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

Molecular Autism

Research

Laura A. Del Rosso¹  Brenda McCowan²  Catherine F. Talbot³  John P. Capitanio⁴  Sreetharan Kanthaswamy⁵  Joseph P. Garner⁶  Karen J. Parker⁷  David Haig⁸ 

[1] California National Primate Research Center, 1 Shields Ave., 95616, Davis, CA, USA;California National Primate Research Center, 1 Shields Ave., 95616, Davis, CA, USA;Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, 4205 VM3B, 95616, Davis, CA, USA;California National Primate Research Center, 1 Shields Ave., 95616, Davis, CA, USA;Department of Psychology, Florida Institute of Technology, 150 W. University Blvd., 32901, Melbourne, FL, USA;California National Primate Research Center, 1 Shields Ave., 95616, Davis, CA, USA;Department of Psychology, University of California, 1 Shields Ave., 95616, Davis, CA, USA;California National Primate Research Center, 1 Shields Ave., 95616, Davis, CA, USA;School of Mathematical and Natural Sciences, Arizona State University West Campus, 4701 W. Thunderbird Rd., 85306, Glendale, AZ, USA;Department of Comparative Medicine, Stanford University, 300 Pasteur Drive, Edwards R348, 94305-5342, Stanford, CA, USA;Department of Psychiatry and Behavioral Sciences, Stanford University, 1201 Welch Road, MSLS, P-104, 94305-5485, Stanford, CA, USA;Department of Comparative Medicine, Stanford University, 300 Pasteur Drive, Edwards R348, 94305-5342, Stanford, CA, USA;Department of Psychiatry and Behavioral Sciences, Stanford University, 1201 Welch Road, MSLS, P-104, 94305-5485, Stanford, CA, USA;California National Primate Research Center, 1 Shields Ave., 95616, Davis, CA, USA;Department of Organismic and Evolutionary Biology, Harvard University, 26 Oxford St., 02138, Cambridge, MA, USA;

关键词: Autism spectrum disorder;    Autistic traits;    Heritability;    Parent of origin effect;    Primate model;    Rhesus macaque;    Social functioning;    Social Responsiveness Scale;   

DOI  :  10.1186/s13229-023-00556-3

 received in 2023-02-28, accepted in 2023-06-19,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundQuantitative 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.MethodsHere 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 σ2g/σ2P (or the proportion of phenotypic variance attributable to genetic variance), as well as narrow sense heritability (h2).ResultsGenetic 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.LimitationsThese data are correlational by nature. A larger sample that includes female subjects, enables deeper pedigree assessments, and supports molecular genetic analyses is warranted.ConclusionsRhesus 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.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

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