Interpreting variants in genes affected by clonal hematopoiesis in population data.

IF 3.8 2区生物学 Q2 GENETICS & HEREDITY

Human Genetics Pub Date : 2024-04-01 Epub Date: 2023-02-04 DOI:10.1007/s00439-023-02526-4

Sanna Gudmundsson, Colleen M Carlston, Anne O'Donnell-Luria

引用次数: 0

Abstract

Reference population databases like the Genome Aggregation Database (gnomAD) have improved our ability to interpret the human genome. Variant frequencies and frequency-derived tools (such as depletion scores) have become fundamental to variant interpretation and the assessment of variant-gene-disease relationships. Clonal hematopoiesis (CH) obstructs variant interpretation as somatic variants that provide proliferative advantage will affect variant frequencies, depletion scores, and downstream filtering. Further, default filtering of variants or genes associated with CH risks filtering bona fide germline variants as variants associated with CH can also cause Mendelian conditions. Here, we provide our insights on interpreting population variant data in genes affected by clonal hematopoiesis, as well as recommendations for careful review of 36 established CH genes associated with neurodevelopmental conditions.

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解读群体数据中受克隆造血影响的基因变异。

基因组聚合数据库（gnomAD）等参考人群数据库提高了我们解读人类基因组的能力。变异频率和频率衍生工具（如损耗分数）已成为变异解读和评估变异-基因-疾病关系的基础。克隆造血（CH）阻碍了变异的解读，因为具有增殖优势的体细胞变异会影响变异频率、损耗分数和下游过滤。此外，默认过滤与CH相关的变体或基因有可能会过滤真正的种系变体，因为与CH相关的变体也会导致孟德尔病症。在此，我们就如何解释受克隆性造血影响的基因中的群体变异数据提出了自己的见解，并就如何仔细审查与神经发育状况相关的 36 个已确定的 CH 基因提出了建议。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Human Genetics 生物-遗传学

CiteScore

10.80

自引率

3.80%

发文量

审稿时长

1 months

期刊介绍： Human Genetics is a monthly journal publishing original and timely articles on all aspects of human genetics. The Journal particularly welcomes articles in the areas of Behavioral genetics, Bioinformatics, Cancer genetics and genomics, Cytogenetics, Developmental genetics, Disease association studies, Dysmorphology, ELSI (ethical, legal and social issues), Evolutionary genetics, Gene expression, Gene structure and organization, Genetics of complex diseases and epistatic interactions, Genetic epidemiology, Genome biology, Genome structure and organization, Genotype-phenotype relationships, Human Genomics, Immunogenetics and genomics, Linkage analysis and genetic mapping, Methods in Statistical Genetics, Molecular diagnostics, Mutation detection and analysis, Neurogenetics, Physical mapping and Population Genetics. Articles reporting animal models relevant to human biology or disease are also welcome. Preference will be given to those articles which address clinically relevant questions or which provide new insights into human biology. Unless reporting entirely novel and unusual aspects of a topic, clinical case reports, cytogenetic case reports, papers on descriptive population genetics, articles dealing with the frequency of polymorphisms or additional mutations within genes in which numerous lesions have already been described, and papers that report meta-analyses of previously published datasets will normally not be accepted. The Journal typically will not consider for publication manuscripts that report merely the isolation, map position, structure, and tissue expression profile of a gene of unknown function unless the gene is of particular interest or is a candidate gene involved in a human trait or disorder.