Hello there bloggies! Sorry this post is a bit last on this Science Sunday. My brother is getting married in a few weeks (exciting!), and we had suit fittings and other activities this weekend. Wedding and spring related activities are really starting to eat into a lot of my time. I am going to have to work on managing all of these things in the next weeks.

So, instead of commentary on science, I wanted to highlight a couple of papers that have caught my interest recently.

1) Large-scale whole-genome sequencing of the Icelandic population

In this study, Gudbjartsson and colleagues sequenced the coding regions of the genome (called the exome) in 2,636 Icelandic individuals in the deCode cohort. After identifying approximately 20 million SNPs and 1.5 million indels, they used this information and existing GWAS data on over 100,000 Icelanders to impute genotype information. Using this and the existing medical record and phenotype data, the authors examined the clinical associations and implications of identified variants. This study is a large undertaking in a large relatively isolated population in Iceland. It represents a unique opportunity to continue to identify and examine the health implications of both rare and common genetic variation.

Reference: Gudbjartsson et al. Large-scale whole-genome sequencing of the Icelandic population. Nature Genetics. PMID: 25807286.

Link: http://www.nature.com/ng/journal/vaop/ncurrent/full/ng.3247.html

2) Exome sequencing in an admixed isolated population indicates NFXL1 variants confer a risk for specific language impairment

Keeping with the theme of exome sequencing and isolate populations, Villanueva and colleagues identified NFXL1 as a risk gene for specific language impairment in a population of the Robinson Crusoe Island in Chile. I honestly had idea where this island was until I read this paper and googled it. Isolate founder populations can have less genetic diversity and help enable researchers to identify risk genetic variants. Plus, this population has a high prevalence of specific language impairment, further increasing power. Using this strategy, this team identified a nonsynonymous variant in NFLX1 associated with specific language impairment in this population and then tried to extend it to a UK cohort. What I enjoyed about this paper was the use of a unique population to ask an interesting question. Human geneticists need to expand studies from mainly European ancestries to all different ancestries to identify more and more contributing genes.

Reference: Villanueva et al. Exome sequencing in an admixed isolated population indicates NFXL1 variants confer a risk for specific language impairment. Plos Genetics. PMID: 25781923

Link: http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1004925#sec009 

3) Neomorphic effects of recurrent somatic mutations in Yin Yang 1 in insulin-producing adenomas.

Here, Cromer and colleagues used whole exome sequencing and follow-up directed sequencing of a modest number of insulinomas (aka pancreas islet tumors that overproduce and release insulin) to identify mutations in the YY1 gene. YY1 is a transcription factor that directly binds DNA and alters gene expression. These recurrent YY1 mutations change the DNA sequence YY1 binds (identified using ChIP-seq), altering the YY1 gene regulation as show using microarray. This paper is a positive example of sequencing specific cancer tumors and identifying how somatic mutations alter gene function/regulation. It’ll be exciting to see how other tumor-specific sequencing studies evolve.

Reference: Cromer et al. Neomorphic effects of recurrent somatic mutations in Yin Yang 1 in insulin-producing adenomas. PNAS. PMID 25787250

Link: http://www.pnas.org/content/early/2015/03/17/1503696112.long

Whole exome sequencing studies can be a really exciting strategy when used in the correct situations. As with all approaches, whole exome sequencing will not resolve all questions in human genetics. But, as shown in these studies, it can be a fantastic way to identify risk genetic variants and their implications both clinically and using basic science.

Thank you for stopping by Science Sunday! What do you all think of these three papers? Or do you have any other interesting whole exome sequencing papers? Comment below or on twitter @DrFsThoughts.

See you all on Tuesday!

-Dr. F