Rhesus macaque social functioning is paternally, but not maternally, inherited by sons: potential implications for autism.

IF 6.3 1区 医学 Q1 GENETICS & HEREDITY Molecular Autism Pub Date : 2023-07-21 DOI:10.1186/s13229-023-00556-3
Joseph P Garner, Catherine F Talbot, Laura A Del Rosso, Brenda McCowan, Sreetharan Kanthaswamy, David Haig, John P Capitanio, Karen J Parker
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Abstract

Background: Quantitative autistic traits are common, heritable, and continuously distributed across the general human population. Patterns of autistic traits within families suggest that more complex mechanisms than simple Mendelian inheritance-in particular, parent of origin effects-may be involved. The ideal strategy for ascertaining parent of origin effects is by half-sibling analysis, where half-siblings share one, but not both, parents and each individual belongs to a unique combination of paternal and maternal half-siblings. While this family structure is rare in humans, many of our primate relatives, including rhesus macaques, have promiscuous breeding systems that consistently produce paternal and maternal half-siblings for a given index animal. Rhesus macaques, like humans, also exhibit pronounced variation in social functioning.

Methods: Here we assessed differential paternal versus maternal inheritance of social functioning in male rhesus macaque offspring (N = 407) using ethological observations and ratings on a reverse-translated quantitative autistic trait measurement scale. Restricted Maximum Likelihood mixed models with unbounded variance estimates were used to estimate the variance components needed to calculate the genetic contribution of parents as the proportion of phenotypic variance (σ2P) between sons that could uniquely be attributed to their shared genetics (σ2g), expressed as σ2g2P (or the proportion of phenotypic variance attributable to genetic variance), as well as narrow sense heritability (h2).

Results: Genetic contributions and heritability estimates were strong and highly significant for sons who shared a father but weak and non-significant for sons who shared a mother. Importantly, these findings were detected using the same scores from the same sons in the same analysis, confirmed when paternal and maternal half-siblings were analyzed separately, and observed with two methodologically distinct behavioral measures. Finally, genetic contributions were similar for full-siblings versus half-siblings that shared only a father, further supporting a selective paternal inheritance effect.

Limitations: These data are correlational by nature. A larger sample that includes female subjects, enables deeper pedigree assessments, and supports molecular genetic analyses is warranted.

Conclusions: Rhesus macaque social functioning may be paternally, but not maternally, inherited by sons. With continued investigation, this approach may yield important insights into sex differences in autism's genetic liability.

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恒河猴的社交功能由父亲而非母亲遗传给儿子:对自闭症的潜在影响。
背景:自闭症的数量性状在整个人类群体中是常见的、可遗传的和持续分布的。自闭症特征在家族中的分布模式表明,其中可能涉及比简单的孟德尔遗传更复杂的机制,特别是父源效应。确定父源效应的理想策略是进行同父异母分析,即同父异母的兄弟姐妹共享一个但不共享双亲,每个个体都属于父系和母系同父异母兄弟姐妹的独特组合。虽然这种家庭结构在人类中很少见,但我们的许多灵长类近亲,包括猕猴,都有杂交育种系统,能为特定的指数动物持续产生父系和母系同父异母或同母异父的兄弟姐妹。方法:在此,我们利用伦理观察和反向翻译的定量自闭症性状测量量表的评分,评估了雄性猕猴后代(N = 407)在社会功能方面父系与母系遗传的差异。使用无约束方差估计的限制最大似然混合模型来估计计算父母遗传贡献所需的方差分量,即可唯一归因于其共同遗传的子代间表型变异(σ2P)的比例(σ2g),表示为σ2g/σ2P(或可归因于遗传变异的表型变异比例),以及狭义遗传率(h2):结果:对于共享父亲的儿子,遗传贡献率和遗传率估计值都很高且非常显著,但对于共享母亲的儿子,遗传贡献率和遗传率估计值都很低且不显著。重要的是,这些结果是在同一分析中使用相同儿子的相同分数检测到的,在分别分析父系和母系同父异母兄弟姐妹时得到了证实,并且是在两种方法不同的行为测量中观察到的。最后,同父异母的兄弟姐妹与同母异父的兄弟姐妹的遗传贡献相似,这进一步证明了父系遗传的选择性效应:局限性:这些数据具有相关性。局限性:这些数据是相关性的,需要更大的样本,包括女性受试者,进行更深入的血统评估,并支持分子遗传分析:恒河猴的社会功能可能由父亲遗传给儿子,而不是由母亲遗传给儿子。结论:恒河猴的社会功能可能由父亲遗传给儿子,而不是由母亲遗传给儿子。随着研究的不断深入,这种方法可能会对自闭症遗传责任的性别差异产生重要影响。
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来源期刊
Molecular Autism
Molecular Autism GENETICS & HEREDITY-NEUROSCIENCES
CiteScore
12.10
自引率
1.60%
发文量
44
审稿时长
17 weeks
期刊介绍: Molecular Autism is a peer-reviewed, open access journal that publishes high-quality basic, translational and clinical research that has relevance to the etiology, pathobiology, or treatment of autism and related neurodevelopmental conditions. Research that includes integration across levels is encouraged. Molecular Autism publishes empirical studies, reviews, and brief communications.
期刊最新文献
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