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Addiction and Immune Enriched Genomic regions may be Influenced by Selection for Hepatitis B Resistance

Finding the genetic markers that influence infectious and chronic disease phenotypes has been an area of significant biological study. Understanding complex disease related traits like addiction has been hampered by the lack of functional insights in to the human genome. We hypothesized that environmental factors such as geographical location, relative pathogen burden and infection rates will identify allele frequency differences in for immune and addiction gene hotspots between populations that are consistent with natural selection within human populations living predominantly in tropical environments.

To test whether there are correlative relationships between ecoregions, disease and population allele frequencies, we use genes contained in addiction and immunity curated by NCBI. Immune associated genes were identified from NCBI gene lists using immune related search terms. These terms were added to 587 genes previously identified as being involved in opiate, dopamine, and GABA reception addiction. These genes were then projected onto the genome to identify cluster regions of genetic importance for immunity and addiction. Clusters were defined as regions of the genome with more than 15 genes within a 1.5Mb linear genomic window. When addiction and immunity gene lists were combined, we found that they created three hotspots located on chromosomes 11, 17, and 19. Human polymorphism data was surveyed from the 1054 individuals comprising 51 populations of the Human Genome Diversity Panel, 1148 individuals comprising the 11 sample populations of the HapMap Project and the 1092 individuals representing the 1000 Genomes dataset. Our analyses demonstrate that when human populations are grouped into tropical versus non-tropical living groups, significant differences in allele frequencies at the hotspot located on chromosome 11 for 5 polymorphisms were found.


Latifa F Jackson, Maksim Shestov, Kim Burrows and Fatimah LC Jackson

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