In addition to the increase in ALDH identification through genomic sequencing, other sources of complexity in the ALDH superfamily are being studied. Transcript sequencing has revealed that many ALDH genes encode multiple mRNA splice variants (for a review of human ALDH splice variants, see Black et al. [30]). Besides splice variants, CNVs have been reported for human ALDH genes. By querying the Database of Genomic Variants, 35 CNVs, 28 InDels and one inversion have been detected in the ALDH family, although these records are usually representative of one or several individuals (Supplementary Table S1 (Table 5)). Of these 64 events, 33 were InDels entirely within intronic regions and may be silent. Others are likely to cause loss of function of the enzyme involved, including loss of the whole gene (11 events; occurred in ALDHs 1A3, 1B1, 3A1, 3B1, 5A1 and 16A1) or duplication, loss or inversion of exons within the coding sequence (16 events; occurred in ALDHs 1A3, 1L1, 1L2, 3A2, 3B2, 6A1 and 9A1). Finally, in a few cases, a region containing the entire gene and surrounding region was duplicated (four events; occurred in ALDH3B1 and ALDH3B2).
