一项关于遗传性缺失的全基因组研究确定了两个与非综合征性单纯性口腔裂隙相关的区域。
A genome-wide study of inherited deletions identified two regions associated with nonsyndromic isolated oral clefts.
作者信息
Younkin Samuel G, Scharpf Robert B, Schwender Holger, Parker Margaret M, Scott Alan F, Marazita Mary L, Beaty Terri H, Ruczinski Ingo
机构信息
Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore.
出版信息
Birth Defects Res A Clin Mol Teratol. 2015 Apr;103(4):276-83. doi: 10.1002/bdra.23362. Epub 2015 Mar 16.
BACKGROUND
DNA 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.
METHODS
We 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.
RESULTS
We 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.
CONCLUSIONS
These genes or nearby regulatory elements may be involved in the etiology of oral clefts.
背景
DNA拷贝数变异在常见出生缺陷如腭裂的发生发展中起重要作用。已表明患有多种出生缺陷（包括腭裂）的个体患者携带小的和大的染色体缺失。
方法
我们通过比较在以腭裂先证者确定的欧洲血统病例-父母三联体与以正常后代确定的三联体中，缺失从父母向后代的传递率，研究多态性拷贝数缺失的作用。使用免费的PennCNV软件中的联合隐马尔可夫模型对三联体中的DNA拷贝数进行分型。所有统计分析均使用开源环境R中的Bioconductor工具进行。
结果
我们在7号染色体q34区域的MGAM基因中鉴定出一个67 kb的区域，以及在8号染色体p11区域与ADAM3A和ADAM5基因重叠的一个206 kb的区域，其中缺失传递给腭裂后代的频率高于对照后代。
结论
这些基因或附近的调控元件可能参与腭裂的病因学。
Zotero 插件