Y and mitochondrial chromosomes in the heterogeneous stock rat population

Faith Okamoto; Apurva S Chitre; Thiago Missfeldt Sanches; Denghui Chen; Daniel Munro; Allegra T Aron; Angela Beeson; Hannah V Bimschleger; Maya Eid; Angel G Garcia Martinez; Wenyan Han; Katie Holl; Tyler Jackson; Benjamin B Johnson; Christopher P King; Brittany N Kuhn; Alexander C Lamparelli; Alesa H Netzley; Khai-Minh H Nguyen; Beverly F Peng; Jordan A Tripi; Tengfei Wang; Kendra S Ziegler; Douglas J Adams; Amelie Baud; Lieselot L G Carrette; Hao Chen; Giordano de Guglielmo; Pieter Dorrestein; Olivier George; Keita Ishiwari; Monica M Jablonski; Thomas C Jhou; Marsida Kallupi; Rob Knight; Paul J Meyer; Leah C Solberg Woods; Oksana Polesskaya; Abraham A Palmer

doi:10.1093/g3journal/jkae213

Y and mitochondrial chromosomes in the heterogeneous stock rat population

G3 (Bethesda). 2024 Nov 6;14(11):jkae213. doi: 10.1093/g3journal/jkae213.

Authors

Faith Okamoto¹, Apurva S Chitre², Thiago Missfeldt Sanches¹, Denghui Chen², Daniel Munro¹, Allegra T Aron^{3

4}, Angela Beeson⁵, Hannah V Bimschleger¹, Maya Eid⁶, Angel G Garcia Martinez⁷, Wenyan Han⁷, Katie Holl⁸, Tyler Jackson⁹, Benjamin B Johnson¹, Christopher P King¹⁰, Brittany N Kuhn¹¹, Alexander C Lamparelli¹², Alesa H Netzley¹³, Khai-Minh H Nguyen¹, Beverly F Peng¹, Jordan A Tripi¹⁰, Tengfei Wang⁷, Kendra S Ziegler¹, Douglas J Adams¹⁴, Amelie Baud^{15

16}, Lieselot L G Carrette¹, Hao Chen⁷, Giordano de Guglielmo¹, Pieter Dorrestein^{3

17

18

19}, Olivier George¹, Keita Ishiwari^{20

21}, Monica M Jablonski²², Thomas C Jhou⁹, Marsida Kallupi¹, Rob Knight^{23

19

24

25}, Paul J Meyer¹⁰, Leah C Solberg Woods⁵, Oksana Polesskaya¹, Abraham A Palmer^{1

26}

Affiliations

¹ Department of Psychiatry, University of California San Diego, La Jolla, CA 92093, USA.
² Bioinformatics and System Biology Program, University of California San Diego, La Jolla, CA 92093, USA.
³ Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA 92093, USA.
⁴ Department of Chemistry and Biochemistry, University of Denver, Denver, CO 80208, USA.
⁵ Department of Internal Medicine, Molecular Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
⁶ Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
⁷ Department of Pharmacology, Addiction Science and Toxicology, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
⁸ Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
⁹ Department of Neurobiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
¹⁰ Department of Psychology, University at Buffalo, Buffalo, NY 14260, USA.
¹¹ Department of Neuroscience, Medical University of South Carolina, Charleston, SC 29425, USA.
¹² Department of Psychology, University of California Los Angeles, Los Angeles, CA 90095, USA.
¹³ Department of Emergency Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
¹⁴ Department of Orthopedics, University of Colorado - Anschutz Medical Campus, Aurora, CO 80045, USA.
¹⁵ Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona, Spain.
¹⁶ Universitat Pompeu Fabra, Barcelona, Spain.
¹⁷ Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA 92093, USA.
¹⁸ Department of Pharmacology, University of California San Diego, La Jolla, CA 92093, USA.
¹⁹ Center for Microbiome Innovation, University of California San Diego, La Jolla, CA 92093, USA.
²⁰ Department of Pharmacology and Toxicology, University at Buffalo, Buffalo, NY 14203, USA.
²¹ Clinical and Research Institute on Addictions, University at Buffalo, Buffalo, NY 14203, USA.
²² Department of Ophthalmology and Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
²³ Department of Pediatrics, University of California San Diego, La Jolla, CA 92093, USA.
²⁴ Department of Computer Science and Engineering, University of California San Diego, La Jolla, CA 92093, USA.
²⁵ Department of Bioengineering, University of California San Diego, La Jolla, CA 92093, USA.
²⁶ Institute for Genomic Medicine, University of California San Diego, La Jolla, CA 92093, USA.

Abstract

Genome-wide association studies typically evaluate the autosomes and sometimes the X Chromosome, but seldom consider the Y or mitochondrial (MT) Chromosomes. We genotyped the Y and MT Chromosomes in heterogeneous stock (HS) rats (Rattus norvegicus), an outbred population created from 8 inbred strains. We identified 8 distinct Y and 4 distinct MT Chromosomes among the 8 founders. However, only 2 types of each nonrecombinant chromosome were observed in our modern HS rat population (generations 81-97). Despite the relatively large sample size, there were virtually no significant associations for behavioral, physiological, metabolome, or microbiome traits after correcting for multiple comparisons. However, both Y and MT Chromosomes were strongly associated with the expression of a few genes located on those chromosomes, which provided a positive control. Our results suggest that within modern HS rats there are no Y and MT Chromosomes differences that strongly influence behavioral or physiological traits. These results do not address other ancestral Y and MT Chromosomes that do not appear in modern HS rats, nor do they address effects that may exist in other rat populations, or in other species.

Keywords: PheWAS; RNA-seq; Y Chromosome; haplotype; heterogeneous stock; low-coverage; mitochondria; rat.

MeSH terms

Animals
Female
Genome-Wide Association Study
Genotype
Male
Mitochondria* / genetics
Rats
Y Chromosome* / genetics

Abstract

MeSH terms

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