ausblenden:
Schlagwörter:
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Zusammenfassung:
Genome-sequencing studies indicate that all humans carry many genetic variants predicted to
cause loss of function (LoF) of protein-coding genes, suggesting unexpected redundancy in the
human genome. Here we apply stringent filters to 2951 putative LoF variants obtained from
185 human genomes to determine their true prevalence and properties. We estimate that human
genomes typically contain ~100 genuine LoF variants with ~20 genes completely inactivated.
We identify rare and likely deleterious LoF alleles, including 26 known and 21 predicted severe
disease
–
causing variants, as well as common LoF variants in nonessential genes. We describe
functional and evolutionary differences between
LoF-tolerant and recessive disease genes and a
method for using these differences to prioritize ca
ndidate genes found in clinical sequencing studies
