A Genome-Wide Study of Inherited Deletions Identified Two Regions Associated with Nonsyndromic Isolated Oral Clefts

作者：Younkin Samuel G; Scharpf Robert B; Schwender Holger; Parker Margaret M; Scott Alan F; Marazita Mary L; Beaty Terri H; Ruczinski Ingo^*

来源：Birth Defects Research Part A: Clinical and Molecular Teratology , 2015, 103(4): 276-283.

DOI：10.1002/bdra.23362

• Oral clefts
• DNA copy numbers
• inherited deletions
• case-parent trios

BackgroundDNA copy number variants play an important part in the development of common birth defects such as oral clefts. Individual patients with multiple birth defects (including oral clefts) have been shown to carry small and large chromosomal deletions.
MethodsWe investigated the role of polymorphic copy number deletions by comparing transmission rates of deletions from parents to offspring in case-parent trios of European ancestry ascertained through a cleft proband with trios ascertained through a normal offspring. DNA copy numbers in trios were called using the joint hidden Markov model in the freely available PennCNV software. All statistical analyses were performed using Bioconductor tools in the open source environment R.
ResultsWe identified a 67 kb region in the gene MGAM on chromosome 7q34, and a 206 kb region overlapping genes ADAM3A and ADAM5 on chromosome 8p11, where deletions are more frequently transmitted to cleft offspring than control offspring.
ConclusionsThese genes or nearby regulatory elements may be involved in the etiology of oral clefts. Birth Defects Research (Part A) 103:276-283, 2015.

• 出版日期2015-4