# The origin, the function and the phenotypic impact of human alleles

> **NIH NIH R35** · HARVARD MEDICAL SCHOOL · 2021 · $583,645

## Abstract

Genetic variation is the primary source of evolutionary innovation and a major factor responsible
for phenotypic variation. Consequently, understanding such variation has great importance in
both basic biology and evolution, and ultimately Mendelian and complex disease.
We will study the origin of genetic variation through spontaneous mutational processes.
Computational analysis of sequencing datasets will shed light on the mechanistic forces
underlying germ-line and somatic cancer mutations in human. We will design new statistical
models of de novo mutation that will have applications in population genetics, cancer genomics
and genetics of neuropsychiatric disease.
Next, we will improve computational methods for interpreting and predicting the effect of
mutation on molecular function, including both coding and non-coding variation. Our methods
integrate data from evolutionary genetics and biophysics and rely on comparative, functional
and structural data. The newly developed methods will have applications in both medical and
population genetics.
We will study the population dynamics of alleles to estimate the forces that shape genetic
variation within populations. We will rely on population genetics models to analyze
evolutionary maintenance and genetic architecture of human phenotypes. Fascinated by the
relationship between genotype and phenotype, we will combine theoretical models and
statistical analysis of large-scale sequencing datasets to infer properties of the allelic
architecture of complex traits. We will design new approaches to characterize and predict the
genetic component of common disease risk. !

## Key facts

- **NIH application ID:** 10553953
- **Project number:** 7R35GM127131-05
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** SHAMIL SUNYAEV
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $583,645
- **Award type:** 7
- **Project period:** 2018-05-11 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10553953

## Citation

> US National Institutes of Health, RePORTER application 10553953, The origin, the function and the phenotypic impact of human alleles (7R35GM127131-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10553953. Licensed CC0.

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