# Population dynamics and medical consequences of sex chromosome evolution

> **NIH NIH R35** · ARIZONA STATE UNIVERSITY-TEMPE CAMPUS · 2024 · $452,352

## Abstract

PROJECT SUMMARY
Sex-bias exists in the human genome in DNA content and gene expression. The human X and Y
chromosomes are useful tools for inferring human demography, and crucial for our understanding of human
health. However, despite the genomics era, X and Y chromosomes are still vastly underutilized, especially in a
genome-wide context. Most established genomics methods and analyses fail to explicitly incorporate sex
chromosomes, missing more than 5% of typical genomic variation, and ignoring regions known to contribute to
disease. The study of sex chromosome evolution therefore addresses deficits in conventional approaches with
critical implications for human health and biology. My research has focused on the integration of these
chromosomes to build comprehensive analyses of human history and utilizing an evolutionary approach to
characterize sex-bias in gene expression. This project will utilize multiple approaches for studying sex
chromosome variation across human and non-human species. First, we will focus on development and
extensive testing of novel methodology for accurately accounting for technical variation that affects alignment
and variant calling on the sex chromosomes. Current alignment pipelines do not account for the shared
homology between the X and Y chromosome, resulting in mis-mapping of reads between the sex
chromosomes and reduced power for variant calling. We will incorporate sex chromosome biology to improve
alignment and variant calling on the sex chromosomes. Second, we will study the evolution of sex
chromosomes and X-inactivation in non-human animals, focused on our close evolutionary relative, the rhesus
macaque. Third, we will study gene expression variation (with an emphasis on X-linked gene expression and
X-inactivation) between the sexes, and between human populations in the human placenta. The placenta is the
one organ routinely expelled from the body that also provides a crucial interface during development, and is
not studied in current large-scale tissue expression projects. In collaboration with a long-term pregnancy
outcome study we will generate and comprehensively analyze population-specific sex-bias in the human
placenta. Fourth, we will study truly genome-wide patterns of variation (autosomes, X chromosome, Y
chromosome, and mtDNA) in African populations. Populations in Africa are the most diverse in the world, and
representation of that diversity is conspicuously absent from global population studies. In collaboration with
anthropologists, who are studying, cultural variation, we will use patterns of variation across the sex
chromosomes and autosomes to infer recent and ancient demography, informed by sex-biased migration and
demography. Finally, we will contribute novel training materials for instructors and study student learning and
self-efficacy as they learn genomics research skills. This work will improve methodology for studying sex-linked
variation, provide estimates of sex-biased human demog...

## Key facts

- **NIH application ID:** 10851762
- **Project number:** 5R35GM124827-07
- **Recipient organization:** ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
- **Principal Investigator:** Melissa A Wilson
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $452,352
- **Award type:** 5
- **Project period:** 2017-09-11 → 2024-12-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10851762

## Citation

> US National Institutes of Health, RePORTER application 10851762, Population dynamics and medical consequences of sex chromosome evolution (5R35GM124827-07). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10851762. Licensed CC0.

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