A genome-wide scan in affected sibling pairs with idiopathic recurrent miscarriage suggests genetic linkage
A genome-wide scan in affected sibling pairs with idiopathic recurrent miscarriage suggests genetic linkage
复制标题
DOI：
10.1093/molehr/gar003
复制
发表时间：
2011-06-01
影响因子：
4
通讯作者：
Christiansen, O. B.
中科院分区：
文献类型：
--
作者：
Kolte, A. M.;Nielsen, H. S.;Christiansen, O. B.
以前，患有特发性复发性流产（特发性复发性流产）的患者的兄弟姐妹已被证明具有较高的流产风险。本研究包括两个部分：（i）流行病学部分，其中我们介绍了244例双胞胎患者的268名同胞中流产频率的数据;（ii）遗传学部分，介绍了38对双胞胎患者的全基因组连锁研究的数据。所有流产患者（先证者）都经历过三次或三次以上的流产，并影响兄弟姐妹两次或两次以上的流产。通过Affyssin GeneChip 50 K XbaI平台对同胞对进行基因分型，并通过软件包Merlin进行非参数连锁分析。我们发现，无论怀孕时的年龄如何，子宫内膜异位症患者的兄弟姐妹的流产频率都高于对照组。我们确定染色体区域LOD得分在2.5和3.0之间的亚组受影响的兄弟姐妹对。在4次事件中确定了最大LOD评分：对于rs 10514716（3p14.2）仅分析姐妹对时;对于rs 10511668（9p22.1）和rs341048（11q13.4）仅分析先证者流产四次或以上的家庭时;以及当仅分析来自每个家族的一个同胞对时，对于RS 10485275（6Q16.3）。我们没有发现创始人突变。总之，我们的研究结果表明，流产患者和他们的兄弟姐妹共享的因素，增加流产的风险。在这第一个全基因组的连锁研究受影响的同胞对与ESTA，我们确定的区域上的染色体3，6，9和11，值得进一步调查，以阐明其假定的作用，在ESTA的发生。
Previously, siblings of patients with idiopathic recurrent miscarriage (IRM) have been shown to have a higher risk of miscarriage. This study comprises two parts: (i) an epidemiological part, in which we introduce data on the frequency of miscarriage among 268 siblings of 244 patients with IRM and (ii) a genetic part presenting data from a genome-wide linkage study of 38 affected sibling pairs with IRM. All IRM patients (probands) had experienced three or more miscarriages and affected siblings two or more miscarriages. The sibling pairs were genotyped by the Affymetrix GeneChip 50K XbaI platform and non-parametric linkage analysis was performed via the software package Merlin. We find that siblings of IRM patients exhibit a higher frequency of miscarriage than population controls regardless of age at the time of pregnancy. We identify chromosomal regions with LOD scores between 2.5 and 3.0 in subgroups of affected sibling pairs. Maximum LOD scores were identified in four occurrences: for rs10514716 (3p14.2) when analyzing sister-pairs only; for rs10511668 (9p22.1) and rs341048 (11q13.4) when only analyzing families where the probands have had four or more miscarriages; and for rs10485275 (6q16.3) when analyzing one sibling pair from each family only. We identify no founder mutations. Concluding, our results imply that IRM patients and their siblings share factors which increase the risk of miscarriage. In this first genome-wide linkage study of affected sibling pairs with IRM, we identify regions on chromosomes 3, 6, 9 and 11 which warrant further investigation in order to elucidate their putative roles in the genesis of IRM.