当卢卡遇到侏儒:人类通用基因的遗传限制。

IF 1.1 Q2 MEDICINE, GENERAL & INTERNAL
Alexandre Fabre, Julien Mancini
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引用次数: 0

摘要

LUCA,最后的普遍共同祖先,是共享普遍基因(UG)的三个生命域的假设的最近的共同祖先。评估UG系统发育是否对当前人类基因约束有影响似乎很有趣。从eggNOG数据库中检索到UG的人类同源物列表。我们分析了LUCA基因(LG)组和gnomAD数据库中随机抽取的500个基因(RG组)。从gnomAD中检索基因约束指标,从OMIM中检索与孟德尔疾病和遗传模式的关联。LG组有277个基因,RG组有492个基因(LG组有8个基因)。LG组38.6%的基因和RG组25.2%的基因与孟德尔病相关(p < 0.0001)。LG组的遗传模式多为常染色体隐性遗传(69.0 vs. 50.5%),常染色体显性遗传(19.0 vs. 31.3%)或混合遗传(6.0 vs. 12.1%) (p = 0.048)。LG组在错义变异(MOEUF, 0.919 vs. 0.997, p < 0.0001)和功能缺失变异(LOEUF, 0.872 vs. 0.947, p = 0.051)方面明显更受限制。这些结果表明,在限制和相关的孟德尔疾病方面,人类的UG与基因组的其他部分不同。这表明,系统发育数据可以解释人类基因的一些特征,并有助于解释变异。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
When LUCA met gnomAD: genetic constraints on universal genes in humans.

LUCA, the last universal common ancestor, is the hypothetical most recent common ancestor of the three domains of life which share the universal genes (UG). It seems interesting to evaluate whether the UG phylogeny has had an impact on current Human gene constraints. A list of human homologs of UG was retrieved from the eggNOG database. We analyzed this LUCA gene (LG) group, and a random sample of 500 genes from the gnomAD database (RG group). Gene constraint metrics were retrieved from gnomAD and associations with Mendelian diseases and modes of inheritance were retrieved from OMIM. The LG group consisted of 277 genes and the RG group, 492 (8 genes were in LG group). 38.6% of the genes in the LG group and 25.2% of the genes in the RG group were associated with a Mendelian disease (p < 0.0001). The mode of inheritance was more often autosomal recessive (69.0 vs. 50.5%), and less often autosomal dominant (19.0 vs. 31.3%), or mixed (6.0 vs. 12.1%) for those associated with the LG group (p = 0.048). The LG group was significantly more constrained for missense variants (MOEUF, 0.919 vs. 0.997, p < 0.0001) and was borderline significantly more constrained for loss-of-function variants (LOEUF, 0.872 vs. 0.947, p = 0.051). These results suggest that the UG in humans differs from the rest of the genome in terms of constraints and associated Mendelian diseases. It suggests that phylogenic data can explain some of the characteristics of human genes and could help in interpreting variants.

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来源期刊
Intractable & rare diseases research
Intractable & rare diseases research MEDICINE, GENERAL & INTERNAL-
CiteScore
2.10
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发文量
29
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