Uzun Alper, Sahin Yavuz, Schuster Jessica S, Zheng Xiaojing, Ryckman Kelli, Feingold Eleanor, Padbury James
Department of Pediatrics, Women & Infants Hospital of Rhode Island, Providence, Rhode Island.
Brown Alpert Medical School, Providence, Rhode Island.
Pediatr Res. 2016 Dec;80(6):829-836. doi: 10.1038/pr.2016.152. Epub 2016 Jul 24.
Runs of homozygosity (ROH) are consecutive homozygous genotypes, which may result from population inbreeding or consanguineous marriages. ROH enhance the expression of recessive traits.
We mapped ROH in a case control study of women delivering at term compared with women delivering at or before 34 wk gestation. Gene sets known to be important in risk of preterm birth were examined for their overlap with identified ROH segments.
While we found no evidence of increased burden of ROH or copy number variations in mothers delivering at or before 34 wk compared with term, we identified 424 genome-wide 50 kb segments with significant difference in abundance of overlapping ROH segments in cases vs. controls, P < 0.05. These regions overlap 199 known genes. We found preterm birth associated genes (CXCR4, MYLK, PAK1) and genes shown to have an evolutionary link to preterm (CXCR4, PPP3CB, C6orf57, DUSP13, and SLC25A45) with significant differences in abundance of overlapping ROH blocks in cases vs. controls, P < 0.001.
We conclude, while we found no significant burden of ROH, we did identify genomic regions with significantly greater abundance of ROH blocks in women delivering preterm that overlapped genes known to be involved in preterm birth.
纯合子连续区域（ROH）是连续的纯合基因型，可能源于群体近亲繁殖或近亲婚姻。ROH会增强隐性性状的表达。
在一项病例对照研究中，我们对足月分娩的女性与妊娠34周及以前分娩的女性进行了ROH定位。对已知在早产风险中起重要作用的基因集进行了检查，以确定它们与所识别的ROH片段的重叠情况。
虽然我们没有发现证据表明与足月分娩的母亲相比，妊娠34周及以前分娩的母亲的ROH负担或拷贝数变异增加，但我们确定了424个全基因组50kb片段，病例组与对照组中重叠ROH片段的丰度存在显著差异，P < 0.05。这些区域与199个已知基因重叠。我们发现早产相关基因（CXCR4、MYLK、PAK1）以及显示与早产有进化联系的基因（CXCR4、PPP3CB、C6orf57、DUSP13和SLC25A45）在病例组与对照组中重叠ROH块的丰度存在显著差异，P < 0.001。
我们得出结论，虽然我们没有发现ROH的显著负担，但我们确实在早产女性中识别出了ROH块丰度显著更高的基因组区域，这些区域与已知参与早产的基因重叠。
