Extremely rare diseases are increasingly recognized due to wide-spread, inexpensive genomic sequencing. Understanding the incidence of rare disease is important for appreciating its health impact and allocating recourses for research. However, estimating incidence of rare disease is challenging because the individual contributory alleles are, themselves, extremely rare. We propose a new method to determine incidence of rare, severe, recessive disease in non-consanguineous populations that use known allele frequencies, estimate the combined allele frequency of observed alleles and estimate the number of causative alleles that are thus far unobserved in a disease cohort. Experiments on simulated and real data show that this approach is a feasible method to estimate the incidence of rare disease in European populations but due to several limitations in our ability to assess the full spectrum of pathogenic mutations serves as a useful tool to provide a lower threshold on disease incidence.

中文翻译：

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确定罕见疾病的发生率。

由于广泛，廉价的基因组测序，人们越来越认识到极为罕见的疾病。了解稀有疾病的发生率对于了解其对健康的影响并分配研究资源至关重要。但是，估计罕见病的发病率具有挑战性，因为个体贡献性等位基因本身极为罕见。我们提出了一种新方法来确定使用已知等位基因频率的非近亲人群中罕见，严重，隐性疾病的发生率，估算观察到的等位基因的组合等位基因频率，并估算迄今为止在疾病队列中尚未发现的致病性等位基因的数量。