Pośpiech Ewelina, Wojas-Pelc Anna, Walsh Susan, Liu Fan, Maeda Hitoshi, Ishikawa Takaki, Skowron Małgorzata, Kayser Manfred, Branicki Wojciech
Department of Genetics and Evolution, Institute of Zoology, Jagiellonian University, Kraków, Poland.
Department of Dermatology, Collegium Medicum of the Jagiellonian University, Kraków, Poland.
Forensic Sci Int Genet. 2014 Jul;11:64-72. doi: 10.1016/j.fsigen.2014.01.012. Epub 2014 Feb 8.
The role of epistatic effects in the determination of complex traits is often underlined but its significance in the prediction of pigmentation phenotypes has not been evaluated so far. The prediction of pigmentation from genetic data can be useful in forensic science to describe the physical appearance of an unknown offender, victim, or missing person who cannot be identified via conventional DNA profiling. Available forensic DNA prediction systems enable the reliable prediction of several eye and hair colour categories. However, there is still space for improvement. Here we verified the association of 38 candidate DNA polymorphisms from 13 genes and explored the extent to which interactions between them may be involved in human pigmentation and their impact on forensic DNA prediction in particular. The model-building set included 718 Polish samples and the model-verification set included 307 independent Polish samples and additional 72 samples from Japan. In total, 29 significant SNP-SNP interactions were found with 5 of them showing an effect on phenotype prediction. For predicting green eye colour, interactions between HERC2 rs12913832 and OCA2 rs1800407 as well as TYRP1 rs1408799 raised the prediction accuracy expressed by AUC from 0.667 to 0.697 and increased the prediction sensitivity by >3%. Interaction between MC1R 'R' variants and VDR rs731236 increased the sensitivity for light skin by >1% and by almost 3% for dark skin colour prediction. Interactions between VDR rs1544410 and TYR rs1042602 as well as between MC1R 'R' variants and HERC2 rs12913832 provided an increase in red/non-red hair prediction accuracy from an AUC of 0.902-0.930. Our results thus underline epistasis as a common phenomenon in human pigmentation genetics and demonstrate that considering SNP-SNP interactions in forensic DNA phenotyping has little impact on eye, hair and skin colour prediction.
上位效应在复杂性状决定中的作用常被强调，但迄今为止其在色素沉着表型预测中的意义尚未得到评估。从遗传数据预测色素沉着在法医学中可能有用，可用于描述无法通过传统DNA分型识别的未知罪犯、受害者或失踪人员的外貌。现有的法医DNA预测系统能够可靠地预测几种眼睛和头发颜色类别。然而，仍有改进空间。在此，我们验证了来自13个基因的38个候选DNA多态性的关联性，并探讨了它们之间的相互作用在人类色素沉着中可能涉及的程度，特别是它们对法医DNA预测的影响。模型构建集包括718个波兰样本，模型验证集包括307个独立的波兰样本以及另外72个来自日本的样本。总共发现了29个显著的单核苷酸多态性（SNP）-SNP相互作用，其中5个对表型预测有影响。为了预测绿眼睛颜色，HERC2基因的rs12913832位点与OCA2基因的rs1800407位点以及TYRP1基因的rs1408799位点之间的相互作用，使曲线下面积（AUC）表示的预测准确性从0.667提高到0.697，并将预测敏感性提高了3%以上。黑素皮质素受体1（MC1R）的“R”变体与维生素D受体（VDR）基因的rs731236位点之间的相互作用，对于浅色皮肤预测的敏感性提高了1%以上，对于深色皮肤颜色预测提高了近3%。VDR基因的rs1544410位点与酪氨酸酶（TYR）基因的rs1042602位点之间的相互作用，以及MC1R的“R”变体与HERC2基因的rs12913832位点之间的相互作用，使红色/非红色头发预测准确性的AUC从0.902提高到0.930。因此，我们的结果强调上位性是人类色素沉着遗传学中的一种常见现象，并表明在法医DNA表型分析中考虑SNP-SNP相互作用对眼睛、头发和皮肤颜色预测影响不大。
