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Graduate student Dana Al-Hindi receives National Science Foundation (Doctoral Dissertation Improvement Grant)

Doctoral Dissertation Research: Characterization and Functional Validation of the Genetic Architecture of Skin Pigmentation

Award Abstract # 2142101
Doctoral Dissertation Research: Characterization and Functional Validation of the Genetic Architecture of Skin Pigmentation

 

NSF Org: BCS
Division Of Behavioral and Cognitive Sci
Awardee: UNIVERSITY OF CALIFORNIA, DAVIS
Initial Amendment Date: April 7, 2022
Latest Amendment Date: April 7, 2022
Award Number: 2142101
Award Instrument: Standard Grant
Program Manager: Rebecca Ferrell
rferrell@nsf.gov  (703)292-7850
BCS  Division Of Behavioral and Cognitive Sci
SBE  Direct For Social, Behav & Economic Scie
Start Date: April 15, 2022
End Date: March 31, 2024 (Estimated)
Total Intended Award Amount: $30,164.00
Total Awarded Amount to Date: $30,164.00
Funds Obligated to Date: FY 2022 = $30,164.00
History of Investigator:
  • Brenna  Henn (Principal Investigator)
    bmhenn@ucdavis.edu
  • Dana  Al-Hindi (Co-Principal Investigator)
Awardee Sponsored Research Office: University of California-Davis
1850 RESEARCH PARK DR, STE 300
DAVIS
CA  US  95618-6153
(530)754-7700
Sponsor Congressional District: 03
Primary Place of Performance: University of California-Davis
209 Young Hall
Davis
CA  US  95616-5270
Primary Place of Performance
Congressional District:
03
Unique Entity Identifier (UEI): TX2DAGQPENZ5
Parent UEI: NUDGYLBB4S99
NSF Program(s): Bio Anthro DDRI
Primary Program Source:
Program Reference Code(s): 1392, 9179
Program Element Code(s): 7608
Award Agency Code: 4900
Fund Agency Code: 4900
Assistance Listing Number(s): 47.075

 

ABSTRACT

Research on the evolution of human skin pigmentation includes the characterization of this characteristic's underlying genetic variation. Recent studies have shown that the number of genes associated with skin pigmentation differs across populations and that much of this genetic variation is still unidentified due to underrepresentation of some populations in human genetic research. This doctoral dissertation project lays the groundwork necessary to model human skin pigmentation evolution by characterizing and functionally validating the genetic architecture of skin pigmentation in a population that has been underrepresented in such research. Data generated from this project can inform several pigmentation research objectives, including understanding the role of natural selection in shaping this human trait. The project can also be used as a model for research on other complex genetic traits and may inform other fields including bioarchaeology and forensic anthropology. Additionally, this project contributes to the skill development of undergraduate and graduate students through wet lab, computational, and fieldwork training.

The research team conducts fieldwork to collect paired genetic and pigmentation data from individuals in a population with high levels of ancestral alleles and higher levels of genetic diversity than other extant human populations. The research presents an opportunity to research pigmentation variation that may have been present in ancestral human populations, and therefore potentially broadens our understanding of pigmentation genetics globally. Newly collected samples will be genotyped and then evaluated using a genome-wide association (GWA) approach. Data from four different descent populations will be meta-analyzed to increase power to detect low-effect size loci. Regions identified in the GWA study are not necessarily causal pigmentation loci, rendering functional validation necessary. Top candidate genes are therefore identified and functionally evaluated for causality with CRISPR (clustered regularly interspaced short palindromic repeats) gene editing in zebrafish, an effective model organism to study human skin pigmentation. Using a rapid automated phenotyping platform to image larvae, pigmentation is analyzed comparing CRISPR- mosaic “knockout” fish with “mock” injected sibling controls. This strategy can functionally verify whether novel associated genes from the GWAS are causal pigmentation genes.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.