Landscape of Long Noncoding RNA Genes, Pseudogenes, and Protein Genes in Segmental Duplications in the Critical Human Chromosomal Region 22q11.2

Abstract

Human chromosomal region 22q11.2 is prone to deletions that result in genetic disorders termed 22q11.2 deletion syndrome. Approximately 1 in 4000 infants are born with this deletion. The 22q11.2 region has a large number of DNA duplicated sequences termed segmental duplications or low-copy repeats (LCR22) that are known to take part in the deletion process. Here we analyze sequences that neighbor LCR22 segmental duplications to help determine their origins. Sequences immediately outside of and within the LCR22 boundaries are found highly conserved relative to analogous sequences in chimpanzee chr22. We propose that neighbor sequences form a framework for LCR22 sequence expansion, and that this framework originated in a common primate ancestor. The second part of this chapter deals with genes contained in LCR22 segmental duplications. Most LCR22 genes have not been analyzed, but they may have a bearing on the molecular basis for developmental abnormalities that result from a loss of 22q11.2. We find the largest LCR22s, LCR22A and LCR22D, primarily contain long noncoding RNA genes and pseudogenes. An analysis of linear and circular RNA transcript expression in developing fetal tissues from these LCR22 genes is also presented; this may be useful in future analyses of ncRNA gene functions in fetal development.