Understanding Sex Differences in Disease

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Understanding Sex Differences in Disease

Sexual dimorphism observed in autoimmune disease (increased in females) and cancer incidence (reduced in females) is proposed to be the result of mismatch between an ancestral environment (being pregnant near constantly) and modern environment (contraception and reduced pregnancies), and is mediated by evolution of the sex chromosomes. Itis proposed that, ancestrally, in a tit-for-tat with this fetal-induced dampening, the maternal immune system had to up-regulate to maintain a sufficient immune response to survive typical environmental attacks. However, in the absence of near-constant pregnancy, and dampening of the maternal immune system, the immune system of modern industrial women is prone to being hyperactive. Given the tremendous role of the immune system in surveying and preventing cancer, we propose that, while this “undampened” immune response may lead to detrimental autoimmune disease, it can also be protective against cancers in women.

 

Published articles

Completed: AZ Alzheimer’s Disease Consortium July 2019 – June 2020 $300K , Co-I: Wilson Sayres (10%)
Active: NIH MIRA Sept 2017 – Aug 2022 $1.65M, “Population dynamics and medical consequences of sex chromosome evolution.” PI: Wilson Sayres (100%)
Olney Kg, Brotman SMu, Valverde-Vesling Vu, Andrews Ju, Wilson MA. 2020. Reference genome and transcriptome informed by the sex chromosome complement of the sample increases ability to detect sex differences in gene expression from RNA-Seq data. Biology of Sex Differences
Wilson MA and Buetow KH. 2019. Novel mechanisms of cancer emerge when accounting for sex as a biological variable (accepted) Cancer Research. doi: 10.1158/0008-5472.CAN-19-2634
Natri Hp, Garcia A, Buetow KH, Trumble B and Wilson MA. 2019. Endogenous retroviruses and the Pregnancy Compensation Hypothesis. Trends in Genetics 36(1):2-3. doi: 10.1016/j.tig.2019.10.006
Garcia A, Natri Hp, Buetow KH, Trumble B and Wilson MA. 2019. Evolution of immune sexual dimorphism in response to placental invasiveness. Trends in Genetics 36(1):5-7. doi: 10.1016/j.tig.2019.10.007
Natri Hp, Wilson MA*, and Buetow K*. 2019. Distinct molecular etiologies of male and female hepatocellular carcinoma. BMC Cancer. 19(951). doi: 10.1186/s12885-019-6167-2
Natri Hp, Garcia A, Buetow KH, Trumble B and Wilson MA. 2019. The Pregnancy Pickle: Evolved immune compensation due to pregnancy underlies sex differences in human diseases. Trends in Genetics 35(7):478-488.
Webster THp, Phung T, Grande B, Karlins E, Richmond P, Couse M, Whitford W, and Wilson MA. 2019. Identifying, understanding, and correcting technical artifacts on the sex chromosomes in next-generation sequencing data. GigaScience 8(7):giz074.
Awarded: Foundation for Women’s Wellness Dec 2018 – Dec 2019 $25K active “The role of X chromosome inactivation in breast cancer.” PI: Wilson Sayres (100%)
Active AZ Alzheimer’s Disease Consortium July 2018 – June 2019 $300K active Co-I: Wilson Sayres (10%)