@article{pmid39815096,

title = {The human and non-human primate developmental GTEx projects},

author = {Tim H H Coorens and Amy Guillaumet-Adkins and Rothem Kovner and Rebecca L Linn and Victoria H J Roberts and Amrita Sule and Patrick M Van Hoose},

doi = {10.1038/s41586-024-08244-9},

issn = {1476-4687},

year  = {2025},

date = {2025-01-01},

urldate = {2025-01-01},

journal = {Nature},

volume = {637},

number = {8046},

pages = {557--564},

abstract = {Many human diseases are the result of early developmental defects. As most paediatric diseases and disorders are rare, children are critically underrepresented in research. Functional genomics studies primarily rely on adult tissues and lack critical cell states in specific developmental windows. In parallel, little is known about the conservation of developmental programmes across non-human primate (NHP) species, with implications for human evolution. Here we introduce the developmental Genotype-Tissue Expression (dGTEx) projects, which span humans and NHPs and aim to integrate gene expression, regulation and genetics data across development and species. The dGTEx cohort will consist of 74 tissue sites across 120 human donors from birth to adulthood, and developmentally matched NHP age groups, with additional prenatal and adult animals, with 126 rhesus macaques (Macaca mulatta) and 72 common marmosets (Callithrix jacchus). The data will comprise whole-genome sequencing, extensive bulk, single-cell and spatial gene expression profiles, and chromatin accessibility data across tissues and development. Through community engagement and donor diversity, the human dGTEx study seeks to address disparities in genomic research. Thus, dGTEx will provide a reference human and NHP dataset and tissue bank, enabling research into developmental changes in expression and gene regulation, childhood disorders and the effect of genetic variation on development.},

keywords = {NHP Genetics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid39808663,

title = {Estimating realized relatedness in free-ranging macaques by inferring identity-by-descent segments},

author = {Annika Freudiger and Vladimir M Jovanovic and Yilei Huang and Noah Snyder-Mackler and Donald F Conrad and Brian Miller and Michael J Montague and Hendrikje Westphal and Peter F Stadler and Stefanie Bley and Julie E Horvath and Lauren J N Brent and Michael L Platt and Angelina Ruiz-Lambides and Jenny Tung and Katja Nowick and Harald Ringbauer and Anja Widdig},

doi = {10.1073/pnas.2401106122},

issn = {1091-6490},

year  = {2025},

date = {2025-01-01},

urldate = {2025-01-01},

journal = {Proc Natl Acad Sci U S A},

volume = {122},

number = {3},

pages = {e2401106122},

abstract = {Biological relatedness is a key consideration in studies of behavior, population structure, and trait evolution. Except for parent-offspring dyads, pedigrees capture relatedness imperfectly. The number and length of identical-by-descent DNA segments (IBD) yield the most precise relatedness estimates. Here, we leverage different methods for estimating IBD segments from low-depth whole genome resequencing data to demonstrate the feasibility and value of resolving fine-scaled gradients of relatedness in free-living animals. Using primarily 4 to 6× depth data from a rhesus macaque () population with long-term pedigree data, we show that we can infer the number and length of IBD segments across the genome with high accuracy even at 0.5× sequencing depth. In line with expectations based on simulation, the resulting estimates demonstrate substantial variation in genetic relatedness within kin classes, leading to overlapping distributions between kin classes. By comparing the IBD-based estimates with pedigree and short tandem repeat-based methods, we show that IBD estimates are more reliable and provide more detailed information on kinship. The inferred IBD segments also identify cryptic genetic relatives not represented in the pedigree and reveal elevated recombination rates in females relative to males, which enables the majority of close maternal and paternal kin to be distinguished with genotype data alone. Our findings represent a breakthrough in the ability to study the predictors and consequences of genetic relatedness in natural populations, contributing to our understanding of a fundamental component of population structure in the wild.},

keywords = {NHP Genetics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37984997,

title = {A naturally occurring variant of  causes maternal germline hypermutation in primates},

author = {Alexandra M Stendahl and Rashesh Sanghvi and Samuel Peterson and Karina Ray and Ana C Lima and Raheleh Rahbari and Donald F Conrad},

doi = {10.1101/gr.277977.123},

issn = {1549-5469},

year  = {2023},

date = {2023-12-01},

journal = {Genome Res},

volume = {33},

number = {12},

pages = {2053--2059},

abstract = {As part of an ongoing genome sequencing project at the Oregon National Primate Research Center, we identified a rhesus macaque with a rare homozygous frameshift mutation in the gene methyl-CpG binding domain 4, DNA glycosylase (). MBD4 is responsible for the repair of C > T deamination mutations at CpG dinucleotides and has been linked to somatic hypermutation and cancer predisposition in humans. We show here that MBD4-associated hypermutation also affects the germline: The six offspring of the -null dam have a fourfold to sixfold increase in de novo mutation burden. This excess burden was predominantly C > T mutations at CpG dinucleotides consistent with  loss of function in the dam. There was also a significant excess of C > T at CpA sites, indicating an important, unappreciated role for MBD4 to repair deamination in CpA contexts. The -null dam developed sustained eosinophilia later in life, but we saw no other signs of neoplastic processes associated with  loss of function in humans nor any obvious disease in the hypermutated offspring. This work provides the first evidence for a genetic factor causing hypermutation in the maternal germline of a mammal and adds to the very small list of naturally occurring variants known to modulate germline mutation rates in mammals.},

keywords = {NHP Genetics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38062027,

title = {TAD evolutionary and functional characterization reveals diversity in mammalian TAD boundary properties and function},

author = {Mariam Okhovat and Jake VanCampen and Kimberly A Nevonen and Lana Harshman and Weiyu Li and Cora E Layman and Samantha Ward and Jarod Herrera and Jackson Wells and Rory R Sheng and Yafei Mao and Blaise Ndjamen and Ana C Lima and Katinka A Vigh-Conrad and Alexandra M Stendahl and Ran Yang and Lev Fedorov and Ian R Matthews and Sarah A Easow and Dylan K Chan and Taha A Jan and Evan E Eichler and Sandra Rugonyi and Donald F Conrad and Nadav Ahituv and Lucia Carbone},

doi = {10.1038/s41467-023-43841-8},

issn = {2041-1723},

year  = {2023},

date = {2023-12-01},

urldate = {2023-12-01},

journal = {Nat Commun},

volume = {14},

number = {1},

pages = {8111},

abstract = {Topological associating domains (TADs) are self-interacting genomic units crucial for shaping gene regulation patterns. Despite their importance, the extent of their evolutionary conservation and its functional implications remain largely unknown. In this study, we generate Hi-C and ChIP-seq data and compare TAD organization across four primate and four rodent species and characterize the genetic and epigenetic properties of TAD boundaries in correspondence to their evolutionary conservation. We find 14% of all human TAD boundaries to be shared among all eight species (ultraconserved), while 15% are human-specific. Ultraconserved TAD boundaries have stronger insulation strength, CTCF binding, and enrichment of older retrotransposons compared to species-specific boundaries. CRISPR-Cas9 knockouts of an ultraconserved boundary in a mouse model lead to tissue-specific gene expression changes and morphological phenotypes. Deletion of a human-specific boundary near the autism-related AUTS2 gene results in the upregulation of this gene in neurons. Overall, our study provides pertinent TAD boundary evolutionary conservation annotations and showcases the functional importance of TAD evolution.},

keywords = {NHP Genetics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37244752,

title = {Rhesus macaque fetal and placental growth demographics: A resource for laboratory animal researchers},

author = {Victoria H J Roberts and Jenna N Castro and Brady M Wessel and Donald F Conrad and Anne D Lewis and Jamie O Lo},

doi = {10.1002/ajp.23526},

issn = {1098-2345},

year  = {2023},

date = {2023-08-01},

urldate = {2023-08-01},

journal = {Am J Primatol},

volume = {85},

number = {8},

pages = {e23526},

abstract = {Rhesus macaques (Macaca mulatta) are amongst the most common nonhuman primate species used in biomedical research. These animals provide a precious resource for translational studies and opportunities to maximize rhesus data use are encouraged. Here we compile data produced from 10 years of investigator-driven pregnancy studies conducted at the Oregon National Primate Research Center (ONPRC). All pregnancies were generated within the consistent and reproducible protocols of the ONPRC time-mated breeding program. The data included are from control animals who did not experience in utero perturbations or experimental manipulations. A total of 86 pregnant rhesus macaques were delivered by cesarean section over a range of gestational days (G) 50 to G159 (where term is G165 ± 10 days in the rhesus macaque), with subsequent immediate tissue harvesting following standardized protocols. Fetal and placental growth measures, and all major organ weights are reported. All data are presented relative to gestational age for the entire cohort and in addition, data are stratified by fetal sex. The outcome is a large reference resource for use by laboratory animal researchers in future comparative fetal development studies.},

keywords = {NHP Genetics},

pubstate = {published},

tppubtype = {article}

}