A genome-wide study of de novo deletions identifies a candidate locus for non-syndromic isolated cleft lip/palate risk.
A genome-wide study of de novo deletions identifies a candidate locus for non-syndromic isolated cleft lip/palate risk.
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DOI：
10.1186/1471-2156-15-24
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发表时间：
2014-02-14
期刊：
影响因子：
2.9
通讯作者：
Ruczinski I
中科院分区：
文献类型：
--
作者：
Younkin SG;Scharpf RB;Schwender H;Parker MM;Scott AF;Marazita ML;Beaty TH;Ruczinski I
拷贝数变异（CNV）可能在常见的出生缺陷（如口裂）的发展中起重要作用，患有多种出生缺陷（包括口裂）的个体患者已被证明携带小和大的染色体缺失。在本文中，我们调查从头缺失定义为DNA片段缺失的口裂先证者，但目前在两个未受影响的父母。我们比较了欧洲血统的儿童与一个孤立的，非综合征性口裂的频率在欧洲血统的儿童随机抽样三重奏从头缺失的频率。我们在染色体7p14.1上发现了一个全基因组显著的62千碱基（kb）非编码区，其中新生缺失在唇裂病例中比对照组更常见。我们还观察到唇腭裂（CLP）病例中的新生缺失比腭裂（CP）和唇裂（CL）病例中的新生缺失更广泛。这项研究提出了一个区域，从头缺失似乎参与了口裂的病因，虽然潜在的生物学机制仍然是未知的。较大的从头缺失更可能干扰正常的颅面发育，并可能导致更严重的裂隙。研究方案和样本DNA来源可能严重影响从头缺失频率的估计。后续研究需要进一步验证这些发现，并可能确定其他结构变异的基础上口裂。
Copy number variants (CNVs) may play an important part in the development of common birth defects such as oral clefts, and individual patients with multiple birth defects (including clefts) have been shown to carry small and large chromosomal deletions. In this paper we investigate de novo deletions defined as DNA segments missing in an oral cleft proband but present in both unaffected parents. We compare de novo deletion frequencies in children of European ancestry with an isolated, non-syndromic oral cleft to frequencies in children of European ancestry from randomly sampled trios. We identified a genome-wide significant 62 kilo base (kb) non-coding region on chromosome 7p14.1 where de novo deletions occur more frequently among oral cleft cases than controls. We also observed wider de novo deletions among cleft lip and palate (CLP) cases than seen among cleft palate (CP) and cleft lip (CL) cases. This study presents a region where de novo deletions appear to be involved in the etiology of oral clefts, although the underlying biological mechanisms are still unknown. Larger de novo deletions are more likely to interfere with normal craniofacial development and may result in more severe clefts. Study protocol and sample DNA source can severely affect estimates of de novo deletion frequencies. Follow-up studies are needed to further validate these findings and to potentially identify additional structural variants underlying oral clefts.
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影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
3.7
作者：
Jugessur A;Shi M;Gjessing HK;Lie RT;Wilcox AJ;Weinberg CR;Christensen K;Boyles AL;Daack-Hirsch S;Trung TN;Bille C;Lidral AC;Murray JC
通讯作者：
Murray JC
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
14.9
作者：
Diskin SJ;Li M;Hou C;Yang S;Glessner J;Hakonarson H;Bucan M;Maris JM;Wang K
通讯作者：
Wang K
影响因子：
3.1
作者：
Mossey, Peter
通讯作者：
Mossey, Peter