Gene gain and loss are crucial factors in shaping evolutionary success of diverse organisms. In the past two decades, more attention has been paid to the significance of gene gain via gene duplication or origin of de novo genes. However, gene loss via natural loss-of-function (LoF) mutations...
A major challenge in genetic association studies is that most associated variants fall in the non-coding part of the human genome. We searched for variants associated with bone mineral density (BMD) after enriching the discovery cohort for loss-of-function (LoF) mutations by sequencing a subset ...
S17 X LOSS OF FUNCTION (LOF) MUTATION IN ANGIOPOIETIN LIKE 3 (ANGPTL3) IS ASSOCIATED WITH INCREASED PLASMA LIPOPROTEIN LIPASE ACTIVITY AND CHANGES IN LIPOP... BACKGROUND AND AIMS: Angiopoietin-like 3 (ANGPTL3) has emerged as a key regulator of lipoprotein metabolism in humans. Homozygous loss...
While there has been much focus on how mutations can disrupt protein structure and thus cause a loss of function (LOF), alternative mechanisms, specifically dominant-negative (DN) and gain-of-function (GOF) effects, are less understood. Here, we investigate the protein-level effects of ...
We show thatSLCO1B1LoF mutations significantly increase the risk of incident heart failure, thus implicating the metabolite in the causal pathway of disease. These results reveal new avenues into gene function and the understanding of disease etiology by integrating -omic technologies into a deeply ...
What causes loss of function mutations? Recessive mutationsinactivate the affected gene and lead to a loss of function. For instance, recessive mutations may remove part of or all the gene from the chromosome, disrupt expression of the gene, or alter the structure of the encoded protein, thereby...
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Sequencing of all exons of 837 RefSeq genes, in 2071 cases and 904 controls, revealed a significantly increased rate of stop gain/loss and splice altering loss-of-function (LOF) mutations, in subsets of candidate genes. Among the individual, LOF variants is a novel de novo premature stop ...
Sequencing of all exons of 837 RefSeq genes, in 2071 cases and 904 controls, revealed a significantly increased rate of stop gain/loss and splice altering loss-of-function (LOF) mutations, in subsets of candidate genes. Among the individual, LOF variants is a novel de novo premature stop ...
The causative role of gain-of-function (GoF) or loss-of-function (LoF) mutations in the Kir6.2/SUR1-dependent pancreatic KATPchannels in neonatal diabetes and congenital hyperinsulinism, respectively, was established nearly two decades ago9,10,11,12. Recently, it has been demonstrated that domi...