Congenital heart disease (CHD) is the leading cause of mortality from birth defects. Exome sequencing of a single cohort of 2,871 CHD probands including 2,645 parent-offspring trios implicated rare inherited mutations in 1.8%, including a recessive founder mutation in GDF1 accounting for ~5% of severe CHD in Ashkenazim, recessive genotypes in MYH6 accounting for ~11% of Shone complex, and dominant FLT4 mutations accounting for 2.3% of Tetralogy of Fallot. De novo mutations (DNMs) accounted for 8% of cases, including ~3% of isolated CHD patients and ~28% with both neurodevelopmental and extra-cardiac congenital anomalies. Seven genes surpassed thresholds for genome-wide significance and 12 genes not previously implicated in CHD had > 70% probability of being disease-related; DNMs in ~440 genes are inferred to contribute to CHD. There was striking overlap between genes with damaging DNMs in probands with CHD and autism.

Congenital heart disease (CHD) patients have increased prevalence of extra-cardiac congenital anomalies (CA) and risk of neurodevelopmental disabilities (NDD). Exome sequencing of 1,213 CHD parent-offspring trios identified an excess of protein-damaging de novo mutations, especially in genes highly expressed in developing heart and brain. These mutations accounted for 20% of patients with CHD, NDD and CA but only 2% with isolated CHD. Mutations altered genes involved in morphogenesis, chromatin modification, and transcriptional regulation, including multiple mutations in RBFOX2, an mRNA splice regulator. Genes mutated in other cohorts ascertained for NDD were enriched in CHD cases, particularly those with coexisting NDD. These findings reveal shared genetic contributions to CHD, NDD, and CA and provide opportunities for improved prognostic assessment and early therapeutic intervention in CHD patients.

Knowledge about the origins and evolution of crop species represents an important prerequisite for efficient conservation and use of existing plant materials. This study was designed to solve the ongoing debate on the origins of the common bean by investigating the nucleotide diversity at five gene loci of a large sample that represents the entire geographical distribution of the wild forms of this species. Our data clearly indicate a Mesoamerican origin of the common bean. They also strongly support the occurrence of a bottleneck during the formation of the Andean gene pool that predates the domestication, which was suggested by recent studies based on multilocus molecular markers. Furthermore, a remarkable result was the genetic structure that was seen for the Mesoamerican accessions, with the identification of four different genetic groups that have different relationships with the sets of wild accessions from the Andes and northern Peru–Ecuador. This finding implies that both of the gene pools from South America originated through different migration events from the Mesoamerican populations that were characteristic of central Mexico