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.

生物分子性别估计有望通过提供具有退化或模棱两可的骨学性别特异性标志物的骨骼遗骸的生物性别估计值来填补生物考古学记录中的主要空白。像所有分析方法一样，基因组和蛋白质组性别估计也有局限性，并且需要框架来解决低信号样本和使用其他方法时不可避免的矛盾结果的问题。蛋白质组性别估计是基于使用质谱检测搪瓷中性别染色体特定的釉原蛋白蛋白片段。来自男性个体的牙釉质包含来自釉原蛋白的X-和Y-染色体版本的釉原蛋白片段，来自女性个体的牙釉质仅包含来自X-染色体蛋白的片段。该方法灵敏，可靠，可定量且可重现。研究人员已经开发并继续开发框架，以解决与检测水平低和性别估计冲突有关的理论问题，而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，在法医学和临床案例研究中已经检测到删除amelogenin基因的Y染色体结构变异。由于这种现象还会导致牙釉质中不存在AMELY蛋白，因此研究人员应将其作为替代假设与质谱中的女性和低肽信号一起提及。Štamfelj在他的荟萃分析中得出的结论是，这是生物分子性别估计的固有局限性，尤其是在检查南亚人群时，并应纳入标准的性别分析估算框架中。在这篇评论中，我们通过检查在1000个基因组计划和外显子组测序计划的系统采样，高覆盖率，大范围和精心策划的人群中AMELY缺失的发生，来检验此断言。在AMELY的开放阅读框中使用SNP位点时，在两个项目中均未检测到结构缺失。无法从空值确定具有相关间隔的可信出现概率。由此我们得出结论，就目前而言，AMELY缺失与常规生物分子性别估算无关。以及1000个基因组计划和外显子组测序计划的精心挑选的人群。在AMELY的开放阅读框中使用SNP位点时，在两个项目中均未检测到结构缺失。无法从空值确定具有相关间隔的可信出现概率。由此我们得出结论，就目前而言，AMELY缺失与常规生物分子性别估算无关。以及1000个基因组计划和外显子组测序计划的精心挑选的人群。在AMELY的开放阅读框中使用SNP位点时，在两个项目中均未检测到结构缺失。无法从空值确定具有相关间隔的可信出现概率。由此我们得出结论，就目前而言，AMELY缺失与常规生物分子性别估算无关。