@article{widmayer_handel_aylor_2020, title={Age and Genetic Background Modify Hybrid Male Sterility in House Mice}, volume={216}, ISSN={["1943-2631"]}, DOI={10.1534/genetics.120.303474}, abstractNote={Hybrid male sterility (HMS) contributes to reproductive isolation commonly observed among house mouse (Mus musculus) subspecies, both in the wild and in laboratory crosses. Incompatibilities involving specific Prdm9 alleles and certain Chromosome (Chr) X genotypes are known determinants of fertility and HMS, and previous work in the field has demonstrated that genetic background modifies these two major loci. We constructed hybrids that have identical genotypes at Prdm9 and identical X chromosomes, but differ widely across the rest of the genome. In each case, we crossed female PWK/PhJ mice representative of the M. m. musculus subspecies to males from a classical inbred strain representative of M. m. domesticus: 129S1/SvImJ, A/J, C57BL/6J, or DBA/2J. We detected three distinct trajectories of fertility among the hybrids using breeding experiments. The PWK129S1 males were always infertile. PWKDBA2 males were fertile, despite their genotypes at the major HMS loci. We also observed age-dependent changes in fertility parameters across multiple genetic backgrounds. The PWKB6 and PWKAJ males were always infertile before 12 weeks and after 35 weeks. However, some PWKB6 and PWKAJ males were transiently fertile between 12 and 35 weeks. This observation could resolve previous contradictory reports about the fertility of PWKB6. Taken together, these results point to multiple segregating HMS modifier alleles, some of which have age-related modes of action. The ultimate identification of these alleles and their age-related mechanisms will advance understanding both of the genetic architecture of HMS and of how reproductive barriers are maintained between house mouse subspecies.}, number={2}, journal={GENETICS}, author={Widmayer, Samuel J. and Handel, Mary Ann and Aylor, David L.}, year={2020}, month={Oct}, pages={585–597} }
 @article{moskowitz_tracey_widmayer_dumont_2019, title={Meeting report: 32nd international mammalian genome conference Abstracts}, volume={30}, ISSN={["1432-1777"]}, DOI={10.1007/s00335-019-09797-1}, abstractNote={Over 150 scientists from more than 50 research institutions and eight countries attended the 32nd annual meeting of the International Mammalian Genome Society (IMGS) held in Rio Mar, Puerto Rico. Attendees included predoctoral and postdoctoral trainees, junior investigators, clinicians, industry professionals, and established leaders in mammalian genetics and genomics. From November 11–14, major scientific advances in the fields of systems genetics, developmental biology, cancer, human disease modeling, and bioinformatics were showcased in a series of 66 poster and 54 platform presentations. Here we provide an overview of the meeting’s proceedings and summarize the exciting, novel research findings communicated by conference participants that, collectively, are advancing the frontiers of mammalian genetics and genomics.}, number={3-4}, journal={MAMMALIAN GENOME}, author={Moskowitz, Jacob and Tracey, Lauren and Widmayer, Samuel and Dumont, Beth}, year={2019}, month={Apr}, pages={43–53} }
 @article{lee_widmayer_huang_aylor_marchuk_2019, title={Novel Neuroprotective Loci Modulating Ischemic Stroke Volume in Wild-Derived Inbred Mouse Strains}, volume={213}, ISSN={["1943-2631"]}, DOI={10.1534/genetics.119.302555}, abstractNote={To identify genes involved in cerebral infarction, we have employed a forward genetic approach in inbred mouse strains, using quantitative trait loci (QTL) mapping for cerebral infarct volume after middle cerebral artery occlusion. We had previously observed that infarct volume is inversely correlated with cerebral collateral vessel density in most strains. In this study, we expanded the pool of allelic variation among classical inbred mouse strains by utilizing the eight founder strains of the Collaborative Cross and found a wild-derived strain, WSB/EiJ, that breaks this general rule that collateral vessel density inversely correlates with infarct volume. WSB/EiJ and another wild-derived strain, CAST/EiJ, show the highest collateral vessel densities of any inbred strain, but infarct volume of WSB/EiJ mice is 8.7-fold larger than that of CAST/EiJ mice. QTL mapping between these strains identified four new neuroprotective loci modulating cerebral infarct volume while not affecting collateral vessel phenotypes. To identify causative variants in genes, we surveyed nonsynonymous coding SNPs between CAST/EiJ and WSB/EiJ and found 96 genes harboring coding SNPs predicted to be damaging and mapping within one of the four intervals. In addition, we performed RNA-sequencing for brain tissue of CAST/EiJ and WSB/EiJ mice and identified 79 candidate genes mapping in one of the four intervals showing strain-specific differences in expression. The identification of the genes underlying these neuroprotective loci will provide new understanding of genetic risk factors of ischemic stroke, which may provide novel targets for future therapeutic intervention of human ischemic stroke.}, number={3}, journal={GENETICS}, author={Lee, Han Kyu and Widmayer, Samuel J. and Huang, Min-Nung and Aylor, David L. and Marchuk, Douglas A.}, year={2019}, month={Nov}, pages={1079–1092} }