We calibrated our DNM calling with segregation of alleles in three-generation families, and subsequently validated our DNM calls with concordance among monozygotic twins. We particularly focused on obtaining quality DNM calls.
This sequencing effort resulted in 39,020,168 autosomal variants passing GATK filters and for the entire variant set we were able to impute 37,127,995 variants into a set of 151,677 chip genotyped Icelanders. Here, we have sequenced 12,803 Icelanders in addition to the previously described 2,417 (ref. The deCODE genetics genealogical databases currently includes records of 819,410 Icelanders 7. A useful feature of the Icelandic population are comprehensive genealogical records going back to 1,600 (and in some instances back to 740). These methods provide genome-wide validation assays with no ascertainment beyond the family relationships of the probands. The analysis of rare variants requires more extensive quality control than the analysis of common variants.įamilies with well understood inheritance patterns provide useful tools for this purpose, such as monozygotic twin concordance and the transmission of DNM alleles to offspring of probands in three-generation families. Furthermore, analysis of singletons and DNMs is complicated since current sequencing technologies and calling algorithms identify a non-trivial number of false-positives 6. In contrast, the analysis of DNMs and other recent mutations requires the sequencing of families in which these recent mutations have occurred.ĭNM detection is hampered by the fact that they are typically only observed in very few individuals (most often a single individual) and sequencing unrelated individuals is of limited value. Sequencing data augmented with chip-typed samples have proven a valuable approach in genome-wide association studies, by combining the low cost of chip typing with the comprehensive characterization of sequence diversity via whole-genome sequencing 1– 3, 5. Advances in sequencing technologies have been instrumental in the creation of whole-genome sequencing data sets on the population level 1– 5.
Scientific Data volume 4, Article number: 170115 ( 2017)Ĭharacterization of genetic diversity is of paramount importance to population genetics.
Whole genome characterization of sequence diversity of 15,220 Icelanders
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