Abstract：
:Genetic studies of human disease have traditionally focused on the detection of disease-causing mutations in afflicted individuals. Here we describe a complementary approach that seeks to identify healthy individuals resilient to highly penetrant forms of genetic childhood disorders. A comprehensive screen of 874 genes in 589,306 genomes led to the identification of 13 adults harboring mutations for 8 severe Mendelian conditions, with no reported clinical manifestation of the indicated disease. Our findings demonstrate the promise of broadening genetic studies to systematically search for well individuals who are buffering the effects of rare, highly penetrant, deleterious mutations. They also indicate that incomplete penetrance for Mendelian diseases is likely more common than previously believed. The identification of resilient individuals may provide a first step toward uncovering protective genetic variants that could help elucidate the mechanisms of Mendelian diseases and new therapeutic strategies.
journal_name
Nat Biotechnoljournal_title
Nature biotechnologyauthors
Chen R,Shi L,Hakenberg J,Naughton B,Sklar P,Zhang J,Zhou H,Tian L,Prakash O,Lemire M,Sleiman P,Cheng WY,Chen W,Shah H,Shen Y,Fromer M,Omberg L,Deardorff MA,Zackai E,Bobe JR,Levin E,Hudson TJ,Groop L,Wang J,doi
10.1038/nbt.3514subject
Has Abstractpub_date
2016-05-01 00:00:00pages
531-8issue
5eissn
1087-0156issn
1546-1696pii
nbt.3514journal_volume
34pub_type
杂志文章abstract：:We have developed a platform for cell analysis based on immunomagnetic selection and magnetic alignment of cells in combination with an epi-illumination tracking and detection system. Whole blood was labeled with ferromagnetic nanoparticles and fluorescent probes, and placed in a magnetic field in a chamber. Cells lab...
journal_title：Nature biotechnology
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