Worldwide carrier frequency and genetic prevalence of autosomal recessive inherited retinal diseases
Worldwide carrier frequency and genetic prevalence of autosomal recessive inherited retinal diseases
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DOI：
10.1073/pnas.1913179117
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发表时间：
2020-02-04
影响因子：
11.1
通讯作者：
Sharon, Dror
中科院分区：
文献类型：
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作者：
Hanany, Mor;Rivolta, Carlo;Sharon, Dror
人类遗传学中的一个主要问题是，在普通人群中，携带致病突变的个体所占比例是多少。基于六个主要世界人群的公开可获得的基因信息，我们创建了一个数据库，其中包括276,921个序列变异的数据，这些变异存在于187个与常染色体隐性遗传(AR)遗传性视网膜疾病(IRD)相关的基因中。对这些变异的评估显示，10,044个被归类为致病突变。我们开发了一种算法来计算特定于基因的疾病患病率，以及健康受试者的突变负担。我们发现，AR-IRDS的遗传流行率约为每1380人中有1例，预计全球将有550万人受到影响。此外，我们计算了许多未受影响的突变携带者，从欧洲人每2.26人中有1人到芬兰人每3.50人中有1人不等。我们的分析表明，全球约有27亿人(占总人口的36%)是至少一种可能导致AR-IRD的突变的健康携带者，这个值可能是人类孟德尔病症中最高的。
One of the major questions in human genetics is what percentage of individuals in the general population carry a disease-causing mutation. Based on publicly available information on genotypes from six main world populations, we created a database including data on 276,921 sequence variants, present within 187 genes associated with autosomal recessive (AR) inherited retinal diseases (IRDs). Assessment of these variants revealed that 10,044 were categorized as disease-causing mutations. We developed an algorithm to compute the gene-specific prevalence of disease, as well as the mutational burden in healthy subjects. We found that the genetic prevalence of AR-IRDs corresponds approximately to 1 case in 1,380 individuals, with 5.5 million people expected to be affected worldwide. In addition, we calculated that unaffected carriers of mutations are numerous, ranging from 1 in 2.26 individuals in Europeans to 1 in 3.50 individuals in the Finnish population. Our analysis indicates that about 2.7 billion people worldwide (36% of the population) are healthy carriers of at least one mutation that can cause AR-IRD, a value that is probably the highest across any group of Mendelian conditions in humans.