# Precision Genomic Medicine in The Plain Communities and its Impact on The Plain and General Population

> **NIH NIH K08** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $182,072

## Abstract

Abstract
The Plain populations (Amish and Mennonites) originated from founder populations with subsequent genetic
bottlenecks and genetic drift; leading to a loss of diversity and an altered genetic disease burden. The Western
PA Plain people are among the least genetically characterized Plain communities in the US. This application
proposes to use Whole Exome Sequencing (WES) to identify novel genetic disorders in this population. Due to
the Plain Populations loss of population genomic complexity, inbreeding, and sociologic isolation, many of the
genetic disorders are inherited in autosomal recessive fashion due to homozygous mutations. This genetic
makeup as well as the large families will facilitate WES analysis to find candidate variants that can potentially be
pathogenic causes of diseases. A multitude of genetic diseases are characterized in the Plain population, and
this proposed study will identify additional diseases, enabling a community-centric personalized medicine
approach to care based on individual genetic risk. In addition, knowledge of genetic disorders originally
developed through study of the Plain Populations, can subsequently be applied in the general population. The
central hypothesis is that the Amish and Mennonite communities will allow the identification of novel genetic
disorders/pathogenic variants of relevance to the Plain communities, and ultimately the general population. The
following aims are proposed: (1) Identification of novel genetic disorders/ disease-causing variants in the Plain
communities. The hypothesis is that genetics studies of the Western PA Plain people using WES will allow for
continued characterization of novel genetic disorders/pathogenic variants that are relevant to both the Plain and
general populations. (2) Performing functional studies for a novel genetic disorder causing dilated
cardiomyopathy (DCM). The hypothesis is that the MTCL1 variant (c.82C>G;p.His28Asp) is pathogenic and
MTCL1 gene mutations are novel cause of DCM. The candidate is firmly committed to a career in translational
genomics research and its implications on the Plain and General populations. She has already worked within
the Plain communities, proving her ability to connect with and perform research within these culturally distinct
groups. These connections, and her research focus on translational research using WES as a diagnosis tool
with functional studies when needed, have already led to the discovery of several mitochondrial disorders and
an AK2 gene mutation as a cause of an immunodeficiency with a novel phenotype in the Amish. The primary
sponsor is a world recognized expert in the field of Genetics with an outstanding track record of training and with
a great working relationship with the candidate. The candidate has developed a comprehensive career
development plan to improve her bioinformatics and WES analysis skills, and will learn to perform functional
studies related to cardiomyopathy.

## Key facts

- **NIH application ID:** 10017282
- **Project number:** 5K08HG010490-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Lina Ghaloul-Gonzalez
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $182,072
- **Award type:** 5
- **Project period:** 2019-09-12 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10017282

## Citation

> US National Institutes of Health, RePORTER application 10017282, Precision Genomic Medicine in The Plain Communities and its Impact on The Plain and General Population (5K08HG010490-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10017282. Licensed CC0.

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