在一个大型中东生物库中绘制可治疗的遗传性代谢紊乱的基因图谱。

IF 6.6 1区 医学 Q1 GENETICS & HEREDITY Genetics in Medicine Pub Date : 2024-09-14 DOI:10.1016/j.gim.2024.101268
Geethanjali Devadoss Gandhi , Elbay Aliyev , Najeeb Syed , Fazulur Rehaman Vempalli , Chadi Saad , Hamdi Mbarek , Omayma Al-Saei , Aljazi Al-Maraghi , Mona Abdi , Navaneethakrishnan Krishnamoorthy , Ramin Badii
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引用次数: 0

摘要

背景迄今为止,已描述了约 1400 种遗传代谢病(IMD),其中一些是可以治疗的。据估计,全球有 2%-3% 的活产婴儿患有可治疗的遗传代谢病。约 80% 的 IMD 为常染色体隐性遗传,因此在近亲结婚率较高的地区发病率可能更高。 研究利用了来自 14,060 名卡塔尔成年参与者的基因组测序(GS)数据,这些参与者由卡塔尔生物库(QBB)招募,并由卡塔尔基因组计划(QGP)进行测序。结果我们的研究发现了 253 个致病/可能致病的 SNVs,它们与 69 种可治疗的 IMDs 有关,其中包括 211 个已知变异和 42 个新的预测功能缺失变异。我们估计,在 46 种可治疗的 IMDs 中,每 13 个无关个体中就有 1 个(8%)携带至少一种杂合致病变体。值得注意的是,苯丙酮尿症/高苯丙氨酸血症和高胱氨酸尿症的携带者频率最高(分别为 68 分之 1 和 85 分之 1)。结论对可治疗的 IMDs 进行基于人群的研究,尤其是在全球研究不足的人群中进行研究,可以确定社区中的高频等位基因分离,并为公共卫生政策提供信息,包括携带者和新生儿筛查。
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Mapping the genetic landscape of treatable inherited metabolic disorders in a large Middle Eastern biobank

Purpose

To date, approximately 1400 inherited metabolic disorders (IMDs) have been described, some of which are treatable. It is estimated that 2% to 3% of live births worldwide are affected by treatable IMDs. Roughly 80% of IMDs are autosomal recessive, leading to a potentially higher incidence in regions with high consanguinity.

Methodology

The study utilized genome sequencing data from 14,060 adult Qatari participants who were recruited by the Qatar Biobank and sequenced by the Qatar Genome Program. The genome sequencing data were analyzed for 125 nuclear genes known to be associated with 115 treatable IMDs.

Results

Our study identified 253 pathogenic/likely pathogenic single-nucleotide variations associated with 69 treatable IMDs, including 211 known and 42 novel predicted loss-of-function variants. We estimated that approximately 1 in 13 unrelated individuals (8%) carry a heterozygous pathogenic variant for at least 1 of 46 treatable IMDs. Notably, phenylketonuria/hyperphenylalaninemia and homocystinuria had among the highest carrier frequencies (1 in 68 and 1 in 85, respectively).

Conclusion

Population-based studies of treatable IMDs, particularly in globally under-studied populations, can identify high-frequency alleles segregating in the community and inform public health policies, including carrier and newborn screening.
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来源期刊
Genetics in Medicine
Genetics in Medicine 医学-遗传学
CiteScore
15.20
自引率
6.80%
发文量
857
审稿时长
1.3 weeks
期刊介绍: Genetics in Medicine (GIM) is the official journal of the American College of Medical Genetics and Genomics. The journal''s mission is to enhance the knowledge, understanding, and practice of medical genetics and genomics through publications in clinical and laboratory genetics and genomics, including ethical, legal, and social issues as well as public health. GIM encourages research that combats racism, includes diverse populations and is written by authors from diverse and underrepresented backgrounds.
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