Congenital heart defect (CHD), also described as congenital heart disease, is the most common type of birth defect; it is thought to have a significant genetic component. Candidate genes identified in a large-scale exome sequencing analysis have been assessed in a fly system using cardiac-targeted gene silencing of orthologous fly genes. Based on experiments using the Drosophila ortholog Ubc6, UBE2B has emerged as a strong candidate gene. The UBE2B protein plays a role in epigenetic transcriptional regulation and is required for postreplication repair of UV-damaged DNA. For the fly gene, Dmel\Ubc6, RNAi targeting constructs and alleles caused by insertional mutagenesis have been generated. Dmel\Ubc6 is also orthologous to a second gene in human, UBE2A.
The human Hsap\UBE2B gene has been introduced into flies, but has not been characterized. Dmel\Ubc6 has also been used to model a disease associated with the paralogous human gene UBE2A (see 'intellectual disability, X-linked, syndromic, Nascimento type' FBhh0000140).
Animals homozygous for loss-of-function mutations of Dmel\Ubc6 die during the larval stage; neurophysiology defects are observed in neuromuscular junctions of homozygous larvae. Targeted knockdown of Ubc6 restricted to the developing heart, effected by RNAi, results in 84% lethality prior to the adult stage; heart morphology defects are observed in larvae and in surviving adults; adult lifespan is reduced. Physical interactions of Dmel\Ubc6 have been described; see below and in the Ubc6 gene report.
[updated Nov. 2018 by FlyBase; FBrf0222196]
A congenital heart defect is a problem with the structure of the heart; it is the most common type of birth defect. The defects can involve the walls of the heart, the valves of the heart, and the arteries and veins near the heart. They can disrupt the normal flow of blood through the heart: the blood flow can slow down, go in the wrong direction or to the wrong place, or be blocked completely (https://medlineplus.gov/congenitalheartdefects.html).
Defects range from simple, which might cause no problems, to complex, which can cause life-threatening complications. The most serious defects are categorized as critical congenital heart defects (CCHD). CCHD is life threatening and requires intervention in infancy; approximately 18 out of 10,000 babies are born with CCHD (https://www.aap.org/en-us/advocacy-and-policy/aap-health-initiatives/PEHDIC/Pages/Newborn-Screening-for-CCHD.aspx).
Genetic causes of congenital heart disease also account for many of the comorbidities seen with increased frequency in congenital heart disease patients, including neurodevelopmental disability, pulmonary disease, arrhythmia, renal disease, heart failure and an increased incidence of malignancy. (Simmons and Brueckner, 2017; pubmed:28872494).
A number of well studied syndromes, including DiGeorge syndrome, Williams-Beuren syndrome, Alagille syndrome, Noonan syndrome, and Holt-Oram syndrome, include congenital heart defect (Pierpont et al., 2007; pubmed:17519398).
Congenital heart defects (CHTD) are among the most common congenital defects, occurring with an incidence of 8/1,000 live births. The etiology of CHTD is complex, with contributions from environmental exposure, chromosomal abnormalities, and gene defects. [from MIM:306955; 2018.11.13]
UBE2B encodes a member of the E2 ubiquitin-conjugating enzyme family; it is is required for postreplication repair of UV-damaged DNA and plays a role in epigenetic transcriptional regulation by catalyzing the monoubiquitination of histone H2B. [Gene Cards, UBE2B; 2018.11.14]
Many to one: 2 human to 1 Drosophila; the second human gene is UBE2A.
High-scoring ortholog of human UBE2A and UBE2B (1 Drosophila to 2 human). Dmel\Ubc6 shares 86-88% identity and 92-93% similarity with the human genes.
