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John Moran

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Primary Appointment: Human Genetics Department
Primary PIBS Dept.: Human Genetics
PubMed Name: Moran JV
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 DESCRIPTION OF RESEARCH
  We are interested in a class of human ‘jumping genes’ known as Long INterspersed Element-1 retrotransposons (LINE-1 or L1). Recent advances in genome sequencing have revealed that LINE-1 retrotransposons comprise ~17% of human DNA; however, we only are beginning to understand how these elements impact human genome evolution.

The average human is estimated to contain ~80-100 active LINE-1 elements that retain the ability to ‘jump’ (i.e., retrotranspose). The proteins encoded by LINE-1 elements also can mobilize non-autonomous retrotransposons (Alu and SVA elements), non-coding RNAs (U6 snRNA), and cellular mRNAs (processed pseudogenes) to new genomic locations. Together, these sequences comprise at least 11% of human DNA. Thus, in total, LINE-1 mediated retrotransposition events account for approximately one-third of human DNA. Indeed, it is estimated that LINE-1-mediated retrotransposition events are responsible for ~1/1000 disease-producing human mutations.

My laboratory uses a combination of genetic, molecular biological and biochemical assays to study LINE-1 retrotransposition in cultured human cells. We use these experimental approaches in concert to answer the following basic science research questions: 1) How does LINE-1 retrotranspose? 2) How does LINE-1 retrotransposition impact the genome? 3) Do host factors regulate LINE-1 retrotransposition? 4) Does LINE-1 retrotransposition activity vary among humans representative of different geographic populations?

Our long-term goal is to understand the molecular and evolutionary mechanisms by which LINE-1 retrotransposition has and continues to sculpt the human genome.