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利用表观遗传参考代码和育种表追踪杂合子的谱系

Keeping Track of the Genealogy of Heterozygotes Using Epigenetic Reference Codes and Breeding Tables.

作者信息

Liberati Anna Sara, Calcaprina Barbara, Adriani Walter

机构信息

Faculty of Psychology, Università Telematica Internazionale "Uninettuno," Rome, Italy.

Center for Behavioral Sciences and Mental Health, Istituto Superiore di Sanità, Rome, Italy.

出版信息

Front Behav Neurosci. 2022 Feb 11;15:781235. doi: 10.3389/fnbeh.2021.781235. eCollection 2021.

Abstract

Studying neurobehavioral consequences of the hypofunctional dopamine transporter (DAT) across several generations entails the need to monitor allelic transmission to offspring, taking into account both maternal and paternal inheritance. Since each type of heterozygote expresses differential phenotypes, based on lineage of inheritance for wild and mutated alleles (from male or female ancestors), it is important to track transgenerational epigenetic effects. We deemed it essential to assign specific abbreviations identifying their characteristics. Therefore, we devised a Mendelian-inspired table to keep track of these. Starting from two progenitors (WT and KO) we named resulting heterozygous progenies MAT and PAT to differentiate them based on inheritance of the wild allele (from the mother or father). Tracing subsequent generations, similar logic has been followed: if coupling HET dams with KO males, initials "M" [(grand)maternal] and "P" [(grand)paternal] are kept, but "AT" is turned into "IX" (MIX and PIX), while if breeding HETs with WTs, "M" is changed to "W" resembling an upside down "M" and "P" to "S" for "sperm" (WAT and SOT). To underline the development within "hyperdopaminergic-uterus" a central letter "U" is added (MUX, PUX, and QULL), while a Greek initial (μAT, μIX, and νIX) underlines the uterine-worsened origin of the allele. In HET × HET breeding (GIX and DIX), the mutated allele can be inherited from both sides of the genealogical line. However, when the mother is MAT, wild and mutated alleles encounter for the first time, causing putative anomalies in the progeny. Replacing dam with a second-generation female (MIX and MUX) may mitigate epigenetic effects on third-generation offspring; therefore suffixes ("-f," "-fu," "-ϕ," and "-ϕu") emphasize that subsequent-generation dams imply that the alleles already encountered in HET (rather than WT) grand-dams.

摘要

研究多巴胺转运体(DAT)功能减退在几代人中的神经行为后果,需要监测等位基因向后代的传递,同时考虑母系和父系遗传。由于每种杂合子根据野生型和突变型等位基因(来自雄性或雌性祖先)的遗传谱系表现出不同的表型,因此追踪跨代表观遗传效应很重要。我们认为为识别它们的特征指定特定缩写至关重要。因此,我们设计了一个受孟德尔启发的表格来记录这些。从两个亲本(野生型和敲除型)开始,我们将产生的杂合子后代命名为MAT和PAT,以便根据野生型等位基因的遗传(来自母亲或父亲)对它们进行区分。追踪后续世代时,遵循了类似的逻辑:如果将杂合子母鼠与敲除型雄鼠交配,首字母“M”[(外)祖母的]和“P”[(外)祖父的]保留,但“AT”变为“IX”(MIX和PIX),而如果将杂合子与野生型交配,“M”变为类似上下颠倒的“M”的“W”,“P”变为代表“精子”的“S”(WAT和SOT)。为了强调“高多巴胺能子宫”内的发育,添加了一个中心字母“U”(MUX、PUX和QULL),而一个希腊首字母(μAT、μIX和νIX)强调等位基因的子宫恶化起源。在杂合子×杂合子繁殖(GIX和DIX)中,突变等位基因可以从谱系的两侧遗传。然而,当母亲是MAT时,野生型和突变型等位基因首次相遇,可能导致后代出现假定的异常。用第二代雌性(MIX和MUX)替代母鼠可能会减轻对第三代后代的表观遗传效应;因此,后缀(“-f”、“-fu”、“-ϕ”和“-ϕu”)强调后续世代的母鼠意味着等位基因已经在杂合子(而非野生型)的祖母中出现过。

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