The influence of Neanderthal alleles on cytotoxic response
Various studies have shown that people of Eurasian origin contain traces of DNA inherited from interbreeding with Neanderthals. Recent studies have demonstrated that these Neanderthal variants influence a range of clinically important traits and diseases. Thus, understanding the genetic factors resp...
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PeerJ Inc.
2018-10-01
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| Online Access: | https://peerj.com/articles/5691.pdf |
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| author | Farida S. Akhtari Tammy M. Havener Masahide Fukudo John R. Jack Howard L. McLeod Tim Wiltshire Alison A. Motsinger-Reif |
| author_facet | Farida S. Akhtari Tammy M. Havener Masahide Fukudo John R. Jack Howard L. McLeod Tim Wiltshire Alison A. Motsinger-Reif |
| author_sort | Farida S. Akhtari |
| collection | DOAJ |
| description | Various studies have shown that people of Eurasian origin contain traces of DNA inherited from interbreeding with Neanderthals. Recent studies have demonstrated that these Neanderthal variants influence a range of clinically important traits and diseases. Thus, understanding the genetic factors responsible for the variability in individual response to drug or chemical exposure is a key goal of pharmacogenomics and toxicogenomics, as dose responses are clinically and epidemiologically important traits. It is well established that ethnic and racial differences are important in dose response traits, but to our knowledge the influence of Neanderthal ancestry on response to xenobiotics is unknown. Towards this aim, we examined if Neanderthal ancestry plays a role in cytotoxic response to anti-cancer drugs and toxic environmental chemicals. We identified common Neanderthal variants in lymphoblastoid cell lines (LCLs) derived from the globally diverse 1000 Genomes Project and Caucasian cell lines from the Children’s Hospital of Oakland Research Institute. We analyzed the effects of these Neanderthal alleles on cytotoxic response to 29 anti-cancer drugs and 179 environmental chemicals at varying concentrations using genome-wide data. We identified and replicated single nucleotide polymorphisms (SNPs) from these association results, including a SNP in the SNORD-113 cluster. Our results also show that the Neanderthal alleles cumulatively lead to increased sensitivity to both the anti-cancer drugs and the environmental chemicals. Our results demonstrate the influence of Neanderthal ancestry-informative markers on cytotoxic response. These results could be important in identifying biomarkers for personalized medicine or in dissecting the underlying etiology of dose response traits. |
| first_indexed | 2024-03-09T08:04:56Z |
| format | Article |
| id | doaj.art-e8418042739a49c09c701da19bdde99b |
| institution | Directory Open Access Journal |
| issn | 2167-8359 |
| language | English |
| last_indexed | 2024-03-09T08:04:56Z |
| publishDate | 2018-10-01 |
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| series | PeerJ |
| spelling | doaj.art-e8418042739a49c09c701da19bdde99b2023-12-03T00:25:01ZengPeerJ Inc.PeerJ2167-83592018-10-016e569110.7717/peerj.5691The influence of Neanderthal alleles on cytotoxic responseFarida S. Akhtari0Tammy M. Havener1Masahide Fukudo2John R. Jack3Howard L. McLeod4Tim Wiltshire5Alison A. Motsinger-Reif6Department of Biological Sciences, North Carolina State University, Raleigh, NC, United States of AmericaPharmacotherapy and Experimental Therapeutics, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States of AmericaDepartment of Pharmacy, Kyoto University, Kyoto, JapanBioinformatics Research Center, North Carolina State University, Raleigh, NC, United States of AmericaThe DeBartolo Family Personalized Medicine Institute, Moffitt Cancer Center, Tampa, FL, United States of AmericaPharmacotherapy and Experimental Therapeutics, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States of AmericaBioinformatics Research Center, North Carolina State University, Raleigh, NC, United States of AmericaVarious studies have shown that people of Eurasian origin contain traces of DNA inherited from interbreeding with Neanderthals. Recent studies have demonstrated that these Neanderthal variants influence a range of clinically important traits and diseases. Thus, understanding the genetic factors responsible for the variability in individual response to drug or chemical exposure is a key goal of pharmacogenomics and toxicogenomics, as dose responses are clinically and epidemiologically important traits. It is well established that ethnic and racial differences are important in dose response traits, but to our knowledge the influence of Neanderthal ancestry on response to xenobiotics is unknown. Towards this aim, we examined if Neanderthal ancestry plays a role in cytotoxic response to anti-cancer drugs and toxic environmental chemicals. We identified common Neanderthal variants in lymphoblastoid cell lines (LCLs) derived from the globally diverse 1000 Genomes Project and Caucasian cell lines from the Children’s Hospital of Oakland Research Institute. We analyzed the effects of these Neanderthal alleles on cytotoxic response to 29 anti-cancer drugs and 179 environmental chemicals at varying concentrations using genome-wide data. We identified and replicated single nucleotide polymorphisms (SNPs) from these association results, including a SNP in the SNORD-113 cluster. Our results also show that the Neanderthal alleles cumulatively lead to increased sensitivity to both the anti-cancer drugs and the environmental chemicals. Our results demonstrate the influence of Neanderthal ancestry-informative markers on cytotoxic response. These results could be important in identifying biomarkers for personalized medicine or in dissecting the underlying etiology of dose response traits.https://peerj.com/articles/5691.pdfNeanderthal allelesCytotoxic responsePharmacogenomicsToxicogenomicsDose responsesNeanderthal ancestry |
| spellingShingle | Farida S. Akhtari Tammy M. Havener Masahide Fukudo John R. Jack Howard L. McLeod Tim Wiltshire Alison A. Motsinger-Reif The influence of Neanderthal alleles on cytotoxic response PeerJ Neanderthal alleles Cytotoxic response Pharmacogenomics Toxicogenomics Dose responses Neanderthal ancestry |
| title | The influence of Neanderthal alleles on cytotoxic response |
| title_full | The influence of Neanderthal alleles on cytotoxic response |
| title_fullStr | The influence of Neanderthal alleles on cytotoxic response |
| title_full_unstemmed | The influence of Neanderthal alleles on cytotoxic response |
| title_short | The influence of Neanderthal alleles on cytotoxic response |
| title_sort | influence of neanderthal alleles on cytotoxic response |
| topic | Neanderthal alleles Cytotoxic response Pharmacogenomics Toxicogenomics Dose responses Neanderthal ancestry |
| url | https://peerj.com/articles/5691.pdf |
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