Ist Teil von

• European journal of medical genetics, 2012-10, Vol.55 (10), p.510-514

Ort / Verlag

Netherlands: Elsevier Masson SAS

Erscheinungsjahr

2012

Quelle

MEDLINE

Beschreibungen/Notizen

• Abstract We have applied a GWAS to 40 consanguineous families segregating cases of non-syndromic cleft lip with or without cleft palate (NS CL/P) (a total of 160 affected and unaffected individuals) in order to trace potential recessive loci that confer susceptibility to this common facial malformation. Pedigree-based association test (PBAT) analyses reported nominal evidence of association and linkage over SNP markers located at 11q25 (rs4937877, P  = 2.7 × 10−6 ), 19p12 (rs4324267, P  = 1.6 × 10−5 ), 5q14.1 (rs4588572, P -value = 3.36 × 10−5 ), and 15q21.1 (rs4774497, P  = 1.08 × 10−4 ). Using the Versatile Gene-Based Association Study to complement the PBAT results, we found clusters of markers located at chromosomes 19p12, 11q25, and 8p23.2 overcome the threshold for GWAS significance ( P  < 1 × 10−7 ). From this study, new recessive loci implicated in NS CL/P include: B3GAT1, GLB1L2, ZNF431, ZNF714, and CSMD1, even though the functional association with the genesis of NS CL/P remains to be elucidated. These results emphasize the importance of using homogeneous populations, phenotypes, and family structures for GWAS combined with gene-based association analyses, and should encourage. other researchers to evaluate these genes on independent patient samples affected by NS CL/P.