Sex differences in health and disease

Date:
September 11, 2020
Source:
Arizona State University
Summary:
Researchers have reviewed current research into patterns of sex
differences in gene expression across the genome, and highlights
sampling biases in the human populations included in such studies.



FULL STORY ========================================================================== Males and females share the vast majority of their genomes. Only a
sprinkling of genes, located on the so-called X and Y sex chromosomes,
differ between the sexes. Nevertheless, the activities of our genes --
their expression in cells and tissues -- generate profound distinctions
between males and females.


==========================================================================
Not only do the sexes differ in outward appearance, their differentially expressed genes strongly affect the risk, incidence, prevalence, severity
and age-of-onset of many diseases, including cancer, autoimmune disorders, cardiovascular disease and neurological afflictions.

Researchers have observed sex-associated differences in gene expression
across a range of tissues including liver, heart, and brain. Nevertheless,
such tissue-specific sex differences remain poorly understood. Most traits
that display variance between males and females appear to result from differences in the expression of autosomal genes common to both sexes,
rather than through expression of sex chromosome genes or sex hormones.

A better understanding of these sex-associated disparities in the behavior
of our genes could lead to improved diagnoses and treatments for a range
of human illnesses.

In a new paper in the PERSPECTIVES section of the journal Science,
Melissa Wilson reviews current research into patterns of sex differences
in gene expression across the genome, and highlights sampling biases in
the human populations included in such studies.

"One of the most striking things about this comprehensive study of sex differences," Wilson said, "is that while aggregate differences span
the genome and contribute to biases in human health, each individual
gene varies tremendously between people." Wilson is a researcher in the Biodesign Center for Mechanisms in Evolution, the Center for Evolution
and Medicine, and ASU's School of Life Sciences.



==========================================================================
A decade ago, an ambitious undertaking, known as the Genotype-Tissue
Expression (GTEx) consortium began to investigate the effects DNA
variation on gene expression across the range of human tissues. Recent findings, appearing in the Science issue under review, indicate that
sex-linked disparities in gene expression are far more pervasive than
once assumed, with more than a third of all genes displaying sex-biased expression in at least one tissue. (The new research highlighted
in Wilson's PERSPECTIVES piece describes gene regulatory differences
between the sexes in every tissue under study.) Sex-linked differences
in gene expression are shared across mammals, though their relative
roles in disease susceptibility remain speculative. Natural selection
likely guided the development of many of these attributes. For example,
the rise of placental mammals some 90 million years ago may have led to differences in immune function between males and females.

Such sex-based distinctions arising in the distant past have left their
imprint on current mammals, including humans, expressed in higher rates
of autoimmune disorders in females and increased cancer rates in males.

Despite their critical importance for understanding disease prevalence
and severity, sex differences in gene expression have only recently
received serious attention in the research community. Wilson and others
suggest that much historical genetic research, using primarily white
male subjects in mid- life, have yielded an incomplete picture.

Such studies often fail to account for sex differences in the design and analysis of experiments, rendering a distorted view of sex-based disease variance, often leading to one-size-fits-all approaches to diagnosis and treatment. The authors therefore advise researchers to be more careful
about generalizations based on existing databases of genetic information, including GTEx.

A more holistic approach is emerging, as researchers investigate the full panoply of effects related to male and female gene expression across a
broader range of human variation.


========================================================================== Story Source: Materials provided by Arizona_State_University. Original
written by Richard Harth. Note: Content may be edited for style and
length.


========================================================================== Journal Reference:
1. Melissa A. Wilson. Searching for sex differences. Science, 2020; 369
(6509): 1298 DOI: 10.1126/science.abd8340 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/09/200911141749.htm

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