When the human genome was first sequenced, it was difficult for many to believe that ‘only 1.5 percent of the 3 billion bases of a haploid genome is actually responsible for protein-coding genes’. Early on, the term “junk DNA” was applied to describe the 95%–98% of the genome having no known function. Now we know this “judgment” was premature. Much of the genome is relevant to cell-specific or organ-specific gene expression––including many functions during development.
“Repetitive elements” appear to comprise 60-70% of the genome. Some are transcribed, but not translated into protein; these include micro-RNAs (miRNAs) and long intergenic non-coding RNAs (lincRNAs). The miRNAs are usually 20-24 nucleotides (nt) in length, whereas the length of lincRNAs ranges from at least 200 nt to ~10 kb, and lincRNAs actually contain 2-4 exons per transcript. The attached report shows an amazing correlation between lincRNA mutations and susceptibility to infection.
Bacteremia (bacterial bloodstream infection) is a major cause of illness and death in sub-Saharan Africa, but little is known about the role of human genetics in susceptibility. Authors [below] carried out a genome-wide association (GWA) study of “bacteremia susceptibility” in more than 5,000 Kenyan children as part of the Wellcome Trust Case Control Consortium 2. Both the blood-culture-proven bacteremia case subjects, and the healthy infants as controls, were recruited from Kilifi, on the east coast of Kenya. Streptococcus pneumoniae is the most common cause of bacteremia in Kilifi and therefore was the focus of this study.
Authors [below] identified an association between polymorphisms in a long intergenic non-coding RNA (lincRNA) locus (AC011288.2) and pneumococcal bacteremia and replicated the results in the same population (P combined = 1.69 ´ 109; OR = 2.47; 95% CI = 1.84–3.31). In this analysis of 429 case and 2,677 control subjects, 17
variants in a single region on chromosome 7 were associated with disease––at a level exceeding (the commonly accepted) genome-wide significance value of P = 5.0 x 10–8). Authors found the peak of that association observed at rs140817150 (P imputed = 7.25 x 10–9); OR = 2.74). The susceptibility allele was found to be African-specific, derived rather than ancestral, and occurs at low frequencies (2.7% in control subjects; 6.4% in case subjects). Authors’ further studies intriguingly demonstrated that AC011288.2 expression only occurs in neutrophils(!!), a cell type well known to play a major role in pneumococcal clearance. Identification of this novel association will greatly expand the focus on the role of lincRNAs in human infectious disease.
Am J Hum Genet 2o16; 98: 1092–1100