View Full Version : Sardinia-Genetic Isolate

28-10-15, 17:12
Three papers are exploring the genetics of Sardinia (yes, again :)) and zeroing in on unique variants and selection. The same kind of study would doubtless reveal the same kinds of things in any isolated population.


"A large collection of human genomes from Sardinia is reported in three linked papers that implicate new genetic variants in the regulation of height, blood lipids, inflammatory markers and hemoglobin levels. These analyses provide new insight into disease susceptibility and evolution in isolated human populations and illuminate the genetics of complex phenotypes."

"In Sidore et al. (page 1272 (http://www.nature.com/ng/journal/v47/n11/full/ng.3368.html)), the team investigated the impact of variants on circulating lipid levels and five inflammatory biomarkers, for which they found 14 signals (two new loci) and 19 signals (two new loci), respectively. Importantly, some of these signals were detected because of highly accurate imputation that was based on the Sardinian sequencing data; these would not have been identified if the analyses had used 1000 Genomes Project data. Two examples of these signals are an HBB mutation (β039, encoding p.Gln40*) that associates with reduced cholesterol levels and an APOA5 missense variant (encoding p.Arg282Ser) that associates with a reduction in triglyceride levels.

In Danjou et al. (page 1264 (http://www.nature.com/ng/journal/v47/n11/full/ng.3307.html)), the authors looked for associations with levels of fetal hemoglobin (HbF) and adult hemoglobins A1 (HbA1) and A2 (HbA2) and identified 23 associations at ten loci, five of which are novel (MPHOSPH9, PLTP-PCIF1, ZFPM1 (FOG1), NFIX and CCND3). Apart from Spain, the NFIX variant seems to be absent in Europeans. These findings have potential clinical value because these loci could act as modifiers of disease severity in patients with hemoglobinopathies.

Finally, in Zoledziewska et al. (page 1352 (http://www.nature.com/ng/journal/v47/n11/full/ng.3403.html)), the authors studied the genetics of adult height variation in Sardinians, who constitute one of the shortest populations in Europe. They found two common variants with large effects: a nonsense mutation in GHR, a gene previously associated with Laron syndrome, and a mutation in the vicinity of KCNQ1. Interestingly, the latter variant is in an imprinted region and shows an association with reduced height when maternally inherited. Height is known to be a highly polygenic phenotype, and there are over 700 reported variants associated with height variation. The authors found that variants previously associated with reduced stature are more frequent than expected by genetic drift. These results suggest that short stature was selected for in Sardinia and seem to illustrate the so-called 'island effect' where the size of large mammals is reduced on island."

Unfortunately, they're behind a pay wall. If what they mean is that the Sardinians have variants that reduce cholesterol and triglycerides, those, in addition to their famously healthy diet, may go some way to explaining their storied longevity.