# Advanced tools for using ancient DNA to study biology and history

> **NIH NIH R01** · HARVARD MEDICAL SCHOOL · 2022 · $79,836

## Abstract

PROJECT SUMMARY / ABSTRACT
Population history shapes human biology, genetic variation, and disease risk. Despite its importance, analytical
methods to study history on a genome-wide scale are limited in both their resolution and qualitative ability to
reconstruct aspects of the past. This makes it a priority to develop new methods that are able to model the
major population mixture events that have been documented as a result of the genomic and ancient DNA data
revolutions in the last decade. At present, the world's ancient DNA data suffer from major technical biases that
are not properly controlled for, the analytical toolkit for studying population mixture with modern and ancient
DNA is inadequate, and we are only beginning to develop methods that realize the potential of ancient DNA to
reveal as much about biology as about history. This proposal aims to address these needs by extending
funding for grant R01 GM100233, which from 2012-2020 supported the PIs' central research program on
developing methods for studying human population history and leveraging this information to learn about
biology, resulting in 70 publications linked to the grant. We propose three new Aims:
 (1) To create an unbiased pipeline for processing ancient DNA, and to use it reanalyze the world's data;
 (2) To extend the capabilities of admixture graphs for population history inference;
 (3) To introduce new tools for analyzing population history and biology.
 This grant will be of value in four ways. (a) It will support the development of methods and user-friendly
and well-documented software that will be important for evolutionary and medical genetics. (b) It will support
work that will result in insights relevant to finding disease genes in human populations that are recently or
anciently admixed. (c) It will lead to new discoveries about human history. (d) It will produce a publicly available
reprocessed version of the world's ancient DNA data that will be of broad use to the community.
 The link to medical genetics is important. In the past, we have been successful at drawing a direct
connection between our laboratory's work on detecting and characterizing population mixture, and human
biology including genetic susceptibility to disease. We leveraged the history of admixture in African Americans
to make new disease gene discoveries (for example, risk factors for prostate cancer), to understand variation
in disease risk across populations, and to document differences in the biology of recombination between
African Americans and people who do not have West African ancestry, which are predicted to lead to different
levels of risk for diseases associated with errors in recombination. Our focus on drawing connections between
population history and disease risk also highlighted the opportunities for discovery of recessive disease genes
in thousands of founder groups in South Asia. We anticipate that the methods and resources we develop with
the support of this grant will c...

## Key facts

- **NIH application ID:** 10586271
- **Project number:** 3R01HG012287-10S1
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** David E Reich
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $79,836
- **Award type:** 3
- **Project period:** 2021-06-15 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10586271

## Citation

> US National Institutes of Health, RePORTER application 10586271, Advanced tools for using ancient DNA to study biology and history (3R01HG012287-10S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10586271. Licensed CC0.

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