Low-pass genome-wide sequencing and variant inference using identity-by-descent in an isolated human population.

Whole-genome sequencing in an isolated population with few founders directly ascertains variants from the population bottleneck that may be rare elsewhere. In such populations, shared haplotypes allow imputation of variants in unsequenced samples without resorting to complex statistical methods as in studies of outbred cohorts. We focus on an isolated population cohort from the Pacific Island of Kosrae, Micronesia, where we previously collected SNP array and rich phenotype data for the majority of the population. We report identification of long regions with haplotypes co-inherited between pairs of individuals and methodology to leverage such shared genetic content for imputation. Our estimates show that sequencing as few as 40 personal genomes allows for inference in up to 60% of the 3000-person cohort at the average locus. We ascertained a pilot data set of whole-genome sequences from seven Kosraean individuals, with average 5× coverage. This assay identified 5,735,306 unique sites of which 1,212,831 were previously unknown. Additionally, these variants are unusually enriched for alleles that are rare in other populations when compared to geographic neighbors (published Korean genome SJK). We used the presence of shared haplotypes between the seven Kosraen individuals to estimate expected imputation accuracy of known and novel homozygous variants at 99.6% and 97.3%, respectively. This study presents whole-genome analysis of a homogenous isolate population with emphasis on optimal rare variant inference.

Detection and characterisation of transforming growth factor-beta in porcine colostrum.

Porcine colostrum and milk collected at different stages of lactation were assessed for transforming growth factor-beta (TGF-beta) activity using an epithelial cell bio-assay. A high level of TGF-beta activity was recorded in all colostrum samples after transient acidification treatment, ranging between 126 and 260 ng/ml for samples collected at the time of parturition and 73 ng/ml for the sample collected 12 h after parturition. Without transient acidification treatment TGF-beta activity was detected only in 2 samples collected at the time of parturition (12 ng/ml) and 12 h after parturition (9 ng/ml), respectively. TGF-beta activity was undetectable in milk collected 5 days after parturition. These results suggest that TGF-beta exists mainly in latent form in porcine colostrum and the concentration declines rapidly as lactation proceeds. After enrichment with cation exchange chromatography a low level of TGF-beta activity was detected in porcine milk. Further separation by size exclusion chromatography revealed two molecular mass forms of TGF-beta in both colostrum and milk samples, a major peak of about 80 kD and a minor peak of about 25 kD representing latent and active forms of TGF-beta, respectively. A further experiment showed that the latent form of TGF-beta in colostrum can be activated at pH 3.5 or less. It is speculated that TGF-beta found in the colostrum may play a physiological role in regulating postnatal adaptation of the gastro-intestinal tract in newborns.