Crawford, R. D. | bioRxiv Science

bioRxiv2020

cognac: rapid generation of concatenated gene alignments for phylogenetic inferencefrom large whole genome sequencing datasets

The quantity of genomic data is expanding at an increasing rate. Tools for phylogenetic analysis which scale to the quantity of available data are required. We present cognac, a user-friendly software package to rapidly generate concatenated gene alignments for phylogenetic analysis. We applied this tool to generate core gene alignments for very large genomic datasets, including a dataset of over 11,000 genomes from the genus Escherichia containing 1,353 genes, which was constructed in less than 17 hours. We have released cognac as an R package (https://github.com/rdcrawford/cognac) with customizable parameters for adaptation to diverse applications.

genomics↗

bioRxiv2018

Genome-wide association study of 1 million people identifies 111 loci for atrial fibrillation

To understand the genetic variation underlying atrial fibrillation (AF), the most common cardiac arrhythmia, we performed a genome-wide association study (GWAS) of > 1 million people, including 60,620 AF cases and 970,216 controls. We identified 163 independent risk variants at 111 loci and prioritized 165 candidate genes likely to be involved in AF. Many of the identified risk variants fall near genes where more deleterious mutations have been reported to cause serious heart defects in humans or mice (MYH6, NKX2-5, PITX2, TBC1D32, TBX5),1,2 or near genes important for striated muscle function and integrity (e.g. MYH7, PKP2, SSPN, SGCA). Experiments in rabbits with heart failure and left atrial dilation identified a heterogeneous distributed molecular switch from MYH6 to MYH7 in the left atrium, which resulted in contractile and functional heterogeneity and may predispose to initiation and maintenance of atrial arrhythmia.

genetics↗