Genetic basis of lactose tolerance in African populations




David and Lyn Silfen University Professor

Project Summary

            The main objective of the Tishkoff lab is to characterize genetic and phenotypic variation in diverse human African populations in order to gain insights into modern human evolutionary history and into the genetic basis of variable traits related to adaptation and disease risk.

My project investigates the genetic basis of lactase persistence in ethnically diverse Cameroonian populations. Lactase is an enzyme responsible for digesting lactose, the primary sugar in milk. This enzyme is encoded by the LCT gene found on chromosome 2. After weaning, in the majority of humans the level of the enzyme lactase decreases and, thus, many people lose the ability to digest lactose. This trait is referred to as being lactase non-persistent (LNP). However, individuals from populations that have a history of milk production and consumption have a strong ability to digest lactose into adulthood as a result of a recent adaptation, and they are referred to as being lactase persistent (LP).

The Cameroonian populations I am examining have traditionally practiced various subsistence patterns, ranging from hunter-gatherers to agriculturalist to pastoralist. My sample size consists of a total of 1200 DNAs and a subset of 255 have phenotypic data for the Lactose Tolerant Test (LTT). Among the several Cameroonian groups I am working with, there is the Fulani, a population that has a nomadic pastoralist lifestyle, meaning that they have a tradition of milk production and consumption. One of my main goals is to identify possible novel mutations that are correlated with the LP trait in the Fulani.   So far, I have sequenced over 600 Cameroonian DNAs for 555 bp of intron 13 of MCM6 gene known to be a candidate region for enhancing the expression of the lactase enzyme during adulthood. LP-associated variants have been previously identified in European and African populations in this region.

I refreshed my knowledge on performing PCR and gel electrophoresis; I learned how to do Sanger sequencing and how to use the Sequencher software to analyze the DNA samples I sequenced. Once all my data will be collected and analyzed, I will also perform a genotype-phenotype association analysis to determine whether any of the variants I have found are associated with the LP phenotype. In preparation for future work in the lab, I also started acquiring more computational skills, such as working in Linux Shell and Windows Powerscript with the intention to run more advanced population genetics analysis software such as PLINK and SHAPE IT.

The experience of working in the Tishkoff lab this summer is one of the most pivotal moments in my education at Penn. Working under the mentorship of Professor Tishkoff and Dr. Ranciaro has provided me with the opportunity to get more familiar with hands on genetics research. I saw a lot of the concepts that I have studied in my Biology classes applied, and I learned more about the process of actual research. Through the work I have been doing this summer I confirmed my goals to pursue further education in the field of Computational Biology.