AMELY deletion is not detected in systematically sampled reference populations: A Reply to Štamfelj
AMELY deletion is not detected in systematically sampled reference populations: A Reply to Štamfelj
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DOI：
10.1016/j.jas.2021.105354
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发表时间：
2021-06
影响因子：
2.8
通讯作者：
G. Parker;Tammy Buonasera;Julia M. Yip;J. Eerkens;M. Salemi;B. Durbin-Johnson;R. Haas;J. Buikstra;H. Klaus;David M. Rocke;B. Phinney
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文献类型：
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作者：
G. Parker;Tammy Buonasera;Julia M. Yip;J. Eerkens;M. Salemi;B. Durbin-Johnson;R. Haas;J. Buikstra;H. Klaus;David M. Rocke;B. Phinney
生物分子性别估计有望填补生物考古记录中的一个主要空白，因为它提供了具有退化或模棱两可的骨学性别特异性标记的骨骼遗骸的生物性别估计。基因组和蛋白质组性别估计和所有分析方法一样，都有局限性，需要框架来解决低信号样本的问题，以及使用其他方法时不可避免的相互冲突的结果。蛋白质组学性别估计是基于使用质谱仪检测牙釉质中的性染色体特异的釉原蛋白片段。男性的釉质含有X和Y染色体版本的釉原蛋白片段，女性的釉质只含有X染色体蛋白的片段。该方法灵敏、可靠、可定量、重现性好。研究人员已经开发并继续开发框架，以解决与低水平检测和性别估计冲突相关的理论问题，当在足够大的数据集上使用多种方法时，这些问题将不可避免地发生。ŠTamFelj提醒读者，在法医学和临床病例工作中已经检测到删除釉原蛋白基因的Y染色体结构变体。由于这种现象也可以解释牙釉质中没有Amely蛋白，因此研究人员应该将其作为另一种假设，与女性性别和质谱学中的低肽信号一起提到。ŠTamFelj在他的荟萃分析中得出结论，这是生物分子性别估计的内在局限性，特别是在检查南亚人口时，应该纳入标准的分析性性别估计框架。在这篇评论中，我们通过检查1000基因组计划和外显子组测序计划中系统抽样、高覆盖率、大规模和精心策划的人群中Amely缺失的发生来检验这一断言。在Amely的开放阅读框中使用SNP基因座时，两个项目都没有检测到结构缺失。不能从空值确定具有关联间隔的可信发生概率。我们由此得出结论，就目前而言，Amely缺失应该不会对常规的生物分子性别估计产生影响。
Biomolecular sex estimation promises to fill a major gap in the bioarchaeological record by providing estimates of biological sex for skeletal remains with degraded or ambiguous osteological sex-specific markers. Genomic and proteomic sex estimation, like all analytical methods, have limitations and require frameworks to address the problems of low signal samples and the inevitable conflicting results when other methods are used. Proteomic sex estimation is based on the detection of sex-chromosome specific amelogenin protein fragments in enamel using mass spectrometry. Enamel from male individuals contains amelogenin fragments from both the X-and Y-chromosome versions of amelogenin, and enamel from female individuals contains fragments from only the X-chromosome protein. The method is sensitive, robust, quantifiable and reproducible. Researchers have developed, and continue to develop, frameworks to address theoretical problems associated with low levels of detection and conflicting sex estimates that will inevitably occur when multiple methods are used on a sufficiently large dataset. Štamfelj reminds readers that structural variants of the Y-chromosome that delete the amelogenin gene have been detected in forensics and clinical casework. Since this phenomenon would also account for the absence of the AMELY protein in enamel it should therefore be mentioned as an alternative hypothesis by investigators, along with female sex and low peptide signals in mass spectrometry. In his meta-analysis Štamfelj concludes that this is an intrinsic limitation of biomolecular sex estimation, particularly when examining South Asian populations, and should be incorporated in standard analytical sex estimation frameworks. In this comment, we test this assertion by examining the occurrence of AMELY deletion in the systematically sampled, high coverage, large scale, and well-curated populations of the 1000 Genomes Project and Exome Sequencing Project. When using SNP loci in the open reading frame of AMELY, structural deletion was not detected in either project. Confident probabilities of occurrence with associated intervals cannot be determined from null values. We conclude from this that, for now, AMELY deletion should have no bearing on routine biomolecular sex estimation.