Andres Bendesky
Columbia University, NY·Genetics
Why do individuals and species differ in key survival behaviors and health, and what genes and hormones underlie those differences? These two projects tackle that question from two angles: how inbreeding harms health and shapes social behavior in a wild mouse population, and how a little-known hormone drives the urge to care for young.
- Fields
Genetics
Ecology & Evolution
Neuroscience
- Topics
inbreeding depression
house mouse
Mus musculus
- Grants
- 2 known grants, through May 2030
What they work on
- Quantify how inbreeding affects reproduction, survival, morphology and social network interactions in a 20-generation wild house mouse population, and map responsible genes with recessive-model genome-wide association studies.
- Identify strongly harmful DNA variants by comparing observed homozygosity with pedigree simulations and transmission distortion in parent-offspring trios, validating candidates with lab crosses and human disease databases.
- Test whether wild house mice actively avoid mating with close kin by building temporal network models of social interactions and comparing observed inbreeding with simulated null models.
- Determine where in the brain the neurosteroid allopregnanediol (Allodiol), derived from the adrenal hormone 20α-OHP, acts to promote parental behavior in monogamous and promiscuous Peromyscus mice.
- Define how Allodiol modulates neurons, including its proposed blocking of δ-subunit-containing extrasynaptic GABA-A receptors, to drive the motivation to care for young.
More about the research
As wildlife populations shrink, mating between relatives becomes common and can expose harmful mutations, a problem called inbreeding depression. The first project studies a closed population of wild house mice living in a barn since 2002, founded by 12 animals. Over 20 generations, researchers recorded behavior, body measurements, survival and reproduction for over 95% of about 20,000 mice, built a detailed pedigree, and genotyped 2.2 million DNA variants in 8,500 descendants by sequencing founders deeply and inferring descendants' genomes from low-coverage data. The project will measure how inbreeding affects reproduction, survival, body form and social networks, and use genome-wide association studies (scans linking DNA variants to traits) to find responsible genes. It will detect strongly harmful variants by comparing observed genotypes to simulations and checking parent-offspring transmission, confirm them with lab crosses, and compare them to human disease databases. Finally, it will model social and mating networks to test whether mice actively avoid mating with close kin.
Why it matters
Identifying the genetic costs of inbreeding and whether animals avoid it could give conservationists practical tools for managing endangered wildlife, and may reveal genetic vulnerabilities shared with human disease. Learning how Allodiol promotes parental care could inform understanding of postpartum depression, which affects about 15% of women, and of parental neglect.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Elizabeth Brainerd
Brown University, RI·Ecology & Evolution
Test whether digging during growth changes limb bone thickness, internal architecture and shape, by raising burrowing oldfield mice and non-burrowing cactus mice with or without digging access and scanning their bones with high-resolution CT.
Kirk Lohmueller
University of California-Los Angeles, CA·Genetics
Infer the distribution of fitness effects for noncoding regulatory mutations by combining large-scale functional genomic data with polymorphism data, since most disease-associated variants fall outside protein-coding genes.
David E Reich
Harvard University, MA·Genetics
Assemble an ancient DNA time series of 34,000 West Eurasians, enough to measure natural selection coefficients as small as about 0.25%, and release it as a public resource before publication.
The school
Columbia University: 89 labs on PI Pages, $1.4B a year on research, 625 research doctorates a year.
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