Aymara whole transcriptome of neutrophils

Molecular basis of Andean Aymara highlanders increased hemoglobin is unknown.We conducted integrative analysis of whole-genome-sequencung and granulocytes transcriptomics of Aymara and Europeans in Bolivia to explore genetic basis of the Aymara high Hb. Differentially expressed and spliced genes in Aymaras were associated with inflammatory and hypoxia-related pathways. We identified novel transcripts with 4th or 5th exon skipping of NFKB1 (AS-NFKB1), key part of NF-kB complex, and their splicing quantitative trait loci; these were increased in Aymaras. AS-NFKB1 transcripts correlated with both transcripts and protein levels of NF-kB and HIF-regulated genes including hemoglobin. While overexpression of the AS-NFKB1 variant led to increased expression of inflammatory and HIF-targeted genes; under inflammatory stress NF-kB protein translocation to the nucleus was attenuated resulting in reduced expression of these genes.Our study reveals the novel AS-NFKB1 splicing events correlating with Aymara increased hemoglobin and their possible protective mechanisms against excessive inflammation.